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Guo SH, Xu J, Gong YQ, Hu WB, Li C, Lu K. Sex-specific association between triglyceride-glucose index and all-cause mortality in patients with osteoporotic fractures: a retrospective cohort study. Front Endocrinol (Lausanne) 2025; 16:1574238. [PMID: 40370776 PMCID: PMC12074978 DOI: 10.3389/fendo.2025.1574238] [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: 02/10/2025] [Accepted: 04/03/2025] [Indexed: 05/16/2025] Open
Abstract
Background Osteoporotic fractures (OPFs) pose a considerable global health burden and are linked with an elevated mortality risk. The triglyceride-glucose index (TyG-I) is a recognized marker of insulin resistance across various populations. The association between all-cause mortality (ACM) and the TyG-I has been widely investigated in a variety of clinical settings. The potential sex-specific differences in this association among OPF patients remain uncertain. Methods In this retrospective cohort study, 2,307 patients ≥ 50 years old admitted to the hospital between January 2018 and August 2023 for surgical treatment of OPFs were included. The TyG-I was determined using fasting triglyceride and glucose levels measured at admission. The association between ACM and the TyG-I was evaluated by Cox proportional hazards regression, adjusting for possible confounding variables. Analyses were categorized by sex, and subgroup analyses evaluated possible interaction effects. The ACM rates among TyG-I tertiles were compared via Kaplan-Meier curves. Results This research study analyzed 2,307 patients, of whom 247 (10.71%) died from any cause during the follow-up period. In females, a linear association of the TyG-I with ACM was observed even after adjusting for confounders, with each unit increase in the TyG-I correlating with a 37% increased risk of death (HR: 1.37, 95% CI: 1.06-1.77, p = 0.02). However, in males, there was a non-linear correlation, where patients in the uppermost TyG-I tertile showed a substantially decreased mortality risk relative to those in the lowest tertile (HR: 0.53, 95% CI: 0.30-0.92, p = 0.02). TyG-I indicated a statistically significant relation with sex (P for interaction = 0.01). Conclusion In patients diagnosed with OPFs, distinct sex-specific variations were observed in the relationship between ACM and the TyG-I. Among female patients, each unit increase in the TyG-I was linked to a 37% greater risk of mortality. Conversely, male patients within the highest TyG-I tertile indicated a lower mortality risk than those in the lowest tertile. Further research is required to confirm these sex-specific associations.
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Affiliation(s)
- Shao-han Guo
- Department of Orthopedics, Affiliated Kunshan Hospital of Jiangsu University, Suzhou, Jiangsu, China
- Kunshan Biomedical Big Data Innovation Application Laboratory, Suzhou, Jiangsu, China
| | - Jian Xu
- Kunshan Biomedical Big Data Innovation Application Laboratory, Suzhou, Jiangsu, China
- Department of Orthopedics, The First People’s Hospital of Kunshan, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China
| | - Ya-qin Gong
- Kunshan Biomedical Big Data Innovation Application Laboratory, Suzhou, Jiangsu, China
- Information Department, Affiliated Kunshan Hospital of Jiangsu University, Suzhou, Jiangsu, China
| | - Wen-bin Hu
- Chronic Disease Department, Kunshan Center for Disease Control and Prevention, Suzhou, Jiangsu, China
| | - Chong Li
- Department of Orthopedics, Affiliated Kunshan Hospital of Jiangsu University, Suzhou, Jiangsu, China
- Kunshan Biomedical Big Data Innovation Application Laboratory, Suzhou, Jiangsu, China
| | - Ke Lu
- Department of Orthopedics, Affiliated Kunshan Hospital of Jiangsu University, Suzhou, Jiangsu, China
- Kunshan Biomedical Big Data Innovation Application Laboratory, Suzhou, Jiangsu, China
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Ponce-Lopez T. Peripheral Inflammation and Insulin Resistance: Their Impact on Blood-Brain Barrier Integrity and Glia Activation in Alzheimer's Disease. Int J Mol Sci 2025; 26:4209. [PMID: 40362446 PMCID: PMC12072112 DOI: 10.3390/ijms26094209] [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] [Subscribe] [Scholar Register] [Received: 03/09/2025] [Revised: 04/22/2025] [Accepted: 04/23/2025] [Indexed: 05/15/2025] Open
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory impairment, and synaptic dysfunction. The accumulation of amyloid beta (Aβ) plaques and hyperphosphorylated tau protein leads to neuronal dysfunction, neuroinflammation, and glial cell activation. Emerging evidence suggests that peripheral insulin resistance and chronic inflammation, often associated with type 2 diabetes (T2D) and obesity, promote increased proinflammatory cytokines, oxidative stress, and immune cell infiltration. These conditions further damage the blood-brain barrier (BBB) integrity and promote neurotoxicity and chronic glial cell activation. This induces neuroinflammation and impaired neuronal insulin signaling, reducing glucose metabolism and exacerbating Aβ accumulation and tau hyperphosphorylation. Indeed, epidemiological studies have linked T2D and obesity with an increased risk of developing AD, reinforcing the connection between metabolic disorders and neurodegeneration. This review explores the relationships between peripheral insulin resistance, inflammation, and BBB dysfunction, highlighting their role in glial activation and the exacerbation of AD pathology.
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Affiliation(s)
- Teresa Ponce-Lopez
- Centro de Investigación en Ciencias de la Salud (CICSA), Facultad de Ciencias de la Salud, Universidad Anáhuac México Campus Norte, Huixquilucan 52786, Mexico
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Baz MH, Valette M, André M, Varin A, Trevisiol E, Sengenès C, Gue AM. Isolation of adipose stromal cells from blood using a two-step microfluidic platform ASCfinder. Sci Rep 2025; 15:10471. [PMID: 40140537 PMCID: PMC11947280 DOI: 10.1038/s41598-025-94353-y] [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: 11/18/2024] [Accepted: 03/13/2025] [Indexed: 03/28/2025] Open
Abstract
Mesenchymal stromal cells (MSCs) hold significant promise for their therapeutic potential and their possible role as disease biomarkers. While evidence suggests the presence of circulating Adipose-derived MSC (ASC) in peripheral blood (PB), isolating them is particularly challenging due to their low abundance, size variability, and incomplete characterization of their native immunophenotype in PB. Consequently, the relationship between ASC frequency in blood and various physiological or pathological conditions has been underexplored. In this study, we introduce ASC-Finder, a label-free isolation method specifically designed for adipose stromal cells (ASCs), a key MSC population. ASC-Finder integrates two independent modules: a size-dependent hydrodynamic filtration unit for sorting erythrocytes directly from PB and a negative enrichment module based on immunological markers to deplete remaining leukocytes. The device enabled removal of 99.98% of erythrocytes while achieving high recovery rates of spiked ASCs (> 81%) at rare-event concentrations (< 100 ASC/mL blood). Remarkably, ASC-Finder operates without clogging, even after multiple runs with donor blood samples. Crucially, our method bypasses the need for harsh lysis, centrifugation, or dilution buffers, preserving both cell integrity and phenotype-key factors for the discovery of novel cellular events. This work represents a significant advancement in the direct enrichment of circulating ASCs from whole PB without cell lysis, offering a crucial step toward investigating the characterization and role of blood-circulating ASCs.
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Affiliation(s)
- Mohammad-H Baz
- LAAS-CNRS, Université de Toulouse, 31031, Toulouse, France.
- RESTORE Research Center, Université de Toulouse, CNRS, Inserm, EFS, Toulouse, France.
| | - Marion Valette
- LAAS-CNRS, Université de Toulouse, 31031, Toulouse, France
| | - Mireille André
- RESTORE Research Center, Université de Toulouse, CNRS, Inserm, EFS, Toulouse, France
| | - Audrey Varin
- RESTORE Research Center, Université de Toulouse, CNRS, Inserm, EFS, Toulouse, France
| | - Emmanuelle Trevisiol
- LAAS-CNRS, Université de Toulouse, 31031, Toulouse, France
- Toulouse Biotechnology Institute (TBI), Université de Toulouse, CNRS, INRAE, INSA, Toulouse, France
| | - Coralie Sengenès
- RESTORE Research Center, Université de Toulouse, CNRS, Inserm, EFS, Toulouse, France
| | - Anne-Marie Gue
- LAAS-CNRS, Université de Toulouse, 31031, Toulouse, France.
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Bian K, Zhang P, Xu G, Sun W. The association between fatigue and cardiometabolic diseases: Insights from the UK biobank study. J Affect Disord 2025; 371:261-267. [PMID: 39577501 DOI: 10.1016/j.jad.2024.11.040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 10/09/2024] [Accepted: 11/11/2024] [Indexed: 11/24/2024]
Abstract
BACKGROUND Cardiometabolic diseases (CMD) are major global health concerns with significant morbidity and mortality. Fatigue, a common but often overlooked symptom, has been postulated as both a potential risk factor for and a consequence of these conditions. However, the relationships between fatigue and CMD remain unclear. This study aimed to investigate the relationship between fatigue and CMD using observational and genetic approaches. METHOD Observational study was conducted in the UK biobank. Genetic method was employed a bidirectional MR approach to examine the causal relationship between fatigue and CMD. Genetic variants associated with fatigue were identified through a GWAS, and summary statistics from the largest available GWAS were used to obtain variants associated with stroke, CAD, T2D, and HF. Inverse variance weighting (IVW) was conducted, with weighted median, MR-Egger, and MR-PRESSO as sensitivity analyses. Multivariable MR and mediation analysis were also employed. RESULTS Observational analyses indicated that individuals with fatigue had a significantly increased risk of developing stroke (HR 1.44, 95 % CI 1.27-1.63), T2D (HR 1.46, 95 % CI 1.41-1.51), CAD (HR 1.45, 95 % CI 1.4-1.5), and HF (HR 1.60, 95 % CI 1.52-1.68). Mendelian randomization analyses further supported a causal relationship. Additionally, observational and genetic analyses showed T2D was found to be associated with increased levels of fatigue. Mediation analysis identified lipid metabolites as mediators in the relationship between fatigue and CMD. CONCLUSION This study highlights a bidirectional relationship between fatigue and CMD, underscoring the importance of considering fatigue in the context of cardiometabolic health. CLINICAL TRIAL NUMBER Not applicable.
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Affiliation(s)
- Keyu Bian
- Department of Neurology, Wujin TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Changzhou, Jiangsu, China; Department of Neurology, Jinling Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China; Department of Neurology, Shenzhen Second People's Hospital, Shenzhen, Guangdong, China
| | - Pan Zhang
- Department of Neurology, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Gelin Xu
- Department of Neurology, Jinling Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China; Department of Neurology, Shenzhen Second People's Hospital, Shenzhen, Guangdong, China; Department of Neurology, First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China.
| | - Wen Sun
- Department of Neurology, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
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Mohan V. Lessons Learned From Epidemiology of Type 2 Diabetes in South Asians: Kelly West Award Lecture 2024. Diabetes Care 2025; 48:153-163. [PMID: 39841965 PMCID: PMC11770170 DOI: 10.2337/dci24-0046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Accepted: 11/15/2024] [Indexed: 01/24/2025]
Abstract
South Asia has high prevalence rates of type 2 diabetes (T2D). Until the 1990s, the prevalence of T2D within South Asia was low but much higher in the South Asian diaspora living abroad. Today, high prevalence rates of T2D are reported among those living in South Asia. T2D in South Asians presents with unique clinical features described as the "South Asian phenotype" that include younger age at onset of diabetes than in White Europeans, much lower BMI, hyperinsulinemia and greater insulin resistance, rapid decline in β-cell function resulting in low insulin reserve, low muscle mass, and greater ectopic fat deposition, especially in the liver. Also, prevalence of impaired fasting glucose is higher among South Asians than prevalence of impaired glucose tolerance. Genetic predisposition combined with intrauterine fetal programming (low vitamin B12 intake and high folate intake) increases susceptibility to T2D, from birth. In later life, overnutrition, especially a high carbohydrate intake with refined grains of higher glycemic index, coupled with low physical activity likely triggers the T2D epidemic in South Asians. Additionally, there are emerging risk factors like air pollution. Preventing T2D in South Asians requires a multifactorial approach, including improvements in maternal and fetal nutrition with special reference to vitamin B12 and folate intake, decreasing refined carbohydrate and increasing protein and fiber intake in the diet, increasing physical activity, and control of air pollution. Lessons learned from epidemiology of T2D in South Asians could be useful to other developing countries that are in earlier stages of epidemiological transition.
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Affiliation(s)
- Viswanathan Mohan
- Madras Diabetes Research Foundation and Dr. Mohan’s Diabetes Specialities Centre, Chennai, India
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Conning-Rowland MS, Giannoudi M, Drozd M, Brown OI, Yuldasheva NY, Cheng CW, Meakin PJ, Straw S, Gierula J, Ajjan RA, Kearney MT, Levelt E, Roberts LD, Griffin KJ, Cubbon RM. The diabetic myocardial transcriptome reveals Erbb3 and Hspa2 as a novel biomarkers of incident heart failure. Cardiovasc Res 2024; 120:1898-1906. [PMID: 39180332 PMCID: PMC11629987 DOI: 10.1093/cvr/cvae181] [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: 01/25/2024] [Revised: 06/18/2024] [Accepted: 07/14/2024] [Indexed: 08/26/2024] Open
Abstract
AIMS Diabetes mellitus (DM) increases heart failure incidence and worsens prognosis, but its molecular basis is poorly defined in humans. We aimed to define the diabetic myocardial transcriptome and validate hits in their circulating protein form to define disease mechanisms and biomarkers. METHODS AND RESULTS RNA-sequencing data from the Genotype-Tissue Expression (GTEx) project was used to define differentially expressed genes (DEGs) in right atrial (RA) and left ventricular (LV) myocardium from people with vs. without DM (type 1 or 2). DEGs were validated as plasma proteins in the UK Biobank cohort, searching for directionally concordant differential expression. Validated plasma proteins were characterized in UK Biobank participants, irrespective of diabetes status, using cardiac magnetic resonance imaging, incident heart failure, and cardiovascular mortality. We found 32 and 32 DEGs associated with DM in the RA and LV, respectively, with no overlap between these. Plasma proteomic data were available for 12, with ERBB3, NRXN3, and HSPA2 (all LV hits) exhibiting directional concordance. Irrespective of DM status, lower circulating ERBB3 and higher HSPA2 were associated with impaired LV contractility and higher LV mass. Participants in the lowest quartile of circulating ERBB3 or highest quartile of circulating HSPA2 had increased incident heart failure and cardiovascular death vs. all other quartiles. CONCLUSION DM is characterized by lower Erbb3 and higher Hspa2 expression in the myocardium, with directionally concordant differences in their plasma protein concentration. These are associated with LV dysfunction, incident heart failure, and cardiovascular mortality.
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Affiliation(s)
- Marcella S Conning-Rowland
- LIGHT Laboratories, Leeds Institute of Cardiovascular and Metabolic Medicine, The University of Leeds, Leeds, UK
| | - Marilena Giannoudi
- LIGHT Laboratories, Leeds Institute of Cardiovascular and Metabolic Medicine, The University of Leeds, Leeds, UK
| | - Michael Drozd
- LIGHT Laboratories, Leeds Institute of Cardiovascular and Metabolic Medicine, The University of Leeds, Leeds, UK
| | - Oliver I Brown
- LIGHT Laboratories, Leeds Institute of Cardiovascular and Metabolic Medicine, The University of Leeds, Leeds, UK
| | - Nadira Y Yuldasheva
- LIGHT Laboratories, Leeds Institute of Cardiovascular and Metabolic Medicine, The University of Leeds, Leeds, UK
| | - Chew W Cheng
- LIGHT Laboratories, Leeds Institute of Cardiovascular and Metabolic Medicine, The University of Leeds, Leeds, UK
| | - Paul J Meakin
- LIGHT Laboratories, Leeds Institute of Cardiovascular and Metabolic Medicine, The University of Leeds, Leeds, UK
| | - Sam Straw
- LIGHT Laboratories, Leeds Institute of Cardiovascular and Metabolic Medicine, The University of Leeds, Leeds, UK
| | - John Gierula
- LIGHT Laboratories, Leeds Institute of Cardiovascular and Metabolic Medicine, The University of Leeds, Leeds, UK
| | - Ramzi A Ajjan
- LIGHT Laboratories, Leeds Institute of Cardiovascular and Metabolic Medicine, The University of Leeds, Leeds, UK
| | - Mark T Kearney
- LIGHT Laboratories, Leeds Institute of Cardiovascular and Metabolic Medicine, The University of Leeds, Leeds, UK
| | - Eylem Levelt
- LIGHT Laboratories, Leeds Institute of Cardiovascular and Metabolic Medicine, The University of Leeds, Leeds, UK
| | - Lee D Roberts
- LIGHT Laboratories, Leeds Institute of Cardiovascular and Metabolic Medicine, The University of Leeds, Leeds, UK
| | - Kathryn J Griffin
- LIGHT Laboratories, Leeds Institute of Cardiovascular and Metabolic Medicine, The University of Leeds, Leeds, UK
| | - Richard M Cubbon
- LIGHT Laboratories, Leeds Institute of Cardiovascular and Metabolic Medicine, The University of Leeds, Leeds, UK
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Saxena A, Tiwari P, Gupta S, Mandia R, Banshiwal RC, Lamoria RK, Anjana RM, Radha V, Mohan V, Mathur SK. Exploring lipodystrophy gene expression in adipocytes: unveiling insights into the pathogenesis of insulin resistance, type 2 diabetes, and clustering diseases (metabolic syndrome) in Asian Indians. Front Endocrinol (Lausanne) 2024; 15:1468824. [PMID: 39444451 PMCID: PMC11496143 DOI: 10.3389/fendo.2024.1468824] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Accepted: 09/16/2024] [Indexed: 10/25/2024] Open
Abstract
Background Studying the molecular mechanisms of lipodystrophy can provide valuable insights into the pathophysiology of insulin resistance (IR), type 2 diabetes (T2D), and other clustering diseases [metabolic syndrome (MetS)] and its underlying adipocentric disease (MetS disease). Methods A high-confidence lipodystrophy gene panel comprising 50 genes was created, and their expressions were measured in the visceral and subcutaneous (both peripheral and abdominal) adipose depots of MetS and non-MetS individuals at a tertiary care medical facility. Results Most lipodystrophy genes showed significant downregulation in MetS individuals compared to non-MetS individuals in both subcutaneous and visceral depots. In the abdominal compartment, all the genes showed relatively higher expression in visceral depot as compared to their subcutaneous counterpart, and this difference narrowed with increasing severity of MetS. Their expression level shows an inverse correlation with T2D, MetS, and HOMA-IR and with other T2D-related intermediate traits. Results also demonstrated that individualization of MetS patients could be done based on adipose tissue expression of just 12 genes. Conclusion Adipose tissue expression of lipodystrophy genes shows an association with MetS and its intermediate phenotypic traits. Mutations of these genes are known to cause congenital lipodystrophy syndromes, whereas their altered expression in adipose tissue contributes to the pathogenesis of IR, T2D, and MetS.
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Affiliation(s)
- Aditya Saxena
- Department of Computer Engineering & Applications, GLA University, Mathura, India
| | - Pradeep Tiwari
- Department of Biotechnology and Bioinformatics, Birla Institute of Scientific Research, Jaipur, India
| | - Shalu Gupta
- Department of General Surgery, Sawai Man Singh (SMS) Medical College and Attached Hospital, Jaipur, India
| | - Rajendra Mandia
- Department of General Surgery, Sawai Man Singh (SMS) Medical College and Attached Hospital, Jaipur, India
| | - Ramesh C. Banshiwal
- Department of Orthopedics, Sawai Man Singh (SMS) Medical College and Attached Hospital, Jaipur, India
| | - Ravinder Kumar Lamoria
- Department of Orthopedics, Sawai Man Singh (SMS) Medical College and Attached Hospital, Jaipur, India
| | - Ranjit Mohan Anjana
- Department of Diabetology, Madras Diabetes Research Foundation, Chennai, Tamil Nadu, India
| | - Venkatesan Radha
- Department of Diabetology, Madras Diabetes Research Foundation, Chennai, Tamil Nadu, India
| | - Viswanathan Mohan
- Department of Diabetology, Madras Diabetes Research Foundation, Chennai, Tamil Nadu, India
| | - Sandeep Kumar Mathur
- Department of Endocrinology, Sawai Man Singh (SMS) Medical College, Jaipur, India
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Anyiam O, Abdul Rashid RS, Bhatti A, Khan-Madni S, Ogunyemi O, Ardavani A, Idris I. A Systematic Review and Meta-Analysis of the Effect of Caloric Restriction on Skeletal Muscle Mass in Individuals with, and without, Type 2 Diabetes. Nutrients 2024; 16:3328. [PMID: 39408294 PMCID: PMC11479040 DOI: 10.3390/nu16193328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2024] [Revised: 09/23/2024] [Accepted: 09/25/2024] [Indexed: 10/20/2024] Open
Abstract
BACKGROUND Severe caloric restriction interventions (such as very-low-calorie diets) are effective for inducing significant weight loss and remission of type 2 diabetes (T2DM). However, suggestions of associated significant muscle mass (MM) loss create apprehension regarding their widespread use. We conducted a systematic review and meta-analysis to provide a quantitative assessment of their effect on measures of MM in individuals with, or without, T2DM. METHODS EMBASE, Medline, Pubmed, CINAHL, CENTRAL and Google Scholar were systematically searched for studies involving caloric restriction interventions up to 900 kilocalories per day reporting any measure of MM, in addition to fat mass (FM) or body weight (BW). RESULTS Forty-nine studies were eligible for inclusion, involving 4785 participants. Individuals with T2DM experienced significant reductions in MM (WMD -2.88 kg, 95% CI: -3.54, -2.22; p < 0.0001), although this was significantly less than the reduction in FM (WMD -7.62 kg, 95% CI: -10.87, -4.37; p < 0.0001). A similar pattern was observed across studies involving individuals without T2DM. MM constituted approximately 25.5% of overall weight loss in individuals with T2DM, and 27.5% in individuals without T2DM. Subgroup analysis paradoxically revealed greater BW and FM reductions with less restrictive interventions. CONCLUSIONS Our review suggests that caloric restriction interventions up to 900 kilocalories per day are associated with a significant reduction in MM, albeit in the context of a significantly greater reduction in FM. Furthermore, MM constituted approximately a quarter of the total weight loss. Finally, our data support the use of less restrictive interventions, which appear to be more beneficial for BW and FM loss.
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Affiliation(s)
- Oluwaseun Anyiam
- MRC/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), School of Medicine, University of Nottingham, Royal Derby Hospital Centre, Derby DE22 3DT, UK
- Department of Endocrinology and Diabetes, University Hospitals of Derby and Burton NHS Foundation Trust, Derby DE22 3NE, UK
| | | | - Aniqah Bhatti
- Nottingham University Hospitals NHS Trust, Nottingham NG7 2UH, UK
| | - Saif Khan-Madni
- School of Medicine, University of Nottingham, Nottingham NG7 2RD, UK
| | - Olakunmi Ogunyemi
- Department of Acute Medicine, University Hospitals of Derby and Burton NHS Foundation Trust, Derby DE22 3NE, UK
- Nuffield Department of Population Health, University of Oxford, Oxford OX1 2JD, UK
| | - Arash Ardavani
- MRC/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), School of Medicine, University of Nottingham, Royal Derby Hospital Centre, Derby DE22 3DT, UK
- Department of Endocrinology and Diabetes, University Hospitals of Derby and Burton NHS Foundation Trust, Derby DE22 3NE, UK
| | - Iskandar Idris
- MRC/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), School of Medicine, University of Nottingham, Royal Derby Hospital Centre, Derby DE22 3DT, UK
- Department of Endocrinology and Diabetes, University Hospitals of Derby and Burton NHS Foundation Trust, Derby DE22 3NE, UK
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Helal E, Elgebaly F, Mousa N, Elbaz S, Abdelsalam M, Abdelkader E, El-Sehrawy A, El-Wakeel N, El-Emam O, Hashem M, Elmetwalli A, Mansour S. Diagnostic performance of new BAST score versus FIB-4 index in predicating of the liver fibrosis in patients with metabolic dysfunction-associated steatotic liver disease. Eur J Med Res 2024; 29:459. [PMID: 39272195 PMCID: PMC11401269 DOI: 10.1186/s40001-024-02032-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Accepted: 08/20/2024] [Indexed: 09/15/2024] Open
Abstract
BACKGROUND AND AIM Metabolic dysfunction-associated steatotic liver disease (MASLD) formerly known as non-alcoholic fatty liver disease (NAFLD) is the most common liver condition globally. The FIB-4 test is used to detect fibrosis in fatty liver disease but has limited accuracy in predicting liver stiffness, resulting in high rates of false positives and negatives. The new BAST scoring system, incorporating waist circumference, AST, and BMI, has been developed to assess the presence of fibrosis in NAFLD patients. This study compares the effectiveness of BAST and FIB-4 in predicting liver fibrosis in MASLD patients. PATIENTS AND METHODS The study included 140 non-diabetic MASLD patients who underwent transient elastography measurement. BAST score and FIB-4 were calculated for each patient. Patients were grouped based on fibrosis severity; F1, F2, and F3-F4. The sensitivity and specificity of the BAST score and FIB-4 were assessed using receiver operating characteristic curves. RESULTS The BAST score increased significantly with fibrosis progression from F1 to F3-F4. In differentiating advanced fibrosis (F2-F3) from mild/moderate fibrosis (F1-F2), the BAST score at cutoff ≤ - 0.451 showed better diagnostic performance with 90.70% sensitivity, 74.07% specificity, 84.8% PPV and 83.3% NPV compared to FIB-4 that had 60.47% sensitivity, 50.0% specificity, 65.8% PPV and 44.3% NPV. Similarly, for differentiating between F1 and F2 fibrosis, the BAST score at cutoff ≤ - 1.11 outperformed FIB-4, with 80.23% sensitivity, 79.49% specificity, 89.6% PPV and 64.6% NPV, while FIB-4 had 59.30% sensitivity, 51.28% specificity, 72.9% PPV and 36% NPV. CONCLUSIONS The BAST score is a better predictor of liver fibrosis in MASLD compared to FIB-4, especially in cases of advanced fibrosis or cirrhosis.
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Affiliation(s)
- Eman Helal
- Department of Tropical Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Fatma Elgebaly
- Department of Tropical Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Nasser Mousa
- Tropical Medicine Department, Mansoura University, Mansoura, Egypt.
| | - Sherif Elbaz
- Internal Medicine Department, Jacobs School of Medicine and Biomedical Sciences, Buffalo University, New York, USA
| | - Mostafa Abdelsalam
- Internal Medicine Department, Mansoura University, Mansoura, Egypt
- Alameen General Hospital, Taif, Kingdom of Saudi Arabia
| | - Eman Abdelkader
- Internal Medicine Department, Mansoura University, Mansoura, Egypt
| | - Amr El-Sehrawy
- Internal Medicine Department, Mansoura University, Mansoura, Egypt
| | - Niveen El-Wakeel
- Medical Microbiology and Immunology Department, Mansoura National University, Mansoura, Egypt
- Medical Microbiology and Immunology Department, Faculty of Medicine, Delta University for Science and Technology, Mansoura, Egypt
| | - Ola El-Emam
- Clinical Pathology Department, Mansoura University, Mansoura, Egypt
| | - Manal Hashem
- Internal Medicine Department, Zagazig University, Zagazig, Egypt
| | - Alaa Elmetwalli
- Department of Clinical Trial Research Unit and Drug Discovery, Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura, Egypt
- Microbiology Division, Higher Technological Institute of Applied Health Sciences, Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura, Egypt
| | - Shimaa Mansour
- Department of Tropical Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt
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Kazeminasab F, Bahrami Kerchi A, Behzadnejad N, Belyani S, Rosenkranz SK, Bagheri R, Dutheil F. The Effects of Exercise Interventions on Ectopic and Subcutaneous Fat in Patients with Type 2 Diabetes Mellitus: A Systematic Review, Meta-Analysis, and Meta-Regression. J Clin Med 2024; 13:5005. [PMID: 39274218 PMCID: PMC11396734 DOI: 10.3390/jcm13175005] [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: 07/18/2024] [Revised: 08/15/2024] [Accepted: 08/21/2024] [Indexed: 09/16/2024] Open
Abstract
Background/Objectives: The aim of the present study was to determine the effects of exercise training on ectopic and subcutaneous fat in patients with type 2 diabetes mellitus (T2DM). Methods: Web of Science, PubMed, and Scopus were searched for original articles published through November 2023 that included exercise versus control interventions on body mass (BM), liver fat percentage, visceral fat area (VFA), subcutaneous fat area (SFA), and intramuscular fat volume or mass (IMF) in patients with T2DM. Weighted mean differences (WMDs) for liver fat and BM, standardized mean differences (SMDs) for VFA, SFA, and IMF, and 95% confidence intervals (95% CIs) were determined using random-effects models. Results: Thirty-six studies comprising 2110 patients with T2DM were included in the present meta-analysis. Exercise training effectively reduced BM [WMD = -2.502 kg, p = 0.001], liver fat% [WMD = -1.559%, p = 0.030], VFA [SMD = -0.510, p = 0.001], and SFA [SMD = -0.413, p = 0.001] in comparison to the control. The IMF [SMD = 0.222, p = 0.118] remained unchanged compared to the controls. Subgroup analyses showed that the type of exercise, duration, and body mass index (BMI) of participants were sources of heterogeneity. Conclusions: The current meta-analysis provides strong evidence that exercise training, particularly aerobic and combined (aerobic and resistance) exercise programs, is effective for reducing BM, VFA, and SFA in patients with T2DM. However, aerobic exercise was more effective for reducing liver fat than combined exercise. The beneficial effects of exercise on VFA and SFA reduction, but not liver fat, are associated with weight loss. These findings highlight the importance of including consistent exercise as a key management component for T2DM and associated ectopic fat deposition, with potential long-term benefits for metabolic health.
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Affiliation(s)
- Fatemeh Kazeminasab
- Department of Physical Education and Sports Science, Faculty of Humanities, University of Kashan, Kashan 87317-53153, Iran
| | - Ali Bahrami Kerchi
- Department of Exercise Physiology, Faculty of Sports Science, Isfahan (Khorasgan) Branch, Islamic Azad University, Isfahan P.O. Box 81551-39998, Iran
| | - Nasim Behzadnejad
- Department of Exercise Physiology, Faculty of Sport Sciences, University of Isfahan, Isfahan P.O. Box 81746-73441, Iran
| | - Saba Belyani
- Human Nutrition Program, Department of Human Sciences, The Ohio State University, Columbus, OH 43210, USA
| | - Sara K Rosenkranz
- Department of Kinesiology and Nutrition Sciences, University of Nevada Las Vegas, Las Vegas, NV 89154, USA
| | - Reza Bagheri
- Department of Exercise Physiology, Faculty of Sport Sciences, University of Isfahan, Isfahan P.O. Box 81746-73441, Iran
| | - Fred Dutheil
- University Hospital of Clermont-Ferrand, Université Clermont Auvergne, CNRS, LaPSCo, Physiological and Psychosocial Stress, CHU Clermont-Ferrand, Occupational and Environmental Medicine, F-63000 Clermont-Ferrand, France
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11
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Sequeira-Bisson IR, Lu LW, Silvestre MP, Plank LD, Middleditch N, Acevedo-Fani A, Parry-Strong A, Hollingsworth KG, Tups A, Miles-Chan JL, Krebs JD, Foster M, Poppitt SD. Glycaemic Response to a Nut-Enriched Diet in Asian Chinese Adults with Normal or High Glycaemia: The Tū Ora RCT. Nutrients 2024; 16:2103. [PMID: 38999851 PMCID: PMC11243085 DOI: 10.3390/nu16132103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 06/27/2024] [Accepted: 06/28/2024] [Indexed: 07/14/2024] Open
Abstract
Nut-based products are a good source of high-quality plant protein in addition to mono- and polyunsaturated fatty acids, and may aid low-glycaemic dietary strategies important for the prevention of type 2 diabetes (T2D). In particular, they may be advantageous in populations susceptible to dysglycaemia, such as Asian Chinese. The present study aimed to compare effects of a higher-protein nut bar (HP-NB, also higher in total fibre and unsaturated fats, comprising mixed almonds and peanuts) vs. an isoenergetic higher-carbohydrate cereal bar (HC-CB) within the diet of 101 Chinese adults with overweight and normo- or hyperglycaemia. Ectopic pancreas and liver fat were characterised using magnetic resonance imaging and spectroscopy (MRI/S) as a secondary outcome. Participants were randomized to receive HP-NB or HC-CB daily as a 1 MJ light meal or snack replacement, in addition to healthy eating advice. Anthropometry and clinical indicators of T2D risk were assessed fasted and during an oral glucose tolerance test (OGTT), pre- and post-intervention. No significant difference was observed between diet groups for body weight, body mass index, waist or hip circumference, blood pressure, glucoregulatory markers, lipid profile or inflammatory markers over 12 weeks (all, p > 0.05). No difference was observed between glycaemic subgroups or those with normal versus high ectopic organ fat. Although HP-NB can attenuate postprandial glycaemia following a meal, no effects were observed for either fasting or glucose-mediated outcomes following longer-term inclusion in the habitual diet of Chinese adults with overweight, including at-risk subgroups.
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Affiliation(s)
- Ivana R. Sequeira-Bisson
- Human Nutrition Unit, School of Biological Sciences, University of Auckland, Auckland 1024, New Zealand; (I.R.S.-B.); (L.W.L.); (M.P.S.); (J.L.M.-C.)
- High Value Nutrition National Science Challenge, Auckland 1023, New Zealand; (N.M.); (A.A.-F.); (J.D.K.); (M.F.)
- Riddet Institute, Massey University, Palmerston North 4442, New Zealand
| | - Louise W. Lu
- Human Nutrition Unit, School of Biological Sciences, University of Auckland, Auckland 1024, New Zealand; (I.R.S.-B.); (L.W.L.); (M.P.S.); (J.L.M.-C.)
- High Value Nutrition National Science Challenge, Auckland 1023, New Zealand; (N.M.); (A.A.-F.); (J.D.K.); (M.F.)
| | - Marta P. Silvestre
- Human Nutrition Unit, School of Biological Sciences, University of Auckland, Auckland 1024, New Zealand; (I.R.S.-B.); (L.W.L.); (M.P.S.); (J.L.M.-C.)
- High Value Nutrition National Science Challenge, Auckland 1023, New Zealand; (N.M.); (A.A.-F.); (J.D.K.); (M.F.)
- Centro de Investigação em Tecnologias e Serviços de Saúde (CINTESIS), NOVA University of Lisbon, 1169-056 Lisbon, Portugal
| | - Lindsay D. Plank
- Department of Surgery, University of Auckland, Auckland 1023, New Zealand;
| | - Nikki Middleditch
- High Value Nutrition National Science Challenge, Auckland 1023, New Zealand; (N.M.); (A.A.-F.); (J.D.K.); (M.F.)
- School of Food and Advanced Technology, Massey University, Palmerston North 4442, New Zealand
| | - Alejandra Acevedo-Fani
- High Value Nutrition National Science Challenge, Auckland 1023, New Zealand; (N.M.); (A.A.-F.); (J.D.K.); (M.F.)
- Riddet Institute, Massey University, Palmerston North 4442, New Zealand
| | - Amber Parry-Strong
- Department of Medicine, University of Otago, Dunedin 9054, New Zealand;
- Centre for Endocrine, Diabetes and Obesity Research (CEDOR), Te Whatu Ora, Capital and Coast Health, Wellington 6242, New Zealand
| | - Kieren G. Hollingsworth
- Translational and Clinical Research Institute, Faculty of Medical Science, Newcastle University, Newcastle-upon-Tyne NE1 7RU, UK
| | - Alexander Tups
- Centre for Neuroendocrinology, University of Otago, Dunedin 9054, New Zealand;
| | - Jennifer L. Miles-Chan
- Human Nutrition Unit, School of Biological Sciences, University of Auckland, Auckland 1024, New Zealand; (I.R.S.-B.); (L.W.L.); (M.P.S.); (J.L.M.-C.)
- High Value Nutrition National Science Challenge, Auckland 1023, New Zealand; (N.M.); (A.A.-F.); (J.D.K.); (M.F.)
- Riddet Institute, Massey University, Palmerston North 4442, New Zealand
| | - Jeremy D. Krebs
- High Value Nutrition National Science Challenge, Auckland 1023, New Zealand; (N.M.); (A.A.-F.); (J.D.K.); (M.F.)
- Department of Medicine, University of Otago, Dunedin 9054, New Zealand;
- Centre for Endocrine, Diabetes and Obesity Research (CEDOR), Te Whatu Ora, Capital and Coast Health, Wellington 6242, New Zealand
| | - Meika Foster
- High Value Nutrition National Science Challenge, Auckland 1023, New Zealand; (N.M.); (A.A.-F.); (J.D.K.); (M.F.)
- Edible Research Ltd., Ohoka, Christchurch 7475, New Zealand
| | - Sally D. Poppitt
- Human Nutrition Unit, School of Biological Sciences, University of Auckland, Auckland 1024, New Zealand; (I.R.S.-B.); (L.W.L.); (M.P.S.); (J.L.M.-C.)
- High Value Nutrition National Science Challenge, Auckland 1023, New Zealand; (N.M.); (A.A.-F.); (J.D.K.); (M.F.)
- Riddet Institute, Massey University, Palmerston North 4442, New Zealand
- Department of Medicine, University of Auckland, Auckland 1023, New Zealand
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12
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Guan J, Abudouaini H, Lin K, Yang K. Emerging insights into the role of IL-1 inhibitors and colchicine for inflammation control in type 2 diabetes. Diabetol Metab Syndr 2024; 16:140. [PMID: 38918878 PMCID: PMC11197348 DOI: 10.1186/s13098-024-01369-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Accepted: 05/30/2024] [Indexed: 06/27/2024] Open
Abstract
Type 2 diabetes mellitus (T2DM), a prevalent chronic metabolic disorder, is closely linked to persistent low-grade inflammation, significantly contributing to its development and progression. This review provides a comprehensive examination of the inflammatory mechanisms underlying T2DM, focusing on the role of the NLRP3 inflammasome and interleukin-1β (IL-1β) in mediating inflammatory responses. We discuss the therapeutic potential of IL-1 inhibitors and colchicine, highlighting their mechanisms in inhibiting the NLRP3 inflammasome and reducing IL-1β production. Recent studies indicate that these agents could effectively mitigate inflammation, offering promising avenues for the prevention and management of T2DM. By exploring the intricate connections between metabolic disturbances and chronic inflammation, this review underscores the need for novel anti-inflammatory strategies to address T2DM and its complications.
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Affiliation(s)
- Jianbin Guan
- Honghui-Hospital, Xi'an Jiaotong University, Xi'an, 710054, Shaanxi, China
| | - Haimiti Abudouaini
- Honghui-Hospital, Xi'an Jiaotong University, Xi'an, 710054, Shaanxi, China
| | - Kaiyuan Lin
- Honghui-Hospital, Xi'an Jiaotong University, Xi'an, 710054, Shaanxi, China.
| | - Kaitan Yang
- Honghui-Hospital, Xi'an Jiaotong University, Xi'an, 710054, Shaanxi, China.
- Truma Rehabilitation Department, Honghui-Hospital，Xi'an Jiaotong University, Xi'an, 710054, Shaanxi, China.
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13
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Lundqvist MH, Pereira MJ, Almby K, Hetty S, Eriksson JW. Regulation of the Cortisol Axis, Glucagon, and Growth Hormone by Glucose Is Altered in Prediabetes and Type 2 Diabetes. J Clin Endocrinol Metab 2024; 109:e675-e688. [PMID: 37708362 PMCID: PMC10795937 DOI: 10.1210/clinem/dgad549] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 08/17/2023] [Accepted: 09/12/2023] [Indexed: 09/16/2023]
Abstract
CONTEXT Insulin-antagonistic, counter-regulatory hormones have been implicated in the development of type 2 diabetes (T2D). OBJECTIVE In this cross-sectional study, we investigated whether glucose-dependent regulation of such hormones differ in individuals with T2D, prediabetes (PD), and normoglycemia (NG). METHODS Fifty-four individuals with or without T2D underwent one hyperinsulinemic-normoglycemic-hypoglycemic and one hyperglycemic clamp with repeated hormonal measurements. Participants with T2D (n = 19) were compared with a group-matched (age, sex, BMI) subset of participants without diabetes (ND, n = 17), and also with participants with PD (n = 18) and NG (n = 17). RESULTS In T2D vs ND, glucagon levels were higher and less suppressed during the hyperglycemic clamp whereas growth hormone (GH) levels were lower during hypoglycemia (P < .05). Augmented ACTH response to hypoglycemia was present in PD vs NG (P < .05), with no further elevation in T2D. In contrast, glucagon and GH alterations were more marked in T2D vs PD (P < .05).In the full cohort (n = 54), augmented responses of glucagon, cortisol, and ACTH and attenuated responses of GH correlated with adiposity, dysglycemia, and insulin resistance. In multilinear regressions, insulin resistance was the strongest predictor of elevated hypoglycemic responses of glucagon, cortisol, and ACTH. Conversely, fasting glucose and HbA1c were the strongest predictors of low GH levels during hypoglycemia and elevated, i.e. less suppressed glucagon levels during hyperglycemia, respectively. Notably, adiposity measures were also strongly associated with the responses above. CONCLUSIONS Altered counter-regulatory hormonal responses to glucose variations are observed at different stages of T2D development and may contribute to its progression by promoting insulin resistance and dysglycemia.
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Affiliation(s)
- Martin H Lundqvist
- Clinical Diabetology and Metabolism, Department of Medical Sciences, Uppsala University, 751 85 Uppsala, Sweden
| | - Maria J Pereira
- Clinical Diabetology and Metabolism, Department of Medical Sciences, Uppsala University, 751 85 Uppsala, Sweden
| | - Kristina Almby
- Clinical Diabetology and Metabolism, Department of Medical Sciences, Uppsala University, 751 85 Uppsala, Sweden
| | - Susanne Hetty
- Clinical Diabetology and Metabolism, Department of Medical Sciences, Uppsala University, 751 85 Uppsala, Sweden
| | - Jan W Eriksson
- Clinical Diabetology and Metabolism, Department of Medical Sciences, Uppsala University, 751 85 Uppsala, Sweden
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14
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Kanner J. Food Polyphenols as Preventive Medicine. Antioxidants (Basel) 2023; 12:2103. [PMID: 38136222 PMCID: PMC10740609 DOI: 10.3390/antiox12122103] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Revised: 12/04/2023] [Accepted: 12/04/2023] [Indexed: 12/24/2023] Open
Abstract
Reactive oxygen species (ROS) are the initiators in foods and in the stomach of oxidized dietary lipids, proteins, and lipid-oxidation end-products (ALEs), inducing in humans the development of several chronic diseases and cancer. Epidemiological, human clinical and animal studies supported the role of dietary polyphenols and derivatives in prevention of development of such chronic diseases. There is much evidence that polyphenols/derivatives at the right timing and concentration, which is critical, acts mostly in the aerobic stomach and generally in the gastrointestinal tract as reducing agents, scavengers of free radicals, trappers of reactive carbonyls, modulators of enzyme activity, generators of beneficial gut microbiota and effectors of cellular signaling. In the blood system, at low concentration, they act as generators of electrophiles and low concentration of H2O2, acting mostly as cellular signaling, activating the PI3K/Akt-mediated Nrf2/eNOS pathways and inhibiting the inflammatory transcription factor NF-κB, inducing the cells, organs and organism for eustress, adaptation and surviving.
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Affiliation(s)
- Joseph Kanner
- Department of Food Science, ARO, Volcani Center, Bet-Dagan 7505101, Israel; or
- Institute of Biochemistry, Food Science and Nutrtion, Faculty of Agriculture Food and Environment, The Hebrew University of Jerusalem, Rehovot 9190501, Israel
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15
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Thomas P, Gallagher MT, Da Silva Xavier G. Beta cell lipotoxicity in the development of type 2 diabetes: the need for species-specific understanding. Front Endocrinol (Lausanne) 2023; 14:1275835. [PMID: 38144558 PMCID: PMC10739424 DOI: 10.3389/fendo.2023.1275835] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Accepted: 11/13/2023] [Indexed: 12/26/2023] Open
Abstract
The propensity to develop type 2 diabetes (T2D) is known to have both environmental and hereditary components. In those with a genetic predisposition to T2D, it is widely believed that elevated concentrations of circulatory long-chain fatty acids (LC-FFA) significantly contribute towards the demise of insulin-producing pancreatic β-cells - the fundamental feature of the development of T2D. Over 25 years of research support that LC-FFA are deleterious to β-cells, through a process termed lipotoxicity. However, the work underpinning the theory of β-cell lipotoxicity is mostly based on rodent studies. Doubts have been raised as to whether lipotoxicity also occurs in humans. In this review, we examine the evidence, both in vivo and in vitro, for the pathogenic effects of LC-FFA on β-cell viability and function in humans, highlighting key species differences. In this way, we aim to uncover the role of lipotoxicity in the human pathogenesis of T2D and motivate the need for species-specific understanding.
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Affiliation(s)
- Patricia Thomas
- Centre for Systems Modelling and Quantitative Biomedicine, University of Birmingham, Birmingham, United Kingdom
- Institute for Metabolism and Systems Research, Birmingham Medical School, University of Birmingham, Birmingham, United Kingdom
| | - Meurig T. Gallagher
- Centre for Systems Modelling and Quantitative Biomedicine, University of Birmingham, Birmingham, United Kingdom
- Institute for Metabolism and Systems Research, Birmingham Medical School, University of Birmingham, Birmingham, United Kingdom
| | - Gabriela Da Silva Xavier
- Institute for Metabolism and Systems Research, Birmingham Medical School, University of Birmingham, Birmingham, United Kingdom
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16
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Herrgårdh T, Simonsson C, Ekstedt M, Lundberg P, Stenkula KG, Nyman E, Gennemark P, Cedersund G. A multi-scale digital twin for adiposity-driven insulin resistance in humans: diet and drug effects. Diabetol Metab Syndr 2023; 15:250. [PMID: 38044443 PMCID: PMC10694923 DOI: 10.1186/s13098-023-01223-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 11/15/2023] [Indexed: 12/05/2023] Open
Abstract
BACKGROUND The increased prevalence of insulin resistance is one of the major health risks in society today. Insulin resistance involves both short-term dynamics, such as altered meal responses, and long-term dynamics, such as the development of type 2 diabetes. Insulin resistance also occurs on different physiological levels, ranging from disease phenotypes to organ-organ communication and intracellular signaling. To better understand the progression of insulin resistance, an analysis method is needed that can combine different timescales and physiological levels. One such method is digital twins, consisting of combined mechanistic mathematical models. We have previously developed a model for short-term glucose homeostasis and intracellular insulin signaling, and there exist long-term weight regulation models. Herein, we combine these models into a first interconnected digital twin for the progression of insulin resistance in humans. METHODS The model is based on ordinary differential equations representing biochemical and physiological processes, in which unknown parameters were fitted to data using a MATLAB toolbox. RESULTS The interconnected twin correctly predicts independent data from a weight increase study, both for weight-changes, fasting plasma insulin and glucose levels, and intracellular insulin signaling. Similarly, the model can predict independent weight-change data in a weight loss study with the weight loss drug topiramate. The model can also predict non-measured variables. CONCLUSIONS The model presented herein constitutes the basis for a new digital twin technology, which in the future could be used to aid medical pedagogy and increase motivation and compliance and thus aid in the prevention and treatment of insulin resistance.
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Affiliation(s)
- Tilda Herrgårdh
- Department of Biomedical Engineering, Linköping University, Linköping, Sweden
| | - Christian Simonsson
- Department of Biomedical Engineering, Linköping University, Linköping, Sweden
- Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden
| | - Mattias Ekstedt
- Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden
- Department of Health, Medicine, and Caring Sciences, Linköping University, Linköping, Sweden
| | - Peter Lundberg
- Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden
- Department of Health, Medicine, and Caring Sciences, Linköping University, Linköping, Sweden
- Department of Radiation Physics, Linköping University, Linköping, Sweden
| | - Karin G Stenkula
- Department of Experimental Medical Science, Lund University, Lund, Sweden
| | - Elin Nyman
- Department of Biomedical Engineering, Linköping University, Linköping, Sweden
| | - Peter Gennemark
- Department of Biomedical Engineering, Linköping University, Linköping, Sweden
- Drug Metabolism and Pharmacokinetics, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), AstraZeneca, BioPharmaceuticals R&D, Gothenburg, Sweden
| | - Gunnar Cedersund
- Department of Biomedical Engineering, Linköping University, Linköping, Sweden.
- Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden.
- School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
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17
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Morsy MHE, Nabil ZI, Darwish ST, Al-Eisa RA, Mehana AE. Anti-Diabetic and Anti-Adipogenic Effect of Harmine in High-Fat-Diet-Induced Diabetes in Mice. Life (Basel) 2023; 13:1693. [PMID: 37629550 PMCID: PMC10455780 DOI: 10.3390/life13081693] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 07/31/2023] [Accepted: 08/03/2023] [Indexed: 08/27/2023] Open
Abstract
One of the most important health issues facing the world today is obesity. It is an important independent risk factor for developing type 2 diabetes. Harmine offers various pharmacological effects, such as anti-inflammatory and anti-tumor effects. The current study aims to investigate Harmine's anti-diabetic and anti-adipogenic properties in albino mice after inducing low-grade inflammation with a high-fat diet (HFD). About forty-eight male albino mice were divided into four groups. Group 1: control mice were injected with daily saline and fed a normal chow diet of 21% protein for 5 months. Group 2: mice were treated daily with IP-injected Harmine (30 mg/kg body weight) and were fed a normal chow diet for 5 months. Group 3: mice were fed HFD to induce type 2 Diabetes Mellitus (T2DM) for 5 months. Group 4: mice were fed HFD for 14 weeks and treated with Harmine for the last 6 weeks. A figh-fat diet caused a significant increase in body and organ weight, lipid profiles, and destructive changes within the pancreas, kidney, and liver tissue. The administration of Harmine led to a remarkable improvement in the histological and ultrastructural changes induced by HFD. The findings indicate that mice cured using Harmine had lower oxidative stress, a higher total antioxidant capacity, and a reduced lipid profile compared to HFD mice. Harmine led to the hepatocytes partly restoring their ordinary configuration. Furthermore, it was noticed that the pathological incidence of damage in the structure of both the kidney and pancreas sections reduced in comparison with the diabetic group. Additional research will be required to fully understand Harmine and its preventive effects on the two forms of diabetes.
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Affiliation(s)
- Menna H E Morsy
- Department of Zoology, Faculty of Science, Arish University, Arish 45511, Egypt
- Department of Zoology, Faculty of Science, Suez Canal University, Ismailia 41522, Egypt
| | - Zohour I Nabil
- Department of Zoology, Faculty of Science, Suez Canal University, Ismailia 41522, Egypt
| | - Samah T Darwish
- Department of Zoology, Faculty of Science, Arish University, Arish 45511, Egypt
| | - Rasha A Al-Eisa
- Department of Biology, College of Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
| | - Amir E Mehana
- Department of Zoology, Faculty of Science, Suez Canal University, Ismailia 41522, Egypt
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18
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Sambashivaiah S, Cope M, Mukherjea R, Selvam S, George N, Kuriyan R, Kurpad AV. The Effect of Soy and Whey Protein Supplementation on Glucose Homeostasis in Healthy Normal Weight Asian Indians. J Nutr Metab 2023; 2023:2622057. [PMID: 37469998 PMCID: PMC10352526 DOI: 10.1155/2023/2622057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 05/05/2023] [Accepted: 06/14/2023] [Indexed: 07/21/2023] Open
Abstract
Milk and legumes are good source of protein foods used to sustain muscle mass, but their effects on postprandial glucose homeostasis and energy metabolism may be different. This is relevant, for example, in the dietetic response to obesity or diabetes, where the intake of high-quality protein is often increased significantly. The objective of this study was to characterize the acute effect of whey and soy protein (15% vs. 30%) on glucose homeostasis, energy metabolism, and satiety. Healthy, normal body mass index (BMI) Indian adult males aged 20-35 years (n = 15) received 4 test meals (2 proteins (soy vs. whey) and 2 doses (15% vs. 30% protein: energy ratio)). Blood samples were collected serially after the meal to calculate the incremental area under the curve for plasma glucose and insulin. Energy expenditure and substrate oxidation were measured after the meal. Satiety was measured with a visual analogue scale. The insulin response, represented by the incremental area under the curve, was significantly higher for the 30% whey compared to the 30% soy protein meal (p < 0.01) but was not significantly different between the 15% protein doses. There were no differences in the plasma glucose response across protein sources or doses. The mean peak fat and carbohydrate oxidation, satiety, and energy expenditure did not differ between the protein sources and doses. In conclusion, at higher doses, whey protein has a greater insulinogenic response, compared to soy protein, and exhibits a dose-response effect. However, at lower doses, whey and soy protein elicit similar insulinogenic responses, making them equally effective protein sources in relation to glucose homoeostasis.
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Affiliation(s)
| | - Mark Cope
- International Flavors & Fragrances Inc., St Louis, MO, USA
| | | | - Sumithra Selvam
- Division of Epidemiology, Biostatistics and Population Health, St John's Research Institute, Bengaluru, India
| | - Nivya George
- Division of Epidemiology, Biostatistics and Population Health, St John's Research Institute, Bengaluru, India
- Currently-Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Rebecca Kuriyan
- Division of Nutrition, Department of Physiology, St John's Medical College, St John's Research Institute, Bengaluru, India
| | - Anura V. Kurpad
- Department of Physiology, St John's Medical College, Bengaluru, India
- Division of Nutrition, Department of Physiology, St John's Medical College, St John's Research Institute, Bengaluru, India
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19
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Fyfe-Johnson AL, Reid MM, Jiang L, Chang JJ, Huyser KR, Hiratsuka VY, Johnson-Jennings MD, Conway CM, Goins TR, Sinclair KA, Steiner JF, Brega AG, Manson SM, O'Connell J. Social Determinants of Health and Body Mass Index in American Indian/Alaska Native Children. Child Obes 2023; 19:341-352. [PMID: 36170116 PMCID: PMC10316527 DOI: 10.1089/chi.2022.0012] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Objective: To examine the associations between social determinants of health (SDOH) and prevalent overweight/obesity status and change in adiposity status among American Indian and Alaska Native (AI/AN) children. Methods: The study sample includes 23,950 AI/AN children 2-11 years of age, who used Indian Health Service (IHS) from 2010 to 2014. Multivariate generalized linear mixed models were used to examine the following: (1) cross-sectional associations between SDOH and prevalent overweight/obesity status and (2) longitudinal associations between SDOH and change in adiposity status over time. Results: Approximately 49% of children had prevalent overweight/obesity status; 18% had overweight status and 31% had obesity status. Prevalent severe obesity status was 20% in 6-11-year olds. In adjusted cross-sectional models, children living in counties with higher levels of poverty had 28% higher odds of prevalent overweight/obesity status. In adjusted longitudinal models, children 2-5 years old living in counties with more children eligible for free or reduced-priced lunch had 15% lower odds for transitioning from normal-weight status to overweight/obesity status. Conclusions: This work contributes to accumulating knowledge that economic instability, especially poverty, appears to play a large role in overweight/obesity status in AI/AN children. Research, clinical practice, and policy decisions should aim to address and eliminate economic instability in childhood.
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Affiliation(s)
| | - Margaret M. Reid
- Health Systems, Management, and Policy, Colorado School of Public Health, University of Colorado, Aurora, CO, USA
| | - Luohua Jiang
- Department of Epidemiology, University of California, Irvine, Irvine, CA, USA
| | - Jenny J. Chang
- School of Medicine, University of California, Irvine, Irvine, CA, USA
| | - Kimberly R. Huyser
- Department of Sociology, University of British Columbia, Vancouver, British Columbia, Canada
| | - Vanessa Y. Hiratsuka
- Center for Human Development, University of Alaska Anchorage, Anchorage, AK, USA
| | | | - Cheryl M. Conway
- Charles George Veterans Medical Center, Veterans Health Administration, Washington, DC, USA
| | - Turner R. Goins
- College of Health and Human Sciences, Western Carolina University, Cullowhee, NC, USA
| | | | - John F. Steiner
- Institute for Health Research, Kaiser Permanente Colorado, Aurora, CO, USA
| | - Angela G. Brega
- Centers for American Indian and Alaska Native Health, Colorado School of Public Health, University of Colorado, Aurora, CO, USA
| | - Spero M. Manson
- Centers for American Indian and Alaska Native Health, Colorado School of Public Health, University of Colorado, Aurora, CO, USA
| | - Joan O'Connell
- Centers for American Indian and Alaska Native Health, Colorado School of Public Health, University of Colorado, Aurora, CO, USA
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20
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Nainu F, Frediansyah A, Mamada SS, Permana AD, Salampe M, Chandran D, Emran TB, Simal-Gandara J. Natural products targeting inflammation-related metabolic disorders: A comprehensive review. Heliyon 2023; 9:e16919. [PMID: 37346355 PMCID: PMC10279840 DOI: 10.1016/j.heliyon.2023.e16919] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Revised: 05/31/2023] [Accepted: 06/01/2023] [Indexed: 06/23/2023] Open
Abstract
Currently, the incidence of metabolic disorders is increasing, setting a challenge to global health. With major advancement in the diagnostic tools and clinical procedures, much has been known in the etiology of metabolic disorders and their corresponding pathophysiologies. In addition, the use of in vitro and in vivo experimental models prior to clinical studies has promoted numerous biomedical breakthroughs, including in the discovery and development of drug candidates to treat metabolic disorders. Indeed, chemicals isolated from natural products have been extensively studied as prospective drug candidates to manage diabetes, obesity, heart-related diseases, and cancer, partly due to their antioxidant and anti-inflammatory properties. Continuous efforts have been made in parallel to improve their bioactivity and bioavailability using selected drug delivery approaches. Here, we provide insights on recent progress in the role of inflammatory-mediated responses on the initiation of metabolic disorders, with particular reference to diabetes mellitus, obesity, heart-related diseases, and cancer. In addition, we discussed the prospective role of natural products in the management of diabetes, obesity, heart-related diseases, and cancers and provide lists of potential biological targets for high throughput screening in drug discovery and development. Lastly, we discussed findings observed in the preclinical and clinical studies prior to identifying suitable approaches on the phytochemical drug delivery systems that are potential to be used in the treatment of metabolic disorders.
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Affiliation(s)
- Firzan Nainu
- Department of Pharmacy, Faculty of Pharmacy, Hasanuddin University, Tamalanrea, Makassar 90245, Indonesia
| | - Andri Frediansyah
- Research Center for Food Technology and Processing (PRTPP), National Research and Innovation Agency (BRIN), Yogyakarta 55861, Indonesia
| | - Sukamto S. Mamada
- Department of Pharmacy, Faculty of Pharmacy, Hasanuddin University, Tamalanrea, Makassar 90245, Indonesia
| | - Andi Dian Permana
- Department of Pharmaceutical Science and Technology, Faculty of Pharmacy, Hasanuddin University, Tamalanrea, Makassar 90245, Indonesia
| | | | - Deepak Chandran
- Department of Veterinary Sciences and Animal Husbandry, Amrita School of Agricultural Sciences, Amrita Vishwa Vidyapeetham University, Coimbatore 642109, India
| | - Talha Bin Emran
- Department of Pathology and Laboratory Medicine, Warren Alpert Medical School & Legorreta Cancer Center, Brown University, Providence, RI 02912, USA
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
- Department of Pharmacy, BGC Trust University Bangladesh, Chittagong 4381, Bangladesh
| | - Jesus Simal-Gandara
- Universidade de Vigo, Nutrition and Bromatology Group, Analytical Chemistry and Food Science Department, Faculty of Science, E32004 Ourense, Spain
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21
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Iqbal N, Ambery P, Logue J, Mallappa A, David Sjöström C. Perspectives In Weight Control In Diabetes - Sglt2 Inhibitors And Glp-1-Glucagon Dual Agonism. Diabetes Res Clin Pract 2023; 199:110669. [PMID: 37075928 DOI: 10.1016/j.diabres.2023.110669] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Accepted: 04/09/2023] [Indexed: 04/21/2023]
Abstract
Treatment of people with type 2 diabetes mellitus (T2D) and obesity should include glycemic control and sustained weight loss. However, organ protection and/or risk reduction for co-morbidities have also emerged as important goals. Here, we define this combined treatment approach as 'weight loss plus' and describe it as a metabolic concept where increased energy expenditure is central to outcomes. We suggest there are currently two drug classes - sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 (GLP-1)-glucagon dual agonists - that can facilitate this 'weight loss plus' approach. We describe evidence supporting that both classes address the underlying pathophysiology of T2D and facilitate normalization of metabolism through increased periods of energy expenditure, which effect other organ systems and may facilitate long-term cardio-renal benefits. These benefits have been demonstrated in trials of SGLT2is, and appear, to some degree, to be independent of glycemia and substantial weight loss. The combined effect of caloric restriction and metabolic correction facilitated by SGLT2i and GLP-1-glucagon dual agonists can be conceptualized as mimicking dietary restriction and physical activity, a phenomenon not previously observed with drugs whose benefits predominantly arise from absolute weight loss, and which may be key to achieving a 'weight loss plus' approach to treatment.
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Affiliation(s)
- Nayyar Iqbal
- Late-Stage Development, Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA
| | - Philip Ambery
- Late-Stage Development, Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
| | - Jennifer Logue
- Early-stage Development, Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK
| | - Ashwini Mallappa
- Late-Stage Development, Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA
| | - C David Sjöström
- Late-Stage Development, Cardiovascular, Renal, and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
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22
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Shan S, Li S, Lu K, Cao J, Sun W, Zhou J, Ren Z, Zhu S, Hou L, Chen D, Song P. Associations of the Triglyceride and Glucose Index With Hypertension Stages, Phenotypes, and Their Progressions Among Middle-Aged and Older Chinese. Int J Public Health 2023; 68:1605648. [PMID: 37020526 PMCID: PMC10067654 DOI: 10.3389/ijph.2023.1605648] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Accepted: 03/06/2023] [Indexed: 04/07/2023] Open
Abstract
Objectives: To assess the associations of the triglyceride and glucose (TyG) index with hypertension stages, phenotypes, and their progressions. Methods: The data originated from the China Health and Retirement Longitudinal Study. Multinomial logistic regression investigated the associations of the TyG index with hypertension stages (stage 1, stage 2), phenotypes (isolated systolic hypertension [ISH], isolated diastolic hypertension [IDH], systolic diastolic hypertension [SDH]), their progressions. Results: Compared with the lowest quartile of TyG index, the highest quartile was associated with increased risks of stage 1 hypertension (OR 1.71, 95% CI 1.38-2.13), stage 2 (1.74, 1.27-2.38), ISH (1.66, 1.31-2.11), IDH (2.52, 1.26-5.05), and SDH (1.65, 1.23-2.23). Similar results were found when TyG index was a continuous variable. From 2011 to 2015, a higher baseline TyG index was associated with normotension to stage 1 (per-unit: 1.39, 1.16-1.65), normotension to ISH (per-unit: 1.28, 1.04-1.56), and normotension to IDH (per-unit: 1.94, 1.27-2.97). Conclusion: The TyG index was associated with different hypertension stages, phenotypes, their progressions, and could be served as a surrogate indicator for early hypertension management.
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Affiliation(s)
- Shiyi Shan
- School of Public Health and Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Shuting Li
- School of Public Health and Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Keyao Lu
- School of Public Health and Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jin Cao
- School of Public Health and Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Weidi Sun
- School of Public Health and Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jiali Zhou
- School of Public Health and Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Ziyang Ren
- School of Public Health and Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Key Laboratory of Reproductive Health, National Health Commission of the People’s Republic of China, Institute of Reproductive and Child Health, Peking University, Beijing, China
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Siyu Zhu
- School of Public Health and Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Leying Hou
- School of Public Health and Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Dingwan Chen
- School of Public Health, Hangzhou Medical College, Hangzhou, China
| | - Peige Song
- School of Public Health and Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
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23
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Sevim BC, Chela H, Ertugrul H, Malik LS, Malik S, Basar O, Daglilar E, Samiullah S, Gaballah AH, Tahan V. Non-Alcoholic Fatty Pancreas Disease: The Unsung Disease. Endocr Metab Immune Disord Drug Targets 2023; 23:485-493. [PMID: 36177623 DOI: 10.2174/1871530322666220929142905] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 06/04/2022] [Accepted: 08/01/2022] [Indexed: 01/10/2023]
Abstract
Non-alcoholic fatty pancreas disease (NAFPD) is a relatively new and emerging disease that is increasingly diagnosed yearly, like non-alcoholic fatty liver disease (NAFLD). It is associated especially with metabolic syndrome and obesity. As awareness of pancreatic steatosis and its clinical implications increase, it is diagnosed more frequently. The researchers have explained the clinical importance of NAFPD and the diseases it causes, such as pancreatitis, pancreatic insufficiency, and pancreatic cancer. Although the definitive treatment is not yet established, the primary treatment approach is weight loss since NAFPD is associated with metabolic syndrome as well as obesity. Although pharmacological agents, such as oral hypoglycemic agents, have been investigated in animal experiments, studies on humans have not been conducted. Since the research on NAFPD is still insufficient, it is a subject that needs to be investigated, and further studies are needed to explore its pathophysiology, clinical impact, and its management.
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Affiliation(s)
- Burak C Sevim
- Department of Radiology, University of Missouri, Columbia, Missouri, USA
| | - Harleen Chela
- Department of Internal Medicine, Division of Gastroenterology, West Virginia University- Charleston Campus, Charleston, West Virginia, USA
| | - Hamza Ertugrul
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Missouri, Columbia, Missouri, USA
| | - Lyiba S Malik
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Missouri, Columbia, Missouri, USA
- Milwaukee College of Letters & Science, Milwaukee, University of Wisconsin, Wisconsin, USA
| | - Suha Malik
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Missouri, Columbia, Missouri, USA
- Milwaukee College of Letters & Science, Milwaukee, University of Wisconsin, Wisconsin, USA
| | - Omer Basar
- Department of Internal Medicine, Division of Gastroenterology, Summa Health System and Northeast Ohio Medical University, Akron, Ohio, USA
| | - Ebubekir Daglilar
- Department of Internal Medicine, Division of Gastroenterology, West Virginia University- Charleston Campus, Charleston, West Virginia, USA
| | - Sami Samiullah
- Department of Internal Medicine, Division of Gastroenterology, Summa Health System and Northeast Ohio Medical University, Akron, Ohio, USA
| | - Ayman H Gaballah
- Department of Radiology, University of Missouri, Columbia, Missouri, USA
| | - Veysel Tahan
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Missouri, Columbia, Missouri, USA
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24
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Lautenbach A, Wernecke M, Mann O, Wagner J, Wolter S, Stoll F, Aberle J. Low-Grade Hepatic Steatosis Is Associated with Long-term Remission of Type 2 Diabetes Independent of Type of Bariatric-Metabolic Surgery. Obes Surg 2023; 33:530-538. [PMID: 36508157 PMCID: PMC9889466 DOI: 10.1007/s11695-022-06406-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2022] [Revised: 11/28/2022] [Accepted: 11/30/2022] [Indexed: 12/15/2022]
Abstract
BACKGROUND Bariatric-metabolic surgery (BS) decreases the grade of steatosis, hepatic inflammation, and fibrosis in patients with severe obesity and non-alcoholic fatty liver disease (NAFLD). Mechanisms include substantial weight loss, but also simultaneous effects on glucose homeostasis. Therefore, we aimed to investigate the association between NAFLD and remission of type 2 diabetes (T2D) up to 8 years following different types of BS. METHODS In a retrospective cohort study including 107 patients with obesity and T2D at baseline, the association between biopsy-proven NAFLD defined as steatosis in > 5% of hepatocytes at the time of surgery and T2D remission up to 8 years following different surgical procedures was investigated. Univariate regression analysis was used to examine the association between NAFLD and remission of T2D. RESULTS Long-term remission of T2D was present in 56% of patients (n = 60). The presence of low-grade liver steatosis (grade 1) was associated with remission of T2D. Patients with a liver steatosis score ≥ 2 showed higher HbA1c levels at baseline. There were no significant differences in preoperative presence of lobular inflammation, hepatocyte ballooning, or fibrosis between patients who achieved T2D remission compared with those with no remission. Type of surgery did not affect remission of T2D. CONCLUSION Our results suggest that the presence of low-grade liver steatosis is associated with remission of T2D following sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). Therefore, BS should be considered at an early NAFLD stage in patients with T2D.
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Affiliation(s)
- Anne Lautenbach
- III Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany.
| | - Marie Wernecke
- III Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany
| | - Oliver Mann
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany
| | - Jonas Wagner
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany
| | - Stefan Wolter
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany
| | - Fabian Stoll
- III Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany
| | - Jens Aberle
- III Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany
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25
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Clement L, Gencer B, Muller O, Klingenberg R, Räber L, Matter CM, Lüscher TF, Windecker S, Mach F, Rodondi N, Nanchen D, Clair C. Smoking Cessation in People With and Without Diabetes After Acute Coronary Syndrome. NICOTINE & TOBACCO RESEARCH : OFFICIAL JOURNAL OF THE SOCIETY FOR RESEARCH ON NICOTINE AND TOBACCO 2023; 25:58-65. [PMID: 35788681 DOI: 10.1093/ntr/ntac161] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 05/24/2022] [Accepted: 06/30/2022] [Indexed: 01/03/2023]
Abstract
INTRODUCTION People with diabetes smoke at similar rates as those without diabetes, with cardiovascular consequences. Smoking cessation rates were compared between people with and without diabetes 1 year after an acute coronary syndrome (ACS). AIMS AND METHODS People with ACS who smoked and were part of an observational prospective multicenter study in Switzerland were included from 2007 to 2017 and followed for 12 months. Seven-day point prevalence abstinence was assessed at 12 months follow-up. Association between diabetes and smoking cessation was assessed using multivariable-adjusted logistical regression model. RESULTS 2457 people with ACS who smoked were included, the mean age of 57 years old, 81.9% were men and 13.3% had diabetes. At 1 year, smoking cessation was 35.1% for people with diabetes and 42.6% for people without diabetes (P-value .01). After adjustment for age, sex, and educational level, people with diabetes who smoked were less likely to quit smoking compared with people without diabetes who smoked (odds ratio [OR] 0.76, 95% confidence interval [CI] 0.59-0.98, P-value = .037). The multivariable-adjusted model, with further adjustments for personal history of previous cardiovascular disease and cardiac rehabilitation attendance, attenuated this association (OR 0.85, 95% CI 0.65-1.12, P-value = .255). Among people with diabetes, cardiac rehabilitation attendance was a positive predictor of smoking cessation, and personal history of cardiovascular disease was a negative predictor of smoking cessation. CONCLUSIONS People with diabetes who smoke are less likely to quit smoking after an ACS and need tailored secondary prevention programs. In this population, cardiac rehabilitation is associated with increased smoking cessation. IMPLICATIONS This study provides new information on smoking cessation following ACSs comparing people with and without diabetes. After an ACS, people with diabetes who smoked were less likely to quit smoking than people without diabetes. Our findings highlight the importance of tailoring secondary prevention to people with diabetes.
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Affiliation(s)
- Ludivine Clement
- Service of Internal Medicine, Department of medicine, Fribourg Hospital, Fribourg, Switzerland
| | - Baris Gencer
- Division of Cardiology, Department of medicine, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland.,Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland
| | - Olivier Muller
- Service of Cardiology, Department Hearth and Vessels, Lausanne University Hospital, Lausanne, Switzerland
| | - Roland Klingenberg
- Department of Cardiology, University Heart Center, University Hospital Zurich, Zurich, Switzerland
| | - Lorenz Räber
- Department of Cardiology, University Hospital Bern, Bern, Switzerland
| | - Christian M Matter
- Department of Cardiology, University Heart Center, University Hospital Zurich, Zurich, Switzerland
| | - Thomas F Lüscher
- Royal Brompton and Harefield Hospital Trust and Imperial College, London, UK
| | - Stephan Windecker
- Department of Cardiology, University Hospital Bern, Bern, Switzerland
| | - François Mach
- Division of Cardiology, Department of medicine, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland
| | - Nicolas Rodondi
- Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland.,Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - David Nanchen
- Center for Primary Care and Public Health (Unisanté), Department of Training Research and Innovation, University of Lausanne, Lausanne, Switzerland
| | - Carole Clair
- Center for Primary Care and Public Health (Unisanté), Department of Training Research and Innovation, University of Lausanne, Lausanne, Switzerland
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26
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Antidiabetic Properties of Chitosan and Its Derivatives. Mar Drugs 2022; 20:md20120784. [PMID: 36547931 PMCID: PMC9782916 DOI: 10.3390/md20120784] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Revised: 12/11/2022] [Accepted: 12/15/2022] [Indexed: 12/23/2022] Open
Abstract
Diabetes mellitus is a chronic metabolic disorder. In addition to taking medication, adjusting the composition of the diet is also considered one of the effective methods to control the levels of blood glucose. Chitosan and its derivatives are natural and versatile biomaterials with health benefits. Chitosan has the potential to alleviate diabetic hyperglycemia by reducing hepatic gluconeogenesis and increasing skeletal muscle glucose uptake and utility. Scientists also focus on the glucose-lowering effect of chitosan oligosaccharide (COS). COS supplementation has the potential to alleviate abnormal glucose metabolism in diabetic rats by inhibiting gluconeogenesis and lipid peroxidation in the liver. Both high and low molecular weight chitosan feeding reduced insulin resistance by inhibiting lipid accumulation in the liver and adipose tissue and ameliorating chronic inflammation in diabetic rats. COS can reduce insulin resistance but has less ability to reduce hepatic lipids in diabetic rats. A clinical trial showed that a 3-month administration of chitosan increased insulin sensitivity and decreased body weight and triglycerides in obese patients. Chitosan and COS are considered Generally Recognized as Safe; however, they are still considered to be of safety concerns. This review highlights recent advances of chitosan and its derivatives in the glucose-lowering/antidiabetic effects and the safety.
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27
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Song Q, diFlorio‐Alexander RM, Patel SD, Sieberg RT, Margron MJ, Ansari SM, Karagas MR, Mackenzie TA, Hassanpour S. Association between fat-infiltrated axillary lymph nodes on screening mammography and cardiometabolic disease. Obes Sci Pract 2022; 8:757-766. [PMID: 36483128 PMCID: PMC9722459 DOI: 10.1002/osp4.608] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 04/08/2022] [Accepted: 04/19/2022] [Indexed: 12/11/2022] Open
Abstract
Objective Ectopic fat deposition within and around organs is a stronger predictor of cardiometabolic disease status than body mass index (BMI). Fat deposition within the lymphatic system is poorly understood. This study examined the association between the prevalence of cardiometabolic disease and ectopic fat deposition within axillary lymph nodes (LNs) visualized on screening mammograms. Methods A cross-sectional study was conducted on 834 women presenting for full-field digital screening mammography. The status of fat-infiltrated LNs was assessed based on the size and morphology of axillary LNs from screening mammograms. The prevalence of cardiometabolic disease was retrieved from the electronic medical records, including type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia, high blood glucose, cardiovascular disease, stroke, and non-alcoholic fatty liver disease. Results Fat-infiltrated axillary LNs were associated with a high prevalence of T2DM among all women (adjusted odds ratio: 3.92, 95% CI: [2.40, 6.60], p-value < 0.001) and in subgroups of women with and without obesity. Utilizing the status of fatty LNs improved the classification of T2DM status in addition to age and BMI (1.4% improvement in the area under the receiver operating characteristic curve). Conclusion Fat-infiltrated axillary LNs visualized on screening mammograms were associated with the prevalence of T2DM. If further validated, fat-infiltrated axillary LNs may represent a novel imaging biomarker of T2DM in women undergoing screening mammography.
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Affiliation(s)
- Qingyuan Song
- Department of Biomedical Data ScienceDartmouth CollegeLebanonNew HampshireUSA
| | | | - Sohum D. Patel
- Department of RadiologyDartmouth‐Hitchcock Medical CenterLebanonNew HampshireUSA
| | - Ryan T. Sieberg
- Department of RadiologyDartmouth‐Hitchcock Medical CenterLebanonNew HampshireUSA
| | - Michael J. Margron
- Department of RadiologyDartmouth‐Hitchcock Medical CenterLebanonNew HampshireUSA
| | - Saif M. Ansari
- Department of RadiologyDartmouth‐Hitchcock Medical CenterLebanonNew HampshireUSA
| | | | - Todd A. Mackenzie
- Department of Biomedical Data ScienceDartmouth CollegeLebanonNew HampshireUSA
| | - Saeed Hassanpour
- Department of Biomedical Data ScienceDartmouth CollegeLebanonNew HampshireUSA
- Department of EpidemiologyDartmouth CollegeLebanonNew HampshireUSA
- Department of Computer ScienceDartmouth CollegeHanoverNew HampshireUSA
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28
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Jahromi MK, Ebadinejad A, Barzin M, Mahdavi M, Niroomand M, Khalili D, Valizadeh M, Azizi F, Hosseinpanah F. Association of cumulative excess weight and waist circumference exposure with transition from metabolically healthy obesity to metabolically unhealthy. Nutr Metab Cardiovasc Dis 2022; 32:2544-2552. [PMID: 36163212 DOI: 10.1016/j.numecd.2022.07.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Revised: 07/02/2022] [Accepted: 07/21/2022] [Indexed: 10/31/2022]
Abstract
BACKGROUND AND AIMS The association between obesity severity and duration with the transition from metabolically healthy obese/overweight (MHO) phenotype to metabolically unhealthy obese (MUO) phenotype is not well understood. METHODS AND RESULTS This study includes the Tehran Lipid and Glucose Study participants who were initially classed as MHO. Cumulative excess weight (CEW) and cumulative excess waist circumference (CEWC) scores, which represent the accumulation of body mass index and waist circumference deviations from expected values over time (kg/m2 ∗ y and cm ∗ y, respectively), were calculated until the transition from MHO to MUO or the end of follow-up. The sex-stratified association of CEW and CWEC with the transition from MHO to MUO was investigated by time-dependent Cox models, adjusting for confounders. Out of 2525 participants, 1732 (68.5%) were women. During 15 years of follow-up, 1886 (74.6%) participants transitioned from MHO to MUO. A significant association was found between CEW and CEWC quartiles with the development of MUO among women participants (fully adjusted hazard ratios in the fourth quartile of CEW and CEWC [95% (CI)]:1.65 [1.37-1.98] and [95% CI]: 1.83 [1.53-2.19]). There was no significant association between CEW and CEWC with the MHO transition to MUO among men participants. CONCLUSION Over 15 years of follow-up in TLGS, general and central obesity accumulation was associated with the increased transition from MHO to MUO among women participants. More research with a larger sample size is needed to confirm and explain why the results are different for men and women.
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Affiliation(s)
- Mitra Kazemi Jahromi
- Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Ebadinejad
- Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Barzin
- Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Mahdavi
- Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahtab Niroomand
- Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Davood Khalili
- Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Majid Valizadeh
- Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fereidoun Azizi
- Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Farhad Hosseinpanah
- Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Abstract
The traditional complications of diabetes mellitus are well known and continue to pose a considerable burden on millions of people living with diabetes mellitus. However, advances in the management of diabetes mellitus and, consequently, longer life expectancies, have resulted in the emergence of evidence of the existence of a different set of lesser-acknowledged diabetes mellitus complications. With declining mortality from vascular disease, which once accounted for more than 50% of deaths amongst people with diabetes mellitus, cancer and dementia now comprise the leading causes of death in people with diabetes mellitus in some countries or regions. Additionally, studies have demonstrated notable links between diabetes mellitus and a broad range of comorbidities, including cognitive decline, functional disability, affective disorders, obstructive sleep apnoea and liver disease, and have refined our understanding of the association between diabetes mellitus and infection. However, no published review currently synthesizes this evidence to provide an in-depth discussion of the burden and risks of these emerging complications. This Review summarizes information from systematic reviews and major cohort studies regarding emerging complications of type 1 and type 2 diabetes mellitus to identify and quantify associations, highlight gaps and discrepancies in the evidence, and consider implications for the future management of diabetes mellitus.
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Affiliation(s)
- Dunya Tomic
- Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
| | - Jonathan E Shaw
- Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
| | - Dianna J Magliano
- Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
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Improvement of Glycemic Control by a Functional Food Mixture Containing Maltodextrin, White Kidney Bean Extract, Mulberry Leaf Extract, and Niacin-Bound Chromium Complex in Obese Diabetic db/db Mice. Metabolites 2022; 12:metabo12080693. [PMID: 35893259 PMCID: PMC9394435 DOI: 10.3390/metabo12080693] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Revised: 07/21/2022] [Accepted: 07/25/2022] [Indexed: 02/05/2023] Open
Abstract
Steady-fiber granule (SFG) is a mixture containing maltodextrin, white kidney bean extract, mulberry leaf extract, and niacin-bound chromium complex. These active ingredients have been shown to be associated with improving either hyperglycemia or hyperlipidemia. This study was undertaken to evaluate the potential of SFG in the regulation of blood glucose homeostasis under obese diabetic conditions. Accordingly, db/db mice (8 weeks old) were administered with SFG at doses of 1.025, 2.05, or 5.125 g/kg BW daily via oral gavage for 4 weeks. No body weight loss was observed after SFG supplementation at all three doses during the experimental period. Supplementation of SFG at 2.05 g/kg BW decreased fasting blood glucose, blood fructosamine, and HbA1c levels in db/db mice. Insulin sensitivity was also improved, as indicated by HOMA-IR assessment and oral glucose tolerance test, although the fasting insulin levels were no different in db/db mice with or without SFG supplementation. Meanwhile, the plasma levels of triglyceride were reduced by SFG at all three doses. These findings suggest that SFG improves glycemic control and insulin sensitivity in db/db mice and can be available as an option for functional foods to aid in management of type 2 diabetes mellitus in daily life.
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31
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Abstract
There are many nonmodifiable and modifiable risk factors for type 2 diabetes. Nonmodifiable risk factors include age, genetics, epigenetics, and social determinants of health (including education level, socioeconomic status, and noise and arsenic exposure). Modifiable risk factors include obesity, the microbiome, diet, cigarette smoking, sleep duration, sleep quality, and sedentary behavior. Major lifestyle interventions to prevent and treat diabetes relate to these risk factors. Weight loss is the lifestyle intervention with the largest benefit for both preventing and treating diabetes. Exercise, even without weight loss, significantly reduces the incidence of type 2 diabetes.
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32
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Fridén M, Kullberg J, Ahlström H, Lind L, Rosqvist F. Intake of Ultra-Processed Food and Ectopic-, Visceral- and Other Fat Depots: A Cross-Sectional Study. Front Nutr 2022; 9:774718. [PMID: 35445063 PMCID: PMC9013765 DOI: 10.3389/fnut.2022.774718] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2021] [Accepted: 03/16/2022] [Indexed: 11/17/2022] Open
Abstract
Introduction The purpose of this study was to investigate associations between intake of ultra-processed food (UPF) and liver fat, pancreas fat and visceral adipose tissue (VAT) but also subcutaneous adipose tissue (SAT), VAT/SAT ratio and total fat mass. Materials and Methods Cross-sectional analysis of n = 286 50-year old men and women. Energy percentage (%E) from UPF was calculated from a semi-quantitative food frequency questionnaire. Food items were categorized according to the NOVA-classification system and fat depots were assessed using magnetic resonance imaging (MRI) and bioelectrical impedance analysis (BIA). Associations were analyzed using linear regression, adjusted for sex, education, physical activity, smoking, dietary factors and BMI. Results Mean intake of UPF was 37.8 ± 10.2 %E and the three largest contributors to this were crisp- and wholegrain breads and spreads, indicating overall healthy food choices. Consumption of UPF was associated with higher intake of energy, carbohydrates and fiber and lower intake of protein and polyunsaturated fat but no differences were observed for total fat, saturated fat (SFA), monounsaturated fat, sugar or alcohol between tertiles of UPF. Intake of UPF was positively associated with liver- and pancreas fat, VAT, VAT/SAT and inversely associated with total fat mass in crude models. The association for VAT remained after full adjustment (β = 0.01 (95% CI: 0.002, 0.02), P = 0.02) and was driven by women. Conclusion Energy intake from UPF is not associated with ectopic fat, SAT or total fat after adjustment for multiple confounders in this population having overall healthy food habits. However, a positive association between UPF and VAT was observed which was driven by women.
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Affiliation(s)
- Michael Fridén
- Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden
| | - Joel Kullberg
- Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden
- Antaros Medical AB, BioVenture Hub, Mölndal, Sweden
| | - Håkan Ahlström
- