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Bryan AD, Skrzynski CJ, Giordano G, Yang J, Stanger M, Bidwell LC, Hutchison KE, Perreault L. Cannabis use is associated with less peripheral inflammation but similar insulin sensitivity as non-use in healthy adults. Am J Med 2025:S0002-9343(25)00281-5. [PMID: 40324550 DOI: 10.1016/j.amjmed.2025.05.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2025] [Revised: 04/21/2025] [Accepted: 05/01/2025] [Indexed: 05/07/2025]
Abstract
OBJECTIVE This study tested whether cannabis affects inflammation and insulin sensitivity and if this varied based on THC:CBD ratios. Participants who currently used cannabis were assigned to use one of three cannabis flower products ad libitum for four weeks and compared to non-using participants. METHODS Healthy participants 21 to 40 years old without diabetes were included. Participants had to engage in ≥ weekly cannabis use for ≥ one year (cannabis use groups) or no cannabis use in the past year (cannabis non-use group). Participants who used cannabis purchased and used a THC-dominant (23% THC, 0% CBD), THC+CBD (10% THC, 8% CBD), or CBD-dominant product (20% CBD, 1% THC). Peripheral inflammation was assessed with several cytokines (TNF-α, IL-1β, IL-4, IL-6, IL-12, IFNG, IL10) and one chemokine (MCP-1). Insulin sensitivity was assessed via the Matsuda Index. RESULTS Models were intent-to-treat and utilized maximum likelihood estimation. Cannabis use was associated with lower peripheral inflammation (p<.001) than non-use. THC:CBD ratio of products used over four weeks did not change peripheral inflammation levels nor affect insulin sensitivity compared to non-use. CONCLUSIONS Habitual cannabis use (vs. non-use) is associated with lower peripheral inflammation with no difference in insulin sensitivity in metabolically healthy, young people.
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Zhou Z, Liu J. Association between body roundness index and incidence of type 2 diabetes in a population-based cohort study. Sci Rep 2025; 15:13186. [PMID: 40240415 PMCID: PMC12003785 DOI: 10.1038/s41598-025-92652-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Accepted: 03/03/2025] [Indexed: 04/18/2025] Open
Abstract
There is limited national data on the association between body roundness index (BRI) and type 2 diabetes (T2D). A total of 10,785 participants from the China Health and Retirement Longitudinal Study (CHARLS) with repeated BRI measurements from 2011 to 2020 were included. We used Cox proportional hazards model and restricted cubic splines (RCS) to examine the association between BRI and T2D. During a mean follow-up of 7.72 years, 1,653 incident T2D cases were documented. Multivariable Cox proportional hazards regression model demonstrated a significant correlation between the BRI and the risk of T2D. Specifically, every 1-SD increase in BRI corresponded to a 27% heightened risk of T2D (HR: 1.27, 95% CI 1.20-1.35). The analysis also uncovered a non-linear pattern in this relationship, pinpointed by an inflection point at a BRI value of 3.96. Before the inflection point, the HR was 0.85 (95% CI 0.74-0.96), while after the inflection point, the HR increased to 1.29 (95% CI 1.18-1.41). In the middle-aged and elderly Chinese population, elevated BRI was significantly and positively associated with T2D risk. BRI could be a valuable addition to current clinical and public health strategies aimed at reducing the burden of T2D.
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Affiliation(s)
- Zigui Zhou
- School of Exercise and Health, Shanghai University of Sport, 200 Hengren Road, Yangpu, Shanghai, 200438, China
| | - Jingjing Liu
- School of Exercise and Health, Shanghai University of Sport, 200 Hengren Road, Yangpu, Shanghai, 200438, China.
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Huang X, Wu Y, Ni Y, Xu H, He Y. Global, regional, and national burden of type 2 diabetes mellitus caused by high BMI from 1990 to 2021, and forecasts to 2045: analysis from the global burden of disease study 2021. Front Public Health 2025; 13:1515797. [PMID: 39916706 PMCID: PMC11798972 DOI: 10.3389/fpubh.2025.1515797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 01/10/2025] [Indexed: 02/09/2025] Open
Abstract
Objective To produce estimates of the global burden of type 2 diabetes mellitus (T2DM) caused by high body mass index (high BMI) and its impact for 2021 and projections for 2045. Methods We downloaded data from the Global Burden of Disease Study 2021(GBD 2021) to estimate the disease burden of T2DM caused by high BMI. Secondary analyses were performed by year, age, gender, region, and socio-demographic index (SDI). Results Globally, the all-ages number of T2DM-related deaths has increased significantly from 238.1 thousand to 723.7 thousand, representing a 203.9% increase since 1990. And the all-ages number of T2DM-raleted DALYs has raised from 10.4 million to 39.3 million, increased by 276.7% from 1990. The burden was expected to continue to increase to 1296.7 thousand by 2045 for all-ages number of deaths, and 85.5 million by 2045 for all-ages number of DALYs. The curves of T2DM-related burden showed an intersection for different genders around the age of 60, beyond which women exhibit a higher burden, compared to men. The disease burden of T2DM caused by high BMI shows a significant upward trend across all SDI groups, with a heavier burden on women, especially in the postmenopausal female population. In 2021, among the 204 countries and territories, the top 3 largest number of T2DM-related burden caused by high BMI occurred in China, India, and United States. The top three countries with highest T2DM-related rate caused by high BMI were Fiji, Marshall Islands, and Kiribati. Conclusion Our study reveals that the disease burden of T2DM caused by high BMI is significantly increasing and is expected to continue rising in the future. Women bear a heavier burden, particularly postmenopausal women, and there are significant differences in the disease burden across different geographical regions, and socioeconomic statuses. Targeted considerations and specific strategies are essential to address these disparities, thereby improving public health and reducing the burden.
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Affiliation(s)
| | | | | | - Haiyan Xu
- Department of Endocrinology and Metabolism, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui Municipal Central Hospital, Lishui, China
| | - Yinhui He
- Department of Endocrinology and Metabolism, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui Municipal Central Hospital, Lishui, China
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Zhang F, Sun Y, Bai Y, Wu R, Yang H. Association of triglyceride-glucose index and diabesity: evidence from a national longitudinal study. Lipids Health Dis 2024; 23:412. [PMID: 39707324 DOI: 10.1186/s12944-024-02403-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Accepted: 12/09/2024] [Indexed: 12/23/2024] Open
Abstract
BACKGROUND Diabesity, a co-occurrence of diabetes and obesity, is a growing public health concern globally. The triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, has been associated with various metabolic disorders. This study aimed to investigate the association between TyG index and new-onset diabesity in a national longitudinal study. METHODS We utilized data from the China Health and Retirement Longitudinal Study (CHARLS). Baseline data from the first wave (2011) and follow-up data from the third wave (2015) were analyzed. A Competing risks model based on Fine and Gray's subdistribution hazard approach was employed to examine the association between the TyG index and developing of three mutually exclusive outcomes: remaining free of diabetes and obesity, diabetes alone, and new-onset diabesity (co-occurrence of diabetes and obesity). RESULTS A total of 6,976 participants were included in the analysis. During a mean follow-up period of 4.0 years, a total of 557 diabetes and 155 diabesity were recorded, respectively. After adjusting for socio-demographic information, lifestyle and comorbidities, compared with participants in the lowest quartile of TyG, the corresponding adjusted subdistribution hazard ratios (HRs) with 95% confidence intervals (95% CIs) for participants in the second, third, and fourth quartiles were 2.112 (95% CI: 1.047-4.259; P-value = 0.037), 2.911 (95% CI: 1.481-5.722, P-value = 0.002), and 4.305 (95% CI: 2.220-8.346, P-value < 0.001). The association between TyG and diabetes alone was equally significant when diabesity treated as the competing risk. Sensitivity analyses proved the robustness of results. CONCLUSION This national longitudinal study in China provides evidence that a higher TyG index is associated with an increased risk of developing diabesity.
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Affiliation(s)
- Fan Zhang
- Department of Nephrology A, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yan Sun
- Department of Cardiology, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yan Bai
- Department of Nephrology A, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Rong Wu
- Department of Nephrology A, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China.
- Department of Endocrine, Longhua Hospital Shanghai University of Traditional Chinese Medicine, No. 725, Wanping South Road, Xuhui District, Shanghai, China.
| | - Hua Yang
- Department of Nephrology A, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China.
- Department of Endocrine, Longhua Hospital Shanghai University of Traditional Chinese Medicine, No. 725, Wanping South Road, Xuhui District, Shanghai, China.
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Stefil M, Gaudino M, Benedetto U, Gerry S, Gray A, Lees B, Podesser B, Krzych L, Sajja LR, Taggart D, Flather M. Influence of diabetes and obesity on ten-year outcomes after coronary artery bypass grafting in the arterial revascularisation trial. Clin Res Cardiol 2024; 113:1515-1522. [PMID: 37741811 DOI: 10.1007/s00392-023-02284-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Accepted: 08/07/2023] [Indexed: 09/25/2023]
Abstract
AIMS Diabetes and obesity are common conditions which can influence outcomes after coronary artery bypass graft (CABG) surgery. The aim of this study was to evaluate the influence of diabetes and obesity, and their interactions, on ten-year outcomes following CABG. METHODS AND RESULTS Patients enrolled in the Arterial Revascularisation Trial (ART) were stratified by diabetes and obesity at baseline. Diabetes was further stratified into insulin and non-insulin dependent. The primary outcome was all-cause mortality at 10 years of follow-up. Secondary outcomes were the composite of all-cause mortality, myocardial infarction or stroke at 10 years, and sternal wound complications at 6 months follow-up. A total of 3096 patients were included in the analysis (24% with diabetes, 30% with obesity). Patients in the "diabetes/no obesity" group had a higher risk of all-cause mortality following CABG (adjusted hazard ratio [aHR] 1.33, 95% confidence interval [CI] 1.08-1.64, p = 0.01) compared to the reference group of "no diabetes/no obesity". No excess risk was observed in the "no diabetes/obesity" or "diabetes/obesity" groups. Patients with insulin dependent diabetes had a significantly higher ten-year mortality risk compared to no diabetes (aHR 1.85, 95% CI 1.41-2.44, p = 0.00). Patients in the "diabetes/no obesity" and "diabetes/obesity groups" had a higher risk of sternal wound complications (HR 2.29, 95% CI 1.39-3.79, p < 0.001 and HR 3.21, 95% CI 1.89-5.45, p < 0.001 respectively). The composite outcome results were consistent with the mortality results. CONCLUSION Diabetes, especially insulin dependent diabetes, is associated with a higher ten-year mortality risk after CABG, in contrast to obesity which does not appear to increase long term mortality compared to non-obese. The interaction between diabetes and obesity shows an apparent "protective" effect of obesity irrespective of diabetes on mortality. Both conditions are associated with a higher risk of post-operative sternal wound infections.
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Affiliation(s)
- Maria Stefil
- Norwich Medical School, University of East Anglia and Norfolk and Norwich University Hospital, Norwich, UK.
| | - Mario Gaudino
- Department of Cardiothoracic Surgery, Weill Cornell Medicine and New York-Presbyterian Hospital, New York, USA
| | - Umberto Benedetto
- School of Clinical Sciences, University of Bristol and Bristol Royal Infirmary, Bristol, UK
| | - Stephen Gerry
- Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK
| | - Alastair Gray
- Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Belinda Lees
- Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford, UK
| | - Bruno Podesser
- Landesklinikum, St. Polten and Center for Biomedical Research, Medical University of Vienna, Vienna, Austria
| | - Lukasz Krzych
- Department of Cardiac Surgery, Medical University of Silesia, Katowice, Poland
| | - Lokeswara Rao Sajja
- Division of Cardiothoracic Surgery, Star Hospitals, Banjara Hills, Hyderabad, India
| | - David Taggart
- Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford, UK
| | - Marcus Flather
- Norwich Medical School, University of East Anglia and Norfolk and Norwich University Hospital, Norwich, UK
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Deybasso HA, Geda YD, Gebaba EM. Central obesity and associated factors among public service employees in Adama Town in Ethiopia. Sci Rep 2024; 14:26367. [PMID: 39487137 PMCID: PMC11530442 DOI: 10.1038/s41598-024-72007-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 09/02/2024] [Indexed: 11/04/2024] Open
Abstract
The prevalence of obesity is rapidly increasing, contributing to 678 million obese adults and rapidly increasing in lower-income countries. This study assessed the magnitude of central obesity and associated factors among public service office employees in Adama Town in the Oromia Regional State in Ethiopia. An institutional-based cross-sectional study was conducted from January 1 to February 26, 2020, among 590 public service employees. The data were collected by using interviewer-administered questionnaires and anthropometric measurements. The data were coded, entered, cleaned, and entered into Epi Info version 7, and subsequently exported to SPSS version 26 for statistical analysis. Binary logistic regression was used to check the associations between the explanatory and outcome variables. The adjusted odds ratio at a 95% confidence interval was used to estimate the strength of associations. A P value < 0.05 indicated statistical significance. The overall prevalence of central obesity among public service office employees was 24.2% (95% CI 20.9, 27.8). In a stratified analysis, the prevalence of central obesity was 29.9% in male and 14.9% in female employees. The multivariate analysis showed that using motorized transportation (AOR = 2.20, 95% CI 1.110, 4.385), eating food out of the home (AOR = 1.76, 95% CI 1.107, 2.800), drinking alcohol (AOR = 1.85, 95% CI 1.104, 3.128), being aged 33-42 years (AOR = 3.83, 95% CI 1.964, 7.472), 43-52 years (AOR = 4.34, 95% CI 2.151, 8.765) and 53 years and above (AOR = 10.33, 95% CI 3.783, 28.242), not engaging in moderate physical activity (AOR = 2.32, 95% CI 1.484, 3.631) and having a chronic illness (AOR = 1.97, 95% CI 1.177, 3.316) were statistically associated with central obesity among public service office employees in the study area. Nearly 25% of public service employees in the town had central obesity, which is a risk factor for metabolic syndromes. Mode of transportation, eating food out of home, drinking alcohol, age, level of physical activity, and presence of chronic illnesses were found to be independent predictors of central obesity. The public administration in the town should design a feasible preventive strategy to reduce the burden of obesity among public service employees in the study setting.
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Affiliation(s)
- Haji Aman Deybasso
- Public Health Department, Adama Hospital Medical College, Adama, Ethiopia.
| | - Yoseph Degaga Geda
- Public Health Department, Adama Hospital Medical College, Adama, Ethiopia
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Rhee TM, Choi J, Lee H, Merino J, Park JB, Kwak SH. Discrepancy Between Genetically Predicted and Observed BMI Predicts Incident Type 2 Diabetes. Diabetes Care 2024; 47:1826-1833. [PMID: 39137145 PMCID: PMC11615119 DOI: 10.2337/dc24-0879] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 07/19/2024] [Indexed: 08/15/2024]
Abstract
OBJECTIVE Obesity is a key predictor of type 2 diabetes (T2D). However, metabolic complications are not solely due to increased BMI. We hypothesized that differences between genetically predicted BMI and observed BMI (BMI-diff) could reflect deviation from individual set point and may predict incident T2D. RESEARCH DESIGN AND METHODS From the UK Biobank cohort, we selected participants of European ancestry without T2D (n = 332,154). The polygenic risk score for BMI was calculated via Bayesian regression and continuous shrinkage priors (PRS-CS). According to the BMI-diff, the 10-year risk of T2D was assessed using multivariable Cox proportional hazards model. Independent data from the Korean Genome and Epidemiology Study (KoGES) cohort from South Korea (n = 7,430) were used for replication. RESULTS Participants from the UK Biobank were divided into train (n = 268,041) and test set (n = 115,119) to establish genetically predicted BMI. In the test set, the genetically predicted BMI explained 7.1% of the variance of BMI, and there were 3,599 T2D cases (3.1%) during a 10-year follow-up. Participants in the higher quintiles of BMI-diff (more obese than genetically predicted) had significantly higher risk of T2D than those in the lowest quintile after adjusting for observed BMI: the adjusted hazard ratio of the 1st quintile (vs. 5th quintile) was 1.61 (95% CI 1.26-2.05, P < 0.001). Results were consistent among individuals in the KoGES study. Moreover, higher BMI than predicted was associated with impaired insulin sensitivity. CONCLUSIONS Having a higher BMI than genetically predicted is associated with an increased risk of T2D. These findings underscore the potential to reassess T2D risk based on individual levels of obesity using genetic thresholds for BMI.
