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Yang Q, Zhu X, Zhang L, Luo F. Dyslipidemia and aging: the non-linear association between atherogenic index of plasma (AIP) and aging acceleration. Cardiovasc Diabetol 2025; 24:181. [PMID: 40281579 PMCID: PMC12023499 DOI: 10.1186/s12933-025-02695-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Accepted: 03/17/2025] [Indexed: 04/29/2025] Open
Abstract
BACKGROUND Dyslipidemia has been proved to play a pivotal role in biological aging. Atherogenic Index of Plasma (AIP), derived from serum triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C), is an effective biomarker of dyslipidemia. However, whether AIP can be used as an indicator of biological aging remains unclear. This study aims to investigate the relationship between AIP and biological aging in the US adult population. METHODS 4,471 American adults with age over 20 years from the National Health and Nutrition Examination Survey (NHANES) database were included in this study. Biological aging was assessed by phenotypic age acceleration (PhenoAgeAccel). Multivariable linear regression models, subgroup analyses and interaction tests were employed to explore the association between AIP and PhenoAgeAccel. Furthermore, adjusted restricted cubic spline (RCS) analyses were employed to assess potential nonlinear relationships, while mediation analysis was utilized to identify the mediating effects of homeostatic model assessment of insulin resistance (HOMA-IR). Besides, network pharmacology was performed to determine the potential mechanisms underlying dyslipidemia-related aging acceleration. RESULTS A total of 4,471 participants were included in this study, the median chronological age, PhenoAge and PhenoAgeAccel for the overall population were 49 (35-64) years, 42.85 (27.30-59.68) years, and - 6.92 (- 10.52 to -2.46) years, respectively. In the fully adjusted model, one unit increase of AIP was correlated with 1.820-year increase in PhenoAgeAccel (β = 1.820, 95% CI: 1.085-2.556), which was more pronounced among individuals being female, diabetic and hypertensive. Furthermore, RCS analysis revealed a nonlinear relationship between AIP and PhenoAgeAccel, with an inflection point identified at -0.043 for AIP via threshold and saturation effect analysis. AIP demonstrated a positive correlation with PhenoAgeAccel both before (β = 6.550, 95% CI: 5.070-8.030) and after (β = 3.898, 95% CI: 2.474-5.322) this inflection point. Additionally, HOMA-IR was found to mediate 39.21% of the association between AIP and PhenoAgeAccel. Finally, network pharmacology analysis identified INS, APOE, APOB, IL6, IL10, PPARG, MTOR, ACE, PPARGC1A, and SERPINE1 as core targets in biological aging, which were functionally linked to key signaling pathways like AMPK, apelin, JAK-STAT, FoxO, etc. CONCLUSIONS: An elevated AIP was notably and positively correlated with accelerated aging, suggesting that AIP may serve as an effective predictor to evaluate accelerated aging.
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Affiliation(s)
- QianKun Yang
- National & Regional United Engineering Lab of Tissue Engineering, Department of Orthopedics, Southwest Hospital, Army Medical University, No.29 Gaotanyan St., Shapingba District, Chongqing, 400038, China.
| | - XianJie Zhu
- National & Regional United Engineering Lab of Tissue Engineering, Department of Orthopedics, Southwest Hospital, Army Medical University, No.29 Gaotanyan St., Shapingba District, Chongqing, 400038, China
- Graduate School of Dalian Medical University, Dalian, 116000, China
| | - Li Zhang
- Department of Hematology, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, No.136 of Zhong Shan Second Road, Yu Zhong District, Chongqing, 400014, China
- Department of Neurology, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, , Children's Hospital of Chongqing Medical University, No.136 of Zhong Shan Second Road, Yu Zhong District, Chongqing, 400014, China
| | - Fei Luo
- National & Regional United Engineering Lab of Tissue Engineering, Department of Orthopedics, Southwest Hospital, Army Medical University, No.29 Gaotanyan St., Shapingba District, Chongqing, 400038, China.
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Juszczak M, Shem K. Treatment of obesity in spinal cord injury with tirzepatide: a case report. Spinal Cord Ser Cases 2025; 11:4. [PMID: 40025019 PMCID: PMC11873185 DOI: 10.1038/s41394-025-00699-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Revised: 02/11/2025] [Accepted: 02/21/2025] [Indexed: 03/04/2025] Open
Abstract
INTRODUCTION Individuals with spinal cord injury (SCI) experience alterations in metabolism that result in increased central obesity, insulin resistance, and dyslipidemia placing them at elevated risk for developing cardiometabolic disease (CMD). Increased exercise and dietary modifications are the primary interventions for preventing CMD. However, people with SCI face unique challenges that prevent them from increasing their physical activity and easily modifying their nutritional intake. Tirzepatide is a medication that has been approved by the Food and Drug Administration to be used in conjunction with lifestyle changes to treat obesity in adults with type 2 diabetes mellitus. CASE PRESENTATION A male in his 40's with C6 American Spinal Injury Association Impairment Scale B SCI 15 years prior with a body mass index of 32 presented to his primary care provider for treatment of obesity. He previously worked with multiple dietitians and increased his physical activity to lose weight. Despite these interventions, he was unable to reduce his weight. He was started on tirzepatide. After 3 months of treatment, he lost 31 pounds and saw improvements in his lipid profile. The only adverse effect reported was heartburn. DISCUSSION The metabolic dysfunction associated with SCI and barriers to adequate exercise for weight loss place individuals with SCI at increased risk for obesity and developing CMD. Tirzepatide may be an effective adjunct therapy to lifestyle interventions to help prevent CMD in those with SCI. Further research is indicated to examine the long-term efficacy, benefits, and adverse effects that may be associated with tirzepatide.
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Affiliation(s)
- Michael Juszczak
- Reading Hospital Rehabilitation at Wyomissing, Tower Health Reading, Wyomissing, PA, USA
| | - Kazuko Shem
- Santa Clara Valley Medical Center, San Jose, CA, USA.
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Choi Y, Kang SJ, Kim J. Association between meeting the 24-hour movement guidelines and cardiometabolic syndrome in Korean adults. Sci Rep 2025; 15:6879. [PMID: 40011645 PMCID: PMC11865427 DOI: 10.1038/s41598-025-91398-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Accepted: 02/20/2025] [Indexed: 02/28/2025] Open
Abstract
Twenty-four-hour movement guidelines are reported to correlate with a reduction in the risk of metabolic disease in all age groups. We explored the association between meeting 24-h Movement Guidelines and cardiometabolic syndrome in the general adult population using data from the Korea National Health and Nutrition Examination Survey (KNHANES). This population-based cross-sectional study used data from the KNHANES 2014-2017 and included 2151 adults. Physical activity and sedentary behavior were measured using a three-axis accelerometer. Sleep time was measured using a self-reported questionnaire. Compared with adherence to none of the three guidelines, the odds ratio (OR) for meeting two of the three guidelines were 0.66 (95% confidence interval 0.45-0.98), whereas the OR for meeting all three guidelines was 0.24 (95% CI 0.10-0.59). In the analysis of specific combinations, the group that met the physical activity and sleep time guidelines had a significantly lower risk of cardiometabolic syndrome (OR 0.45, 95% CI 0.21-0.90). Consequently, we suggest that adherence to two or more physical activity guidelines may reduce the risk of cardiometabolic syndrome in Korean adults. Furthermore, meeting all three guidelines is more closely associated with cardiometabolic health owing to their synergistic effects.
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Affiliation(s)
- Yunseo Choi
- Sports and Exercise Medicine Laboratory, Graduated School of Sports Convergence, Korea Maritime and Ocean University, 727 Taejong-ro, Yeongdo-gu, Busan, 49112, Republic of Korea
- Korea Institute of Ocean Science and Technology (KIOST), Busan, Republic of Korea
| | - Suh-Jung Kang
- Department of Sports and Health Care Major, College of Culture & Arts, Sang Myung University, Seoul, Republic of Korea
| | - Junghoon Kim
- Sports and Exercise Medicine Laboratory, Graduated School of Sports Convergence, Korea Maritime and Ocean University, 727 Taejong-ro, Yeongdo-gu, Busan, 49112, Republic of Korea.
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Capasso L, De Masi L, Sirignano C, Maresca V, Basile A, Nebbioso A, Rigano D, Bontempo P. Epigallocatechin Gallate (EGCG): Pharmacological Properties, Biological Activities and Therapeutic Potential. Molecules 2025; 30:654. [PMID: 39942757 PMCID: PMC11821029 DOI: 10.3390/molecules30030654] [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: 12/19/2024] [Revised: 01/26/2025] [Accepted: 01/29/2025] [Indexed: 02/16/2025] Open
Abstract
Epigallocatechin gallate (EGCG), the predominant catechin in green tea, comprises approximately 50% of its total polyphenol content and has garnered widespread recognition for its significant therapeutic potential. As the principal bioactive component of Camellia sinensis, EGCG is celebrated for its potent antioxidant, anti-inflammatory, cardioprotective, and antitumor properties. The bioavailability and metabolism of EGCG within the gut microbiota underscore its systemic effects, as it is absorbed in the intestine, metabolized into bioactive compounds, and transported to target organs. This compound has been shown to influence key physiological pathways, particularly those related to lipid metabolism and inflammation, offering protective effects against a variety of diseases. EGCG's ability to modulate cell signaling pathways associated with oxidative stress, apoptosis, and immune regulation highlights its multifaceted role in health promotion. Emerging evidence underscores EGCG's therapeutic potential in preventing and managing a range of chronic conditions, including cancer, cardiovascular diseases, neurodegenerative disorders, and metabolic syndromes. Given the growing prevalence of lifestyle-related diseases and the increasing interest in natural compounds, EGCG presents a promising avenue for novel therapeutic strategies. This review aims to summarize current knowledge on EGCG, emphasizing its critical role as a versatile natural bioactive agent with diverse clinical applications. Further exploration in both experimental and clinical settings is essential to fully unlock its therapeutic potential.
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Affiliation(s)
- Lucia Capasso
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. De Crecchio 7, 80138 Naples, Italy; (L.C.); (A.N.)
| | - Luigi De Masi
- National Research Council (CNR), Institute of Biosciences and BioResources (IBBR), Via Università 133, 80055 Portici, Italy;
| | - Carmina Sirignano
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via Domenico Montesano 49, 80131 Naples, Italy;
| | - Viviana Maresca
- Department of Life Science, Health, and Health Professions, Link Campus University, 00165 Rome, Italy;
| | - Adriana Basile
- Department of Biology, University of Naples Federico II, 80126 Naples, Italy;
| | - Angela Nebbioso
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. De Crecchio 7, 80138 Naples, Italy; (L.C.); (A.N.)
| | - Daniela Rigano
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via Domenico Montesano 49, 80131 Naples, Italy;
| | - Paola Bontempo
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. De Crecchio 7, 80138 Naples, Italy; (L.C.); (A.N.)
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Shu J, Zheng R. Association between the triglycerides and glucose index and critically ill stroke in non-obese population: An observational study on eICU database. J Clin Neurosci 2025; 132:110980. [PMID: 39673840 DOI: 10.1016/j.jocn.2024.110980] [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: 09/08/2024] [Revised: 11/14/2024] [Accepted: 12/05/2024] [Indexed: 12/16/2024]
Abstract
BACKGROUND Both the triglyceride glucose (TyG) index and stroke are associated with insulin resistance (IR). Studies have shown that TyG is associated with stroke. However, the relationship between TyG index and stroke in non-obese population remains unclear. This study investigated the association between TyG and the prognosis of severe stroke in non-obese individuals. METHODS This was a retrospective observational study. TyG was determined at baseline and stroke mortality was assessed at follow-up. All data were extracted from the eICU Collaborative Research Database. Hospital and intensive care unit (ICU) mortality rates were determined as endpoints. Smoothing curves were performed to estimate the relationship between TyG and stroke mortality. Multivariate logistic regression analysis and restricted cubic spline regression were used to evaluate the independent effect of TyG on stroke mortality. RESULTS A total of 1946 eligible subjects were included. The hospital and ICU mortality rates were 10.6 % and 5.3 %, respectively. In univariate analysis, for per unit increase in TyG, the odds ratio (OR) for in-hospital mortality and ICU mortality of stroke were 1.85 (95 %CI 1.50-2.28) and 2.08 (95 %CI 1.58-2.75), respectively. After fully adjusting for confounding factors, the OR for in-hospital mortality and ICU mortality of stroke were 8.64 (95 %CI 4.25-17.55) and 9.30 (95 %CI 3.73-23.20), respectively. The restricted cubic spline regression model indicated a linear increase in hospital and ICU mortality with rising TyG index. Subgroup analysis showed consistent effect sizes and directions across different subgroups, demonstrating the stability of the findings. CONCLUSION In the non-obese population, an increase in TyG was related to higher stroke mortality. TyG may have clinical significance in identifying poor prognosis of stroke patients.
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Affiliation(s)
- Jie Shu
- Department of General Medicine, The First Affiliated Hospital of Ningbo University, Ningbo, 315000, Zhejiang, China
| | - Rui Zheng
- Department of Critical Care Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, Zhejiang, China.
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Hewage N, Wijesekara U, Perera R. Prevalence of Subclinical Hypothyroidism in a Non-Diabetic Young Female Population and Its Impact on Diabetes and Cardiometabolic Risk. Endocrinol Metab (Seoul) 2024; 39:864-876. [PMID: 39497456 PMCID: PMC11695472 DOI: 10.3803/enm.2024.2015] [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: 04/11/2024] [Revised: 05/07/2024] [Accepted: 06/21/2024] [Indexed: 01/01/2025] Open
Abstract
BACKGRUOUND We evaluated the influence of subclinical hypothyroidism (SCH) on insulin resistance (IR), cardiometabolic risk, and obesity in childbearing-age women without diabetes. METHODS This cross-sectional investigation included 282 women, aged 18 to 35 years, from rural and suburban Sri Lanka. Anthropometric and biochemical parameters, including IR and lipid/thyroid profiles, were recorded. Data were compared between SCH and euthyroidism (EU) for controls (normal weight) and cases (overweight/obese). RESULTS The overall rates of SCH, EU, IR, and metabolic syndrome (MetS) were 40.42%, 59.57%, 73.40%, and 24.46%, respectively. Both controls and cases included individuals with SCH; overall, 168 participants (59.57%) had EU, while 114 (40.42%) exhibited SCH. IR was significantly associated with SCH in both weight groups (P<0.05). Among those with SCH, the odds ratios (ORs) for IR were >2 (95% confidence interval [CI], 0.45 to 3.87) in controls and >6 (95% CI, 3.52 to 8.41) in cases. Similarly, the ORs for MetS were >1 (95% CI, 0.38 to 4.16) in controls and >11 (95% CI, 8.73 to 15.01) in cases. Dyslipidemia and hypertriglyceridemia were significantly more prevalent in the SCH group (P<0.05). Women with SCH exhibited higher mean values for all obesity indices compared to their EU counterparts, surpassing normal thresholds (P<0.05). Among obesity measures, visceral adiposity index (VAI) demonstrated the highest area under the curve and sensitivity for assessing SCH and cardiovascular disease (CVD) risk. CONCLUSION SCH must be identified and managed in young women to help prevent diabetes and cardiometabolic disorders. VAI may aid in precisely detecting SCH and CVD.
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Affiliation(s)
- Nawoda Hewage
- Department of Biochemistry, Faculty of Medical Sciences, University of Sri Jayewardenepura, Nugegoda, Sri Lanka
| | - Udaya Wijesekara
- Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, University of Sri Jayewardenepura, Nugegoda, Sri Lanka
| | - Rasika Perera
- Department of Biochemistry, Faculty of Medical Sciences, University of Sri Jayewardenepura, Nugegoda, Sri Lanka
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Gu L, Du Y, Liang F. Meta-Analysis and Network Analysis Differentially Detect Various Pro-Inflammatory Mediators and Risk Factors for Type 2 Diabetes in the Elderly. Horm Metab Res 2024; 56:727-736. [PMID: 38195796 DOI: 10.1055/a-2241-5281] [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] [Indexed: 01/11/2024]
Abstract
Type 2 diabetes (T2D) has a pathophysiological component that includes inflammation. Inflammation-sensitive marker measurement may be helpful in determining the risk of complications for both older T2D patients and the public. This study aimed to investigate the association between blood pro-inflammatory mediators and the characteristics of elderly patients with T2D using meta and network analyses. The Web of Science, Scopus, PubMed, and Cochrane Library databases were selected as study methodology. The Quality in Prognosis Studies (QUIPS) tool in the meta-analysis assessed the studies' methodological quality. The selected studies were statistically analyzed using the META-MAR tool based on the standardized mean difference (SMD). The selected studies included nine examinations involving 6399 old people [+>+55 years old, 65.9+±+4.09 (mean+±+SD)]. The meta-analysis showed that pro-inflammatory mediators (SMD 0.82) and patient-related variables [risk factors (SMD 0.71)] were significantly associated with T2D (p+<+0.05). Subgroup analysis revealed that tumor necrosis factor alpha (TNF-α; SMD 1.08), body mass index (SMD 0.64), high-density lipoprotein (HDL; SMD -0.61), body weight (SMD 0.50), and blood pressure (SMD 1.11) were factors significantly associated with T2D (p+<+0.05). Network analysis revealed that among patient characteristics, diastolic blood pressure and, among inflammatory mediators, leptin were the most closely associated factors with T2D in older adults. Moreover, network analysis showed that TNF-α and systolic blood pressure were most closely associated with leptin. Overall, alternate techniques, such as meta-analysis and network analysis, might identify different markers for T2D in older people. A therapeutic decision-making process needs to consider these differences in advance.
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Affiliation(s)
- Linlin Gu
- Endocrine Metabolism Department and Geriatric Department, 7th People's Hospital of Chengdu, Chengdu, China
| | - Yue Du
- Endocrine Metabolism Department and Geriatric Department, 7th People's Hospital of Chengdu, Chengdu, China
| | - Fang Liang
- General Medicine Department, 7th People's Hospital of Chengdu, Chengdu, China
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Fan C, Guo M, Chang S, Wang Z, An T. Elevated TyG-BMI index predicts incidence of chronic kidney disease. Clin Exp Med 2024; 24:203. [PMID: 39196406 PMCID: PMC11358226 DOI: 10.1007/s10238-024-01472-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2024] [Accepted: 08/18/2024] [Indexed: 08/29/2024]
Abstract
Chronic kidney disease (CKD) represents a significant global public health issue, with its incidence and prevalence escalating annually. Metabolic disorders are one of the major etiological factors of CKD. This study investigates the relationship between the emerging metabolic index triglyceride-glucose body mass index (TyG-BMI) and the onset of CKD. Our study enrolled 3,485 healthy participants (1,576 men and 1,909 women), with a follow-up period of 3 years. The primary outcome was the emergence of CKD, defined by an eGFR less than 60 mL/(min × 1.73 m2) or the onset of proteinuria. To examine the TyG-BMI and CKD onset relationship, we used univariate and multivariate logistic regression analyses, stratified analyses, and receiver operating characteristic (ROC) curves. After a three-year follow-up, CKD developed in 2% (n = 70) of the participants. Subjects were divided into three equal groups based on their TyG-BMI values, from lowest to highest. After adjusting for potential confounders, the highest TyG-BMI group exhibited a multifactor-adjusted odds ratio (OR) of 4.24 (95% CI 1.30-13.78, P = 0.016) compared to the lowest group. Stratified analyses revealed that the association between TyG-BMI and CKD onset was stronger among females, individuals younger than 60 years, and those with a BMI ≥ 24 kg/m2. Furthermore, TYG-BMI was effective in predicting the incidence of CKD. Our findings indicate that TyG-BMI is an independent risk factor for the onset of CKD and that assessment of TyG-BMI may be useful for the early identification of individuals at high risk for CKD.
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Affiliation(s)
- Cheng Fan
- Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Mengyuan Guo
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Shuye Chang
- Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Zhaohui Wang
- Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Tianhui An
- Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
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Tsuruoka N, Haga Y. Minimally Invasive Needle for Local Glucose Tolerance Tests in Skin. ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. ANNUAL INTERNATIONAL CONFERENCE 2024; 2024:1-4. [PMID: 40039223 DOI: 10.1109/embc53108.2024.10782748] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/06/2025]
Abstract
Impaired insulin secretion and insulin resistance are abnormalities leading to the development of type 2 diabetes. Assessment of impaired insulin secretion and insulin resistance are critical to determining the type of diabetes and planning optimal management and preventive strategies in clinical practice. In order to measure insulin resistance, a minimally invasive needle with measurement and administration flow channels for local glucose tolerance tests was fabricated. This needle was inserted into the skin. Glucose was administrated through the flow channel, and glucose concentration in the skin was measured by microperfusion before and after administration. The needle's administration and glucose-collecting functions were evaluated in the skin of mice.
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Cuervo Sánchez ML, Prado Spalm FH, Furland NE, Vallés AS. Pregestational fructose-induced metabolic syndrome in Wistar rats causes sexually dimorphic behavioral changes in their offspring. Dev Neurobiol 2024; 84:142-157. [PMID: 38664979 DOI: 10.1002/dneu.22940] [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: 11/28/2023] [Revised: 04/04/2024] [Accepted: 04/06/2024] [Indexed: 07/17/2024]
Abstract
Metabolic syndrome (MetS), marked by enduring metabolic inflammation, has detrimental effects on cognitive performance and brain structure, influencing behavior. This study aimed to investigate whether maternal MetS could negatively impact the neurodevelopment and metabolism of offspring. To test this hypothesis, 2 months old female Wistar rats were subjected to a 10-week regimen of tap water alone or supplemented with 20% fructose to induce MetS. Dams were mated with healthy males to generate litters: OC (offspring from control dams) and OMetS (offspring from dams with MetS). To isolate prenatal effects, all pups were breastfed by control nurse dams, maintaining a standard diet and water ad libitum until weaning. Behavioral assessments were conducted between postnatal days (PN) 22 and 95, and metabolic parameters were analyzed post-sacrifice on PN100. Results from the elevated plus maze, the open field, and the marble burying tests revealed a heightened anxiety-like phenotype in OMetS females. The novel object recognition test showed that exclusively OMetS males had long-term memory impairment. In the reciprocal social interaction test, OMetS displayed a lower number of social interactions, with a notable increase in "socially inactive" behavior observed exclusively in females. Additionally, in the three-chamber test, social preference and social novelty indexes were found to be lower solely among OMetS females. An increase in visceral fat concomitantly with hypertriglyceridemia was the relevant postmortem metabolic finding in OMetS females. In summary, maternal MetS leads to enduring damage and adverse effects on offspring neurobehavior and metabolism, with notable sexual dimorphism.
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Affiliation(s)
- Marié L Cuervo Sánchez
- Nutrition and Neurodevelopmental Laboratory, INIBIBB-CONICET-UNS, Bahía Blanca, Argentina
| | - Facundo H Prado Spalm
- Nutrition and Neurodevelopmental Laboratory, INIBIBB-CONICET-UNS, Bahía Blanca, Argentina
| | - Natalia E Furland
- Nutrition and Neurodevelopmental Laboratory, INIBIBB-CONICET-UNS, Bahía Blanca, Argentina
| | - Ana S Vallés
- Nutrition and Neurodevelopmental Laboratory, INIBIBB-CONICET-UNS, Bahía Blanca, Argentina
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Lertwanichwattana T, Suwannahitatorn P, Mungthin M, Rangsin R. Prognostic nomogram for uncontrolled type 2 diabetes using Thailand nation-wide cross-sectional studies. PLoS One 2024; 19:e0298010. [PMID: 38598507 PMCID: PMC11006157 DOI: 10.1371/journal.pone.0298010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Accepted: 01/16/2024] [Indexed: 04/12/2024] Open
Abstract
BACKGROUND Uncontrolled type 2 diabetes (T2DM) and limited hemoglobin A1c (HbA1c) levels examination are a burden in community hospitals in Thailand. The nomogram from the patients' information might be a practical solution to identify a high-risk group of diabetic complications. Thus, this study aimed to establish an effective prognostic nomogram for patients with uncontrolled T2DM. METHODS Sequential nationwide cross-sectional studies of T2DM patients in 2018 and 2015 were utilized for development and validation groups, respectively, with this chronological order aiming to capture recent trends during development and assess the nomogram's robustness across diverse timeframes. The predictive outcome was uncontrolled T2DM, defined as HbA1c ≥9%. The model was determined by multivariable regression analysis and established an effective prognostic nomogram. The receiver operating characteristic curve, Hosmer-Lemeshow goodness of fit test, and decision curve analysis (DCA) was applied to evaluate the performance of the nomogram. RESULTS In 2018, 24% of the 38,568 participants in the development group had uncontrolled T2DM (defined as Hba1c ≥9%). The predictive nomogram of uncontrolled diabetes consisted of demographic characteristics, prescription medications, history of diabetic complications, and laboratory results (C-statistic of 0.77). The goodness of fit test and DCA showed good agreement between the result and clinical application for T2DM. CONCLUSION The predictive nomogram demonstrates simplicity, accuracy, and valuable prediction to enhance diabetic care in resource-limited countries, including Thailand.
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Affiliation(s)
| | | | - Mathirut Mungthin
- Department of Parasitology, Phramongkutklao College of Medicine, Bangkok, Thailand
| | - Ram Rangsin
- Department of Military and Community Medicine, Phramongkutklao College of Medicine, Bangkok, Thailand
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Rehman A, Lathief S, Charoenngam N, Pal L. Aging and Adiposity-Focus on Biological Females at Midlife and Beyond. Int J Mol Sci 2024; 25:2972. [PMID: 38474226 DOI: 10.3390/ijms25052972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 02/10/2024] [Accepted: 02/20/2024] [Indexed: 03/14/2024] Open
Abstract
Menopause is a physiological phase of life of aging women, and more than 1 billion women worldwide will be in menopause by 2025. The processes of global senescence parallel stages of reproductive aging and occur alongside aging-related changes in the body. Alterations in the endocrine pathways accompany and often predate the physiologic changes of aging, and interactions of these processes are increasingly being recognized as contributory to the progression of senescence. Our goal for this review is to examine, in aging women, the complex interplay between the endocrinology of menopause transition and post-menopause, and the metabolic transition, the hallmark being an increasing tendency towards central adiposity that begins in tandem with reproductive aging and is often exacerbated post menopause. For the purpose of this review, our choice of the terms 'female' and 'woman' refer to genetic females.
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Affiliation(s)
- Amna Rehman
- Department of Internal Medicine, Berkshire Medical Center, Pittsfield, MA 02101, USA
| | - Sanam Lathief
- Division of Endocrinology, Mount Auburn Hospital, Cambridge, MA 02138, USA
- Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
| | - Nipith Charoenngam
- Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
- Department of Medicine, Mount Auburn Hospital, Cambridge, MA 02138, USA
- Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Lubna Pal
- Division of Reproductive Endocrinology & Infertility, Department of Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine, New Haven, CT 06510, USA
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13
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Mora-Gonzalez D, Moreno-Cabañas A, Alvarez-Jimenez L, Morales-Palomo F, Ortega JF, Mora-Rodriguez R. Glucose volume of distribution affects insulin sensitivity measured by intravenous glucose tolerance test. Scand J Med Sci Sports 2024; 34:e14574. [PMID: 38389141 DOI: 10.1111/sms.14574] [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: 08/08/2023] [Revised: 12/31/2023] [Accepted: 01/24/2024] [Indexed: 02/24/2024]
Abstract
AIM To determine whether glucose volume of distribution (VdGLUCOSE ) affects the diagnosis of impaired insulin sensitivity (IS) when using an intravenous glucose tolerance test (IVGTT). METHODS Individuals with distinct levels of IS underwent IVGTT after an overnight fast. The prediabetic group (Prediab; n = 33) differed from the healthy group (Healthy; n = 14) in their larger glycosylated hemoglobin (HbA1c of 5.9 ± 0.3 vs. 5.4 ± 0.1%; 41 ± 4 vs. 36 ± 1 mmol/mol; p < 0.001), percent body fat (37 ± 6 vs. 24 ± 3%; p < 0.001) and cardiovascular fitness level (VO2MAX 22 ± 5 vs. 44 ± 5 mL of O2 ·kg-1 ·min-1 ; p < 0.001). Ten minutes after intravenous infusion of the glucose bolus (i.e., 35 g in a 30% solution), VdGLUCOSE was assessed from the increases in plasma glucose concentration. IS was calculated during the next 50 min using the slope of glucose disappearance and the insulin time-response curve. RESULTS VdGLUCOSE was higher in Healthy than in Prediab (230 ± 49 vs. 185 ± 21 mL·kg-1 ; p < 0.001). VdGLUCOSE was a strong predictor of IS (β standardized coefficient 0.362; p = 0.004). VO2MAX was associated with VdGLUCOSE and IS (Pearson r = 0.582 and 0.704, respectively; p < 0.001). However, body fat was inversely associated with VdGLUCOSE and IS (r = -0.548 and -0.555, respectively; p < 0.001). CONCLUSIONS Since fat mass is inversely related to VdGLUCOSE and in turn, VdGLUCOSE affects the calculations of IS, the IV glucose bolus dose should be calculated based on fat-free mass rather than body weight for a more accurate diagnosis of impaired IS.
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Affiliation(s)
- Diego Mora-Gonzalez
- Department of Nursing, Physiotherapy and Occupational Therapy, University of Castilla-La Mancha, Toledo, Spain
| | - Alfonso Moreno-Cabañas
- Exercise Physiology Lab at Toledo, University of Castilla-La Mancha, Toledo, Spain
- Center for Nutrition, Exercise and Metabolism, University of Bath, Bath, UK
| | | | - Felix Morales-Palomo
- Exercise Physiology Lab at Toledo, University of Castilla-La Mancha, Toledo, Spain
| | - Juan Fernando Ortega
- Exercise Physiology Lab at Toledo, University of Castilla-La Mancha, Toledo, Spain
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14
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Shemirani H, Hosseini A. Does metabolic syndrome increase contrast-induced nephropathy in patients with normal renal function? JOURNAL OF RESEARCH IN MEDICAL SCIENCES : THE OFFICIAL JOURNAL OF ISFAHAN UNIVERSITY OF MEDICAL SCIENCES 2024; 29:5. [PMID: 38524741 PMCID: PMC10956558 DOI: 10.4103/jrms.jrms_136_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Revised: 01/17/2022] [Accepted: 01/19/2022] [Indexed: 03/26/2024]
Abstract
Background Contrast-induced nephropathy (CIN) is associated with increased mortality and morbidity in patients undergoing coronary angiography (CAG) and percutaneous coronary intervention. This study aimed to compare the incidence of CIN in two groups of patients with and without metabolic syndrome (Mets) with baseline normal renal function. Materials and Methods In this case - control study, 260 patient candidates for CAG, 130 patients with Mets and 130 patients without Mets participated, and their serum creatinine (Cr) level before and the 48 and 72 h after the angiography was measured. The incidence of CIN was compared in two groups. Two-way analysis of variance with repeated measures and univariate and multivariate logistic regression models. Results The results showed a higher chance of being Mets with raising in triglyceride (adjusted odds ratio = 1.05, 95% confidence interval = (1.03-1.06), P < 0.001), Fasting blood glucose (1.010 [1.001-1.019], P = 0.025), and diastolic blood pressure (1.07 [1.07-1.20], P < 0.001), but declining in high-density lipoprotein-cholesterol (HDL-C) (0.91 [0.85-0.98], P = 0.008). Furthermore, blood urea nitrogen (BUN) and Cr level was raised in 48 and 72 h after contrast injection in both groups (All P < 0.001). Furthermore, in 48 h (3.11 [1.12-9.93], P = 0.016) and 72 h (2.82 [1.07-8.28], P = 0.021) after injection, a total of 25 patients had an increased Cr level and a significant difference between Mets and without Mets groups. The developing Mets had a significant association with the increased risk of AKI, which increased the chance of developing nephropathy (7.14 [2.27-22.5], P = 0.001). Conclusion Mets, together with other risk factors, increased the overall risk of CIN development. Therefore, the incidence of CIN in patients Mets is significantly higher than that of patients without Mets, indicating a more important CIN risk factor.
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Affiliation(s)
- Hasan Shemirani
- Cardiology Department, Isfahan Cardiovascular Research Center, Cardiovascular Research Institute and Chamran Cardiovascular and Medical Research Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Ali Hosseini
- Chamran Cardiovascular and Medical Research Hospital and Cardiac Rehabilitation Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
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15
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Xuan X, Sun R, Peng C, Liu L, Huang T, Huang C. The nonlinear association between triglyceride glucose-body mass index and femoral neck BMD in nondiabetic elderly men: NHANES 2005-March 2020. PLoS One 2024; 19:e0296935. [PMID: 38261591 PMCID: PMC10805317 DOI: 10.1371/journal.pone.0296935] [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: 11/08/2022] [Accepted: 12/20/2023] [Indexed: 01/25/2024] Open
Abstract
BACKGROUND The triglyceride glucose-body mass index (TyG-BMI) has been considered a surrogate marker for assessing insulin resistance. We aimed to correlate the TyG-BMI, triglyceride glucose combined with body mass index, with femoral neck bone mineral density (FN BMD) in non-diabetic elderly men. METHODS Using data from the National Health and Nutrition Examination Survey (NHANES) database, totally, 1182 eligible men aged ≥ 50 years without diabetes were included in the current study. Smoothed curves were obtained by a two-piecewise linear regression model and the threshold effects were explored by using a smoothing function. RESULTS TyG-BMI was positive related with and FN BMD with or without adjustment for confounders. However, no typical dose-dependent positive association between TyG-BMI and FN BMD was observed across the TyG-BMI tertiles, indicating a non-linear association. Further analysis by the weighted two-piecewise linear regression model and recursive algorithm suggested that per SD increase in TyG-BMI increased FN BMD by 0.266 gm/cm2 when TyG-BMI lower than 168.20. However, when TyG-BMI is higher than 168.20, FN BMD only increased 0.046 gm/cm2 for per SD increase of TyG-BMI after fully adjustment (OR = 11.258, 95%CI: 6.034, 16.481). Moreover, subgroup analyses showed that higher TyG-BMI levels were related to elevated FN BMD in all groups, suggesting the consistency of the positive association within these stratas. CONCLUSIONS This study demonstrated that TyG-BMI is positively associated with FN BMD in a nonlinear fashion among elderly men without diabetes, which may be a reliable marker for the early identification of individuals with lower FN BMD.
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Affiliation(s)
- Xiuping Xuan
- Department of Endocrinology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Rong Sun
- Department of Ophthalmology, Taihe Hospital, Hubei University of Medical, Shiyan, 442000, Hubei, China
| | - Caibi Peng
- Bishan Maternity and Child Hospital of Chongqing, Bishan, Chongqing, 402760, China
| | - Lijuan Liu
- Department of Endocrinology, Bishan Hospital of Chongqing, Bishan Hospital of Chongqing Medical University, Bishan, Chongqing, 402760, China
| | - Tiantian Huang
- Department of Endocrinology, Bishan Hospital of Chongqing, Bishan Hospital of Chongqing Medical University, Bishan, Chongqing, 402760, China
| | - Chenghu Huang
- Department of Endocrinology, Bishan Hospital of Chongqing, Bishan Hospital of Chongqing Medical University, Bishan, Chongqing, 402760, China
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16
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Kommera SP, Kumar A, Chitkara D, Mittal A. Pramlintide an Adjunct to Insulin Therapy: Challenges and Recent Progress in Delivery. J Pharmacol Exp Ther 2024; 388:81-90. [PMID: 37863489 DOI: 10.1124/jpet.123.001679] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2023] [Revised: 09/28/2023] [Accepted: 10/02/2023] [Indexed: 10/22/2023] Open
Abstract
Dysregulation of various glucoregulatory hormones lead to failure of insulin monotherapy in patients with diabetes mellitus due to various reasons, including severe hypoglycemia, glycemic hypervariability, and an increased risk of microvascular complications. However, pramlintide as an adjunct to insulin therapy enhances glucagon suppression and thereby offers improved glycemic control. Clinical studies have shown that pramlintide improves glycemic control, reduces postprandial glucose excursions, and promotes weight loss in patients with type 1 and type 2 diabetes. Although clinical benefits of pramlintide are well reported, there still exists a high patient resistance for the therapy, as separate injections for pramlintide and insulin must be administered. Although marketed insulin formulations generally demonstrate a peak action in 60-90 minutes, pramlintide elicits its peak concentration at around 20-30 minutes after administration. Thus, owing to the significant differences in pharmacokinetics of exogenously administered pramlintide and insulin, the therapy fails to elicit its action otherwise produced by the endogenous hormones. Hence, strategies such as delaying the release of pramlintide by using inorganic polymers like silica, synthetic polymers like polycaprolactone, and lipids have been employed. Also, approaches like noncovalent conjugation, polyelectrolyte complexation, and use of amphiphilic excipients for codelivery of insulin and pramlintide have been explored to address the issues with pramlintide delivery and improve patient adherence to the therapy. This approach may usher in a new era of diabetes management, offering patients multiple options to tailor their treatment and improve their quality of life. SIGNIFICANCE STATEMENT: To our knowledge, this is the first report that summarizes various challenges in insulin and pramlintide codelivery and strategies to overcome them. The paper also provides deeper insights into various novel formulation strategies for pramlintide that could further broaden the reader's understanding of peptide codelivery.
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Affiliation(s)
- Sai Pradyuth Kommera
- Department of Pharmacy, Birla Institute of Technology and Science (BITS PILANI), Pilani, Rajasthan, India
| | - Ankur Kumar
- Department of Pharmacy, Birla Institute of Technology and Science (BITS PILANI), Pilani, Rajasthan, India
| | - Deepak Chitkara
- Department of Pharmacy, Birla Institute of Technology and Science (BITS PILANI), Pilani, Rajasthan, India
| | - Anupama Mittal
- Department of Pharmacy, Birla Institute of Technology and Science (BITS PILANI), Pilani, Rajasthan, India
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17
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Ryu SW, Moon JC, Oh BS, Yu SY, Bak JE, Heo ES, Jeong JH, Lee JH. Anti-obesity activity of human gut microbiota Bacteroides stercoris KGMB02265. Arch Microbiol 2023; 206:19. [PMID: 38086977 DOI: 10.1007/s00203-023-03750-2] [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: 09/15/2023] [Revised: 11/16/2023] [Accepted: 11/16/2023] [Indexed: 12/18/2023]
Abstract
Obesity is a global health threat that causes various complications such as type 2 diabetes and nonalcoholic fatty liver disease. Gut microbiota is closely related to obesity. In particular, a higher Firmicutes to Bacteroidetes ratio has been reported as a biomarker of obesity, suggesting that the phylum Bacteroidetes may play a role in inhibiting obesity. Indeed, the genus Bacteroides was enriched in the healthy subjects based on metagenome analysis. In this study, we determined the effects of Bacteroides stercoris KGMB02265, a species belonging to the phylum Bacteroidetes, on obesity both in vitro and in vivo. The cell-free supernatant of B. stercoris KGMB02265 inhibited lipid accumulation in 3T3-L1 preadipocytes, in which the expression of adipogenic marker genes was repressed. In vivo study showed that the oral administration of B. stercoris KGMB02265 substantially reduced body weight and fat weight in high-fat diet induced obesity in mice. Furthermore, obese mice orally administered with B. stercoris KGMB02265 restored glucose sensitivity and reduced leptin and triglyceride levels. Taken together, our study reveals that B. stercoris KGMB02265 has anti-obesity activity and suggests that it may be a promising candidate for treating obesity.
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Affiliation(s)
- Seoung Woo Ryu
- Korean Collection for Type Cultures, Biological Resource Center, Institute of Bioscience and Biotechnology, Jeongeup, 56212, Republic of Korea
- BioMedical Sciences Graduate Program, Chonnam National University, Hwasun, 58128, Republic of Korea
| | - Jeong Chan Moon
- National Institute of Ecology, Yeongyang, 36531, Republic of Korea
| | - Byeong Seob Oh
- Korean Collection for Type Cultures, Biological Resource Center, Institute of Bioscience and Biotechnology, Jeongeup, 56212, Republic of Korea
| | - Seung Yeob Yu
- Korean Collection for Type Cultures, Biological Resource Center, Institute of Bioscience and Biotechnology, Jeongeup, 56212, Republic of Korea
- BioMedical Sciences Graduate Program, Chonnam National University, Hwasun, 58128, Republic of Korea
| | - Jeong Eun Bak
- Korean Collection for Type Cultures, Biological Resource Center, Institute of Bioscience and Biotechnology, Jeongeup, 56212, Republic of Korea
- BioMedical Sciences Graduate Program, Chonnam National University, Hwasun, 58128, Republic of Korea
| | - Eun Seo Heo
- Korean Collection for Type Cultures, Biological Resource Center, Institute of Bioscience and Biotechnology, Jeongeup, 56212, Republic of Korea
- University of Science and Technology (UST), Daejeon, 34113, Republic of Korea
| | - Jae-Ho Jeong
- BioMedical Sciences Graduate Program, Chonnam National University, Hwasun, 58128, Republic of Korea.
| | - Ju Huck Lee
- Korean Collection for Type Cultures, Biological Resource Center, Institute of Bioscience and Biotechnology, Jeongeup, 56212, Republic of Korea.
- University of Science and Technology (UST), Daejeon, 34113, Republic of Korea.
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18
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Wang H, Akbari-Alavijeh S, Parhar RS, Gaugler R, Hashmi S. Partners in diabetes epidemic: A global perspective. World J Diabetes 2023; 14:1463-1477. [PMID: 37970124 PMCID: PMC10642420 DOI: 10.4239/wjd.v14.i10.1463] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 08/01/2023] [Accepted: 09/01/2023] [Indexed: 10/09/2023] Open
Abstract
There is a recent increase in the worldwide prevalence of both obesity and diabetes. In this review we assessed insulin signaling, genetics, environment, lipid metabolism dysfunction and mitochondria as the major determinants in diabetes and to identify the potential mechanism of gut microbiota in diabetes diseases. We searched relevant articles, which have key information from laboratory experiments, epidemiological evidence, clinical trials, experimental models, meta-analysis and review articles, in PubMed, MEDLINE, EMBASE, Google scholars and Cochrane Controlled Trial Database. We selected 144 full-length articles that met our inclusion and exclusion criteria for complete assessment. We have briefly discussed these associations, challenges, and the need for further research to manage and treat diabetes more efficiently. Diabetes involves the complex network of physiological dysfunction that can be attributed to insulin signaling, genetics, environment, obesity, mitochondria and stress. In recent years, there are intriguing findings regarding gut microbiome as the important regulator of diabetes. Valid approaches are necessary for speeding medical advances but we should find a solution sooner given the burden of the metabolic disorder - What we need is a collaborative venture that may involve laboratories both in academia and industries for the scientific progress and its application for the diabetes control.
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Affiliation(s)
- Huan Wang
- College of Bioscience and Biotechnology, Shenyang Agricultural University, Shenyang 110866, Liaoning Province, China
- Rutgers Center for Vector Biology, Rutgers University, New Brunswick, NJ 08901, United States
| | - Safoura Akbari-Alavijeh
- Rutgers Center for Vector Biology, Rutgers University, New Brunswick, NJ 08901, United States
- Department of Food Science and Technology, College of Agriculture, Isfahan University of Technology, Isfahan 84156-83111, Iran
| | - Ranjit S Parhar
- Department of Biological and Medical Research, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia
| | - Randy Gaugler
- Rutgers Center for Vector Biology, Rutgers University, New Brunswick, NJ 08901, United States
| | - Sarwar Hashmi
- Rutgers Center for Vector Biology, Rutgers University, New Brunswick, NJ 08901, United States
- Research and Diagnostics, Ghazala and Sanya Hashmi Foundation, Holmdel, NJ 07733, United States
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19
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Adil SO, Musa KI, Uddin F, Shafique K, Khan A, Islam MA. Role of anthropometric indices as a screening tool for predicting metabolic syndrome among apparently healthy individuals of Karachi, Pakistan. Front Endocrinol (Lausanne) 2023; 14:1223424. [PMID: 37876536 PMCID: PMC10593443 DOI: 10.3389/fendo.2023.1223424] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Accepted: 09/19/2023] [Indexed: 10/26/2023] Open
Abstract
INTRODUCTION Anthropometric indices are affordable and non-invasive methods for screening metabolic syndrome (MetS). However, determining the most effective index for screening can be challenging. OBJECTIVE To investigate the accuracy of anthropometric indices as a screening tool for predicting MetS among apparently healthy individuals in Karachi, Pakistan. METHODS A community-based cross-sectional survey was conducted in Karachi, Pakistan, from February 2022 to August 2022. A total of 1,065 apparently healthy individuals aged 25 years and above were included. MetS was diagnosed using International Diabetes Federation guidelines. Anthropometric indices were defined based on body mass index (BMI), neck circumference (NC), mid-upper arm circumference (MUAC), waist circumference (WC), waist to height ratio (WHtR), conicity index, reciprocal ponderal index (RPI), body shape index (BSI), and visceral adiposity index (VAI). The analysis involved the utilization of Pearson's correlation test and independent t-test to examine inferential statistics. The receiver operating characteristic (ROC) analysis was also applied to evaluate the predictive capacities of various anthropometric indices regarding metabolic risk factors. Moreover, the area under the curve (AUC) was computed, and the chosen anthropometric indices' optimal cutoff values were determined. RESULTS All anthropometric indices, except for RPI in males and BSI in females, were significantly higher in MetS than those without MetS. VAI [AUC 0.820 (95% CI 0.78-0.86)], WC [AUC 0.751 (95% CI 0.72-0.79)], WHtR [AUC 0.732 (95% CI 0.69-0.77)], and BMI [AUC 0.708 (95% CI 0.66-0.75)] had significantly higher AUC for predicting MetS in males, whereas VAI [AUC 0.693 (95% CI 0.64-0.75)], WHtR [AUC 0.649 (95% CI 0.59-0.70)], WC [AUC 0.646 (95% CI 0.59-0.61)], BMI [AUC 0.641 (95% CI 0.59-0.69)], and MUAC [AUC 0.626 (95% CI 0.57-0.68)] had significantly higher AUC for predicting MetS in females. The AUC of NC for males was 0.656 (95% CI 0.61-0.70), while that for females was 0.580 (95% CI 0.52-0.64). The optimal cutoff points for all anthropometric indices exhibited a high degree of sensitivity and specificity in predicting the onset of MetS. CONCLUSION BMI, WC, WHtR, and VAI were the most important anthropometric predictors for MetS in apparently healthy individuals of Pakistan, while BSI was found to be the weakest indicator.
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Affiliation(s)
- Syed Omair Adil
- Department of Community Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
- School of Public Health, Dow University of Health Sciences (DUHS), Karachi, Pakistan
| | - Kamarul Imran Musa
- Department of Community Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
| | - Fareed Uddin
- National Institute of Diabetes & Endocrinology, DUHS, Karachi, Pakistan
| | - Kashif Shafique
- School of Public Health, Dow University of Health Sciences (DUHS), Karachi, Pakistan
| | - Asima Khan
- Public Health Department, Baqai Institute of Diabetology & Endocrinology, Karachi, Pakistan
| | - Md Asiful Islam
- WHO Collaborating Centre for Global Women’s Health, Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom
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20
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Tatti P, Singh P. Insulin Resistance: An Unresolved Riddle. J Clin Med 2023; 12:6394. [PMID: 37835038 PMCID: PMC10573251 DOI: 10.3390/jcm12196394] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Revised: 09/11/2023] [Accepted: 09/13/2023] [Indexed: 10/15/2023] Open
Abstract
Insulin resistance (IR) is a rather common condition that is often diagnosed on the basis of an arbitrary "increased insulin value" or the presence of symptoms indicative of the Metabolic Syndrome [...].
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21
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Rashid B, Glasser MF, Nichols T, Van Essen D, Juttukonda MR, Schwab NA, Greve DN, Yacoub E, Lovely A, Terpstra M, Harms MP, Bookheimer SY, Ances BM, Salat DH, Arnold SE. Cardiovascular and metabolic health is associated with functional brain connectivity in middle-aged and older adults: Results from the Human Connectome Project-Aging study. Neuroimage 2023; 276:120192. [PMID: 37247763 PMCID: PMC10330931 DOI: 10.1016/j.neuroimage.2023.120192] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 05/15/2023] [Accepted: 05/24/2023] [Indexed: 05/31/2023] Open
Abstract
Several cardiovascular and metabolic indicators, such as cholesterol and blood pressure have been associated with altered neural and cognitive health as well as increased risk of dementia and Alzheimer's disease in later life. In this cross-sectional study, we examined how an aggregate index of cardiovascular and metabolic risk factor measures was associated with correlation-based estimates of resting-state functional connectivity (FC) across a broad adult age-span (36-90+ years) from 930 volunteers in the Human Connectome Project Aging (HCP-A). Increased (i.e., worse) aggregate cardiometabolic scores were associated with reduced FC globally, with especially strong effects in insular, medial frontal, medial parietal, and superior temporal regions. Additionally, at the network-level, FC between core brain networks, such as default-mode and cingulo-opercular, as well as dorsal attention networks, showed strong effects of cardiometabolic risk. These findings highlight the lifespan impact of cardiovascular and metabolic health on whole-brain functional integrity and how these conditions may disrupt higher-order network integrity.
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Affiliation(s)
- Barnaly Rashid
- Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, 149 13th St., Charlestown, MA 02129, United States; Harvard Medical School, Boston, MA, United States.
| | - Matthew F Glasser
- Washington University School of Medicine, St. Louis, MO, United States
| | | | - David Van Essen
- Washington University School of Medicine, St. Louis, MO, United States
| | - Meher R Juttukonda
- Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, 149 13th St., Charlestown, MA 02129, United States; Harvard Medical School, Boston, MA, United States
| | - Nadine A Schwab
- Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, 149 13th St., Charlestown, MA 02129, United States; Harvard Medical School, Boston, MA, United States
| | - Douglas N Greve
- Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, 149 13th St., Charlestown, MA 02129, United States; Harvard Medical School, Boston, MA, United States
| | - Essa Yacoub
- Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States
| | - Allison Lovely
- Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, 149 13th St., Charlestown, MA 02129, United States; Harvard Medical School, Boston, MA, United States
| | | | - Michael P Harms
- Washington University in St. Louis, St. Louis, MO, United States
| | | | - Beau M Ances
- Washington University School of Medicine, St. Louis, MO, United States; Washington University in St. Louis, St. Louis, MO, United States
| | - David H Salat
- Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, 149 13th St., Charlestown, MA 02129, United States; Harvard Medical School, Boston, MA, United States.
| | - Steven E Arnold
- Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, 149 13th St., Charlestown, MA 02129, United States; Harvard Medical School, Boston, MA, United States.
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22
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James A, Wang K, Wang Y. Therapeutic Activity of Green Tea Epigallocatechin-3-Gallate on Metabolic Diseases and Non-Alcoholic Fatty Liver Diseases: The Current Updates. Nutrients 2023; 15:3022. [PMID: 37447347 DOI: 10.3390/nu15133022] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2023] [Revised: 06/26/2023] [Accepted: 06/29/2023] [Indexed: 07/15/2023] Open
Abstract
Green tea polyphenols have numerous functions including antioxidation and modulation of various cellular proteins and are thus beneficial against metabolic diseases including obesity, type 2 diabetes, cardiovascular and non-alcoholic fatty liver diseases, and their comorbidities. Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol in green tea and is attributed to antioxidant and free radical scavenging activities, and the likelihood of targeting multiple metabolic pathways. It has been shown to exhibit anti-obesity, anti-inflammatory, anti-diabetic, anti-arteriosclerotic, and weight-reducing effects in humans. Worldwide, the incidences of metabolic diseases have been escalating across all age groups in modern society. Therefore, EGCG is being increasingly investigated to address the problems. This review presents the current updates on the effects of EGCG on metabolic diseases, and highlights evidence related to its safety. Collectively, this review brings more evidence for therapeutic application and further studies on EGCG and its derivatives to alleviate metabolic diseases and non-alcoholic fatty liver diseases.
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Affiliation(s)
- Armachius James
- Key Laboratory of Geriatric Nutrition and Health, Ministry of Education, Beijing Technology and Business University, Beijing 100048, China
- Tanzania Agricultural Research Institute (TARI), Makutupora Center, Dodoma P.O. Box 1676, Tanzania
| | - Ke Wang
- Key Laboratory of Geriatric Nutrition and Health, Ministry of Education, Beijing Technology and Business University, Beijing 100048, China
- Rizhao Huawei Institute of Comprehensive Health Industries, Shandong Keepfit Biotech. Co., Ltd., Rizhao 276800, China
| | - Yousheng Wang
- Key Laboratory of Geriatric Nutrition and Health, Ministry of Education, Beijing Technology and Business University, Beijing 100048, China
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Paul ER, Östman L, Heilig M, Mayberg HS, Hamilton JP. Towards a multilevel model of major depression: genes, immuno-metabolic function, and cortico-striatal signaling. Transl Psychiatry 2023; 13:171. [PMID: 37208333 DOI: 10.1038/s41398-023-02466-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 04/24/2023] [Accepted: 05/03/2023] [Indexed: 05/21/2023] Open
Abstract
Biological assay and imaging techniques have made visible a great deal of the machinery of mental illness. Over fifty years of investigation of mood disorders using these technologies has identified several biological regularities in these disorders. Here we present a narrative connecting genetic, cytokine, neurotransmitter, and neural-systems-level findings in major depressive disorder (MDD). Specifically, we connect recent genome-wide findings in MDD to metabolic and immunological disturbance in this disorder and then detail links between immunological abnormalities and dopaminergic signaling within cortico-striatal circuitry. Following this, we discuss implications of reduced dopaminergic tone for cortico-striatal signal conduction in MDD. Finally, we specify some of the flaws in the current model and propose ways forward for advancing multilevel formulations of MDD most efficiently.
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Affiliation(s)
- Elisabeth R Paul
- Center for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
- Center for Medical Imaging and Visualization, Linköping University, Linköping, Sweden
| | - Lars Östman
- Center for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
- Department of Psychiatry, Region Östergötland, Linköping, Sweden
| | - Markus Heilig
- Center for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
- Department of Psychiatry, Region Östergötland, Linköping, Sweden
| | | | - J Paul Hamilton
- Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.
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Cannabinoids Transmogrify Cancer Metabolic Phenotype via Epigenetic Reprogramming and a Novel CBD Biased G Protein-Coupled Receptor Signaling Platform. Cancers (Basel) 2023; 15:cancers15041030. [PMID: 36831374 PMCID: PMC9954791 DOI: 10.3390/cancers15041030] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Revised: 01/29/2023] [Accepted: 02/03/2023] [Indexed: 02/09/2023] Open
Abstract
The concept of epigenetic reprogramming predicts long-term functional health effects. This reprogramming can be activated by exogenous or endogenous insults, leading to altered healthy and different disease states. The exogenous or endogenous changes that involve developing a roadmap of epigenetic networking, such as drug components on epigenetic imprinting and restoring epigenome patterns laid down during embryonic development, are paramount to establishing youthful cell type and health. This epigenetic landscape is considered one of the hallmarks of cancer. The initiation and progression of cancer are considered to involve epigenetic abnormalities and genetic alterations. Cancer epigenetics have shown extensive reprogramming of every component of the epigenetic machinery in cancer development, including DNA methylation, histone modifications, nucleosome positioning, non-coding RNAs, and microRNA expression. Endocannabinoids are natural lipid molecules whose levels are regulated by specific biosynthetic and degradative enzymes. They bind to and activate two primary cannabinoid receptors, type 1 (CB1) and type 2 (CB2), and together with their metabolizing enzymes, form the endocannabinoid system. This review focuses on the role of cannabinoid receptors CB1 and CB2 signaling in activating numerous receptor tyrosine kinases and Toll-like receptors in the induction of epigenetic landscape alterations in cancer cells, which might transmogrify cancer metabolism and epigenetic reprogramming to a metastatic phenotype. Strategies applied from conception could represent an innovative epigenetic target for preventing and treating human cancer. Here, we describe novel cannabinoid-biased G protein-coupled receptor signaling platforms (GPCR), highlighting putative future perspectives in this field.
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Sato A, Yumita Y, Kagami K, Ishinoda Y, Kimura T, Osaki A, Toya T, Namba T, Endo S, Ido Y, Nagatomo Y, Satoh Y, Adachi T. Endothelial Extracellular Signal-Regulated Kinase/Thromboxane A2/Prostanoid Receptor Pathway Aggravates Endothelial Dysfunction and Insulin Resistance in a Mouse Model of Metabolic Syndrome. J Am Heart Assoc 2022; 11:e027538. [PMID: 36382966 PMCID: PMC9851435 DOI: 10.1161/jaha.122.027538] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Background Metabolic syndrome is characterized by insulin resistance, which impairs intracellular signaling pathways and endothelial NO bioactivity, leading to cardiovascular complications. Extracellular signal-regulated kinase (ERK) is a major component of insulin signaling cascades that can be activated by many vasoactive peptides, hormones, and cytokines that are elevated in metabolic syndrome. The aim of this study was to clarify the role of endothelial ERK2 in vivo on NO bioactivity and insulin resistance in a mouse model of metabolic syndrome. Methods and Results Control and endothelial-specific ERK2 knockout mice were fed a high-fat/high-sucrose diet (HFHSD) for 24 weeks. Systolic blood pressure, endothelial function, and glucose metabolism were investigated. Systolic blood pressure was lowered with increased NO products and decreased thromboxane A2/prostanoid (TP) products in HFHSD-fed ERK2 knockout mice, and Nω-nitro-l-arginine methyl ester (L-NAME) increased it to the levels observed in HFHSD-fed controls. Acetylcholine-induced relaxation of aortic rings was increased, and aortic superoxide level was lowered in HFHSD-fed ERK2 knockout mice. S18886, an antagonist of the TP receptor, improved endothelial function and decreased superoxide level only in the rings from HFHSD-fed controls. Glucose intolerance and the impaired insulin sensitivity were blunted in HFHSD-fed ERK2 knockout mice without changes in body weight. In vivo, S18886 improved endothelial dysfunction, systolic blood pressure, fasting serum glucose and insulin levels, and suppressed nonalcoholic fatty liver disease scores only in HFHSD-fed controls. Conclusions Endothelial ERK2 increased superoxide level and decreased NO bioactivity, resulting in the deterioration of endothelial function, insulin resistance, and steatohepatitis, which were improved by a TP receptor antagonist, in a mouse model of metabolic syndrome.
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Affiliation(s)
- Atsushi Sato
- Department of CardiologyNational Defense Medical CollegeTokorozawaJapan
| | - Yusuke Yumita
- Department of CardiologyNational Defense Medical CollegeTokorozawaJapan
| | - Kazuki Kagami
- Department of CardiologyNational Defense Medical CollegeTokorozawaJapan
| | - Yuki Ishinoda
- Department of CardiologyNational Defense Medical CollegeTokorozawaJapan
| | - Toyokazu Kimura
- Department of CardiologyNational Defense Medical CollegeTokorozawaJapan
| | - Ayumu Osaki
- Department of CardiologyNational Defense Medical CollegeTokorozawaJapan
| | - Takumi Toya
- Department of CardiologyNational Defense Medical CollegeTokorozawaJapan
| | - Takayuki Namba
- Department of CardiologyNational Defense Medical CollegeTokorozawaJapan
| | - Shogo Endo
- Department of Aging NeuroscienceTokyo Metropolitan Institute of GerontologyTokyoJapan
| | - Yasuo Ido
- Department of CardiologyNational Defense Medical CollegeTokorozawaJapan
| | - Yuji Nagatomo
- Department of CardiologyNational Defense Medical CollegeTokorozawaJapan
| | - Yasushi Satoh
- Department of BiochemistryNational Defense Medical CollegeTokorozawaJapan
| | - Takeshi Adachi
- Department of CardiologyNational Defense Medical CollegeTokorozawaJapan
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Đukić-Ćosić D, Baralić K, Javorac D, Bulat Z, Ćurčić M, Antonijević B, Đorđević V, Repić A, Buha Djordjevic A. Exploring the relationship between blood toxic metal(oid)s and serum insulin levels through benchmark modelling of human data: Possible role of arsenic as a metabolic disruptor. ENVIRONMENTAL RESEARCH 2022; 215:114283. [PMID: 36088992 DOI: 10.1016/j.envres.2022.114283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/10/2022] [Revised: 09/01/2022] [Accepted: 09/03/2022] [Indexed: 06/15/2023]
Abstract
The major goal of this study was to estimate the correlations and dose-response pattern between the measured blood toxic metals (cadmium (Cd), mercury (Hg), chromium (Cr), nickel (Ni))/metalloid (arsenic (As)) and serum insulin level by conducting Benchmark dose (BMD) analysis of human data. The study involved 435 non-occupationally exposed individuals (217 men and 218 women). The samples were collected at health care institutions in Belgrade, Serbia, from January 2019 to May 2021. Blood sample preparation was conducted by microwave digestion. Cd was measured by graphite furnace atomic absorption spectrophotometry (GF-AAS), while inductively coupled plasma-mass spectrometry (ICP-MS) was used to measure Hg, Ni, Cr and As. BMD analysis of insulin levels represented as quantal data was done using the PROAST software version 70.1 (model averaging methodology, BMD response: 10%). In the male population, there was no correlation between toxic metal/metalloid concentrations and insulin level. However, in the female population/whole population, a high positive correlation for As and Hg, and a strong negative correlation for Ni and measured serum insulin level was established. BMD modelling revealed quantitative associations between blood toxic metal/metalloid concentrations and serum insulin levels. All the estimated BMD intervals were wide except the one for As, reflecting a high degree of confidence in the estimations and possible role of As as a metabolic disruptor. These results indicate that, in the case of As blood concentrations, even values higher than BMD (BMDL): 3.27 (1.26) (male population), 2.79 (0.771) (female population), or 1.18 (2.96) μg/L (whole population) might contribute to a 10% higher risk of insulin level alterations, meaning 10% higher risk of blood insulin increasing from within reference range to above reference range. The obtained results contribute to the current body of knowledge on the use of BMD modelling for analysing human data.
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Affiliation(s)
- Danijela Đukić-Ćosić
- Department of Toxicology "Akademik Danilo Soldatović", University of Belgrade - Faculty of Pharmacy, Vojvode Stepe 450, 11221, Belgrade, Serbia
| | - Katarina Baralić
- Department of Toxicology "Akademik Danilo Soldatović", University of Belgrade - Faculty of Pharmacy, Vojvode Stepe 450, 11221, Belgrade, Serbia.
| | - Dragana Javorac
- Department of Toxicology "Akademik Danilo Soldatović", University of Belgrade - Faculty of Pharmacy, Vojvode Stepe 450, 11221, Belgrade, Serbia
| | - Zorica Bulat
- Department of Toxicology "Akademik Danilo Soldatović", University of Belgrade - Faculty of Pharmacy, Vojvode Stepe 450, 11221, Belgrade, Serbia
| | - Marijana Ćurčić
- Department of Toxicology "Akademik Danilo Soldatović", University of Belgrade - Faculty of Pharmacy, Vojvode Stepe 450, 11221, Belgrade, Serbia
| | - Biljana Antonijević
- Department of Toxicology "Akademik Danilo Soldatović", University of Belgrade - Faculty of Pharmacy, Vojvode Stepe 450, 11221, Belgrade, Serbia
| | - Vladimir Đorđević
- First Surgical Clinic, Clinical Center of Serbia, Koste Todorovića 5, 11000, Belgrade, Serbia
| | - Aleksandra Repić
- Institute of Forensic Medicine, Faculty of Medicine University of Belgrade, 11000, Belgrade, Serbia
| | - Aleksandra Buha Djordjevic
- Department of Toxicology "Akademik Danilo Soldatović", University of Belgrade - Faculty of Pharmacy, Vojvode Stepe 450, 11221, Belgrade, Serbia
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Cyclosorus terminans Extract Ameliorates Insulin Resistance and Non-Alcoholic Fatty Liver Disease (NAFLD) in High-Fat Diet (HFD)-Induced Obese Rats. Nutrients 2022; 14:nu14224895. [PMID: 36432581 PMCID: PMC9693870 DOI: 10.3390/nu14224895] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Revised: 11/10/2022] [Accepted: 11/17/2022] [Indexed: 11/22/2022] Open
Abstract
Interruptins A and B exhibited anti-diabetic, anti-inflammatory, and anti-oxidative effects. This study aimed to investigate the therapeutic ability of extract enriched by interruptins A and B (EEI) from an edible fern Cyclosorus terminans on insulin resistance and non-alcoholic fatty liver disease (NAFLD) in a high-fat diet (HFD)-induced obese rats and elucidate their possible mechanisms. HFD-induced obese rats were treated with EEI for 2 weeks. Real-time polymerase chain reaction (PCR) was used to examine the molecular basis. We found that EEI supplementation significantly attenuated body and liver weight gain, glucose intolerance, and insulin resistance. Concurrently, EEI increased liver and soleus muscle glycogen storage and serum high-density lipoprotein (HDL) levels. EEI also attenuated NAFLD, as indicated by improving liver function. These effects were associated with enhanced expression of insulin signaling genes (Slc2a2, Slc2a4, Irs1 and Irs2) along with diminished expression of inflammatory genes (Il6 and Tnf). Furthermore, EEI led to the suppression of lipogenesis genes, Srebf1 and Fasn, together with an increase in fatty acid oxidation genes, Ppara and Cpt2, in the liver. These findings suggest that EEI could ameliorate HFD-induced insulin resistance and NAFLD via improving insulin signaling pathways, inflammatory response, lipogenesis, and fatty acid oxidation.
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Ferreira JRS, Zandonade E, de Paula Alves Bezerra OM, Salaroli LB. Insulin resistance by the triglyceride-glucose index in a rural Brazilian population. ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2022; 66:848-855. [PMID: 35929905 PMCID: PMC10118758 DOI: 10.20945/2359-3997000000509] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/22/2023]
Abstract
Objective The aim of this study was to estimate the prevalence of insulin resistance (IR) in a rural population in Brazil, to verify its association with sociodemographic, labor, lifestyle, and health factors. Subjects and methods This is a cross-sectional study with 790 farmers in the state of Espírito Santo/Brazil. Triglyceride-glucose (TyG) was calculated and a cut-off point of Ln 4.52 was used. A hierarchical logistic regression for the association of insulin resistance with sociodemographic, labor, lifestyle and health variables of farmers living in Espírito Santo was performed. Results The prevalence of insulin resistance was 33.7% (n = 266), and the association with insulin resistance was found in the age group 31 to 40 years of age (OR = 1.85; 95% CI 1.19-2.87); in smokers or former smokers (OR = 1.63; 95% CI 1.08-2.48) and overweight (OR = 3.06; 95% CI 2.22-4.23). Conclusion The prevalence of insulin resistance was high in a rural population of Brazil, and was mainly associated with age, smoking and obesity. The use of TyG as an instrument for assessing the health of individuals living in areas where access to health services is difficult, such as rural areas, can represent an important advance in terms of health promotion, protection and recovery. In addition, by identifying the risk factors associated with IR, as well as their consequences, a more adequate scheme for the prevention and treatment of these comorbidities can be defined.
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Affiliation(s)
| | - Eliana Zandonade
- Programa de Pós-graduação em Saúde Pública, Universidade Federal do Espírito Santo (UFES), Vitória, ES, Brasil
| | | | - Luciane Bresciani Salaroli
- Programa de Pós-graduação em Saúde Pública, Universidade Federal do Espírito Santo (UFES), Vitória, ES, Brasil
- Programa de Pós-graduação em Nutrição e Saúde, Universidade Federal do Espírito Santo (UFES), Vitória, ES, Brasil
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Zhou C, Wu Q, Ye Z, Zhang Y, Zhang Y, Yang S, Liu M, He P, Qin X. Regular use of ibuprofen or paracetamol and incident type 2 diabetes: A prospective cohort study in the UK Biobank. DIABETES & METABOLISM 2022; 48:101388. [PMID: 36122870 DOI: 10.1016/j.diabet.2022.101388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 08/19/2022] [Accepted: 08/29/2022] [Indexed: 10/14/2022]
Abstract
BACKGROUND The relation of regular ibuprofen or paracetamol use with the risk of type 2 diabetes (T2DM) remained undetermined. We aimed to evaluate the prospective association between regular ibuprofen or paracetamol use and incidence of T2DM. METHODS This cohort included 372,843 participants with available data of ibuprofen, paracetamol use and without diabetes at baseline from the UK Biobank. The primary outcome was incident T2DM. Cox proportional hazards models were applied to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of T2DM. RESULTS During a median of 12.1 years' follow-up, 11,527 (3.1%) participants developed T2DM. Overall, participants with regular use of paracetamol showed a significantly higher risk of incident T2DM (adjusted HR, 1.25; 95%CI: 1.19,1.31), compared with non-users. Moreover, a stronger positive association of paracetamol use with incident T2DM was found among those aged <60 years (vs. ≥60 years, P-interaction =0.008), free of cardiovascular diseases (CVD) (vs. CVD patients, P-interaction =0.01), and without the use of anti-hypertensive drugs (vs. users, P-interaction =0.016) at baseline. However, there was no significant association between regular use of ibuprofen (users vs. non-users; adjusted HR, 1.05; 95%CI: 0.99,1.12) and incident T2DM. More importantly, genetic risks of T2DM did not significantly modify the relations of ibuprofen, or paracetamol use with incident T2DM (Both P-interactions >0.05). CONCLUSIONS Regular use of paracetamol, but not ibuprofen, was associated with a significantly higher risk of incident T2DM among middle aged UK adults. Our current findings highlight the need for greater consideration in the clinical selection of paracetamol or ibuprofen.
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Affiliation(s)
- Chun Zhou
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou 510515, China
| | - Qimeng Wu
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou 510515, China
| | - Ziliang Ye
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou 510515, China
| | - Yuanyuan Zhang
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou 510515, China
| | - Yanjun Zhang
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou 510515, China
| | - Sisi Yang
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou 510515, China
| | - Mengyi Liu
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou 510515, China
| | - Panpan He
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou 510515, China
| | - Xianhui Qin
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou 510515, China.
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Salvatori B, Linder T, Eppel D, Morettini M, Burattini L, Göbl C, Tura A. TyGIS: improved triglyceride-glucose index for the assessment of insulin sensitivity during pregnancy. Cardiovasc Diabetol 2022; 21:215. [PMID: 36258194 PMCID: PMC9580191 DOI: 10.1186/s12933-022-01649-8] [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: 08/25/2022] [Accepted: 09/28/2022] [Indexed: 11/21/2022] Open
Abstract
Background The triglyceride-glucose index (TyG) has been proposed as a surrogate marker of insulin resistance, which is a typical trait of pregnancy. However, very few studies analyzed TyG performance as marker of insulin resistance in pregnancy, and they were limited to insulin resistance assessment at fasting rather than in dynamic conditions, i.e., during an oral glucose tolerance test (OGTT), which allows more reliable assessment of the actual insulin sensitivity impairment. Thus, first aim of the study was exploring in pregnancy the relationships between TyG and OGTT-derived insulin sensitivity. In addition, we developed a new version of TyG, for improved performance as marker of insulin resistance in pregnancy. Methods At early pregnancy, a cohort of 109 women underwent assessment of maternal biometry and blood tests at fasting, for measurements of several variables (visit 1). Subsequently (26 weeks of gestation) all visit 1 analyses were repeated (visit 2), and a subgroup of women (84 selected) received a 2 h-75 g OGTT (30, 60, 90, and 120 min sampling) with measurement of blood glucose, insulin and C-peptide for reliable assessment of insulin sensitivity (PREDIM index) and insulin secretion/beta-cell function. The dataset was randomly split into 70% training set and 30% test set, and by machine learning approach we identified the optimal model, with TyG included, showing the best relationship with PREDIM. For inclusion in the model, we considered only fasting variables, in agreement with TyG definition. Results The relationship of TyG with PREDIM was weak. Conversely, the improved TyG, called TyGIS, (linear function of TyG, body weight, lean body mass percentage and fasting insulin) resulted much strongly related to PREDIM, in both training and test sets (R2 > 0.64, p < 0.0001). Bland–Altman analysis and equivalence test confirmed the good performance of TyGIS in terms of association with PREDIM. Different further analyses confirmed TyGIS superiority over TyG. Conclusions We developed an improved version of TyG, as new surrogate marker of insulin sensitivity in pregnancy (TyGIS). Similarly to TyG, TyGIS relies only on fasting variables, but its performances are remarkably improved than those of TyG. Supplementary Information The online version contains supplementary material available at 10.1186/s12933-022-01649-8.
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Affiliation(s)
| | - Tina Linder
- Department of Obstetrics and Gynaecology, Medical University of Vienna, 1090, Vienna, Austria
| | - Daniel Eppel
- Department of Obstetrics and Gynaecology, Medical University of Vienna, 1090, Vienna, Austria
| | - Micaela Morettini
- Department of Information Engineering, Università Politecnica Delle Marche, 60131, Ancona, Italy
| | - Laura Burattini
- Department of Information Engineering, Università Politecnica Delle Marche, 60131, Ancona, Italy
| | - Christian Göbl
- Department of Obstetrics and Gynaecology, Medical University of Vienna, 1090, Vienna, Austria
| | - Andrea Tura
- CNR Institute of Neuroscience, Corso Stati Uniti 4, 35127, Padua, Italy.
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Association between Obesity, Overweight, Elevated Waist Circumference, and Insulin Resistance Markers among Brazilian Adolescent Students. Nutrients 2022; 14:nu14173487. [PMID: 36079745 PMCID: PMC9458155 DOI: 10.3390/nu14173487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 08/17/2022] [Accepted: 08/19/2022] [Indexed: 11/17/2022] Open
Abstract
(1) Background: There is still controversy concerning the most effective and efficient strategy to identify insulin resistance in adolescents. We estimated the level of fasting insulin (fasting insulin equivalent, FIeq) that would replicate the strength of the associations of obesity, overweight, and waist circumference with two insulin resistance markers: triglyceride/high-density lipoprotein (TG/HDL) and triglyceride/glucose (TyG); (2) Methods: We studied approximately 38,000 adolescents aged 12 to 17 years, sampled from a multicenter Brazilian school-based survey, The Study of Cardiovascular Risk Factors in Adolescents (Portuguese acronym, ERICA), conducted in 2013–2014. Fasting insulin equivalents for adiposity variables were calculated by dividing the beta coefficient of each adiposity measure by the fasting insulin beta coefficient from linear regression analysis according to age (12–14, 15–17 years old) and sex, and adjusted by smoking, alcohol consumption, physical inactivity, sedentary behavior, socioeconomic status, and Tanner stage; (3) Results: The FIeqs for obesity were greater than those for overweight and elevated waist circumference for both TG/HDL and TyG in early adolescence. The FIeqs for elevated WC were greater than those for obesity and overweight in adolescents aged 15 to 17 years; (4) Conclusions: Our study suggests that WC measurements might be useful to identify adolescents with insulin resistance, particularly in late adolescence.
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Sato A, Shiraishi Y, Kimura T, Osaki A, Kagami K, Ido Y, Adachi T. Resistance to Obesity in SOD1 Deficient Mice with a High-Fat/High-Sucrose Diet. Antioxidants (Basel) 2022; 11:antiox11071403. [PMID: 35883894 PMCID: PMC9312060 DOI: 10.3390/antiox11071403] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Revised: 07/11/2022] [Accepted: 07/15/2022] [Indexed: 02/01/2023] Open
Abstract
Metabolic syndrome (Mets) is an important condition because it may cause stroke and heart disease in the future. Reactive oxygen species (ROSs) influence the pathogenesis of Mets; however, the types of ROSs and their localization remain largely unknown. In this study, we investigated the effects of SOD1, which localize to the cytoplasm and mitochondrial intermembrane space and metabolize superoxide anion, on Mets using SOD1 deficient mice (SOD1−/−). SOD1−/− fed on a high-fat/high-sucrose diet (HFHSD) for 24 weeks showed reduced body weight gain and adipose tissue size compared to wild-type mice (WT). Insulin secretion was dramatically decreased in SOD1−/− fed on HFHSD even though blood glucose levels were similar to WT. Ambulatory oxygen consumption was accelerated in SOD1−/− with HFHSD; however, ATP levels of skeletal muscle were somewhat reduced compared to WT. Reflecting the reduced ATP, the expression of phosphorylated AMPK (Thr 172) was more robust in SOD1−/−. SOD1 is involved in the ATP production mechanism in mitochondria and may contribute to visceral fat accumulation by causing insulin secretion and insulin resistance.
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Affiliation(s)
- Atsushi Sato
- Department of Internal Medicine, Division of Cardiovascular Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa 359-8513, Saitama, Japan; (A.S.); (T.K.); (A.O.); (K.K.); (Y.I.)
| | - Yasunaga Shiraishi
- Division of Environmental Medicine, National Defense Medical College Research Institute, 3-2 Namiki, Tokorozawa 359-8513, Saitama, Japan;
| | - Toyokazu Kimura
- Department of Internal Medicine, Division of Cardiovascular Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa 359-8513, Saitama, Japan; (A.S.); (T.K.); (A.O.); (K.K.); (Y.I.)
| | - Ayumu Osaki
- Department of Internal Medicine, Division of Cardiovascular Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa 359-8513, Saitama, Japan; (A.S.); (T.K.); (A.O.); (K.K.); (Y.I.)
| | - Kazuki Kagami
- Department of Internal Medicine, Division of Cardiovascular Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa 359-8513, Saitama, Japan; (A.S.); (T.K.); (A.O.); (K.K.); (Y.I.)
| | - Yasuo Ido
- Department of Internal Medicine, Division of Cardiovascular Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa 359-8513, Saitama, Japan; (A.S.); (T.K.); (A.O.); (K.K.); (Y.I.)
| | - Takeshi Adachi
- Department of Internal Medicine, Division of Cardiovascular Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa 359-8513, Saitama, Japan; (A.S.); (T.K.); (A.O.); (K.K.); (Y.I.)
- Correspondence: or ; Tel.: +81-4-2995-1597
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Bacha AA, Din ZU, Khan I. Effect of Psyllium husk fiber and lifestyle modification on human body insulin resistance. Nutr Metab Insights 2022; 15:11786388221107797. [PMID: 35769394 PMCID: PMC9234916 DOI: 10.1177/11786388221107797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Accepted: 05/31/2022] [Indexed: 11/16/2022] Open
Abstract
Insulin resistance is a metabolic disorder that is increasing worldwide and is associated with some of the most common diseases affecting modern societies including diabetes, hypertension, obesity, and coronary heart disease. Changes in diet and physical activity have a profound effect on lowering the risk and cost of managing insulin resistance compared to the pharmacological approach. An interventional study of 16 weeks explored the effect of Psyllium husk fiber in combination with lifestyle modification on insulin resistance among the centrally obese school teachers of district Malakand Khyber Pakhtunkhwa. One Hundred twenty school teachers with central obesity, aged 40-60 years, with no chronic disease history were divided into four subgroups (n = 30) with equal gender bifurcation; a control group, lifestyle modification (LSM) group, psyllium husk fiber (PSH) group, and the combined intervention of LSM & PSH group. Fasting serum was collected to analyze fasting blood glucose, and insulin resistance by using the HOMA-IR method at baseline and post-intervention. A significant effect of the intervention was observed on fasting blood glucose. The combined group of LSM&PSH showed the highest mean change of -7.5 ± 2.6 mg/dl (-9%), followed by the PSH group with a mean change of -6.3 ± 2.1 mg/dl, (-7%). Likewise a significant effect (P < 0.05) on HOMA-IR was observed in the combined group of LSM&PSH with a mean of 1.02 ± 0.14 molar units (-58%), followed by the PSH group with a mean of 1.55 ± 0.14 molar units (-33%). The current study was carried out to assess the effect of regular consumption of Psyllium husk fiber in combination with lifestyle modification on insulin resistance and fasting blood glucose.
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Affiliation(s)
- Amjad Ali Bacha
- Department of Human Nutrition, the University of Agriculture Peshawar, Peshawar, Pakistan
| | - Zia Ud Din
- Department of Human Nutrition, the University of Agriculture Peshawar, Peshawar, Pakistan
| | - Imran Khan
- Department of Human Nutrition, the University of Agriculture Peshawar, Peshawar, Pakistan
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Banaszak M, Górna I, Przysławski J. Non-Pharmacological Treatments for Insulin Resistance: Effective Intervention of Plant-Based Diets—A Critical Review. Nutrients 2022; 14:nu14071400. [PMID: 35406013 PMCID: PMC9002735 DOI: 10.3390/nu14071400] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Revised: 03/19/2022] [Accepted: 03/25/2022] [Indexed: 01/22/2023] Open
Abstract
Plant-based diets are becoming increasingly popular. Vegetarian diets are better for the environment and exhibit health benefits. A correctly balanced plant-based diet is appropriate at every stage of life. Compared to omnivores, vegetarians consume more fruits and vegetables, more fibre, vitamins C and E, magnesium and less saturated fats. In general, they have better nutrition knowledge, and they are slimmer, healthier and live longer than omnivores. It also seems that following a plant-based diet prevents the onset of chronic diseases such as cardiovascular diseases, hypertension, type 2 diabetes, obesity and some cancers. Food intake has a key influence on insulin resistance. Consumption of calorie-rich and highly processed foods, meats and sweetened beverages is a characteristic element of Western diets. They promote and elevate insulin resistance and type 2 diabetes. In contrast, intake of pulses and exclusion of meats as well as animal products bring significant benefits to vegetarian diets. According to studies, vegetarians and vegans have better blood parameters, including better glucose, insulin, total cholesterol, and LDL cholesterol levels. Their homeostatic model assessment for insulin resistance (HOMA-IR) test results are also better. More plant-based foods and fewer animal foods in a diet result in lower insulin resistance and a lower risk of prediabetes and type 2 diabetes. The aim of the study was to investigate the effect of plant-based diets on insulin resistance. In this review, we focused on presenting the positive effects of vegetarian and vegan diets on insulin resistance while showing possible clinical applications of plant-based diets in the treatment and prevention of modern-age diseases. Current and reliable publications meeting the requirements of Evidence-Based Medicine (EBM) were taken into account in this review.
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Affiliation(s)
- Michalina Banaszak
- Faculty of Medical Sciences, Poznan University of Medical Sciences, 60-812 Poznan, Poland;
| | - Ilona Górna
- Department of Bromatology, Poznan University of Medical Sciences, 60-806 Poznan, Poland;
- Correspondence: ; Tel.: +48-61-641-83-90
| | - Juliusz Przysławski
- Department of Bromatology, Poznan University of Medical Sciences, 60-806 Poznan, Poland;
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Trimarco V, Manzi MV, Mancusi C, Strisciuglio T, Fucile I, Fiordelisi A, Pilato E, Izzo R, Barbato E, Lembo M, Morisco C. Insulin Resistance and Vitamin D Deficiency: A Link Beyond the Appearances. Front Cardiovasc Med 2022; 9:859793. [PMID: 35369303 PMCID: PMC8968037 DOI: 10.3389/fcvm.2022.859793] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Accepted: 02/17/2022] [Indexed: 12/23/2022] Open
Abstract
Vitamin D is a steroid hormone that plays a key role in the regulation of body homeostasis, including cardiovascular function. Although the chronic deficiency of vitamin D is associated with cardiovascular risk factors, as well as with an adverse prognosis, randomized controlled trials have failed in demonstrating that dietary vitamin D supplementation could ameliorate the prognosis of patients with cardiovascular diseases, and suggested that vitamin D deficiency is the expression of the effects of other determinants of cardiovascular risk. Thus, the supplementation of vitamin D is not sufficient to improve the cardiovascular risk profile and prognosis. Insulin resistance is a complex phenomenon that plays a key role in the pathogenesis of conventional cardiovascular risk factors. Interestingly, defects of vitamin D and insulin resistance have a superimposable epidemiological distribution. According to the common view, Insulin resistance is considered the direct or indirect consequence of vitamin D deficiency. However, it is also reasonable to speculate that the deficit or the impaired action of vitamin D, in some circumstances, could be the result of the same pathogenic mechanisms responsible of insulin resistance development. In this case, vitamin D deficiency could be considered an epiphenomenon of insulin resistance. Insulin resistance is a reversible condition, being possibly ameliorated by physical activity and hypocaloric diets. Notably, both physical exercise and energy-restricted dietary regimens are associated with an increase of vitamin D levels. These findings indicate that improving insulin resistance condition is a necessary step to ameliorate vitamin D supplementation-based strategies in cardiovascular prevention.
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Affiliation(s)
- Valentina Trimarco
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Maria Virginia Manzi
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Costantino Mancusi
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Teresa Strisciuglio
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Ilaria Fucile
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Antonella Fiordelisi
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Emanuele Pilato
- Department of Cardiac Surgery, School of Medicine, University of Naples Federico II, Naples, Italy
| | - Raffaele Izzo
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Emanuele Barbato
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Maria Lembo
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
- *Correspondence: Maria Lembo
| | - Carmine Morisco
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
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Rafaqat S, Rafaqat S, Rafaqat S. Pathophysiological aspects of insulin resistance in Atrial Fibrillation: novel therapeutic approaches. INTERNATIONAL JOURNAL OF ARRHYTHMIA 2022. [DOI: 10.1186/s42444-021-00057-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Abstract
Background
Insulin resistance is associated with metabolic disorders including diabetes, obesity, hypertension, and inflammation which are the risk factors for Atrial Fibrillation. Many studies have reported that type 2 diabetes and AF are related and also their prevalence is increasing globally. Moreover, insulin resistance begins the type 2 diabetes.
Main body
This review explains the pathophysiological aspects of insulin resistance in AF patients and discusses the drugs that are used to manage insulin resistance including Biguanides (metformin), thiazolidinediones (TZDs) [Pioglitazone, rosiglitazone], Sodium-glucose cotransporter 2 (SGLT2) inhibitors, Concentrated Insulin Products, Dipeptidyl peptidase-4 (DPP-4) Inhibitors, Glucagon-like peptide 1 (GLP-1) receptor Agonists, Pramlintide, Sulfonylureas, Meglitinides, α-Glucosidase Inhibitors, Colesevelam, Bromocriptine. This review will highlight a few major drugs that played a significant role in AF patients. For this purpose, many databases were used for reviewing the literature and keywords are used such as Insulin Resistance, Pathophysiology, Atrial Fibrillation, and Drugs.
Conclusion
This review article concludes that insulin resistance is related to AF. It also provides an outlook on the recent pathophysiological aspects of insulin resistance in AF; however, more studies are needed to clarify the management of insulin resistance in AF patients to prevent the development of type 2 diabetes.
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Aryanian Z, Shirzadian A, Hatami P, Dadras H. High Incidence of Metabolic Syndrome Components in Lichen Planus Patients: A Prospective Cross-Sectional Study. Int J Clin Pract 2022; 2022:7184678. [PMID: 35685585 PMCID: PMC9159182 DOI: 10.1155/2022/7184678] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Revised: 12/06/2021] [Accepted: 12/13/2021] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Lichen planus (LP) is a chronic inflammatory dermatosis, involving the skin, appendages, and mucous membranes. There is a growing body of evidence about higher risk of metabolic syndrome and dyslipidemia in some dermatoses including LP. AIM To evaluate lipid profile, leptin, and CRP status among Iranian LP patients, compared to healthy controls, and peruse the relationship between abnormal values of these parameters with the disease duration and physical characteristics of patients. METHODS 40 LP patients and 40 age- and sex-matched healthy controls were enrolled in the study. Data on weight, height, lipid profile, leptin, and CRP values were recorded and compared. RESULTS The mean values for leptin, CRP, and lipid profile parameters (except for HDL) were higher in patients, compared to controls. Total cholesterol level was negatively associated with disease duration in patients (P value: 0.039, r: -0.33). Serum leptin level was positively correlated with BMI both in patients and controls (P value: 0.037 and 0.003, respectively). In the patient group, LDL level, although insignificant, was higher in men, but HDL and leptin levels were significantly higher in women in comparison with men (P value: 0.018). CONCLUSION Screening of LP patients in regard to their lipid profile might be more reasonable in men or those who have other cardiovascular risk factors to prevent morbidity and mortality in result of developing cardiovascular events.
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Affiliation(s)
- Zeinab Aryanian
- Autoimmune Bullous Diseases Research Center, Tehran University of Medical Sciences, Tehran, Iran
- Department of Dermatology, Babol University of Medical Sciences, Babol, Iran
| | - Azar Shirzadian
- Department of Dermatology, Babol University of Medical Sciences, Babol, Iran
| | - Parvaneh Hatami
- Autoimmune Bullous Diseases Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Hadiyeh Dadras
- Department of Dermatology, Babol University of Medical Sciences, Babol, Iran
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Wang P, Li Q, Guo X, Zhou Y, Li Z, Yang H, Yu S, Sun G, Zheng L, Sun Y, Zhang X. Usefulness of metabolic score for insulin resistance index in estimating the risk of mildly reduced estimate glomerular filtration rate: a cross-sectional study of rural population in China. BMJ Open 2021; 11:e050907. [PMID: 34916312 PMCID: PMC8679137 DOI: 10.1136/bmjopen-2021-050907] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
OBJECTIVES This study aimed to reveal the association between metabolic score for insulin resistance (MetS-IR) and the risk of mildly decreased estimated glomerular filtration rate (eGFR), and explore the evaluation effect of MetS-IR on the progress of eGFR decline. STUDY DESIGN A cross-sectional study. SETTING AND PARTICIPANTS A total of 11 956 rural participants (aged ≥35 years) from northeastern China were enrolled in the study. After excluding the subjects whose data were not integrated or who met the exclusion criteria, we finally obtained 11 042 participants in the present study. MAIN OUTCOME MEASURES Mildly decreased eGFR was defined as 60-90 mL/min/1.73 m2. RESULTS The prevalence of mildly decreased eGFR in the general population was 36.9%. After adjustment of covariates, each SD increment of MetS-IR could bring 26.3% additional risk of mildly decreased eGFR (OR: 1.263, 95% CI: 1.066 to 1.497, p=0.007). When MetS-IR was classified into four levels by quartile, we observed participants in the top level had 3.032-fold risk of mildly decreased eGFR (OR: 3.032, 95% CI: 1.841 to 4.991, p<0.001) compared with those from the bottom level. Further, we found the participants with higher MetS-IR score were more likely to aggravate into a worse renal state which presented as higher risk of accelerated decline of eGFR, by additional 28.3% risk in whole participants (OR: 1.283, 95% CI: 1.150 to 1.430, p<0.001) and 41.9% in men (OR: 1.419, 95% CI: 1.183 to 1.701, p<0.001). CONCLUSION High MetS-IR was associated with high risk of mildly reduced eGFR and often accompanied by a high risk of accelerated decline in eGFR. Hence, we believed MetS-IR was a suitable indicator to evaluate the risk of early-stage renal dysfunction.
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Affiliation(s)
- Pengbo Wang
- Department of Cardiology, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Qiyu Li
- Department of Cardiology, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Xiaofan Guo
- Department of Cardiology, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Ying Zhou
- Department of Cardiology, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Zhao Li
- Department of Cardiology, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Hongmei Yang
- Department of Cardiology, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Shasha Yu
- Department of Cardiology, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Guozhe Sun
- Department of Cardiology, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Liqiang Zheng
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Yingxian Sun
- Department of Cardiology, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Xingang Zhang
- Department of Cardiology, The First Hospital of China Medical University, Shenyang, Liaoning, China
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Figueiredo C, Padilha C, Dorneles G, Peres A, Krüger K, Rosa Neto JC, Lira F. Type and Intensity as Key Variable of Exercise in Metainflammation diseases: A Review. Int J Sports Med 2021; 43:743-767. [PMID: 34902867 DOI: 10.1055/a-1720-0369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Monocyte and lymphocyte subpopulations exhibit functions that vary between the anti- and pro-inflammatory spectrum, such as classic CD16- and non-classical CD16+ monocytes, as well as T helper 2 lymphocytes (Th2), the Th1/Th17 lymphocytes ratio, and T regulatory lymphocytes (Treg). Metabolic disease-associated inflammation is accompanied by an imbalance in monocyte and lymphocyte phenotypes and functionality, as well as a stronger proportion of inflammatory subpopulations. These changes appear to be important for the development and progression of diseases like diabetes and cardiovascular disease. On the other hand, the regular practice of physical exercise is an important tool to restore the functionality of monocytes and lymphocytes, and to balance the subtypes ratio. However, key variables regarding exercise prescription, such as the type of exercise, intensity, and volume differentially impact on the acute and chronic immune response in individuals diagnosed with meta inflammation diseases. Here, we discuss the impact of different physical exercise protocols, acutely and chronically, on monocytes and lymphocytes of individuals with metabolic disease-associated inflammation. In this review, we focus on the best effects of different exercise protocols to dose the "exercise pill" in different inflammatory status.
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Affiliation(s)
- Caique Figueiredo
- Physical Education, Universidade Estadual Paulista Julio de Mesquita Filho - Campus de Presidente Prudente, Presidente Prudente, Brazil
| | - Camila Padilha
- Physical Education, Universidade Estadual de Londrina, Londrina, Brazil
| | - Gilson Dorneles
- Immunology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil
| | - Alessandra Peres
- Immunology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil
| | - Karsten Krüger
- Dept. of Sport Medicine, Institute of Sport Science, Giessen, Germany
| | | | - Fábio Lira
- Department of Physical Education, Unesp, Presidente Prudente, Brazil
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Heckelman LN, Wesorick BR, DeFrate LE, Lee RH. Diabetes is associated with a lower minimum moment of inertia among older women: An analysis of 3D reconstructions of clinical CT scans. J Biomech 2021; 128:110707. [PMID: 34488049 PMCID: PMC9985487 DOI: 10.1016/j.jbiomech.2021.110707] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 08/19/2021] [Accepted: 08/23/2021] [Indexed: 12/16/2022]
Abstract
Hip fractures are a significant burden on the aging population, often resulting in reduced mobility, loss of independence, and elevated risk of mortality. While fracture risk is generally inversely related to bone mineral density (BMD), people with diabetes suffer a higher fracture rate despite having a higher BMD. To better understand the connection between diabetes and fracture risk, we developed a method to measure the minimum moment of inertia (mMOI; a geometric factor associated with fracture risk) from clinical CT scans of the pelvis. Since hip fractures are more prevalent in women, we focused on females in this study. We hypothesized that females with diabetes would have a lower mMOI along the femoral neck than those without diabetes, indicative of a higher fracture risk. Three-dimensional models of each hip were created from clinical CT scans of 40 older women (27 with diabetes: 10 fracture/17 non-fractured; 13 without diabetes: non-fractured controls). The mMOI of each hip (n = 80) was reported as the average from three trials. People with diabetes had an 18% lower mMOI as compared to those without diabetes after adjusting for age and BMI (p = 0.02). No differences in the mMOIs between the fractured and contralateral hips in the diabetic group were observed (p = 0.78). Similarly, no differences were observed between the fractured and non-fractured hips of people with diabetes (p = 0.29) when accounting for age and BMI. This suggests structural differences in the hips of individuals with diabetes (measured by the mMOI) may be associated with their elevated fracture risk.
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Affiliation(s)
- Lauren N Heckelman
- Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, NC, USA; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, USA
| | - Benjamin R Wesorick
- Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, NC, USA; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, USA
| | - Louis E DeFrate
- Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, NC, USA; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC, USA; Department of Mechanical Engineering and Materials Science, Pratt School of Engineering, Duke University, Durham, NC, USA.
| | - Richard H Lee
- Department of Medicine, Duke University School of Medicine, Durham, NC, USA; Durham Veterans Affairs Medical Center, Durham, NC, USA
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Jeong SH, Joo HJ, Kwon J, Park EC. Association Between Smoking Behavior and Insulin Resistance Using Triglyceride-Glucose Index Among South Korean Adults. J Clin Endocrinol Metab 2021; 106:e4531-e4541. [PMID: 34160623 DOI: 10.1210/clinem/dgab399] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Indexed: 11/19/2022]
Abstract
CONTEXT Insulin resistance is a determinant of diabetes. With the increasing popularity of electronic smoking, the number of dual smokers (smoking both cigarettes and electronic cigarettes [e-cigarettes]) is increasing. However, few studies have assessed the association between insulin resistance and smoking behavior, including dual smoking. OBJECTIVE This work aims to investigate the association between smoking behaviors and insulin resistance. METHODS This prospective, cross-sectional study took place among the general community. A total of 11 653 participants (4721 male and 6932 female) aged 19 years or older from the 2016 to 2018 Korea National Health and Nutrition Examination Survey were divided based on their smoking behaviors: dual smokers (both cigarettes and e-cigarettes), single smokers (cigarette smokers), previous smokers, and nonsmokers. Insulin resistance was determined based on the triglyceride-glucose index. Multiple logistic regression analysis was performed to investigate the association between smoking behavior and insulin resistance. RESULTS Among the participants, 205 males (3.9%) and 40 females (0.5%) were dual smokers, and 1581 males (29.9%) and 350 females (4.5%) were single smokers. Male and female smokers (dual and single) both had higher odds of being in a group with higher insulin resistance than nonsmokers (male, dual: OR = 2.19; 95% CI, 1.39-3.44; single: OR = 1.78; 95% CI, 1.43-2.22; female, dual: OR = 2.32; 95% CI, 1.01-5.34; single: OR = 1.76; 95% CI, 1.28-2.42). CONCLUSION This study suggests that single and dual smoking both may increase the risk of insulin resistance in the general population. Education on the adverse effects of smoking behaviors may be an important strategy to improve the health of the population.
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Affiliation(s)
- Sung Hoon Jeong
- Department of Public Health, Graduate School, Yonsei University, Seoul 03722, Republic of Korea
- Institute of Health Services Research, Yonsei University, Seoul 03722, Republic of Korea
| | - Hye Jin Joo
- Department of Public Health, Graduate School, Yonsei University, Seoul 03722, Republic of Korea
- Institute of Health Services Research, Yonsei University, Seoul 03722, Republic of Korea
| | - Junhyun Kwon
- Department of Public Health, Graduate School, Yonsei University, Seoul 03722, Republic of Korea
- Institute of Health Services Research, Yonsei University, Seoul 03722, Republic of Korea
| | - Eun-Cheol Park
- Institute of Health Services Research, Yonsei University, Seoul 03722, Republic of Korea
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
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Changes in metabolic syndrome affect the health-related quality of life of community-dwelling adults. Sci Rep 2021; 11:20267. [PMID: 34642379 PMCID: PMC8511017 DOI: 10.1038/s41598-021-99767-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Accepted: 09/24/2021] [Indexed: 01/10/2023] Open
Abstract
Metabolic syndrome (MetS) is associated with cardiovascular diseases, type 2 diabetes, chronic renal diseases, and all-cause mortality. Furthermore, MetS is associated with poor health-related quality of life (HRQOL). However, the impact of dynamic changes in MetS on changes in the HRQOL was not previously explored. This was an eight-year, prospective cohort study in which 906 middle-aged adults from Shipai, Taipei in northern Taiwan were enrolled during 2009–2010 (baseline). Of those sampled, 427 participants completed the follow-up investigation after 8 years. The HRQOL was measured using the Short Form Health Survey (SF-36). Other variables including age, sex, marital status, level of education, smoking, alcohol consumption, baseline body mass index, and changes in physical activity were adjusted. Compared with adults who never experienced MetS, adults with persistent MetS had a negative change in mental HRQOL (β − 4.20, 95% CI − 7.54 to − 0.86, p = 0.01). The negative changes of persistent MetS on the HRQOL were in the domains of vitality and mental health (β − 4.42, 95% CI − 8.10 to − 0.73 and β − 3.47, 95% CI − 6.90 to − 0.04, respectively). Women and overweight adults were vulnerable to the detrimental effects of persistent MetS. For better HRQOL, more resources should be devoted to reversing MetS in public health.
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Rodríguez-Rodríguez AE, Donate-Correa J, Luis-Lima S, Díaz-Martín L, Rodríguez-González C, Pérez-Pérez JA, Acosta-González NG, Fumero C, Navarro-Díaz M, López-Álvarez D, Villacampa-Jiménez J, Navarro-González JA, Ortiz A, Porrini E. Obesity and metabolic syndrome induce hyperfiltration, glomerulomegaly, and albuminuria in obese ovariectomized female mice and obese male mice. Menopause 2021; 28:1296-1306. [PMID: 34581293 DOI: 10.1097/gme.0000000000001842] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE Obese patients with metabolic syndrome have a high risk of chronic kidney disease. The prevalence of obesity, metabolic syndrome, and insulin resistance increase in women after menopause, as does the risk of chronic kidney disease. This may indicate an interaction between obesity, metabolic syndrome, and menopause in the induction of renal damage. However, the pathogenesis of kidney disease in postmenopausal obese women is poorly understood. METHODS We investigated the interaction of an obesogenic diet and menopause on renal dysfunction in ovariectomized and non-ovariectomized lean (n = 8 and 17) and obese (n = 12 and 20) female mice. Obese (n = 12) and lean (n = 10) male mice were also studied. Glucose metabolism, insulin resistance, and kidney function were evaluated with gold standards procedures. Changes in kidney histology and lipid deposition were analyzed. Females had a lower number of glomeruli than males at baseline. RESULTS Only female ovariectomized obese animals developed insulin resistance, hyperglycemia, and kidney damage, evidenced as glomerulomegaly, glomerular hyperfiltration, and increased urinary albumin excretion, despite a similar increase in weight than obese non-ovariectomized female mice. Male obese mice developed hyperglycemia, insulin resistance, and hyperfiltration without major renal histological changes. Males on high fat diet showed higher renal lipid content and females on high fat diet (ovariectomized or non-ovariectomized) showed higher total cholesterol content than males. CONCLUSIONS In mice, there is a clear interplay between obesity, metabolic syndrome, and menopause in the induction of kidney damage.
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Affiliation(s)
- Ana Elena Rodríguez-Rodríguez
- Research Unit, Hospital Universitario de Canarias, La Laguna, Tenerife, Spain
- Fundacion General de la Universidad, University of La Laguna, Tenerife, Spain
| | - Javier Donate-Correa
- Research Unit, Hospital Universitario de Nuestra Señora de La Candelaria, La Laguna, Tenerife, Spain
- GEENDIAB (Grupo Español para el Estudio de la Nefropatía Diabética), Sociedad Española de Nefrología, Santander, Spain
| | - Sergio Luis-Lima
- Department of Nephology and Hypertension, IIS-Fundación Jimenez Díaz, UAM, Madrid, Spain
| | - Laura Díaz-Martín
- Research Unit, Hospital Universitario de Canarias, FIISC (Fundación Canaria Investigación Sanitaria de Canarias), La Laguna, Tenerife, Spain
| | | | | | | | - Cecilia Fumero
- Research Unit, Hospital Universitario de Canarias, FIISC (Fundación Canaria Investigación Sanitaria de Canarias), La Laguna, Tenerife, Spain
| | | | | | | | | | - Alberto Ortiz
- GEENDIAB (Grupo Español para el Estudio de la Nefropatía Diabética), Sociedad Española de Nefrología, Santander, Spain
- Department of Nephology and Hypertension, IIS-Fundación Jimenez Díaz, UAM, Madrid, Spain
| | - Esteban Porrini
- Research Unit, Hospital Universitario de Canarias, University of La Laguna, Faculty of Medicine, Tenerife, Spain
- ITB (Instituto Tecnologías Biomédicas), University of La Laguna, Tenerife, Spain
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44
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Park SY, Gautier JF, Chon S. Assessment of Insulin Secretion and Insulin Resistance in Human. Diabetes Metab J 2021; 45:641-654. [PMID: 34610719 PMCID: PMC8497920 DOI: 10.4093/dmj.2021.0220] [Citation(s) in RCA: 107] [Impact Index Per Article: 26.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 09/15/2021] [Indexed: 12/11/2022] Open
Abstract
The impaired insulin secretion and increased insulin resistance (or decreased insulin sensitivity) play a major role in the pathogenesis of all types of diabetes mellitus (DM). It is very important to assess the pancreatic β-cell function and insulin resistance/ sensitivity to determine the type of DM and to plan an optimal management and prevention strategy for DM. So far, various methods and indices have been developed to assess the β-cell function and insulin resistance/sensitivity based on static, dynamic test and calculation of their results. In fact, since the metabolism of glucose and insulin is made through a complex process related with various stimuli in several tissues, it is difficult to fully reflect the real physiology. In order to solve the theoretical and practical difficulties, research on new index is still in progress. Also, it is important to select the appropriate method and index for the purpose of use and clinical situation. This review summarized a variety of traditional methods and indices to evaluate pancreatic β-cell function and insulin resistance/sensitivity and introduced novel indices.
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Affiliation(s)
- So Young Park
- Department of Endocrinology and Metabolism, Kyung Hee University Hospital, Seoul, Korea
| | - Jean-François Gautier
- Department of Diabetes, Clinical Investigation Centre (CIC-9504), Lariboisière Hospital, University Paris-Diderot, Paris, France
- Faculty of Medicine, University Paris-Diderot, Paris, France
- Jean-François Gautier, https://orcid.org/0000-0001-6458-2001, Department of Diabetes and Endocrinology, Lariboisière Hospital, University Paris 7, 2 Rue Ambroise Paré, Paris 75010, France E-mail:
| | - Suk Chon
- Department of Endocrinology and Metabolism, Kyung Hee University Hospital, Seoul, Korea
- Department of Endocrinology and Metabolism, College of Medicine, Kyung Hee University, Seoul, Korea
- Corresponding authors: Suk Chon, https://orcid.org/0000-0001-5921-2989, Department of Endocrinology & Metabolism, College of Medicine, Kyung Hee University, 26 Kyunghee-dearo, Dongdaemungu, Seoul 02447, Korea E-mail:
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45
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Chaudhary P, Das-Earl P, Schreihofer AM. Preserved glycemic control and baroreflex efficacy in young adult hypertensive female obese Zucker rats. Am J Physiol Regul Integr Comp Physiol 2021; 321:R62-R78. [PMID: 33978481 PMCID: PMC8321785 DOI: 10.1152/ajpregu.00341.2020] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Obese Zucker rats (OZRs) develop hypertension and hyperinsulinemia by 3 mo of age. Male OZRs also have diminished baroreflex-mediated activation of nucleus tractus solitarius (NTS) and bradycardia, which are improved by correcting their hyperglycemia. Conversely, 3-mo-old female OZRs and lean Zucker rats (LZRs) have equivalent baroreflex-mediated bradycardia that is impaired in 6-mo-old OZRs. We hypothesized that 3-mo-old female OZRs maintain NTS activation and baroreflexes coincident with glycemic control. We also hypothesized that 6-mo-old female OZRs develop impaired baroreflexes with hyperglycemia and diminished NTS activation. In 12- to 16-wk-old females, sympathetic nerve activity (SNA) and arterial pressure (AP) were higher in OZRs than LZRs. However, baroreflex-mediated inhibition of SNA and bradycardia were equivalent in female OZRs and LZRs. Unlike deficits in male OZRs, female OZRs and LZRs had no differences in phenylephrine-induced c-Fos expression in NTS or decreases in SNA and AP evoked by glutamate into NTS. Compared with hyperglycemia in male OZRs (217.9 ± 34.4 mg/dL), female OZRs had normal fed blood glucose levels (108.2 ± 1.6 mg/dL in LZRs and 113.6 ± 3.5 mg/dL in OZRs) with emerging glucose intolerance. Conscious 24- to 27-wk-old female OZRs had impaired baroreflex-mediated bradycardia, but fed blood glucose was modestly elevated (124.2 ± 5.2 mg/dL) and phenylephrine-induced c-Fos expression in NTS was comparable to LZRs. These data suggest that better glycemic control in 3-mo-old female OZRs prevents diminished NTS activation and baroreflexes, supporting the notion that hyperglycemia impairs these responses in male OZRs. However, 6-mo-old female OZRs had impaired baroreflex efficacy without diminished NTS activation or pronounced hyperglycemia, suggesting baroreflex deficits develop by different mechanisms in female and male OZRs.
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Affiliation(s)
- Parul Chaudhary
- Department of Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, Texas
| | - Paromita Das-Earl
- Department of Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, Texas
| | - Ann M Schreihofer
- Department of Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, Texas
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46
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Ding C, Egli L, Bosco N, Sun L, Goh HJ, Yeo KK, Yap JJL, Actis-Goretta L, Leow MKS, Magkos F. Plasma Branched-Chain Amino Acids Are Associated With Greater Fasting and Postprandial Insulin Secretion in Non-diabetic Chinese Adults. Front Nutr 2021; 8:664939. [PMID: 33996878 PMCID: PMC8113402 DOI: 10.3389/fnut.2021.664939] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Accepted: 03/30/2021] [Indexed: 12/22/2022] Open
Abstract
Background: Plasma branched-chain amino acids (BCAA) are consistently elevated in subjects with obesity and type 2 diabetes (T2DM) and correlate with insulin resistance. The association of BCAA with insulin secretion and clearance rates has not been adequately described. Objective: To evaluate the relationships between fasting and postprandial plasma BCAA, insulin secretion and insulin clearance. Design: Ninety-five non-diabetic Chinese subjects (43 females) underwent a mixed-meal tolerance test; blood biomarkers including BCAAs (leucine, isoleucine, valine) were measured for 6 h. Fasting and postprandial insulin secretion rates (ISR) and insulin clearance were determined by oral minimal modeling of glucose and C-peptide. Results: Fasting and postprandial plasma BCAA correlated strongly with each other (ρ = 0.796, P < 0.001), and both were positively associated with basal ISR (ρ = 0.45/0.36, P < 0.001), total postprandial ISR AUC (ρ = 0.37/0.45, P < 0.001), and negatively with insulin clearance (ρ = -0.29/-0.29, P < 0.01), after adjusting for sex and body mass index. These relationships largely persisted after adjusting further for insulin resistance and postprandial glucose. Compared with subjects in the middle and lowest tertiles for fasting or postprandial plasma BCAA, subjects in the highest tertile had significantly greater postprandial glucose (by 7-10%) and insulin (by 74-98%) concentrations, basal ISRs (by 34-53%), postprandial ISR AUCs (by 41-49%), and lower insulin clearance rates (by 17-22%) (all P < 0.05). Conclusions: Fasting and postprandial plasma BCAA levels are associated with greater fasting and postprandial insulin secretion and reduced insulin clearance in healthy Chinese subjects. These observations potentially highlight an additional layer of involvement of BCAA in the regulation of glucose homeostasis.
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Affiliation(s)
| | - Leonie Egli
- Nestlé Institute of Health Sciences, Nestlé Research, Lausanne, Switzerland
| | - Nabil Bosco
- Nestlé Research, Singapore, Singapore
- Nestlé Institute of Health Sciences, Nestlé Research, Lausanne, Switzerland
| | - Lijuan Sun
- Singapore Institute for Clinical Sciences, Singapore, Singapore
| | - Hui Jen Goh
- Singapore Institute for Clinical Sciences, Singapore, Singapore
| | - Khung Keong Yeo
- Duke-NUS Medical School, Singapore, Singapore
- National Heart Centre Singapore, Singapore, Singapore
| | - Jonathan Jiunn Liang Yap
- National Heart Centre Singapore, Singapore, Singapore
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
| | | | - Melvin Khee-Shing Leow
- Singapore Institute for Clinical Sciences, Singapore, Singapore
- Duke-NUS Medical School, Singapore, Singapore
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Endocrinology, Tan Tock Seng Hospital, Singapore, Singapore
| | - Faidon Magkos
- Department of Nutrition, Exercise & Sports, University of Copenhagen, Frederiksberg, Denmark
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47
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Carnagarin R, Tan K, Adams L, Matthews VB, Kiuchi MG, Marisol Lugo Gavidia L, Lambert GW, Lambert EA, Herat LY, Schlaich MP. Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)-A Condition Associated with Heightened Sympathetic Activation. Int J Mol Sci 2021; 22:ijms22084241. [PMID: 33921881 PMCID: PMC8073135 DOI: 10.3390/ijms22084241] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 04/15/2021] [Accepted: 04/16/2021] [Indexed: 02/06/2023] Open
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common liver disease affecting a quarter of the global population and is often associated with adverse health outcomes. The increasing prevalence of MAFLD occurs in parallel to that of metabolic syndrome (MetS), which in fact plays a major role in driving the perturbations of cardiometabolic homeostasis. However, the mechanisms underpinning the pathogenesis of MAFLD are incompletely understood. Compelling evidence from animal and human studies suggest that heightened activation of the sympathetic nervous system is a key contributor to the development of MAFLD. Indeed, common treatment strategies for metabolic diseases such as diet and exercise to induce weight loss have been shown to exert their beneficial effects at least in part through the associated sympathetic inhibition. Furthermore, pharmacological and device-based approaches to reduce sympathetic activation have been demonstrated to improve the metabolic alterations frequently present in patients with obesity, MetSand diabetes. Currently available evidence, while still limited, suggests that sympathetic activation is of specific relevance in the pathogenesis of MAFLD and consequentially may offer an attractive therapeutic target to attenuate the adverse outcomes associated with MAFLD.
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Affiliation(s)
- Revathy Carnagarin
- Dobney Hypertension Centre, School of Medicine—Royal Perth Hospital Unit, RPH Research Foundation, Faculty of Medicine, Dentistry and Health Sciences, The University of Western Australia, Perth, WA 6000, Australia; (R.C.); (K.T.); (V.B.M.); (M.G.K.); (L.M.L.G.); (L.Y.H.)
| | - Kearney Tan
- Dobney Hypertension Centre, School of Medicine—Royal Perth Hospital Unit, RPH Research Foundation, Faculty of Medicine, Dentistry and Health Sciences, The University of Western Australia, Perth, WA 6000, Australia; (R.C.); (K.T.); (V.B.M.); (M.G.K.); (L.M.L.G.); (L.Y.H.)
| | - Leon Adams
- Medical School, Faculty of Medicine, Dentistry and Health Sciences, The University of Western Australia, Perth, WA 6009, Australia;
| | - Vance B. Matthews
- Dobney Hypertension Centre, School of Medicine—Royal Perth Hospital Unit, RPH Research Foundation, Faculty of Medicine, Dentistry and Health Sciences, The University of Western Australia, Perth, WA 6000, Australia; (R.C.); (K.T.); (V.B.M.); (M.G.K.); (L.M.L.G.); (L.Y.H.)
| | - Marcio G. Kiuchi
- Dobney Hypertension Centre, School of Medicine—Royal Perth Hospital Unit, RPH Research Foundation, Faculty of Medicine, Dentistry and Health Sciences, The University of Western Australia, Perth, WA 6000, Australia; (R.C.); (K.T.); (V.B.M.); (M.G.K.); (L.M.L.G.); (L.Y.H.)
| | - Leslie Marisol Lugo Gavidia
- Dobney Hypertension Centre, School of Medicine—Royal Perth Hospital Unit, RPH Research Foundation, Faculty of Medicine, Dentistry and Health Sciences, The University of Western Australia, Perth, WA 6000, Australia; (R.C.); (K.T.); (V.B.M.); (M.G.K.); (L.M.L.G.); (L.Y.H.)
| | - Gavin W. Lambert
- Iverson Health Innovation Research Institute and School of Health Sciences, Swinburne University of Technology, Melbourne, VIC 3122, Australia; (G.W.L.); (E.A.L.)
- Human Neurotransmitter Lab, Melbourne, VIC 3004, Australia
| | - Elisabeth A. Lambert
- Iverson Health Innovation Research Institute and School of Health Sciences, Swinburne University of Technology, Melbourne, VIC 3122, Australia; (G.W.L.); (E.A.L.)
- Human Neurotransmitter Lab, Melbourne, VIC 3004, Australia
| | - Lakshini Y. Herat
- Dobney Hypertension Centre, School of Medicine—Royal Perth Hospital Unit, RPH Research Foundation, Faculty of Medicine, Dentistry and Health Sciences, The University of Western Australia, Perth, WA 6000, Australia; (R.C.); (K.T.); (V.B.M.); (M.G.K.); (L.M.L.G.); (L.Y.H.)
| | - Markus P. Schlaich
- Dobney Hypertension Centre, School of Medicine—Royal Perth Hospital Unit, RPH Research Foundation, Faculty of Medicine, Dentistry and Health Sciences, The University of Western Australia, Perth, WA 6000, Australia; (R.C.); (K.T.); (V.B.M.); (M.G.K.); (L.M.L.G.); (L.Y.H.)
- Neurovascular Hypertension and Kidney Disease Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia
- Departments of Cardiology and Nephrology, Royal Perth Hospital, Perth, WA 6000, Australia
- Correspondence: ; Tel.: +61-8-9224-0382; Fax: +61-8-9224-0374
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48
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Watson KT, Simard JF, Henderson VW, Nutkiewicz L, Lamers F, Rasgon N, Penninx B. Association of Insulin Resistance With Depression Severity and Remission Status: Defining a Metabolic Endophenotype of Depression. JAMA Psychiatry 2021; 78:439-441. [PMID: 33263725 PMCID: PMC7711568 DOI: 10.1001/jamapsychiatry.2020.3669] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
This study investigates whether insulin resistance was positively associated with the presence, severity, or chronicity of major depression.
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Affiliation(s)
- Kathleen T. Watson
- Department of Epidemiology and Population Health, Stanford School of Medicine, Stanford, California,Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine, Stanford, California
| | - Julia F. Simard
- Department of Epidemiology and Population Health, Stanford School of Medicine, Stanford, California
| | - Victor W. Henderson
- Department of Epidemiology and Population Health, Stanford School of Medicine, Stanford, California,Department of Neurology and Neurological Sciences, Stanford University, Stanford, California
| | - Lexi Nutkiewicz
- Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine, Stanford, California
| | - Femke Lamers
- Department of Psychiatry and Amsterdam Public Health Research Institute, Amsterdam, the Netherlands
| | - Natalie Rasgon
- Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine, Stanford, California
| | - Brenda Penninx
- Department of Psychiatry and Amsterdam Public Health Research Institute, Amsterdam, the Netherlands
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49
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Elsayed AK, Vimalraj S, Nandakumar M, Abdelalim EM. Insulin resistance in diabetes: The promise of using induced pluripotent stem cell technology. World J Stem Cells 2021; 13:221-235. [PMID: 33815671 PMCID: PMC8006014 DOI: 10.4252/wjsc.v13.i3.221] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Revised: 02/07/2021] [Accepted: 03/11/2021] [Indexed: 02/06/2023] Open
Abstract
Insulin resistance (IR) is associated with several metabolic disorders, including type 2 diabetes (T2D). The development of IR in insulin target tissues involves genetic and acquired factors. Persons at genetic risk for T2D tend to develop IR several years before glucose intolerance. Several rodent models for both IR and T2D are being used to study the disease pathogenesis; however, these models cannot recapitulate all the aspects of this complex disorder as seen in each individual. Human pluripotent stem cells (hPSCs) can overcome the hurdles faced with the classical mouse models for studying IR. Human induced pluripotent stem cells (hiPSCs) can be generated from the somatic cells of the patients without the need to destroy a human embryo. Therefore, patient-specific hiPSCs can generate cells genetically identical to IR individuals, which can help in distinguishing between genetic and acquired defects in insulin sensitivity. Combining the technologies of genome editing and hiPSCs may provide important information about the genetic factors underlying the development of different forms of IR. Further studies are required to fill the gaps in understanding the pathogenesis of IR and diabetes. In this review, we summarize the factors involved in the development of IR in the insulin-target tissues leading to diabetes. Also, we highlight the use of hPSCs to understand the mechanisms underlying the development of IR.
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Affiliation(s)
- Ahmed K Elsayed
- Diabetes Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, Doha 34110, Qatar
| | | | - Manjula Nandakumar
- Diabetes Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, Doha 34110, Qatar
| | - Essam M Abdelalim
- Diabetes Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, Doha 34110, Qatar
- College of Health and Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Doha 34110, Qatar
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50
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Valente V, Izzo R, Manzi MV, De Luca MR, Barbato E, Morisco C. Modulation of insulin resistance by renin angiotensin system inhibitors: implications for cardiovascular prevention. Monaldi Arch Chest Dis 2021; 91. [PMID: 33792231 DOI: 10.4081/monaldi.2021.1602] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Accepted: 12/28/2020] [Indexed: 11/23/2022] Open
Abstract
Insulin resistance (IR) and the related hyperinsulinamia play a key role in the genesis and progression of the continuum of cardiovascular (CV) disease. Thus, it is reasonable to pursue in primary and secondary CV prevention, the pharmacological strategies that are capable to interfere with the development of IR. The renin-angiotensin-aldosterone system (RAAS) plays an important role in the pathogenesis of IR. In particular, angiotensin II (Ang II) through the generation of reactive oxygen species, induces a low grade of inflammation, which impairs the insulin signal transduction. The angiotensin converting enzyme (ACE) inhibitors are effective not only as blood pressure-lowering agents, but also as modulators of metabolic abnormalities. Indeed, experimental evidence indicates that in animal models of IR, ACE inhibitors are capable to ameliorate the insulin sensitivity. The Ang II receptor blockers (ARBs) modulate the peroxisome proliferator-activated receptor (PPAR)-γ activity. PPARâ€"γ is a transcription factor that controls the gene expression of several key enzymes of glucose metabolism. A further mechanism that accounts for the favorable metabolic properties of ARBs is the capability to modulate the hypothalamicâ€"pituitary-adrenal (HPA) axis. The available clinical evidence is consistent with the concept that both ACE inhibitors and ARBs are able to interfere with the development of IR and its consequences like type 2 diabetes. In addition, pharmacological inhibition of the RAAS has favourable effects on dyslipidaemias, metabolic syndrome and obesity. Therefore, the pharmacological antagonism of the RAAS, nowadays, represents the first choice in the prevention of cardio-metabolic diseases.
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Affiliation(s)
- Valeria Valente
- Department of Translational Medicine, Federico II University of Naples, Italy.
| | - Raffaele Izzo
- Department of Advanced Biomedical Sciences, Federico II University of Naples, Italy.
| | - Maria Virginia Manzi
- Department of Advanced Biomedical Sciences, Federico II University of Naples, Italy.
| | | | - Emanuele Barbato
- Department of Translational Medicine, Federico II University of Naples, Italy.
| | - Carmine Morisco
- Department of Translational Medicine, Federico II University of Naples, Italy.
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