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Affiliation(s)
- Tae-Min Rhee
- Department of Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea
| | - Jaewon Choi
- Innovative Biomedical Technology Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
| | - Hyunsuk Lee
- Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea
- Department of Translational Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- Genomic Medicine Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jordi Merino
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
| | - Jun-Bean Park
- Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea
| | - Soo Heon Kwak
- Innovative Biomedical Technology Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
- Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea
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Kim DH, Lee MJ, Kang D, Khang AR, Bae JH, Kim JY, Kim SH, Kang YH, Yi D. Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Transcription Regulation of AgRP and POMC Genes. Curr Issues Mol Biol 2024; 46:7505-7515. [PMID: 39057086 PMCID: PMC11275895 DOI: 10.3390/cimb46070445] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 07/10/2024] [Accepted: 07/12/2024] [Indexed: 07/28/2024] Open
Abstract
Sodium-glucose cotransporter 2 (SGLT2) inhibitors regulate plasma glucose levels in patients with type 2 diabetes mellitus (T2DM) by inhibiting renal glucose reabsorption. This study investigated the impact of empagliflozin (EMPA), an SGLT2 inhibitor, on hypothalamic energy regulation. To directly investigate the role of SGLT2 inhibitors in the hypothalamus, we administered EMPA through intracerebroventricular (i.c.v.) injections into the murine ventricles. After dental cementing the i.c.v. cannula onto the skull, the mice were given 5 days to recover before receiving vehicle or EMPA (50 nM/2 μL) injections. In a high-fat diet (HFD)-induced obesity model, we determined the gene expression levels of agouti-related peptide (AgRP) and pro-opiomelanocortin (POMC) in the hypothalamus. Additionally, we assessed FoxO1 expression, which regulates AgRP and POMC gene transcription in hypothalamic cell lines. We found that EMPA directly influenced the expression of endogenous mRNA of POMC and AgRP, which are critical for energy homeostasis, and modulated their transcription in high-fat diet-induced obese mice. Additionally, EMPA affected the expression of FoxO1, a key transcriptional regulator of glucose homeostasis, thereby regulating the transcriptional activity of POMC and AgRP. These results indicate that EMPA significantly influences hypothalamic energy homeostasis, highlighting its potential as a regulator in obesity and T2DM management.
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Affiliation(s)
- Dong Hee Kim
- Department of BIT Fusion Technology Center, Pusan National University, Busan 46241, Republic of Korea;
- Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea; (M.J.L.); (A.R.K.); (J.H.B.); (J.Y.K.); (S.H.K.); (Y.H.K.)
| | - Min Jin Lee
- Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea; (M.J.L.); (A.R.K.); (J.H.B.); (J.Y.K.); (S.H.K.); (Y.H.K.)
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea
| | - Dasol Kang
- Department of Biological Sciences, College of National Sciences, University of Ulsan, Ulsan 44919, Republic of Korea;
| | - Ah Reum Khang
- Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea; (M.J.L.); (A.R.K.); (J.H.B.); (J.Y.K.); (S.H.K.); (Y.H.K.)
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea
| | - Ji Hyun Bae
- Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea; (M.J.L.); (A.R.K.); (J.H.B.); (J.Y.K.); (S.H.K.); (Y.H.K.)
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea
| | - Joo Yeon Kim
- Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea; (M.J.L.); (A.R.K.); (J.H.B.); (J.Y.K.); (S.H.K.); (Y.H.K.)
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea
| | - Su Hyun Kim
- Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea; (M.J.L.); (A.R.K.); (J.H.B.); (J.Y.K.); (S.H.K.); (Y.H.K.)
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea
| | - Yang Ho Kang
- Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea; (M.J.L.); (A.R.K.); (J.H.B.); (J.Y.K.); (S.H.K.); (Y.H.K.)
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea
| | - Dongwon Yi
- Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea; (M.J.L.); (A.R.K.); (J.H.B.); (J.Y.K.); (S.H.K.); (Y.H.K.)
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea
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Ajjan RA, Battelino T, Cos X, Del Prato S, Philips JC, Meyer L, Seufert J, Seidu S. Continuous glucose monitoring for the routine care of type 2 diabetes mellitus. Nat Rev Endocrinol 2024; 20:426-440. [PMID: 38589493 DOI: 10.1038/s41574-024-00973-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/29/2024] [Indexed: 04/10/2024]
Abstract
Although continuous glucose monitoring (CGM) devices are now considered the standard of care for people with type 1 diabetes mellitus, the uptake among people with type 2 diabetes mellitus (T2DM) has been slower and is focused on those receiving intensive insulin therapy. However, increasing evidence now supports the inclusion of CGM in the routine care of people with T2DM who are on basal insulin-only regimens or are managed with other medications. Expanding CGM to these groups could minimize hypoglycaemia while allowing efficient adaptation and escalation of therapies. Increasing evidence from randomized controlled trials and observational studies indicates that CGM is of clinical value in people with T2DM on non-intensive treatment regimens. If further studies confirm this finding, CGM could soon become a part of routine care for T2DM. In this Perspective we explore the potential benefits of widening the application of CGM in T2DM, along with the challenges that must be overcome for the evidence-based benefits of this technology to be delivered for all people with T2DM.
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Affiliation(s)
- Ramzi A Ajjan
- The LIGHT Laboratories, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
| | - Tadej Battelino
- Faculty of Medicine, University of Ljubljana Medical Centre, Ljubljana, Slovenia
| | - Xavier Cos
- DAP Cat Research Group, Foundation University Institute for Primary Health Care Research Jordi Gol i Gorina, Barcelona, Spain
| | - Stefano Del Prato
- Section of Diabetes and Metabolic Diseases, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | | | - Laurent Meyer
- Department of Endocrinology, Diabetes and Nutrition, University Hospital, Strasbourg, France
| | - Jochen Seufert
- Division of Endocrinology and Diabetology, Department of Medicine II, Medical Centre, University of Freiburg, Freiburg, Germany
| | - Samuel Seidu
- Leicester Real World Evidence Unit, Diabetes Research Centre, University of Leicester, Leicester, UK.
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Salamah HM, Marey A, Elsayed E, Hasan MT, Mahmoud A, Abualkhair KA, Abo-Elnour DE, Abdelhaleem IA, Abd-Elgawad M. Efficacy and safety of polyethylene glycol loxenatide in type 2 diabetic patients: a systematic review and meta-analysis of randomized controlled trials. Sci Rep 2023; 13:19041. [PMID: 37923756 PMCID: PMC10624877 DOI: 10.1038/s41598-023-46274-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2023] [Accepted: 10/30/2023] [Indexed: 11/06/2023] Open
Abstract
Polyethylene glycol loxenatide (PEX168) is a novel glucagon-like peptide-1 receptor agonist with a longer half-life developed by modifying the chemical structure of exenatide. This study aims to assess the efficacy and safety of PEX168 and determine the best dose. We searched PubMed, Scopus, Cochrane Library, and Web of Science databases from inception to April 25, 2023, for randomized controlled trials (RCTs) comparing PEX168 therapy alone or in combination with metformin versus other therapies. We used the risk ratio (RR) for dichotomous outcomes and the mean difference (MD) for continuous outcomes, both with 95% confidence intervals (CI). Six RCTs, including 1248 participants, were included. PEX168 added to metformin was significantly better than metformin alone regarding fasting blood glucose (MD = -1.20, 95% CI (-1.78, - 0.62), p < 0.0001), HbA1c (MD = -1.01, 95% CI (-1.48, - 0.53), p < 0.0001), and postprandial glycemia (MD = -1.94, 95% CI (-2.99, - 0.90), p = 0.0003). Similarly, for glycemic control, PEX168 monotherapy was superior to placebo (P < 0.05). No significant effects were noticed in terms of triglycerides, low-density lipoprotein, or high-density lipoprotein (p > 0.05). Body weight was significantly reduced in obese diabetic patients receiving PEX168 compared to the control group (MD = -5.46, 95% CI (-7.90, - 3.01), p < 0.0001) but not in non-obese patients (MD = 0.06, 95% CI (-0.47, 0.59), p = 0.83). People who received PEX168 alone or with metformin showed more common gastrointestinal adverse effects, especially nausea and vomiting (p < 0.05). PEX168 100, 200, and 300 ug monotherapy demonstrated comparable safety and diabetes control to metformin, but when combined with metformin, PEX168 100 and 200 ug showed significant effects on diabetes control; however, only the latter showed a significantly higher incidence of nausea and vomiting (p < 0.05). PEX168 could be a viable option for treating diabetic patients whose metformin control is inadequate or who cannot tolerate metformin. PEX168 at 100 ug in combination with metformin was found to be safe and more effective compared to metformin; however, due to the small number of trials included, these findings should be interpreted with caution, and additional trials are required.
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Affiliation(s)
| | - Ahmed Marey
- Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Esraa Elsayed
- Faculty of Medicine, Zagazig University, Zagazig, 44519, Egypt
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11
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Waataja JJ, Asp AJ, Billington CJ. Combining Celiac and Hepatic Vagus Nerve Neuromodulation Reverses Glucose Intolerance and Improves Glycemic Control in Pre- and Overt-Type 2 Diabetes Mellitus. Biomedicines 2023; 11:2452. [PMID: 37760895 PMCID: PMC10525327 DOI: 10.3390/biomedicines11092452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 08/16/2023] [Accepted: 08/18/2023] [Indexed: 09/29/2023] Open
Abstract
Neurological disorders and type 2 diabetes mellitus (T2DM) are deeply intertwined. For example, autonomic neuropathy contributes to the development of T2DM and continued unmanaged T2DM causes further progression of nerve damage. Increasing glycemic control has been shown to prevent the onset and progression of diabetic autonomic neuropathies. Neuromodulation consisting of combined stimulation of celiac vagal fibers innervating the pancreas with concurrent electrical blockade of neuronal hepatic vagal fibers innervating the liver has been shown to increase glycemic control in animal models of T2DM. The present study demonstrated that the neuromodulation reversed glucose intolerance in alloxan-treated swine in both pre- and overt stages of T2DM. This was demonstrated by improved performance on oral glucose tolerance tests (OGTTs), as assessed by area under the curve (AUC). In prediabetic swine (fasting plasma glucose (FPG) range: 101-119 mg/dL) the median AUC decreased from 31.9 AUs (IQR = 28.6, 35.5) to 15.9 AUs (IQR = 15.1, 18.3) p = 0.004. In diabetic swine (FPG range: 133-207 mg/dL) the median AUC decreased from 54.2 AUs (IQR = 41.5, 56.6) to 16.0 AUs (IQR = 15.4, 21.5) p = 0.003. This neuromodulation technique may offer a new treatment for T2DM and reverse glycemic dysregulation at multiple states of T2DM involved in diabetic neuropathy including at its development and during progression.
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Affiliation(s)
| | - Anders J. Asp
- Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN 55605, USA
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12
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Weintraub MA, D’Angelo D, Tchang BG, Sahagun AD, Andre C, Aronne LJ, Shukla AP. Five-year Weight Loss Maintenance With Obesity Pharmacotherapy. J Clin Endocrinol Metab 2023; 108:e832-e841. [PMID: 36810608 PMCID: PMC10438886 DOI: 10.1210/clinem/dgad100] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 02/10/2023] [Accepted: 02/15/2023] [Indexed: 02/24/2023]
Abstract
CONTEXT Long-term treatment of obesity with lifestyle changes alone is unsustainable for most individuals because of several factors including adherence and metabolic adaptation. Medical management of obesity has proven efficacy for up to 3 years in randomized controlled trials. However, there is a dearth of information regarding real-world outcomes beyond 3 years. OBJECTIVE This work aimed to assess long-term weight loss outcomes over a 2.5- to 5.5-year period with US Food and Drug Administration (FDA)-approved and off-label antiobesity medications (AOMs). METHODS A cohort of 428 patients with overweight or obesity were treated with AOMs at an academic weight management center with an initial visit between April 1, 2014, and April 1, 2016. Intervention included FDA-approved and off-label AOMs. The primary outcome was percentage weight loss from initial to final visit. Key secondary outcomes included weight reduction targets as well as demographic and clinical predictors of long-term weight loss. RESULTS The average weight loss was 10.4% at a mean follow-up duration of 4.4 years. The proportions of patients who met the weight reduction targets of 5% or greater, 10% or greater, 15% or greater, and 20% or greater were 70.8%, 48.1%, 29.9%, and 17.1%, respectively. On average, 51% of maximum weight loss was regained, while 40.2% of patients maintained their weight loss. In a multivariable regression analysis, a higher number of clinic visits was associated with more weight loss. Metformin, topiramate, and bupropion were associated with increased odds of maintaining 10% or greater weight loss. CONCLUSION Clinically significant long-term weight loss of 10% or more beyond 4 years is achievable in clinical practice settings with obesity pharmacotherapy.
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Affiliation(s)
- Michael A Weintraub
- Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Comprehensive Weight Control Center, Weill Cornell Medicine, New York, NY 10021, USA
| | - Debra D’Angelo
- Division of Biostatistics, Department of Population Health Sciences, Weill Cornell Medicine, New York, NY 10021, USA
| | - Beverly G Tchang
- Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Comprehensive Weight Control Center, Weill Cornell Medicine, New York, NY 10021, USA
| | - Ageline D Sahagun
- Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Comprehensive Weight Control Center, Weill Cornell Medicine, New York, NY 10021, USA
| | - Clarissa Andre
- Department of Internal Medicine, New York Presbyterian Hospital–Weill Cornell, New York, NY 10021, USA
| | - Louis J Aronne
- Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Comprehensive Weight Control Center, Weill Cornell Medicine, New York, NY 10021, USA
| | - Alpana P Shukla
- Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Comprehensive Weight Control Center, Weill Cornell Medicine, New York, NY 10021, USA
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13
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Ayodeji SA, Bao B, Teslow EA, Polin LA, Dyson G, Bollig-Fischer A, Fehl C. Hyperglycemia and O-GlcNAc transferase activity drive a cancer stem cell pathway in triple-negative breast cancer. Cancer Cell Int 2023; 23:102. [PMID: 37231419 PMCID: PMC10210312 DOI: 10.1186/s12935-023-02942-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2022] [Accepted: 05/10/2023] [Indexed: 05/27/2023] Open
Abstract
BACKGROUND Enhanced glucose metabolism is a feature of most tumors, but downstream functional effects of aberrant glucose flux are difficult to mechanistically determine. Metabolic diseases including obesity and diabetes have a hyperglycemia component and are correlated with elevated pre-menopausal cancer risk for triple-negative breast cancer (TNBC). However, determining pathways for hyperglycemic disease-coupled cancer risk remains a major unmet need. One aspect of cellular sugar utilization is the addition of the glucose-derived protein modification O-GlcNAc (O-linked N-acetylglucosamine) via the single human enzyme that catalyzes this process, O-GlcNAc transferase (OGT). The data in this report implicate roles of OGT and O-GlcNAc within a pathway leading to cancer stem-like cell (CSC) expansion. CSCs are the minor fraction of tumor cells recognized as a source of tumors as well as fueling metastatic recurrence. The objective of this study was to identify a novel pathway for glucose-driven expansion of CSC as a potential molecular link between hyperglycemic conditions and CSC tumor risk factors. METHODS We used chemical biology tools to track how a metabolite of glucose, GlcNAc, became linked to the transcriptional regulatory protein tet-methylcytosine dioxygenase 1 (TET1) as an O-GlcNAc post-translational modification in three TNBC cell lines. Using biochemical approaches, genetic models, diet-induced obese animals, and chemical biology labeling, we evaluated the impact of hyperglycemia on CSC pathways driven by OGT in TNBC model systems. RESULTS We showed that OGT levels were higher in TNBC cell lines compared to non-tumor breast cells, matching patient data. Our data identified that hyperglycemia drove O-GlcNAcylation of the protein TET1 via OGT-catalyzed activity. Suppression of pathway proteins by inhibition, RNA silencing, and overexpression confirmed a mechanism for glucose-driven CSC expansion via TET1-O-GlcNAc. Furthermore, activation of the pathway led to higher levels of OGT production via feed-forward regulation in hyperglycemic conditions. We showed that diet-induced obesity led to elevated tumor OGT expression and O-GlcNAc levels in mice compared to lean littermates, suggesting relevance of this pathway in an animal model of the hyperglycemic TNBC microenvironment. CONCLUSIONS Taken together, our data revealed a mechanism whereby hyperglycemic conditions activated a CSC pathway in TNBC models. This pathway can be potentially targeted to reduce hyperglycemia-driven breast cancer risk, for instance in metabolic diseases. Because pre-menopausal TNBC risk and mortality are correlated with metabolic diseases, our results could lead to new directions including OGT inhibition for mitigating hyperglycemia as a risk factor for TNBC tumorigenesis and progression.
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Affiliation(s)
- Saheed A Ayodeji
- Department of Chemistry, Wayne State University, 5101 Cass Avenue, Detroit, MI, USA
| | - Bin Bao
- Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, 48201, USA
| | - Emily A Teslow
- Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, 48201, USA
| | - Lisa A Polin
- Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, 48201, USA
| | - Greg Dyson
- Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, 48201, USA
| | - Aliccia Bollig-Fischer
- Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, 48201, USA
| | - Charlie Fehl
- Department of Chemistry, Wayne State University, 5101 Cass Avenue, Detroit, MI, USA.
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Stannard S, Berrington A, Alwan NA. Exploring the associations between number of children, multi-partner fertility and risk of obesity at midlife: Findings from the 1970 British Cohort Study (BCS70). PLoS One 2023; 18:e0282795. [PMID: 37053250 PMCID: PMC10101483 DOI: 10.1371/journal.pone.0282795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Accepted: 02/22/2023] [Indexed: 04/14/2023] Open
Abstract
BACKGROUND Early parenthood, high parity, and partnership separation are associated with obesity. However, the emergence of non-marital partnerships, serial partnering and childbearing across unions, means that it is important to consider their association to obesity. This paper examined the associations between number of biological children and multi-partner fertility (MPF)-defined as having biological children with more than one partner, with obesity at midlife. METHOD The sample consisted of 2940 fathers and 3369 mothers in the 1970 British Cohort Study. The outcome was obesity (BMI 30 or over) at age 46. Fertility and partnership histories ascertained the number of live biological children and MPF status by age 42. The associations were tested using logistic regression adjusting for confounders at birth, age 10 and age 16. Adult factors recorded at age 42 including age at first birth, smoking status, alcohol dependency, educational attainment and housing tenure were considered as mediators. RESULTS For fathers, obesity odds did not differ according to number of children or MPF. In unadjusted models, mothers with one child (OR 1.24 95%CI 1.01-1.51), mothers who had two children with two partners (OR 1.45 95%CI 1.05-1.99), and mothers who had three or more children with two or more partners (OR 1.51 95%CI 1.18-1.93) had higher odds of obesity. In adjusted models, there remained an association between mothers with one child and odds of obesity (OR 1.30 95%CI 1.05-1.60). All other associations were attenuated when confounders were included. CONCLUSIONS Mothers who had children with multiple partners had higher odds of obesity. However this association was completely attenuated when parental and child confounders were accounted for; suggesting that this association may be explained by confounding. Mothers who had one child only may be at increased odds of obesity, however this could be due to multiple factors including age at first birth.
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Affiliation(s)
- Sebastian Stannard
- Department of Social Statistics and Demography, University of Southampton, Southampton, United Kingdom
- ESRC Centre for Population Change, University of Southampton, Southampton, United Kingdom
- Faculty of Medicine, School of Primary Care and Population Sciences, University of Southampton, Southampton, United Kingdom
| | - Ann Berrington
- Department of Social Statistics and Demography, University of Southampton, Southampton, United Kingdom
- ESRC Centre for Population Change, University of Southampton, Southampton, United Kingdom
| | - Nisreen A. Alwan
- Faculty of Medicine, School of Primary Care and Population Sciences, University of Southampton, Southampton, United Kingdom
- NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom
- NIHR Applied Research Collaboration Wessex, Southampton, United Kingdom
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15
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Smith ML, Bull CJ, Holmes MV, Davey Smith G, Sanderson E, Anderson EL, Bell JA. Distinct metabolic features of genetic liability to type 2 diabetes and coronary artery disease: a reverse Mendelian randomization study. EBioMedicine 2023; 90:104503. [PMID: 36870196 PMCID: PMC10009453 DOI: 10.1016/j.ebiom.2023.104503] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 02/13/2023] [Accepted: 02/13/2023] [Indexed: 03/06/2023] Open
Abstract
BACKGROUND Type 2 diabetes (T2D) and coronary artery disease (CAD) both have known genetic determinants, but the mechanisms through which their associated genetic variants lead to disease onset remain poorly understood. METHODS We used large-scale metabolomics data in a two-sample reverse Mendelian randomization (MR) framework to estimate effects of genetic liability to T2D and CAD on 249 circulating metabolites in the UK Biobank (N = 118,466). We examined the potential for medication use to distort effect estimates by conducting age-stratified metabolite analyses. FINDINGS Using inverse variance weighted (IVW) models, higher genetic liability to T2D was estimated to decrease high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) (e.g. , HDL-C -0.05 SD; 95% CI -0.07 to -0.03, per doubling of liability), whilst increasing all triglyceride groups and branched chain amino acids (BCAAs). IVW estimates for CAD liability suggested an effect on reducing HDL-C as well as raising very-low density lipoprotein cholesterol (VLDL-C) and LDL-C. In pleiotropy-robust models, T2D liability was still estimated to increase BCAAs, but several estimates for higher CAD liability reversed and supported decreased LDL-C and apolipoprotein-B. Estimated effects of CAD liability differed substantially by age for non-HDL-C traits, with higher CAD liability lowering LDL-C only at older ages when statin use was common. INTERPRETATION Overall, our results support largely distinct metabolic features of genetic liability to T2D and CAD, illustrating both challenges and opportunities for preventing these commonly co-occurring diseases. FUNDING Wellcome Trust [218495/Z/19/Z], UK MRC [MC_UU_00011/1; MC_UU_00011/4], the University of Bristol, Diabetes UK [17/0005587], World Cancer Research Fund [IIG_2019_2009].
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Affiliation(s)
- Madeleine L Smith
- Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
| | - Caroline J Bull
- Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK; School of Translational Health Sciences, University of Bristol, Bristol, UK
| | - Michael V Holmes
- Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - George Davey Smith
- Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Eleanor Sanderson
- Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Emma L Anderson
- Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Joshua A Bell
- Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
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16
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Ağbaht K, Pişkinpaşa SV. Serum TSH, 25(OH) D and phosphorus levels predict weight loss in individuals with diabetes/prediabetes and morbid obesity: a single-center retrospective cohort analysis. BMC Endocr Disord 2022; 22:282. [PMID: 36401211 PMCID: PMC9673446 DOI: 10.1186/s12902-022-01202-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 11/05/2022] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND To evaluate the association of vitamin D and thyroid-stimulating hormone (TSH) with weight loss (WL) percentage (%) in patients with diabetes/prediabetes and Class II/III obesity. METHODS A retrospective cohort study was designed. Data were collected from a database of a referral endocrinology clinic that is prospectively and systematically generated. After exclusion of unavailable cases, the study enrolled 285 patients (51 ± 11 years old, female/male = 208/77; diabetes/prediabetes = 159/126; no/on levothyroxine replacement = 176/109; Class II/III obesity = 184/101, respectively) who maintained euthyroidism and were followed up for ≥6 months. The data were analyzed to determine the predictors of WL%. RESULTS Compared with baseline, in the median 22 months of follow-up, the whole study group lost 5.1% of their baseline body weight. As most obesity management trials define success as 'at least 10% of WL compared to baseline', we stratified the patients based on WL% extents. The distribution was as follow: Group 1 (n = 61) lost ≥10% body weight, Group 2 (n = 162) lost < 10% body weight, while Group 3 (n = 62) gained weight by the final visit. In groups 1 and 2 (weight losers), the serum thyroid stimulatig hormone (TSH) and parathyroid hormone (PTH) levels decreased and the free thyroxine (fT4), calcium, phosphorus, and 25-hydroxyvitamin D (25(OH)D) levels increased. In Group 3 (weight gainers), these changes were not observed (except for an increase in calcium levels). Regression analysis revealed that the final visit TSH (β = - 0.14, p < 0.05), 25(OH) D (β = 0.15, p < 0.05), and phosphorus (β = 0.20, p < 0.05) levels predicted WL%. However, if patients with autoimmune thyroiditis were excluded from the analysis, the decrease in TSH levels was not statistically significant. CONCLUSIONS Serum TSH, phosphorus, and 25(OH) D levels predict WL% in euthyroid patients with diabetes/prediabetes and morbid obesity. TSH predictivity seems to be a function of thyroid autoimmunity present with increased frequency in this cohort. Greater levels of phosphorus within the reference range and a sufficient vitamin D status are associated with a greater WL%.
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Affiliation(s)
- Kemal Ağbaht
- Defne Hospital, Endocrinology and Metabolic Diseases Department, Odabaşı Mahallesi, Uğur Mumcu Bulvarı, No: 101, Antakya, Hatay, Turkey.
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17
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Salehidoost R, Taghipour Boroujeni G, Feizi A, Aminorroaya A, Amini M. Effect of oral magnesium supplement on cardiometabolic markers in people with prediabetes: a double blind randomized controlled clinical trial. Sci Rep 2022; 12:18209. [PMID: 36307427 PMCID: PMC9616938 DOI: 10.1038/s41598-022-20277-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 09/12/2022] [Indexed: 12/31/2022] Open
Abstract
To evaluate the effect of magnesium supplementation on insulin resistance and cardiovascular markers in people with prediabetes. A 12 week double-blind placebo-controlled randomized clinical trial was conducted at Isfahan Endocrine and Metabolism Research Center, Iran, on people with prediabetes (n = 86) to compare the effects of magnesium oxide 250 mg/day versus a placebo on anthropometric indices, blood pressure, fasting glucose, insulin, HOMA-IR index, C-reactive protein, uric acid and lipid profile. Both groups had similar distributions of anthropometric and biochemical variables at baseline. Those who received magnesium supplementation had significantly higher levels of HDL-cholesterol compared to the placebo group at the end of the study (49.7 ± 10.9 vs 43.6 ± 7.2 mg/dL, P = 0.003). The mean changes of HOMA-IR index, total cholesterol, LDL-cholesterol, triglyceride, uric acid and C-reactive protein levels as well as anthropometric indices and blood pressure in supplemented and placebo groups did not differ significantly. Magnesium supplementation increased HDL-cholesterol levels in people with prediabetes. However, other cardiometabolic markers were not improved by magnesium supplementation at the above dosage and duration.
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Affiliation(s)
- Rezvan Salehidoost
- grid.411036.10000 0001 1498 685XIsfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Golshan Taghipour Boroujeni
- grid.440800.80000 0004 0382 5622Internal Medicine Department, Medical University of Shahrekord, Shahrekord, Iran
| | - Awat Feizi
- grid.411036.10000 0001 1498 685XBiostatistics and Epidemiology Department, School of Public Health, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Ashraf Aminorroaya
- grid.411036.10000 0001 1498 685XIsfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, 8187698191 Iran
| | - Masoud Amini
- grid.411036.10000 0001 1498 685XIsfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, 8187698191 Iran
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18
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Yacamán Méndez D, Zhou M, Trolle Lagerros Y, Gómez Velasco DV, Tynelius P, Gudjonsdottir H, Ponce de Leon A, Eeg-Olofsson K, Östenson CG, Brynedal B, Aguilar Salinas CA, Ebbevi D, Lager A. Characterization of data-driven clusters in diabetes-free adults and their utility for risk stratification of type 2 diabetes. BMC Med 2022; 20:356. [PMID: 36253773 PMCID: PMC9578256 DOI: 10.1186/s12916-022-02551-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 09/02/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The prevention of type 2 diabetes is challenging due to the variable effects of risk factors at an individual level. Data-driven methods could be useful to detect more homogeneous groups based on risk factor variability. The aim of this study was to derive characteristic phenotypes using cluster analysis of common risk factors and to assess their utility to stratify the risk of type 2 diabetes. METHODS Data on 7317 diabetes-free adults from Sweden were used in the main analysis and on 2332 diabetes-free adults from Mexico for external validation. Clusters were based on sex, family history of diabetes, educational attainment, fasting blood glucose and insulin levels, estimated insulin resistance and β-cell function, systolic and diastolic blood pressure, and BMI. The risk of type 2 diabetes was assessed using Cox proportional hazards models. The predictive accuracy and long-term stability of the clusters were then compared to different definitions of prediabetes. RESULTS Six risk phenotypes were identified independently in both cohorts: very low-risk (VLR), low-risk low β-cell function (LRLB), low-risk high β-cell function (LRHB), high-risk high blood pressure (HRHBP), high-risk β-cell failure (HRBF), and high-risk insulin-resistant (HRIR). Compared to the LRHB cluster, the VLR and LRLB clusters showed a lower risk, while the HRHBP, HRBF, and HRIR clusters showed a higher risk of developing type 2 diabetes. The high-risk clusters, as a group, had a better predictive accuracy than prediabetes and adequate stability after 20 years. CONCLUSIONS Phenotypes derived using cluster analysis were useful in stratifying the risk of type 2 diabetes among diabetes-free adults in two independent cohorts. These results could be used to develop more precise public health interventions.
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Affiliation(s)
- Diego Yacamán Méndez
- Department of Global Public Health, Karolinska Institutet, SE-171 77, Stockholm, Sweden. .,Center for Epidemiology and Community Medicine (CES), Stockholm Health Care Services, Stockholm, Sweden. .,Obesity Center, Academic Specialist Center, Stockholm Health Care Services, Stockholm, Sweden.
| | - Minhao Zhou
- Center for Epidemiology and Community Medicine (CES), Stockholm Health Care Services, Stockholm, Sweden
| | - Ylva Trolle Lagerros
- Obesity Center, Academic Specialist Center, Stockholm Health Care Services, Stockholm, Sweden.,Clinical Epidemiology Division, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Donaji V Gómez Velasco
- Unidad de Investigación de Enfermedades Metabólicas, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Mexico City, Mexico
| | - Per Tynelius
- Department of Global Public Health, Karolinska Institutet, SE-171 77, Stockholm, Sweden.,Center for Epidemiology and Community Medicine (CES), Stockholm Health Care Services, Stockholm, Sweden
| | - Hrafnhildur Gudjonsdottir
- Department of Global Public Health, Karolinska Institutet, SE-171 77, Stockholm, Sweden.,Center for Epidemiology and Community Medicine (CES), Stockholm Health Care Services, Stockholm, Sweden
| | - Antonio Ponce de Leon
- Center for Epidemiology and Community Medicine (CES), Stockholm Health Care Services, Stockholm, Sweden
| | - Katarina Eeg-Olofsson
- Department of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Claes-Göran Östenson
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - Boel Brynedal
- Department of Global Public Health, Karolinska Institutet, SE-171 77, Stockholm, Sweden.,Center for Epidemiology and Community Medicine (CES), Stockholm Health Care Services, Stockholm, Sweden
| | - Carlos A Aguilar Salinas
- Unidad de Investigación de Enfermedades Metabólicas, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Mexico City, Mexico
| | - David Ebbevi
- Department of Global Public Health, Karolinska Institutet, SE-171 77, Stockholm, Sweden.,Center for Epidemiology and Community Medicine (CES), Stockholm Health Care Services, Stockholm, Sweden
| | - Anton Lager
- Department of Global Public Health, Karolinska Institutet, SE-171 77, Stockholm, Sweden.,Center for Epidemiology and Community Medicine (CES), Stockholm Health Care Services, Stockholm, Sweden
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Ekun OA, Fagbemi OF, Adejumo EN, Ekun OO, Wojuade KS, Oshundun FM, Adefolaju FO, Oyegbami SR. Assessment of electrolytes, markers of glycaemic control and renal dysfunction among adult Nigerians recently diagnosed with type 2 diabetes mellitus. Afr Health Sci 2022; 22:296-306. [PMID: 36910351 PMCID: PMC9993265 DOI: 10.4314/ahs.v22i3.31] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Background Diabetes mellitus is a chronic and progressive endocrine disorder that may result in macro and microvascular complications. Objective This study assessed some biochemical analytes in Nigerians who were recently (≤ 6 months) diagnosed with Type 2 diabetes mellitus (T2DM). Methods 160 T2DM and 90 non-diabetic control participated in this study. Blood samples were collected and analyzed for Heart-type fatty acid-binding protein (HFABP), high sensitivity C-reactive protein (hs-CRP), electrolytes, lipid and renal profile parameters, glycated haemoglobin (HBA1C) and fasting blood glucose (FBG), using standard guidelines. Result The body mass index (BMI) of the T2DM volunteers was higher than control (P <0.001). The lipid profile, potassium, glucose, HBA1C, urea and creatinine values were elevated (P <0.001) while estimated glomerular filtration rate (eGFR) was lower (P<0.05) in diabetes. The median HFABP and hs-CRP were raised (P <0.05) in T2DM. Positive associations existed between FBG and urea (P <0.001), Creatinine and HBAIC (P <0.001). A logistic regression analysis, shows that an increased BMI, HBA1C, FBG, Cholesterol, urea and creatinine were associated with higher odds (p<0.001) of cardiovascular and renal complications. Conclusion Elevated hs-CRP, glycated haemoglobin, urea and creatinine among T2DM increase the odds of cardiovascular and renal insults in this population.
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Affiliation(s)
- Oloruntoba A Ekun
- Department of Medical Laboratory Science, College of Medicine University of Lagos
| | | | - Esther N Adejumo
- Department of Medical Laboratory science Babcock University Ilishan Remo, Ogun State
| | - Oyeronke O Ekun
- Department of Medical Laboratory Science, College of Medicine University of Lagos
| | - Kehinde S Wojuade
- School of Medical Laboratory Science, Lagos University Teaching Hospital
| | - Folu M Oshundun
- Department of Medical Laboratory Science, College of Medicine University of Lagos
| | - Florence O Adefolaju
- Department of Haematology and Blood group Serology, College of Medicine University of Lagos
| | - Sade R Oyegbami
- Department of Medical Laboratory Science, College of Medicine University of Lagos
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20
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Giha HA, Joatar FE, AlDehaini DMB, Malalla ZHA, Ali ME, Al Qarni AA. Association of obesity in T2DM with differential polymorphism of ghrelin, growth hormone secretagogue receptor-1 and telomeres maintenance genes. Horm Mol Biol Clin Investig 2022; 43:297-306. [PMID: 35446515 DOI: 10.1515/hmbci-2021-0063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Accepted: 03/12/2022] [Indexed: 11/15/2022]
Abstract
BACKGROUND Although obesity and T2DM comorbidity is too frequent, the molecular basis of diabetic obesity is largely unexplained and barely investigated. MATERIALS Cross-sectional studies were conducted in Kingdom of Saudi Arabia (KSA) in 2013 and Kuwait in 2019. Fasting blood samples were obtained from a total of 216 T2DM patients (104 from KSA) and 193 nondiabetic subjects (93 from KSA) after their consents. Eight SNPs in 5 genes known to be associated with both obesity and T2DM, ghrelin (GHRL) and growth hormone secretagogue receptor -GHSR (KSA) and telomeres maintenance genes (Kuwait) were genotyped by rtPCR. Both patients and controls were grouped into obese and non-obese and sub-grouped into 4-BMI- grades: normal, overweight (OW), obese (OBS) and severely obese (SOBS). RESULTS Showed that the only SNP which was distinguished between all groups/subgroups in all study subjects was the ACYP2 rs6713088G/C, where the common CC genotype was under-expressed in the obese compared to non-obese diabetics (17.8% vs. 40.4%, p 0.01) and between the 4-BMI-grade (p 0.025). Interestingly the same genotype was over-expressed in obese compared to non-obese non-diabetics (50% vs. 27.6%, p 0.04). Furthermore, the GHRL (rs27647C/T), GHSR (rs509030G/C) and TERC (rs12696304G/C) MAFs were significantly low in normal BMI patients; p=0.034, 0.008 and 0.011, respectively. CONCLUSIONS This is the first report about the molecular distinction between the obese and non-obese diabetics, it showed the association of rs6713088G/C mutant allele with diabetic obesity, while the GHRL, GHSR and TERC SNPs were differentially expressed based on the BMI-grades.
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Affiliation(s)
- Hayder A Giha
- Medical Biochemistry and Molecular Biology, Khartoum, Sudan
| | - Faris E Joatar
- Clinical Biochemistry Laboratory, King Abdulaziz Hospital, Ministry of National Guard Health affairs, Al Ahsa, Saudi Arabia
| | | | - Zainab H A Malalla
- Medical Department of Biochemistry, College of Medicine and Medical Sciences (CMMS), Arabian Gulf University (AGU), Manama, Kingdom of Bahrain
| | - Muhalab E Ali
- Medical Department of Biochemistry, College of Medicine and Medical Sciences (CMMS), Arabian Gulf University (AGU), Manama, Kingdom of Bahrain
| | - Ali A Al Qarni
- Endocrinology and Metabolism Section, King Abdulaziz Hospital, Ministry of National Guard Health Affairs, King Abdullah Medical Research Center-Estern Region, Al Ahsa, Saudi Arabia
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21
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Touré M, Hichami A, Sayed A, Suliman M, Samb A, Khan NA. Association between polymorphisms and hypermethylation of CD36 gene in obese and obese diabetic Senegalese females. Diabetol Metab Syndr 2022; 14:117. [PMID: 35982478 PMCID: PMC9386198 DOI: 10.1186/s13098-022-00881-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Accepted: 07/26/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Obesity and related metabolic disorders are associated with genetic and epigenetic alterations. In this study, we have examined the association between polymorphisms and hypermethylation of the CD36 gene promoter with obesity in Senegalese females with or without type 2 diabetes mellitus to identify novel molecular markers of these pathologies (obesity and type 2 diabetes mellitus). MATERIALS AND METHODS The study was conducted in Senegal with healthy lean control, obese, and obese diabetic (age; 49.98 years ± 7.52 vs 50.50 years ± 8.76 vs 51.06 ± 5.78, and body mass index (BMI); 24.19 kg/m2 ± 2.74 vs 34.30 kg/m2 ± 4.41 vs 33.09 kg/m2 ± 4.30). We determined three genetic polymorphisms of CD36 i.e., rs1761667, rs1527483, and rs3211867 by real-time polymerase chain reaction, and methylation of CPG islands of CD36 was assessed by methylation-specific polymerase chain reaction (MS-PCR) in DNA isolated from peripheral blood of each participant. Plasma sCD36 levels and DNA methyltransferase 3a (DNMT3a) levels were determined by enzyme-linked immunosorbent assay (ELISA). According to the standard laboratory protocol, all biochemical parameters were analyzed from fasting serum or plasma. RESULTS For rs1761667, obese and obese diabetic subjects had statistically significant different parameters depending on the genotypic distribution. These were waist size for obese and HDL cholesterol for obese diabetic, they were significantly higher in subjects harboring GG genotype of rs1761667 (respectively p = 0.04 and p = 0.04). For rs3211867, obese subjects harboring the AA/AC genotype had significantly higher BMI (p = 0.02) and total cholesterol (p = 0.03) than obese subjects harboring the CC genotype. At the same time, the obese diabetic subjects harboring the AA/AC genotype had total cholesterol levels significantly higher than the obese diabetic subjects harboring the CC genotype (p = 0.03). For rs1527483, only the control subjects had statistically significant different parameters depending on the genotypic distribution. The control subjects harboring the GG genotype had a significantly higher BMI than the control subjects harboring the AA/AG genotype (p = 0.003). The CD36 gene methylation was significantly 1.36 times more frequent in obese and obese diabetic compared to lean control (RR = 1.36; p = 0.04). DNMT3a levels were higher in subjects with CD36 gene methylation than in subjects without CD36 gene methylation in each group. Obese diabetic subjects with CD36 gene methylation had significantly fewer plasmas sCD36 (p = 0.03) and more LDL-cholesterol (p = 0.01) than obese diabetic subjects without CD36 gene methylation. In the control group, an increase in sCD36 levels would be associated with a decrease in total cholesterol and triglyceride levels (coef = -7647.56 p = 0.01 and coef = -2528.50 p = 0.048, respectively) would be associated with an increase in LDL cholesterol levels. For the obese group, an increase in sCD36 levels would be associated with an increase in fasting insulin levels (coef = 490.99 p = 0.02) and a decrease in glycated hemoglobin levels (coef = -1196.26 p = 0.03). An increase in the sCD36 levels would be associated with an increase in the triglyceride levels in the obese diabetic group (coef = 9937.41 p = 0.02). The AA/AC genotype of SNP rs3211867 polymorphism was significantly associated with CD36 gene methylation in the control and obese diabetic groups (respectively p = 0.05, p = 0.002; 95% CI). CONCLUSION These observations suggest that polymorphisms and epigenetic changes in CD36 gene promoters may be implicated in the onset of obesity and its related complication type 2 diabetes mellitus.
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Affiliation(s)
- Maïmouna Touré
- Laboratoire de Physiologie Humaine et d'Explorations Fonctionnelles, Faculté de Médecine, de Pharmacie et d'Odonto-Stomatologie (FMPOS) de l'Université Cheikh Anta Diop (UCAD), Dakar, Sénégal.
- Physiologie de La Nutrition & Toxicologie, INSERM U1231, Université de Bourgogne-Franche Comté (UBFC), Dijon AgroSup, 21000, Dijon, France.
- IRL3189 ESS (Environnement, Santé, Sociétés ), CNRS, CNRST, Bamoko-UCAD, Dakar, Sénégal.
| | - Aziz Hichami
- Physiologie de La Nutrition & Toxicologie, INSERM U1231, Université de Bourgogne-Franche Comté (UBFC), Dijon AgroSup, 21000, Dijon, France
| | - Amira Sayed
- Physiologie de La Nutrition & Toxicologie, INSERM U1231, Université de Bourgogne-Franche Comté (UBFC), Dijon AgroSup, 21000, Dijon, France
| | - Muhtadi Suliman
- Physiologie de La Nutrition & Toxicologie, INSERM U1231, Université de Bourgogne-Franche Comté (UBFC), Dijon AgroSup, 21000, Dijon, France
| | - Abdoulaye Samb
- Laboratoire de Physiologie Humaine et d'Explorations Fonctionnelles, Faculté de Médecine, de Pharmacie et d'Odonto-Stomatologie (FMPOS) de l'Université Cheikh Anta Diop (UCAD), Dakar, Sénégal
- IRL3189 ESS (Environnement, Santé, Sociétés ), CNRS, CNRST, Bamoko-UCAD, Dakar, Sénégal
| | - Naim Akhtar Khan
- Physiologie de La Nutrition & Toxicologie, INSERM U1231, Université de Bourgogne-Franche Comté (UBFC), Dijon AgroSup, 21000, Dijon, France
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22
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Garvey WT, Umpierrez GE, Dunn JP, Kwan AYM, Varnado OJ, Konig M, Levine JA. Examining the evidence for weight management in individuals with type 2 diabetes. Diabetes Obes Metab 2022; 24:1411-1422. [PMID: 35545861 DOI: 10.1111/dom.14764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 04/29/2022] [Accepted: 05/08/2022] [Indexed: 11/28/2022]
Abstract
The obesity epidemic has been linked to the worsening diabetes epidemic. Despite this, weight reduction for individuals with obesity is seen as a secondary, or even tertiary, consideration in the treatment of type 2 diabetes (T2D). The aim of this review is to examine the benefits of weight management in individuals with T2D. A literature review of current available published data on the benefits of weight reduction in individuals with T2D was conducted. In individuals with T2D who have obesity or overweight, modest and sustained weight reduction results in improvement in glycaemic control and decreased utilization of glucose-lowering medication. A total body weight loss of 5% or higher reduces HbA1c levels and contributes to mitigating risk factors of cardiovascular disease, such as hyperlipidaemia and hypertension, as well as other disease-related complications of obesity. Progressive improvements in glycaemic control and cardiometabolic risk factors can occur when the total body weight loss increases to 10% or more. In the approach to treating patients with T2D and obesity, prioritizing weight management and the use of therapeutics that offer glycaemic control as well as the additional weight loss should be emphasized given their potential to attenuate the progression and severity of T2D.
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Affiliation(s)
- W Timothy Garvey
- University of Alabama at Birmingham, UAB Diabetes Research Center, Birmingham, Alabama
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23
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Vigna L, Tirelli AS, Gaggini M, Di Piazza S, Tomaino L, Turolo S, Moroncini G, Chatzianagnostou K, Bamonti F, Vassalle C. Insulin resistance and cardiometabolic indexes: comparison of concordance in working-age subjects with overweight and obesity. Endocrine 2022; 77:231-241. [PMID: 35665880 DOI: 10.1007/s12020-022-03087-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 05/21/2022] [Indexed: 11/03/2022]
Abstract
PURPOSE The aim of the study was to evaluate indexes of insulin resistance and cardiometabolic risk in a large population of workers with overweight or obesity, in order to identify a possible efficient, cheap and simple strategy to apply in workers' health surveillance. METHODS The evaluation of IR and cardiometabolic risk indexes (HOMA, QUICKI, Ty/HDLC, TyG, insuTAG, Castelli risk indexes 1 and 2, non-HDLC, TRL-C, AIP, and VAI) was performed in a population of 1195 working-age subjects with overweight or obesity (322 males, mean age 49 ± 11 years). RESULTS The prevalence of IR and cardiometabolic risk was higher among males for all indexes. Aging, waist circumference, BMI, blood pressure, glucose, CRP, fibrinogen and uric acid were correlated more frequently with IR/cardiometabolic indexes in women, homocysteine in men. The percentage of the workers identified as insulin resistant (IR+) or at higher cardiometabolic risk greatly vary according to the different index used. CONCLUSION With a small group of biomarkers and anthropometric measures (fasting glucose and insulin, lipid profile, BMI and waist circumference) is possible to calculate a number of IR/cardiometabolic indexes, which, likely reflecting different pathophysiological aspects also related to gender, might help in a personalized evaluation of IR and cardiometabolic risk. Graphical abstract.
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Affiliation(s)
- Luisella Vigna
- Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico. Occupational Health Unit, Obesity and Work Center, EASO Collaborating Center for Obesity Management, Milan, Italy
| | - Amedea Silvia Tirelli
- Fondazione IRCCS Cà Grande Ospedale Maggiore Policlinico. Clinical Chemistry and Microbiology Bacteriology and Virology Units, Milan, Italy
| | - Melania Gaggini
- Cardiometabolic Risk Unit, Institute of Clinical Physiology, CNR, Pisa, Italy
| | - Salvina Di Piazza
- Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico. Occupational Health Unit, Obesity and Work Center, EASO Collaborating Center for Obesity Management, Milan, Italy
| | - Laura Tomaino
- Emergency Medicine Residency Program, Marche Polytechnic University, Ancona, Italy
| | - Stefano Turolo
- Fondazione IRCCS Cà Grande Ospedale Maggiore Policlinico. UOC Pediatric Nephrology, Dialysis and Transplantation, Milan, Italy
| | - Gianluca Moroncini
- Clinica Medica, Azienda Ospedali Riuniti, Department of Internal Medicine, Azienda ospedaliera Universitaria Ospedali Riuniti, Ancona, Italy
| | | | - Fabrizia Bamonti
- Former Associate Professor of Clinical Biochemistry, Board Certify in Clinical Chemistry and Biochemistry, Università degli Studi di Milano, Milan, Italy
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24
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Tang Q, Assali DR, Güler AD, Steele AD. Dopamine systems and biological rhythms: Let's get a move on. Front Integr Neurosci 2022; 16:957193. [PMID: 35965599 PMCID: PMC9364481 DOI: 10.3389/fnint.2022.957193] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Accepted: 07/06/2022] [Indexed: 02/05/2023] Open
Abstract
How dopamine signaling regulates biological rhythms is an area of emerging interest. Here we review experiments focused on delineating dopamine signaling in the suprachiasmatic nucleus, nucleus accumbens, and dorsal striatum to mediate a range of biological rhythms including photoentrainment, activity cycles, rest phase eating of palatable food, diet-induced obesity, and food anticipatory activity. Enthusiasm for causal roles for dopamine in the regulation of circadian rhythms, particularly those associated with food and other rewarding events, is warranted. However, determining that there is rhythmic gene expression in dopamine neurons and target structures does not mean that they are bona fide circadian pacemakers. Given that dopamine has such a profound role in promoting voluntary movements, interpretation of circadian phenotypes associated with locomotor activity must be differentiated at the molecular and behavioral levels. Here we review our current understanding of dopamine signaling in relation to biological rhythms and suggest future experiments that are aimed at teasing apart the roles of dopamine subpopulations and dopamine receptor expressing neurons in causally mediating biological rhythms, particularly in relation to feeding, reward, and activity.
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Affiliation(s)
- Qijun Tang
- Department of Biology, University of Virginia, Charlottesville, VA, United States
| | - Dina R. Assali
- Department of Biological Sciences, California State Polytechnic University Pomona, Pomona, CA, United States
| | - Ali D. Güler
- Department of Biology, University of Virginia, Charlottesville, VA, United States
- Program in Fundamental Neuroscience, University of Virginia, Charlottesville, VA, United States
- Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, VA, United States
| | - Andrew D. Steele
- Department of Biological Sciences, California State Polytechnic University Pomona, Pomona, CA, United States
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25
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Takase M, Nakamura T, Hirata T, Tsuchiya N, Kogure M, Itabashi F, Nakaya N, Hamanaka Y, Sugawara J, Suzuki K, Fuse N, Uruno A, Kodama EN, Kuriyama S, Tsuji I, Kure S, Hozawa A. Association between fat mass index, fat-free mass index and hemoglobin A1c in a Japanese population: The Tohoku Medical Megabank Community-based Cohort Study. J Diabetes Investig 2022; 13:858-867. [PMID: 34860465 PMCID: PMC9077739 DOI: 10.1111/jdi.13729] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Revised: 11/30/2021] [Accepted: 12/01/2021] [Indexed: 12/25/2022] Open
Abstract
AIMS/INTRODUCTION Fat mass and fat-free mass affect glycated hemoglobin A1c (HbA1c) levels and blood glucose levels, respectively. The aim of the present study was to examine the association between the fat mass index and fat-free mass index with HbA1c. MATERIALS AND METHODS We carried out a cross-sectional study that included 3,731 men and 9,191 women aged ≥20 years, living in Miyagi Prefecture, Japan, who were not treated for diabetes. The fat mass index and fat-free mass index were calculated as fat mass and fat-free mass divided by the height squared, respectively. The indices were classified into sex-specific quartiles and combined into 16 groups. An analysis of covariance was used to assess associations between the combined fat mass index and fat-free mass index with HbA1c adjusted for potential confounders. The linear trend test was carried out by stratifying the fat mass index and fat-free mass index, entering the number as a continuous term in the regression model. RESULTS In multivariable models, a higher fat mass index was related to higher HbA1c levels in men and women in all fat-free mass index subgroups (P < 0.001 for linear trend). When we excluded the participants who had been identified as having diabetes, the fat-free mass index was also related to higher HbA1c levels in most fat mass index subgroups (P < 0.05 for linear trend). CONCLUSIONS Fat mass index was positively related to HbA1c levels. The fat-free mass index was also related to HbA1c levels when we excluded participants who had been identified as having have diabetes.
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Affiliation(s)
- Masato Takase
- Graduate School of MedicineTohoku UniversitySendaiJapan
| | - Tomohiro Nakamura
- Graduate School of MedicineTohoku UniversitySendaiJapan
- Tohoku Medical Megabank OrganizationTohoku UniversitySendaiJapan
| | - Takumi Hirata
- Tohoku Medical Megabank OrganizationTohoku UniversitySendaiJapan
- Department of Public HealthFaculty of MedicineHokkaido UniversitySapporoJapan
| | - Naho Tsuchiya
- Graduate School of MedicineTohoku UniversitySendaiJapan
- Tohoku Medical Megabank OrganizationTohoku UniversitySendaiJapan
| | - Mana Kogure
- Graduate School of MedicineTohoku UniversitySendaiJapan
- Tohoku Medical Megabank OrganizationTohoku UniversitySendaiJapan
| | - Fumi Itabashi
- Graduate School of MedicineTohoku UniversitySendaiJapan
- Tohoku Medical Megabank OrganizationTohoku UniversitySendaiJapan
| | - Naoki Nakaya
- Tohoku Medical Megabank OrganizationTohoku UniversitySendaiJapan
- Department of Health SciencesSaitama Prefectural UniversityKoshigayaJapan
| | - Yohei Hamanaka
- Tohoku Medical Megabank OrganizationTohoku UniversitySendaiJapan
| | - Junichi Sugawara
- Graduate School of MedicineTohoku UniversitySendaiJapan
- Tohoku Medical Megabank OrganizationTohoku UniversitySendaiJapan
- Tohoku University HospitalTohoku UniversitySendaiJapan
| | - Kichiya Suzuki
- Tohoku Medical Megabank OrganizationTohoku UniversitySendaiJapan
| | - Nobuo Fuse
- Tohoku Medical Megabank OrganizationTohoku UniversitySendaiJapan
| | - Akira Uruno
- Tohoku Medical Megabank OrganizationTohoku UniversitySendaiJapan
| | - Eiichi N Kodama
- Tohoku Medical Megabank OrganizationTohoku UniversitySendaiJapan
- International Research Institute of Disaster ScienceTohoku UniversitySendaiJapan
| | - Shinichi Kuriyama
- Graduate School of MedicineTohoku UniversitySendaiJapan
- Tohoku Medical Megabank OrganizationTohoku UniversitySendaiJapan
- International Research Institute of Disaster ScienceTohoku UniversitySendaiJapan
| | - Ichiro Tsuji
- Graduate School of MedicineTohoku UniversitySendaiJapan
- Tohoku Medical Megabank OrganizationTohoku UniversitySendaiJapan
| | - Shigeo Kure
- Graduate School of MedicineTohoku UniversitySendaiJapan
- Tohoku Medical Megabank OrganizationTohoku UniversitySendaiJapan
- Tohoku University HospitalTohoku UniversitySendaiJapan
| | - Atsushi Hozawa
- Graduate School of MedicineTohoku UniversitySendaiJapan
- Tohoku Medical Megabank OrganizationTohoku UniversitySendaiJapan
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26
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Awad SF, A Toumi A, A Al-Mutawaa K, A Alyafei S, A Ijaz M, A H Khalifa S, B Kokku S, C M Mishra A, V Poovelil B, B Soussi M, G El-Nahas K, O Al-Hamaq A, A Critchley J, H Al-Thani M, Abu-Raddad LJ. Type 2 diabetes epidemic and key risk factors in Qatar: a mathematical modeling analysis. BMJ Open Diabetes Res Care 2022; 10:10/2/e002704. [PMID: 35443971 PMCID: PMC9021773 DOI: 10.1136/bmjdrc-2021-002704] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Accepted: 03/27/2022] [Indexed: 12/23/2022] Open
Abstract
INTRODUCTION We aimed to characterize and forecast type 2 diabetes mellitus (T2DM) disease burden between 2021 and 2050 in Qatar where 89% of the population comprises expatriates from over 150 countries. RESEARCH DESIGN AND METHODS An age-structured mathematical model was used to forecast T2DM burden and the impact of key risk factors (obesity, smoking, and physical inactivity). The model was parametrized using data from T2DM natural history studies, Qatar's 2012 STEPwise survey, the Global Health Observatory, and the International Diabetes Federation Diabetes Atlas, among other data sources. RESULTS Between 2021 and 2050, T2DM prevalence increased from 7.0% to 14.0%, the number of people living with T2DM increased from 170 057 to 596 862, and the annual number of new T2DM cases increased from 25 007 to 45 155 among those 20-79 years of age living in Qatar. Obesity prevalence increased from 8.2% to 12.5%, smoking declined from 28.3% to 26.9%, and physical inactivity increased from 23.1% to 26.8%. The proportion of incident T2DM cases attributed to obesity increased from 21.9% to 29.9%, while the contribution of smoking and physical inactivity decreased from 7.1% to 6.0% and from 7.3% to 7.2%, respectively. The results showed substantial variability across various nationality groups residing in Qatar-for example, in Qataris and Egyptians, the T2DM burden was mainly due to obesity, while in other nationality groups, it appeared to be multifactorial. CONCLUSIONS T2DM prevalence and incidence in Qatar were forecasted to increase sharply by 2050, highlighting the rapidly growing need of healthcare resources to address the disease burden. T2DM epidemiology varied between nationality groups, stressing the need for prevention and treatment intervention strategies tailored to each nationality.
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Affiliation(s)
- Susanne F Awad
- Infectious Disease Epidemiology Group, Weill Cornell Medicine - Qatar, Doha, Qatar
- World Health Organization Collaborating Centre for Disease Epidemiology Analytics on HIV/AIDS, Sexually Transmitted Infections, and Viral Hepatitis, Weill Cornell Medicine-Qatar, Doha, Dawha, Qatar
- Department of Population Health Sciences, Weill Cornell Medicine, Cornell University, New York City, New York, USA
| | - Amine A Toumi
- Public Health Department, Ministry of Public Health Qatar, Doha, Ad Dawhah, Qatar
| | - Kholood A Al-Mutawaa
- Public Health Department, Ministry of Public Health Qatar, Doha, Ad Dawhah, Qatar
| | - Salah A Alyafei
- Public Health Department, Ministry of Public Health Qatar, Doha, Ad Dawhah, Qatar
| | - Muhammad A Ijaz
- Public Health Department, Ministry of Public Health Qatar, Doha, Ad Dawhah, Qatar
| | | | - Suresh B Kokku
- Public Health Department, Ministry of Public Health Qatar, Doha, Ad Dawhah, Qatar
| | - Amit C M Mishra
- Public Health Department, Ministry of Public Health Qatar, Doha, Ad Dawhah, Qatar
| | - Benjamin V Poovelil
- Public Health Department, Ministry of Public Health Qatar, Doha, Ad Dawhah, Qatar
| | - Mounir B Soussi
- Public Health Department, Ministry of Public Health Qatar, Doha, Ad Dawhah, Qatar
| | | | | | - Julia A Critchley
- Population Health Research Institute, St. George's, University of London, London, UK
| | - Mohammed H Al-Thani
- Public Health Department, Ministry of Public Health Qatar, Doha, Ad Dawhah, Qatar
| | - Laith J Abu-Raddad
- Infectious Disease Epidemiology Group, Weill Cornell Medicine - Qatar, Doha, Qatar
- World Health Organization Collaborating Centre for Disease Epidemiology Analytics on HIV/AIDS, Sexually Transmitted Infections, and Viral Hepatitis, Weill Cornell Medicine-Qatar, Doha, Dawha, Qatar
- Department of Population Health Sciences, Weill Cornell Medicine, Cornell University, New York City, New York, USA
- Department of Public Health, College of Health Sciences, QU Health, Qatar University, Doha, Qatar
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27
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Swilam N, Nawwar MAM, Radwan RA, Mostafa ES. Antidiabetic Activity and In Silico Molecular Docking of Polyphenols from Ammannia baccifera L. subsp. Aegyptiaca (Willd.) Koehne Waste: Structure Elucidation of Undescribed Acylated Flavonol Diglucoside. PLANTS (BASEL, SWITZERLAND) 2022; 11:plants11030452. [PMID: 35161433 PMCID: PMC8840488 DOI: 10.3390/plants11030452] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 01/12/2022] [Accepted: 01/13/2022] [Indexed: 05/24/2023]
Abstract
Chemical investigation of the aerial parts of Ammania aegyptiaca ethanol extract (AEEE) showed high concentrations of polyphenol and flavonoid content, with notable antioxidant activity. Undescribed acylated diglucoside flavonol myricetin 3-O-β-4C1-(6″-O-galloyl glucopyranoside) 7-O-β-4C1-glucopyranoside (MGGG) was isolated from the aerial parts of AEEE, along with four known polyphenols that had not been characterized previously from AEEE. The inhibitory effects of MGGG, AEEE, and all compounds against α-amylase, pancreatic lipase and β-glucosidase were assessed. In addition, molecular docking was used to determine the inhibition of digestive enzymes, and this confirmed that the MGGG interacted strongly with the active site residues of these enzymes, with the highest binding free energy against α-amylase (-8.99 kcal/mol), as compared to the commercial drug acarbose (-5.04 kcal/mol), thus justifying its use in the potential management of diabetes. In streptozotocin (STZ)-induced diabetic rats, AEEE significantly decreased high serum glucose, α-amylase activity and serum liver and kidney function markers, as well as increasing insulin blood level. Moreover, AEEE improved the lipid profile of diabetic animals, increased superoxide dismutase (SOD) activity, and inhibited lipid peroxidation. Histopathological studies proved the decrease in pancreas damage and supported the biochemical findings. These results provide evidence that AEEE and MGGG possess potent antidiabetic activity, which warrants additional investigation.
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Affiliation(s)
- Noha Swilam
- Department of Pharmacognosy, Faculty of Pharmacy, The British University in Egypt (BUE), El Sherouk City 11837, Egypt
| | - Mahmoud A. M. Nawwar
- National Research Centre, Department of Phytochemistry and Plant Systematic, Dokki 12622, Egypt;
| | - Rasha A. Radwan
- Department of Biochemistry, Faculty of Pharmacy, Sinai University-Kantara Branch, El Ismailia 41611, Egypt;
| | - Eman S. Mostafa
- Department of Pharmacognosy, Faculty of Pharmacy, October University of Modern Sciences and Arts (MSA University), Giza 11787, Egypt;
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28
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Kaze AD, Santhanam P, Erqou S, Ahima RS, Bertoni AG, Echouffo-Tcheugui JB. Body Weight Variability and Risk of Cardiovascular Outcomes and Death in the Context of Weight Loss Intervention Among Patients With Type 2 Diabetes. JAMA Netw Open 2022; 5:e220055. [PMID: 35179583 PMCID: PMC8857684 DOI: 10.1001/jamanetworkopen.2022.0055] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
IMPORTANCE Body weight fluctuation is associated with greater risks of adverse health outcomes. Whether intensive weight loss interventions affect the association of variability in adiposity measures with adverse health outcomes in individuals with type 2 diabetes has not been studied previously. OBJECTIVE To evaluate the associations of long-term variability in adiposity indices with cardiovascular disease (CVD) outcomes and whether these associations are affected by an intensive lifestyle intervention among adults with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study included participants in the Action for Health in Diabetes (Look AHEAD) trial without CVD at baseline (August 2001 to April 2004). The Look AHEAD study included 16 centers in the United States. Data analysis was performed from December 2020 to June 2021. EXPOSURES Variability of body mass index (BMI) and waist circumference (WC) across 4 annual visits, assessed using the coefficient of variation (CV), variability independent of the mean (VIM), and standard deviation (SD). MAIN OUTCOMES AND MEASURES Main outcomes were (1) all-cause mortality, (2) cardiovascular deaths (deaths from myocardial infarction [MI] or stroke), and (3) CVD events (MI, stroke, and/or death from cardiovascular causes). RESULTS Among 3604 study participants (mean [SD] age, 58.4 [6.6] years; 2240 [62.3%] women; 1364 [37.7%] Black participants; 2404 [66%] White participants), there were 216 CVD events, 33 CVD deaths, and 166 deaths over a median of 6.7 years. In the control group, the hazard ratios (HRs) for the highest quartile (quartile 4) compared with the lowest quartile (quartile 1) of CV of BMI were 4.06 (95% CI, 2.17-7.57), 15.28 (95% CI, 2.89-80.90), and 2.16 (95% CI, 1.21-3.87) for all-cause mortality, CVD mortality, and cardiovascular events, respectively. In the intervention group, the corresponding HRs were 0.99 (95% CI, 0.45-2.16), 1.14 (95% CI, 0.12-10.53), and 0.77 (95% CI, 0.40-1.49) for quartile 4 vs quartile 1. Regarding WC, in the control group, HRs for quartile 4 vs quartile 1 were 1.84 (95% CI, 1.01-3.35), 6.46 (95% CI, 1.16-36.01), and 1.28 (95% CI, 0.72-2.29). In the intervention group, HRs were 1.23 (95% CI, 0.61-2.46), 0.55 (95% CI, 0.15-2.11), and 0.70 (95% CI, 0.39-1.25) for quartile 4 vs quartile 1. CONCLUSIONS AND RELEVANCE In this cohort study of individuals with type 2 diabetes, higher variability of adiposity indices was associated with significantly increased risk of CVD outcomes and death in the control group but not in the intensive lifestyle intervention group.
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Affiliation(s)
- Arnaud D. Kaze
- Department of Medicine, SOVAH Health, Danville, Maryland
| | - Prasanna Santhanam
- Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland
| | - Sebhat Erqou
- Department of Medicine, Providence VA Medical Center, Providence, Rhode Island
- Alpert Medical School, Brown University, Providence, Rhode Island
| | - Rexford S. Ahima
- Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland
| | - Alain G. Bertoni
- Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina
| | - Justin B. Echouffo-Tcheugui
- Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland
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29
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Hung HHY, Chan EYY, Chow EYK, Chung GKK, Lai FTT, Yeoh E. Non-skilled occupation as a risk factor of diabetes among working population: A population-based study of community-dwelling adults in Hong Kong. HEALTH & SOCIAL CARE IN THE COMMUNITY 2022; 30:e86-e94. [PMID: 34169598 PMCID: PMC9291875 DOI: 10.1111/hsc.13415] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Revised: 03/05/2021] [Accepted: 04/04/2021] [Indexed: 06/13/2023]
Abstract
Diabetes among working population brings to society concerns on productivity and social welfare cost, in addition to healthcare burden. While lower socio-economic status has been recognised as a risk factor of diabetes; occupation, compared with other socio-economic status indicators (e.g., education and income), has received less attention. There is some evidence from studies conducted in Europe that occupation is associated with diabetes risk, but less is known in Asia, which has different organisational cultures and management styles from the West. This study examines the association between occupation and diabetes risk in a developed Asian setting, which is experiencing an increasing number of young onset of diabetes and aging working population at the same time. This is a cross-sectional study of working population aged up to 65 with data from a population-based survey collecting demographic, socio-economic, behavioural and metabolic data from Hong Kong residents, through both self-administered questionnaires and clinical health examinations (1,429 participants). Non-skilled occupation was found to be an independent risk factor for diabetes, with an odds ratio (OR) of 3.38 (p < 0.001) and adjusted OR of 2.59 (p = 0.022) after adjusting for demographic, behavioural and metabolic risk factors. Older age (adjusted OR = 1.08, p < 0.001), higher body mass index (adjusted OR = 1.23, p < 0.001) and having hypertriglyceridemia (adjusted OR = 1.93, p = 0.033) were also independently associated with diabetes. Non-skilled workers were disproportionately affected by diabetes with the highest age-standardized prevalence (6.3%) among all occupation groups (4.9%-5.0%). This study provides evidence that non-skilled occupation is an independent diabetes risk factor in a developed Asian setting. Health education on improving lifestyle practices and diabetes screening should prioritise non-skilled workers, in particular through company-based and sector-based diabetes screening programmes. Diabetes health service should respond to the special needs of non-skilled workers, including service at non-office hour and practical health advice in light of their work setting.
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Affiliation(s)
- Heidi H. Y. Hung
- The Jockey Club School of Public Health and Primary CareThe Chinese University of Hong KongHong KongChina
| | - Emily Y. Y. Chan
- The Jockey Club School of Public Health and Primary CareThe Chinese University of Hong KongHong KongChina
- Collaborating Centre for Oxford University and CUHK for Disaster and Medical Humanitarian Response (CCOUC), The Jockey Club School of Public Health and Primary CareThe Chinese University of Hong KongHong KongChina
- Nuffield Department of MedicineUniversity of OxfordOxfordUK
- François‐Xavier Bagnoud Center for Health & Human RightsHarvard UniversityBostonMAUSA
| | - Elaine Y. K. Chow
- Department of Medicine and TherapeuticsThe Chinese University of Hong KongHong KongChina
| | - Gary K. K. Chung
- The Jockey Club School of Public Health and Primary CareThe Chinese University of Hong KongHong KongChina
- CUHK Institute of Health EquityThe Chinese University of Hong KongHong KongChina
| | - Francisco T. T. Lai
- The Jockey Club School of Public Health and Primary CareThe Chinese University of Hong KongHong KongChina
- Department of Pharmacology and PharmacyThe University of Hong KongHong KongChina
- Laboratory of Data Discovery for Health (D24H)Hong Kong Science and Technology ParkHong KongChina
| | - Eng‐Kiong Yeoh
- Centre for Health Systems and Policy ResearchThe Jockey Club School of Public Health and Primary CareThe Chinese University of Hong KongHong KongChina
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30
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Yagi N, Komiya I, Arai K, Oishi M, Fukumoto Y, Shirabe S, Yokoyama H, Yamazaki K, Sugimoto H, Maegawa H. Current status of oral antidiabetic drug prescribing patterns based on the body mass index for Japanese type 2 diabetes mellitus patients and yearly changes in diabetologists' prescribing patterns from 2002 to 2019 (JDDM61). J Diabetes Investig 2022; 13:65-73. [PMID: 34191401 PMCID: PMC8756302 DOI: 10.1111/jdi.13621] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 06/18/2021] [Accepted: 06/27/2021] [Indexed: 01/12/2023] Open
Abstract
AIMS/INTRODUCTION Type 2 diabetes mellitus is caused by a relative imbalance between insulin secretion and sensitivity related to the body mass index (BMI). Seven categories of oral antidiabetic drugs (OADs) are available in Japan. It is important to assess the OAD utilization patterns based on patients' BMI levels. MATERIALS AND METHODS OAD prescribing patterns from 2002 to 2019 were analyzed using the data collected in the computerized diabetes care database provided by the Japan Diabetes Clinical Data Management Study Group; OAD utilization patterns in 25,751 OAD-treated type 2 diabetes mellitus patients registered in 2019 were analyzed after classifying them into five categories of BMI. RESULTS Comparing OAD usage between 2002 and 2019, sulfonylureas decreased from 44.5 to 23.2%, and biguanides (BGs) increased from 19.3 to 50.3%. Dipeptidyl peptidase-4 inhibitors (DPP4is) increased to 56.9% in 2019. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) increased to 23.6% in 2019. About 90% of type 2 diabetes mellitus patients had BMI < 30 kg/m2 . DPP4is were the most used OADs in 2019. When BMI exceeded 30 kg/m2 , use of BGs and sodium-glucose cotransporter 2 inhibitors increased, and use of sulfonylureas and DPP4is decreased. Although DPP4is were the most used OADs for patients with BMI <30 kg/m2 , they were the third most prescribed OADs for patients with BMI >35 kg/m2 after BGs and sodium-glucose cotransporter 2 inhibitors . CONCLUSIONS DPP4i usage was as high as that of BG in the analysis of Japanese type 2 diabetes mellitus patients with relatively low BMI. This was considered to be a treatment option appropriate for the pathophysiology in Japanese patients.
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Affiliation(s)
| | - Ichiro Komiya
- Yagi Medical ClinicOkinawaJapan
- Department of Internal MedicineOkinawa Medical HospitalOkinawaJapan
| | | | | | | | | | | | | | | | - Hiroshi Maegawa
- Department of MedicineShiga University of Medical ScienceShigaJapan
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31
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Rodriguez LA, Kanaya AM, Shiboski SC, Fernandez A, Herrington D, Ding J, Bradshaw PT. Does NAFLD mediate the relationship between obesity and type 2 diabetes risk? evidence from the multi-ethnic study of atherosclerosis (MESA). Ann Epidemiol 2021; 63:15-21. [PMID: 34293421 PMCID: PMC8500945 DOI: 10.1016/j.annepidem.2021.07.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 07/09/2021] [Accepted: 07/13/2021] [Indexed: 02/08/2023]
Abstract
PURPOSE To estimate the effect of obesity on type 2 diabetes (T2DM) risk and evaluate to what extent non-alcoholic fatty liver disease (NAFLD) mediates this association. METHODS Data came from 4,522 adults ages 45-84 participating in the Multi-Ethnic Study of Atherosclerosis cohort. Baseline obesity was defined using established BMI categories. NAFLD was measured by CT scans at baseline and incident T2DM defined as fasting glucose ≥126 mg/dL or use of diabetes medications. RESULTS Over a median 9.1 years of follow-up between 2000 and 2012, 557 new cases of T2DM occurred. After adjusting for age, sex, race/ethnicity, education, diet and exercise, those with obesity had 4.5 times the risk of T2DM compared to normal weight (hazard ratio [HR] = 4.5, 95% confidence interval [CI]: 3.0, 5.9). The mediation analysis suggested that NAFLD accounted for ~36% (95% CI: 27, 44) of the effect (direct effect HR = 3.2, 95% CI: 2.3, 4.6; indirect effect through NAFLD, HR = 1.4, 95% CI: 1.3, 1.5). CONCLUSIONS These data suggest that the association between obesity and T2DM risk is partially explained by the presence of NAFLD. Future studies should evaluate if NAFLD could be an effective target to reduce the effect of obesity on T2DM.
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Affiliation(s)
- Luis A Rodriguez
- University of California, San Francisco, Department of Epidemiology & Biostatistics, San Francisco, CA; Kaiser Permanente Northern California, Division of Research, Oakland, CA.
| | - Alka M Kanaya
- University of California, San Francisco, Department of Epidemiology & Biostatistics, San Francisco, CA; University of California, San Francisco, Division of General Internal Medicine, San Francisco, CA
| | - Stephen C Shiboski
- University of California, San Francisco, Department of Epidemiology & Biostatistics, San Francisco, CA
| | - Alicia Fernandez
- University of California, San Francisco, Department of Medicine, San Francisco, CA
| | - David Herrington
- Wake Forest School of Medicine, Department of Internal Medicine, Winston-Salem, NC
| | - Jingzhong Ding
- Wake Forest School of Medicine, Sticht Center on Aging, Winston-Salem, NC
| | - Patrick T Bradshaw
- University of California, Berkeley, School of Public Health, Division of Epidemiology & Biostatistics, Berkeley, CA
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32
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Kumar S, Mankowski RT, Anton SD, Babu Balagopal P. Novel insights on the role of spexin as a biomarker of obesity and related cardiometabolic disease. Int J Obes (Lond) 2021; 45:2169-2178. [PMID: 34253845 DOI: 10.1038/s41366-021-00906-2] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 06/15/2021] [Accepted: 07/01/2021] [Indexed: 02/06/2023]
Abstract
Spexin (SPX) is a 14-amino acid neuropeptide, discovered recently using bioinformatic techniques. It is encoded by the Ch12:orf39 gene that is widely expressed in different body tissues/organs across species, and secreted into systemic circulation. Recent reports have highlighted a potentially important regulatory role of SPX in obesity and related comorbidities. SPX is also ubiquitously expressed in human tissues, including white adipose tissue. The circulating concentration of SPX is significantly lower in individuals with obesity compared to normal weight counterparts. SPX's role in obesity appears to be related to various factors, such as the regulation of energy expenditure, appetite, and eating behaviors, increasing locomotion, and inhibiting long-chain fatty acid uptake into adipocytes. Recent reports have also suggested SPX's relationship with novel biomarkers of cardiovascular disease (CVD) and glucose metabolism and evoked the potential role of SPX as a key biomarker/player in the early loss of cardiometabolic health and development of CVD and diabetes later in life. Data on age-related changes in SPX and SPX's response to various interventions are also emerging. The current review focuses on the role of SPX in obesity and related comorbidities across the life span, and its response to interventions in these conditions. It is expected that this article will provide new ideas for future research on SPX and its metabolic regulation, particularly related to cardiometabolic diseases.
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Affiliation(s)
- Seema Kumar
- Division of Pediatric Endocrinology, Mayo Clinic, Rochester, MN, USA.,Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA
| | - Robert T Mankowski
- Department of Aging and Geriatric Research, Institute on Aging, University of Florida, Gainesville, FL, USA
| | - Stephen D Anton
- Department of Aging and Geriatric Research, Institute on Aging, University of Florida, Gainesville, FL, USA
| | - P Babu Balagopal
- Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA. .,Department of Biomedical Research, Nemours Children's Health System, Jacksonville, FL, USA.
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33
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D'Esposito V, Ambrosio MR, Liguoro D, Perruolo G, Lecce M, Cabaro S, Aprile M, Marino A, Pilone V, Forestieri P, Miele C, Bruzzese D, Terracciano D, Beguinot F, Formisano P. In severe obesity, subcutaneous adipose tissue cell-derived cytokines are early markers of impaired glucose tolerance and are modulated by quercetin. Int J Obes (Lond) 2021; 45:1811-1820. [PMID: 33993191 DOI: 10.1038/s41366-021-00850-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 04/19/2021] [Accepted: 04/27/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND Excessive adiposity provides an inflammatory environment. However, in people with severe obesity, how systemic and local adipose tissue (AT)-derived cytokines contribute to worsening glucose tolerance is not clear. METHODS Ninty-two severely obese (SO) individuals undergoing bariatric surgery were enrolled and subjected to detailed clinical phenotyping. Following an oral glucose tolerance test, participants were included in three groups, based on the presence of normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or type 2 diabetes (T2D). Serum and subcutaneous AT (SAT) biopsies were obtained and mesenchymal stem cells (MSCs) were isolated, characterized, and differentiated in adipocytes in vitro. TNFA and PPARG mRNA levels were determined by qRT-PCR. Circulating, adipocyte- and MSC-released cytokines, chemokines, and growth factors were assessed by multiplex ELISA. RESULTS Serum levels of IL-9, IL-13, and MIP-1β were increased in SO individuals with T2D, as compared with those with either IGT or NGT. At variance, SAT samples obtained from SO individuals with IGT displayed levels of TNFA which were threefold higher compared to those with NGT, but not different from those with T2D. Elevated levels of TNFα were also found in differentiated adipocytes, isolated from the SAT specimens of individuals with IGT and T2D, compared to those with NGT. Consistent with the pro-inflammatory milieu, IL-1β and IP-10 secretion was significantly higher in adipocytes from individuals with IGT and T2D. Moreover, increased levels of TNFα, both mRNA and secreted protein were detected in MSCs obtained from IGT and T2D, compared to NGT SO individuals. Exposure of T2D and IGT-derived MSCs to the anti-inflammatory flavonoid quercetin reduced TNFα levels and was paralleled by a significant decrease of the secretion of inflammatory cytokines. CONCLUSION In severe obesity, enhanced SAT-derived inflammatory phenotype is an early step in the progression toward T2D and maybe, at least in part, attenuated by quercetin.
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Affiliation(s)
- Vittoria D'Esposito
- URT "Genomics of Diabetes, Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Naples, Italy.,Department of Translational Medicine, "Federico II" University of Naples, Naples, Italy
| | - Maria Rosaria Ambrosio
- URT "Genomics of Diabetes, Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Naples, Italy.,Department of Translational Medicine, "Federico II" University of Naples, Naples, Italy
| | - Domenico Liguoro
- URT "Genomics of Diabetes, Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Naples, Italy.,Department of Translational Medicine, "Federico II" University of Naples, Naples, Italy
| | - Giuseppe Perruolo
- URT "Genomics of Diabetes, Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Naples, Italy.,Department of Translational Medicine, "Federico II" University of Naples, Naples, Italy
| | - Manuela Lecce
- URT "Genomics of Diabetes, Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Naples, Italy.,Department of Translational Medicine, "Federico II" University of Naples, Naples, Italy
| | - Serena Cabaro
- URT "Genomics of Diabetes, Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Naples, Italy.,Department of Translational Medicine, "Federico II" University of Naples, Naples, Italy
| | - Marianna Aprile
- Institute of Genetics and Biophysics "Adriano Buzzati-Traverso," CNR, Naples, Italy
| | - Ada Marino
- Department of Translational Medicine, "Federico II" University of Naples, Naples, Italy
| | - Vincenzo Pilone
- Department of Medicine, Surgery and Dentistry, University of Salerno, Salerno, Italy
| | - Pietro Forestieri
- Department of Medicine, Surgery and Dentistry, University of Salerno, Salerno, Italy.,Department of Clinical Medicine and Surgery, "Federico II" University of Naples, Naples, Italy
| | - Claudia Miele
- URT "Genomics of Diabetes, Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Naples, Italy.,Department of Translational Medicine, "Federico II" University of Naples, Naples, Italy
| | - Dario Bruzzese
- Department of Public Health, "Federico II" University of Naples, Naples, Italy
| | - Daniela Terracciano
- URT "Genomics of Diabetes, Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Naples, Italy.,Department of Translational Medicine, "Federico II" University of Naples, Naples, Italy
| | - Francesco Beguinot
- URT "Genomics of Diabetes, Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Naples, Italy.,Department of Translational Medicine, "Federico II" University of Naples, Naples, Italy
| | - Pietro Formisano
- URT "Genomics of Diabetes, Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Naples, Italy. .,Department of Translational Medicine, "Federico II" University of Naples, Naples, Italy.
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Life-course trajectories of weight and their impact on the incidence of type 2 diabetes. Sci Rep 2021; 11:12494. [PMID: 34127722 PMCID: PMC8203741 DOI: 10.1038/s41598-021-91910-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2021] [Accepted: 06/01/2021] [Indexed: 12/25/2022] Open
Abstract
Although exposure to overweight and obesity at different ages is associated to a higher risk of type 2 diabetes, the effect of different patterns of exposure through life remains unclear. We aimed to characterize life-course trajectories of weight categories and estimate their impact on the incidence of type 2 diabetes. We categorized the weight of 7203 participants as lean, normal or overweight at five time-points from ages 7–55 using retrospective data. Participants were followed for an average of 19 years for the development of type 2 diabetes. We used latent class analysis to describe distinctive trajectories and estimated the risk ratio, absolute risk difference and population attributable fraction (PAF) associated to different trajectories using Poisson regression. We found five distinctive life-course trajectories. Using the stable-normal weight trajectory as reference, the stable overweight, lean increasing weight, overweight from early adulthood and overweight from late adulthood trajectories were associated to higher risk of type 2 diabetes. The estimated risk ratios and absolute risk differences were statistically significant for all trajectories, except for the risk ratio of the lean increasing trajectory group among men. Of the 981 incident cases of type 2 diabetes, 47.4% among women and 42.9% among men were attributable to exposure to any life-course trajectory different from stable normal weight. Most of the risk was attributable to trajectories including overweight or obesity at any point of life (36.8% of the cases among women and 36.7% among men). The overweight from early adulthood trajectory had the highest impact (PAF: 23.2% for woman and 28.5% for men). We described five distinctive life-course trajectories of weight that were associated to increased risk of type 2 diabetes over 19 years of follow-up. The variability of the effect of exposure to overweight and obesity on the risk of developing type 2 diabetes was largely explained by exposure to the different life-course trajectories of weight.
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Al-Mrabeh A. β-Cell Dysfunction, Hepatic Lipid Metabolism, and Cardiovascular Health in Type 2 Diabetes: New Directions of Research and Novel Therapeutic Strategies. Biomedicines 2021; 9:226. [PMID: 33672162 PMCID: PMC7927138 DOI: 10.3390/biomedicines9020226] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 02/09/2021] [Accepted: 02/17/2021] [Indexed: 02/06/2023] Open
Abstract
Cardiovascular disease (CVD) remains a major problem for people with type 2 diabetes mellitus (T2DM), and dyslipidemia is one of the main drivers for both metabolic diseases. In this review, the major pathophysiological and molecular mechanisms of β-cell dysfunction and recovery in T2DM are discussed in the context of abnormal hepatic lipid metabolism and cardiovascular health. (i) In normal health, continuous exposure of the pancreas to nutrient stimulus increases the demand on β-cells. In the long term, this will not only stress β-cells and decrease their insulin secretory capacity, but also will blunt the cellular response to insulin. (ii) At the pre-diabetes stage, β-cells compensate for insulin resistance through hypersecretion of insulin. This increases the metabolic burden on the stressed β-cells and changes hepatic lipoprotein metabolism and adipose tissue function. (iii) If this lipotoxic hyperinsulinemic environment is not removed, β-cells start to lose function, and CVD risk rises due to lower lipoprotein clearance. (iv) Once developed, T2DM can be reversed by weight loss, a process described recently as remission. However, the precise mechanism(s) by which calorie restriction causes normalization of lipoprotein metabolism and restores β-cell function are not fully established. Understanding the pathophysiological and molecular basis of β-cell failure and recovery during remission is critical to reduce β-cell burden and loss of function. The aim of this review is to highlight the link between lipoprotein export and lipid-driven β-cell dysfunction in T2DM and how this is related to cardiovascular health. A second aim is to understand the mechanisms of β-cell recovery after weight loss, and to explore new areas of research for developing more targeted future therapies to prevent T2DM and the associated CVD events.
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Affiliation(s)
- Ahmad Al-Mrabeh
- Faculty of Medical Sciences, Translational and Clinical Research Institute, Magnetic Resonance Centre, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
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36
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Burgoine T, Monsivais P, Sharp SJ, Forouhi NG, Wareham NJ. Independent and combined associations between fast-food outlet exposure and genetic risk for obesity: a population-based, cross-sectional study in the UK. BMC Med 2021; 19:49. [PMID: 33588846 PMCID: PMC7885578 DOI: 10.1186/s12916-021-01902-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 01/05/2021] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND Characteristics of the built environment, such as neighbourhood fast-food outlet exposure, are increasingly recognised as risk factors for unhealthy diet and obesity. Obesity also has a genetic component, with common genetic variants explaining a substantial proportion of population-level obesity susceptibility. However, it is not known whether and to what extent associations between fast-food outlet exposure and body weight are modified by genetic predisposition to obesity. METHODS We used data from the Fenland Study, a population-based sample of 12,435 UK adults (mean age 48.6 years). We derived a genetic risk score associated with BMI (BMI-GRS) from 96 BMI-associated single nucleotide polymorphisms. Neighbourhood fast-food exposure was defined as quartiles of counts of outlets around the home address. We used multivariable regression models to estimate the associations of each exposure, independently and in combination, with measured BMI, overweight and obesity, and investigated interactions. RESULTS We found independent associations between BMI-GRS and risk of overweight (RR = 1.34, 95% CI 1.23-1.47) and obesity (RR = 1.73, 95% CI 1.55-1.93), and between fast-food outlet exposure and risk of obesity (highest vs lowest quartile RR = 1.58, 95% CI 1.21-2.05). There was no evidence of an interaction of fast-food outlet exposure and genetic risk on BMI (P = 0.09), risk of overweight (P = 0.51), or risk of obesity (P = 0.27). The combination of higher BMI-GRS and highest fast-food outlet exposure was associated with 2.70 (95% CI 1.99-3.66) times greater risk of obesity. CONCLUSIONS Our study demonstrated independent associations of both genetic obesity risk and neighbourhood fast-food outlet exposure with adiposity. These important drivers of the obesity epidemic have to date been studied in isolation. Neighbourhood fast-food outlet exposure remains a potential target of policy intervention to prevent obesity and promote the public's health.
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Affiliation(s)
- Thomas Burgoine
- UKCRC Centre for Diet and Activity Research (CEDAR), MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
| | - Pablo Monsivais
- UKCRC Centre for Diet and Activity Research (CEDAR), MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK
- Present address: Department of Nutrition and Exercise Physiology, Elson S. Floyd College of Medicine, Washington State University, Spokane, Washington, USA
| | - Stephen J Sharp
- UKCRC Centre for Diet and Activity Research (CEDAR), MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK
| | - Nita G Forouhi
- UKCRC Centre for Diet and Activity Research (CEDAR), MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK
| | - Nicholas J Wareham
- UKCRC Centre for Diet and Activity Research (CEDAR), MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK
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Wallis N, Raffan E. The Genetic Basis of Obesity and Related Metabolic Diseases in Humans and Companion Animals. Genes (Basel) 2020; 11:E1378. [PMID: 33233816 PMCID: PMC7699880 DOI: 10.3390/genes11111378] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 11/13/2020] [Accepted: 11/16/2020] [Indexed: 12/18/2022] Open
Abstract
Obesity is one of the most prevalent health conditions in humans and companion animals globally. It is associated with premature mortality, metabolic dysfunction, and multiple health conditions across species. Obesity is, therefore, of importance in the fields of medicine and veterinary medicine. The regulation of adiposity is a homeostatic process vulnerable to disruption by a multitude of genetic and environmental factors. It is well established that the heritability of obesity is high in humans and laboratory animals, with ample evidence that the same is true in companion animals. In this review, we provide an overview of how genes link to obesity in humans, drawing on a wealth of information from laboratory animal models, and summarise the mechanisms by which obesity causes related disease. Throughout, we focus on how large-scale human studies and niche investigations of rare mutations in severely affected patients have improved our understanding of obesity biology and can inform our ability to interpret results of animal studies. For dogs, cats, and horses, we compare the similarities in obesity pathophysiology to humans and review the genetic studies that have been previously reported in those species. Finally, we discuss how veterinary genetics may learn from humans about studying precise, nuanced phenotypes and implementing large-scale studies, but also how veterinary studies may be able to look past clinical findings to mechanistic ones and demonstrate translational benefits to human research.
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Affiliation(s)
- Natalie Wallis
- Anatomy Building, Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK
| | - Eleanor Raffan
- Anatomy Building, Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK
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Combinations of Legume Protein Hydrolysates Synergistically Inhibit Biological Markers Associated with Adipogenesis. Foods 2020; 9:foods9111678. [PMID: 33212815 PMCID: PMC7696775 DOI: 10.3390/foods9111678] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Revised: 11/10/2020] [Accepted: 11/12/2020] [Indexed: 12/20/2022] Open
Abstract
The objective was to investigate the anti-adipogenesis potential of selected legume protein hydrolysates (LPH) and combinations using biochemical assays and in silico predictions. Black bean, green pea, chickpea, lentil and fava bean protein isolates were hydrolyzed using alcalase (A) or pepsin/pancreatin (PP). The degree of hydrolysis ranged from 15.5% to 35.5% for A-LPH and PP-LPH, respectively. Antioxidant capacities ranged for ABTS•+ IC50 from 0.3 to 0.9 Trolox equivalents (TE) mg/mL, DPPH• IC50 from 0.7 to 13.5 TE mg/mL and nitric oxide (NO) inhibition IC50 from 0.3 to 1.3 mg/mL. LPH from PP–green pea, A–green pea and A–black bean inhibited pancreatic lipase (PL) (IC50 = 0.9 mg/mL, 2.2 mg/mL and 1.2 mg/mL, respectively) (p < 0.05). For HMG-CoA reductase (HMGR) inhibition, the LPH from A–chickpea (0.15 mg/mL), PP–lentil (1.2 mg/mL), A–green pea (1.4 mg/mL) and PP–green pea (1.5 mg/mL) were potent inhibitors. Combinations of PP–green pea + A–black bean (IC50 = 0.4 mg/mL), A–green pea + PP–green pea (IC50 = 0.9 mg/mL) and A–black bean + A–green pea (IC50 = 0.6 mg/mL) presented synergistic effects to inhibit PL. A–chickpea + PP–lentil (IC50 = 0.8 mg/mL) and PP–lentil + A–green pea (IC50 = 1.3 mg/mL) interacted additively to inhibit HMGR and synergistically in the combination of A–chickpea + PP–black bean (IC50 = 1.3 mg/mL) to block HMGR. Peptides FEDGLV and PYGVPVGVR inhibited PL and HMGR in silico, showing predicted binding energy interactions of −7.6 and −8.8 kcal/mol, respectively. Combinations of LPH from different legume protein sources could increase synergistically their anti-adipogenic potential.
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Kim YH, Han KD, Jung JH, Yoo SJ, Lee SS, Lee WY, Park HS, Kim SM. Weight change and the incidence of heart failure in the Korean population: data from the National Health Insurance Health checkup 2005-2015. Eur J Prev Cardiol 2020; 28:1767-1773. [PMID: 33823535 DOI: 10.1093/eurjpc/zwaa049] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Revised: 06/26/2020] [Accepted: 08/11/2020] [Indexed: 01/24/2023]
Abstract
AIMS Heart failure (HF) is associated with obesity, but the relationship between weight change and HF is inconsistent. We examined the relationship between weight change and the incidence of HF in the Korean population. DESIGN Retrospective cohort study design. METHODS AND RESULTS A total of 11 210 394 subjects (6 198 542 men and 5 011 852 women) >20 years of age were enrolled in this study. Weight change over 4 years divided into seven categories from weight loss ≥15% to weight gain ≥15%. The hazard ratios (HRs) and 95% confidence intervals for the incidence of HF were analysed. The HR of HF showed a slightly reverse J-shaped curve by increasing weight change in total and >15% weight loss shows the highest HR (HR 1.647) followed by -15 to -10% weight loss (HR = 1.444). When using normal body mass index with stable weight group as a reference, HR of HF decreased as weight increased in underweight subjects and weight gain ≥15% in obesity Stage II showed the highest HR (HR = 2.97). Sustained weight for 4 years in the underweight and obesity Stages I and II increased the incidence of HF (HR = 1.402, 1.092, and 1.566, respectively). CONCLUSION Both weight loss and weight gain increased HR for HF. Sustained weight in the obesity or underweight categories increased the incidence of HF.
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Affiliation(s)
| | - Kyung-do Han
- Department of Statistics and Actuarial Science, Soongsil University, 369 Sangdo-Ro, Dongjak-Gu, Seoul 06978, Korea
| | - Jin-Hyung Jung
- Department of Statistics and Actuarial Science, Soongsil University, 369 Sangdo-Ro, Dongjak-Gu, Seoul 06978, Korea
| | - Soon Jib Yoo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, The Catholic University of Korea, 222 Banpo-daero Secho-gu, Seoul 06591, Korea
| | - Seong-Su Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, The Catholic University of Korea, 222 Banpo-daero Secho-gu, Seoul 06591, Korea
| | - Won-Young Lee
- Department of Family Medicine, Ulsan University College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea
| | - Hye-Soon Park
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29, Saemunan-ro, Jongno-gu, Seoul 03181, Korea
| | - Seon Mee Kim
- Department of Family Medicine, Korea University College of Medicine, 73 Goryeodae-ro Seongbuk-gu, Seoul 02841, Korea
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Tino S, Mayanja BN, Mubiru MC, Eling E, Ddumba E, Kaleebu P, Nyirenda M. Prevalence and factors associated with overweight and obesity among patients with type 2 diabetes mellitus in Uganda-a descriptive retrospective study. BMJ Open 2020; 10:e039258. [PMID: 33148749 PMCID: PMC7643505 DOI: 10.1136/bmjopen-2020-039258] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 08/31/2020] [Accepted: 10/04/2020] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVES To assess the prevalence and risk factors of overweight and obesity among type 2 diabetes mellitus (T2DM) patients in Uganda. DESIGN Retrospective chart review. SETTING This study was conducted in the outpatient's T2DM clinic in St. Francis Hospital-Nsambya, Uganda between March and May 2017. PARTICIPANTS Type 2 diabetes patients registered in the diabetes clinic between July 2003 and September 2016. OUTCOME MEASURES Overweight and obesity defined as body mass index (kg/m2) of 25.0-29.9 and obesity as 30.0 or higher. RESULTS Of 1275 T2DM patients, the median age was 54 (IQR: 44-65) years, 770 (60.40%) were females, 887 (69.6%) had hypertension, 385 (28%) had controlled glycaemia, 349 (27%) were obese, while 455 (36%) were overweight. Overweight/obesity were lower among men (OR: 0.45, 95% CI: 0.340 to 0.593, p≤0.001) and among patients aged ≥65 years (OR: 0.52, 95% CI: 0.350 to 0.770, p=0.001); patients who rarely ate fruits and vegetables (OR: 0.66, 95% CI: 0.475 to 0.921, p=0.014) but higher among patients of middle (OR: 1.83, 95% CI: 1.320 to 2.550, p≤0.001) and upper (OR: 2.10, 95% CI: 1.450 to 2.990, p≤0.001) socioeconomic status; on dual therapy (OR: 2.17, 95% CI: 1.024 to 4.604, p=0.043); with peripheral neuropathy (OR: 1.40, 95% CI: 1.039 to 1.834, p=0.026) and hypertension (OR: 1.70, 95% CI: 1.264 to 2.293, p≤0.001). CONCLUSIONS Overweight and obesity are high among T2DM patients in this population and may contribute significantly to poor outcomes of T2DM. Therefore, strategies to address this problem are urgently needed.
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Affiliation(s)
- Salome Tino
- Non-Communicable Diseases, MRC/UVRI Uganda Research Unit On AIDS, Entebbe, Wakiso, Uganda
| | - Billy N Mayanja
- Non-Communicable Diseases, MRC/UVRI Uganda Research Unit On AIDS, Entebbe, Wakiso, Uganda
| | | | - Emmanuel Eling
- Statistics, MRC/UVRI Uganda Research Unit On AIDS, Entebbe, Wakiso, Uganda
| | - Edward Ddumba
- Internal Medicine, Saint Raphael of Saint Francis Hospital Nsambya, Kampala, Uganda
| | - Pontiano Kaleebu
- Non-Communicable Diseases, MRC/UVRI Uganda Research Unit On AIDS, Entebbe, Wakiso, Uganda
- London School of Hygiene and Tropical Medicine, London, UK
| | - Moffat Nyirenda
- Non-Communicable Diseases, MRC/UVRI Uganda Research Unit On AIDS, Entebbe, Wakiso, Uganda
- London School of Hygiene and Tropical Medicine, London, UK
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Type II diabetes mellitus: a review on recent drug based therapeutics. Biomed Pharmacother 2020; 131:110708. [DOI: 10.1016/j.biopha.2020.110708] [Citation(s) in RCA: 89] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 08/23/2020] [Accepted: 08/28/2020] [Indexed: 12/15/2022] Open
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Díaz-López A, Iglesias-Vázquez L, Pallejà-Millán M, Rey Reñones C, Flores Mateo G, Arija V. Association between Iron Status and Incident Type 2 Diabetes: A Population-Based Cohort Study. Nutrients 2020; 12:nu12113249. [PMID: 33114064 PMCID: PMC7690731 DOI: 10.3390/nu12113249] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Revised: 10/19/2020] [Accepted: 10/20/2020] [Indexed: 02/08/2023] Open
Abstract
Type 2 diabetes poses a major public health challenge. Here, we conducted a cohort study with a large sample size to determine the association of baseline serum ferritin (SF), a marker of iron status, with incident type 2 diabetes in primary healthcare patients in Catalonia, a western Mediterranean region. A total of 206,115 patients aged 35–75 years without diabetes and with available baseline SF measurements were eligible. The variables analyzed included sociodemographic characteristics, anthropometry, lifestyle, morbidity and iron status (SF, serum iron and hemoglobin). Incident type 2 diabetes during follow-up (2006–2016) was ascertained using the International Classification of Diseases, 10th edition. Cox proportional-hazards models adjusted for multiple baseline confounders/mediators were used to estimate hazard ratios (HRs). Over a median follow-up of 8.4 years, 12,371 new cases of type 2 diabetes were diagnosed, representing an incidence rate of 7.5 cases/1000 persons/year. Since at baseline, the median SF concentration was higher in subjects who developed type 2 diabetes (107.0 µg/L vs. 60.3 µg/L; p < 0.001), SF was considered an independent risk predictor for type 2 diabetes; the multivariable-adjusted HRs for incident type 2 diabetes across SF quartiles 1–4 were 1.00 (reference), 0.95 (95% CI = 0.85–1.06), 1.18 (95% CI = 1.65–1.31) and 1.51 (95% CI = 1.36–1.65), respectively. Our study suggested that higher baseline SF was significantly associated with an increased risk of new-onset type 2 diabetes in Catalan primary healthcare users, supporting the relevance of monitoring iron stores in order to improve the diagnosis and management of diabetes in clinical practice.
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Affiliation(s)
- Andrés Díaz-López
- Medicine and Health Sciences Faculty, Universitat Rovira i Virgili (URV), 43201 Reus, Spain; (A.D.-L.); (L.I.-V.)
- Institute of Health Research Pere Virgili (IISPV), 43204 Reus, Spain
- Center of Biomedical Research in Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, 28029 Madrid, Spain
| | - Lucía Iglesias-Vázquez
- Medicine and Health Sciences Faculty, Universitat Rovira i Virgili (URV), 43201 Reus, Spain; (A.D.-L.); (L.I.-V.)
- Institute of Health Research Pere Virgili (IISPV), 43204 Reus, Spain
- Research Group in Nutrition and Mental Health (NUTRISAM), URV, 43201 Reus, Spain
| | - Meritxell Pallejà-Millán
- Unit of Research Support Reus-Tarragona, Jordi Gol University Institute for Primary Care Research (IDIAP), 43202 Tarragona, Spain; (M.P.-M.); (C.R.R.); (G.F.M.)
| | - Cristina Rey Reñones
- Unit of Research Support Reus-Tarragona, Jordi Gol University Institute for Primary Care Research (IDIAP), 43202 Tarragona, Spain; (M.P.-M.); (C.R.R.); (G.F.M.)
| | - Gemma Flores Mateo
- Unit of Research Support Reus-Tarragona, Jordi Gol University Institute for Primary Care Research (IDIAP), 43202 Tarragona, Spain; (M.P.-M.); (C.R.R.); (G.F.M.)
| | - Victoria Arija
- Medicine and Health Sciences Faculty, Universitat Rovira i Virgili (URV), 43201 Reus, Spain; (A.D.-L.); (L.I.-V.)
- Institute of Health Research Pere Virgili (IISPV), 43204 Reus, Spain
- Research Group in Nutrition and Mental Health (NUTRISAM), URV, 43201 Reus, Spain
- Unit of Research Support Reus-Tarragona, Jordi Gol University Institute for Primary Care Research (IDIAP), 43202 Tarragona, Spain; (M.P.-M.); (C.R.R.); (G.F.M.)
- Correspondence: ; Tel.: +34-977-75-93-34
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Hwang AC, Lee WJ, Peng LN, Liu LK, Lin MH, Loh CH, Chen LK. Unfavorable body composition and quality of life among community-dwelling middle-aged and older adults: What really matters? Maturitas 2020; 140:34-40. [DOI: 10.1016/j.maturitas.2020.05.024] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 04/19/2020] [Accepted: 05/29/2020] [Indexed: 12/25/2022]
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Syring KE, Bosma KJ, Goleva SB, Singh K, Oeser JK, Lopez CA, Skaar EP, McGuinness OP, Davis LK, Powell DR, O’Brien RM. Potential positive and negative consequences of ZnT8 inhibition. J Endocrinol 2020; 246:189-205. [PMID: 32485672 PMCID: PMC7351606 DOI: 10.1530/joe-20-0138] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Accepted: 06/02/2020] [Indexed: 12/31/2022]
Abstract
SLC30A8 encodes the zinc transporter ZnT8. SLC30A8 haploinsufficiency protects against type 2 diabetes (T2D), suggesting that ZnT8 inhibitors may prevent T2D. We show here that, while adult chow fed Slc30a8 haploinsufficient and knockout (KO) mice have normal glucose tolerance, they are protected against diet-induced obesity (DIO), resulting in improved glucose tolerance. We hypothesize that this protection against DIO may represent one mechanism whereby SLC30A8 haploinsufficiency protects against T2D in humans and that, while SLC30A8 is predominantly expressed in pancreatic islet beta cells, this may involve a role for ZnT8 in extra-pancreatic tissues. Consistent with this latter concept we show in humans, using electronic health record-derived phenotype analyses, that the 'C' allele of the non-synonymous rs13266634 SNP, which confers a gain of ZnT8 function, is associated not only with increased T2D risk and blood glucose, but also with increased risk for hemolytic anemia and decreased mean corpuscular hemoglobin (MCH). In Slc30a8 KO mice, MCH was unchanged but reticulocytes, platelets and lymphocytes were elevated. Both young and adult Slc30a8 KO mice exhibit a delayed rise in insulin after glucose injection, but only the former exhibit increased basal insulin clearance and impaired glucose tolerance. Young Slc30a8 KO mice also exhibit elevated pancreatic G6pc2 gene expression, potentially mediated by decreased islet zinc levels. These data indicate that the absence of ZnT8 results in a transient impairment in some aspects of metabolism during development. These observations in humans and mice suggest the potential for negative effects associated with T2D prevention using ZnT8 inhibitors.
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Affiliation(s)
- Kristen E. Syring
- Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine
| | - Karin J. Bosma
- Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine
| | - Slavina B. Goleva
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232
| | - Kritika Singh
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232
| | - James K. Oeser
- Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine
| | - Christopher A. Lopez
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232
| | - Eric P. Skaar
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232
| | - Owen P. McGuinness
- Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine
| | - Lea K. Davis
- Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232
| | - David R. Powell
- Lexicon Pharmaceuticals Incorporated, 8800 Technology Forest Place, The Woodlands, Texas 77381
| | - Richard M. O’Brien
- Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine
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Wang ST, Lin YK, Weng SF, Huang CL, Huang HC, Chiu YC, Hu S. Skeletal Muscle Ratio: A Complete Mediator of Physical Activity and HbA1C in Type 2 Diabetes. Biol Res Nurs 2020; 22:536-543. [PMID: 32691603 DOI: 10.1177/1099800420942884] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND An increase in the physical activity level reduces body weight, decreases body fat, increases skeletal muscle mass, and improves serum glucose; however, the influence of body composition parameters on the relationship between physical activity and serum glucose remains unclear. OBJECTIVE This study investigated whether skeletal muscle and visceral fat affect the relationship between high physical activity and long-term serum glucose goals. METHOD This cross-sectional study recruited patients with type 2 diabetes. The Chinese version of the International Physical Activity Questionnaire was used for estimating the physical activity level, and a bioimpedance device was used to measure the skeletal muscle ratio (skeletal muscle mass/total body weight, %) and visceral fat area (cm2). Hierarchical logistic regression models and mediation tests were conducted according to Hayes' procedures. RESULTS Of the total 543 Chinese individuals with type 2 diabetes enrolled, HbA1C levels of fewer than half (n = 243, 44.8%) met the target of ≤7.0%. The skeletal muscle ratio was found to be a complete mediator (OR = 0.920, 95% CI: 0.848 to 0.998; indirect effect: -0.238, 95% CI: -0.525 to -0.020) of the relationship between high physical activity and the target HbA1C level after controlling for visceral fat area (indirect effect: -0.013, 95% CI: -0.183 to 0.156), age, time since diabetes diagnosis, and rice intake. CONCLUSION Nurses should include an increase in the skeletal muscle ratio as an objective in physical activity interventions for patients with type 2 diabetes to help them achieve their long-term serum glucose goals.
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Affiliation(s)
- Sen-Te Wang
- Department of Family Medicine, School of Medicine, College of Medicine, 38032Taipei Medical University, Taipei City.,Department of Family Medicine, 63474Taipei Medical University Hospital, Taipei City.,Health Management Center, 63474Taipei Medical University Hospital, Taipei City
| | - Yen-Kuang Lin
- Biostatistics Center, 38032Taipei Medical University, Taipei City
| | - Shuen-Fu Weng
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Medical University Hospital, Taipei City.,Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei City
| | - Chen-Ling Huang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Medical University Hospital, Taipei City
| | - Hui-Chuan Huang
- School of Nursing, College of Nursing, Taipei Medical University, Taipei City
| | - Yi-Chun Chiu
- Urology Division, Surgical Department, Heping Fuyou Branch, Taipei City Hospital, Taipei City.,Urology Department, School of Medicine, National Yang-Ming University, Taipei City
| | - Sophia Hu
- Department of Nursing, School of Nursing, 34882National Yang-Ming University, Taipei City
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Yu Y, Xie K, Lou Q, Xia H, Wu D, Dai L, Hu C, Wang K, Shan S, Hu Y, Tang W. The achievement of comprehensive control targets among type 2 diabetes mellitus patients of different ages. Aging (Albany NY) 2020; 12:14066-14079. [PMID: 32699183 PMCID: PMC7425513 DOI: 10.18632/aging.103358] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Accepted: 05/20/2020] [Indexed: 12/11/2022]
Abstract
Objective: To evaluate achievement of comprehensive controls among patients with type 2 diabetes mellitus (T2DM) in different age groups. Results: The elderly patients had higher control rates for BMI (44.36%), TC (50.83%) and LDL-C (48.27%) than those aged 60-80 years and younger patients (all P <0.05). Multiple logistic regression revealed that elderly patients were more likely to achieve control targets for HbA1c (odd ratio (OR) = 2.19), TC (OR = 1.32), HDL-C (OR = 1.35), and TG (OR = 1.74) than younger patients. This effect was stronger in males (ORHbA1c = 2.27; ORTC = 1.41; ORHDL-C = 1.51; ORTG = 1.80). By contrast, elderly females were only more likely to achieve HbA1c < 7.0% (OR=1.88). Conclusions: Our findings suggest that comprehensive control strategies still should be strengthened. Methods: A total of 3126 T2DM patients were included, and detected blood pressure (BP), body mass index (BMI), glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C). We divided patients into three age groups (<60, 60-80 and ≥ 80 years), to assess the differences in achieving the control targets.
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Affiliation(s)
- Yun Yu
- Department of Endocrinology and Metabolism, Geriatric Hospital of Nanjing Medical University, Nanjing, China.,Division of Geriatrics, Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, China
| | - Kaipeng Xie
- Nanjing Maternity and Child Health Care Institute, Nanjing Maternity and Child Health Care Hospital, Women's Hospital of Nanjing Medical University, Nanjing, China
| | - Qinglin Lou
- Department of Endocrinology and Metabolism, Geriatric Hospital of Nanjing Medical University, Nanjing, China
| | - Hui Xia
- Department of Endocrinology and Metabolism, Geriatric Hospital of Nanjing Medical University, Nanjing, China
| | - Dan Wu
- Department of Endocrinology and Metabolism, Geriatric Hospital of Nanjing Medical University, Nanjing, China
| | - Lingli Dai
- Department of Endocrinology and Metabolism, Geriatric Hospital of Nanjing Medical University, Nanjing, China
| | - Cuining Hu
- Department of Endocrinology and Metabolism, Geriatric Hospital of Nanjing Medical University, Nanjing, China
| | - Kunlin Wang
- Department of Endocrinology and Metabolism, Geriatric Hospital of Nanjing Medical University, Nanjing, China
| | - Shan Shan
- Department of Endocrinology and Metabolism, Geriatric Hospital of Nanjing Medical University, Nanjing, China
| | - Yun Hu
- Division of Geriatrics, Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, China
| | - Wei Tang
- Department of Endocrinology and Metabolism, Geriatric Hospital of Nanjing Medical University, Nanjing, China
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Yamazaki H, Tauchi S, Wang J, Dohke M, Hanawa N, Kodama Y, Katanuma A, Saisho Y, Kamitani T, Fukuhara S, Yamamoto Y. Longitudinal association of fatty pancreas with the incidence of type-2 diabetes in lean individuals: a 6-year computed tomography-based cohort study. J Gastroenterol 2020; 55:712-721. [PMID: 32246380 DOI: 10.1007/s00535-020-01683-x] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Accepted: 03/19/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Only a few studies have longitudinally evaluated whether fatty pancreas increases the risk of type-2 diabetes (T2D), and their results were inconsistent. Fatty pancreas is closely linked to overweight and obesity, but previous studies did not exclude overweight or obese individuals. Therefore, in this cohort study, we investigated the association between fatty pancreas and T2D incidence in lean individuals. METHODS Between 2008 and 2013, 1478 nondiabetic lean individuals (i.e. body-mass index < 25 kg/m2) underwent health examinations including computed tomography (CT) and were followed for a median of 6.19 years. Fatty pancreas was evaluated by a histologically-validated method using pancreas attenuation (Hounsfield units [HU]) on CT at baseline; lower pancreas attenuation indicates more pancreatic fat. To detect incident T2D, we used fasting plasma glucose, HbA1c, and self-reports of prescribed anti-diabetes medications. Odds ratios (OR) for the association between pancreas attenuation and incident T2D were estimated using logistic regression models adjusted for likely confounders. RESULTS T2D occurred in 61 participants (4.13%) during the follow-up period. Lower pancreas attenuation (i.e. more pancreatic fat) at baseline was associated with incident T2D (unadjusted OR per 10 HU lower attenuation: 1.56 [95% CI 1.28-1.91], p < 0.001). The multivariable-adjusted analysis revealed a similar association (adjusted OR per 10 HU lower attenuation: 1.32 [95% CI 1.06-1.63], p = 0.012). CONCLUSIONS T2D was likely to develop in lean individuals with the fatty pancreas. Among people who are neither obese nor overweight, the fatty pancreas can be used to define a group at high risk for T2D.
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Affiliation(s)
- Hajime Yamazaki
- Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan. .,Section of Clinical Epidemiology, Department of Community Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Syogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
| | - Shinichi Tauchi
- Department of Radiology, Keijinkai Maruyama Clinic, 3-16, Odori Nishi 26-chome, Chuo-ku, Sapporo, 064-0820, Japan
| | - Jui Wang
- Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan.,Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Room 517, No. 17, Xu-Zhou Road, Taipei, 100, Taiwan
| | - Mitsuru Dohke
- Department of Health Checkup and Promotion, Keijinkai Maruyama Clinic, 3-16, Odori Nishi 26-chome, Chuo-ku, Sapporo, 064-0820, Japan
| | - Nagisa Hanawa
- Department of Health Checkup and Promotion, Keijinkai Maruyama Clinic, 3-16, Odori Nishi 26-chome, Chuo-ku, Sapporo, 064-0820, Japan
| | - Yoshihisa Kodama
- Department of Radiology, Teine Keijinkai Hospital, 1-40, 1-jo 12-chome, Maeda, Teine-ku, Sapporo, 006-8555, Japan
| | - Akio Katanuma
- Center for Gastroenterology, Teine Keijinkai Hospital, 1-40, 1-jo 12-chome, Maeda, Teine-ku, Sapporo, 006-8555, Japan
| | - Yoshifumi Saisho
- Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Tsukasa Kamitani
- Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan
| | - Shunichi Fukuhara
- Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan
| | - Yosuke Yamamoto
- Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan
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Nie H, Zhang K, Xu J, Liao K, Zhou W, Fu Z. Combining Bioinformatics Techniques to Study Diabetes Biomarkers and Related Molecular Mechanisms. Front Genet 2020; 11:367. [PMID: 32425976 PMCID: PMC7204005 DOI: 10.3389/fgene.2020.00367] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Accepted: 03/25/2020] [Indexed: 01/16/2023] Open
Abstract
Objective To explore the mechanism of plasma circulating miRNA-126 and miRNA-28-3p in diabetes mellitus (DM) patients, and to identify the related bioinformatics analysis. Methods Randomly selected 120 DM patients as the observation group and 120 non- DM patients as the control group. The plasma circulating miRNA-126 and miRNA-28-3p were analyzed by qRT-PCR, and their target genes, biological information, related lncRNA and circRNA were predicted. Results The circulating miRNA-126 (0.1162 ± 0.0236 vs. 0.0018 ± 0.0862) and miRNA-28-3p (0.1378 ± 0.0268 vs. 0.0006 ± 0.0167) levels in the observation group were significantly higher than those in the control group, and differences were statistically significant (P < 0.01). The Pearson correlation coefficient of miRNA-126 and miRNA- 28-3p was 0.4337 (P < 0.01). ROC curve analysis of miRNA-126 and miRNA-28-3p showed that the differences of the area under curve were statistically significant between the two groups (P < 0.01). Bioinformatics prediction showed that miRNA-126 and miRNA-28-3p may be involved in regulation of the insulin signaling pathway, insulin receptor signaling pathway, insulin/insulin growth factor signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway and angiogenesis. Moreover, it may be associated with a variety of lncRNA and cir-cRNA. Conclusion Circulating miRNA-126 and miRNA-28-3p can be a potential biomarker of DM and it may play an important role in the DM by regulating insulin or insulin growth factor related signaling pathways.
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Affiliation(s)
- Han Nie
- Department of Vascular Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Kaihua Zhang
- Department of General Surgery, Jiujiang Hospital Affiliated to Nanchang University, Nanchang, China
| | - Jiasheng Xu
- Department of Vascular Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Kaili Liao
- Department of Clinical Laboratory, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Weimin Zhou
- Department of Vascular Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Zhonghua Fu
- Department of Burns, The First Affiliated Hospital of Nanchang University, Nanchang, China
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Moh MC, Low S, Ng TP, Wang J, Ang SF, Tan C, Ang K, Tavintharan S, Sum CF, Kwan PY, Lee SBM, Tang WE, Lim SC. Association of traditional and novel measures of central obesity with cognitive performance in older multi-ethnic Asians with type 2 diabetes. Clin Obes 2020; 10:e12352. [PMID: 32020768 DOI: 10.1111/cob.12352] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Revised: 12/10/2019] [Accepted: 12/15/2019] [Indexed: 01/04/2023]
Abstract
Literature evaluating the relationship between central obesity and cognitive deficits in type 2 diabetes (T2DM) remains scarce. This cross-sectional analysis explored the association of novel and traditional central obesity measures with cognitive performance in older (aged ≥60 years) non-demented multi-ethnic Asians with T2DM, including a stratified analysis by body mass index (BMI). Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status. Central obesity measures including visceral fat area (VFA), waist circumference, waist:hip ratio, waist:height ratio, abdominal volume index, body roundness index and conicity index were measured and/or computed. In our cohort (N = 677; mean age = 67 ± 5 years, 51.7% men), VFA emerged as an associate of overall cognitive performance after covariate adjustment and Bonferroni correction (β = -.10, 95% CI = -0.18, -0.03), outperforming the other adiposity indices. Specifically, VFA was inversely associated with delayed memory and language scores. Additionally, compared with normal-weight individuals, excess visceral obesity (VFA ≥100 cm2 ) was independently associated with lower cognitive scores to a greater extent in normal BMI (<23 kg/m2 ) adults than in those with high BMI (≥23 kg/m2 ). Assessment and management of visceral adiposity may help to prevent cognitive decline in older people with T2DM, and reduce the global burden of dementia in ageing populations.
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Affiliation(s)
- Mei Chung Moh
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Singapore
| | - Serena Low
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Singapore
- Diabetes Centre, Admiralty Medical Centre, Khoo Teck Puat Hospital, Singapore, Singapore
| | - Tze Pin Ng
- Gerontology Research Programme, Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Jiexun Wang
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Singapore
| | - Su Fen Ang
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Singapore
| | - Clara Tan
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Singapore
| | - Keven Ang
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Singapore
| | - Subramaniam Tavintharan
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Singapore
- Diabetes Centre, Admiralty Medical Centre, Khoo Teck Puat Hospital, Singapore, Singapore
| | - Chee Fang Sum
- Diabetes Centre, Admiralty Medical Centre, Khoo Teck Puat Hospital, Singapore, Singapore
| | - Pek Yee Kwan
- National Healthcare Group Polyclinics, Singapore, Singapore
| | | | - Wern Ee Tang
- National Healthcare Group Polyclinics, Singapore, Singapore
| | - Su Chi Lim
- Clinical Research Unit, Khoo Teck Puat Hospital, Singapore, Singapore
- Diabetes Centre, Admiralty Medical Centre, Khoo Teck Puat Hospital, Singapore, Singapore
- Saw Swee Hock School of Public Health, National University Hospital, Singapore, Singapore
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Ranjan A, Choubey M, Yada T, Krishna A. Nesfatin-1 ameliorates type-2 diabetes-associated reproductive dysfunction in male mice. J Endocrinol Invest 2020; 43:515-528. [PMID: 31691259 DOI: 10.1007/s40618-019-01136-0] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2019] [Accepted: 10/25/2019] [Indexed: 12/19/2022]
Abstract
PURPOSE The present study was aimed to demonstrate the recuperative effect of nesfatin-1 on testicular dysfunction in the high-fat diet (HFD)/streptozotocin (STZ)-induced type-2 diabetes mellitus (T2DM) mice. METHOD AND RESULTS Three experimental groups were formed: (1) vehicle control (VC), (2) T2DM mice, (3) T2DM + nesf-1. The mice with blood glucose level higher than 300 mg/dL following HFD and a single dose of STZ were used for the experiment. The T2DM mice showed increases in body mass, blood glucose and insulin levels, reductions in spermatogenesis and steroidogenesis, production of antioxidative enzymes, and disturbed lipid profile. These alterations were all ameliorated by administration of nesfatin-1 at 20 μg/Kg BW for 15 days. Nesfatin-1 treatment also increased the production of testosterone (T), improved insulin sensitivity, and effectively ameliorated the testicular aberrations, and increased spermatogenesis and steroidogenesis. In addition, nesfatin-1 treatment upregulated the PCNA and Bcl2 expression and inhibited the caspase-3 and prohibitin expression in T2DM mice. Nesfatin-1 increased insulin receptor (IR) and GLUT8 expressions, and lactate production, the changes that further substantiate the increase of energy influx to the testis. CONCLUSION Altogether, the results suggest the ameliorative effect of nesfatin-1 against T2DM-associated testicular dysfunctions and improved insulin sensitivity along with promoting T production and fertility in T2DM mice.
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Affiliation(s)
- A Ranjan
- Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India
| | - M Choubey
- Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India
| | - T Yada
- Division of Integrative Physiology, Kansai Electric Power Medical Research Institute, Kobe, 650-0047, Japan
- Division of System Neuroscience, Kobe University Graduate School of Medicine, Kobe, 650-0017, Japan
| | - A Krishna
- Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India.
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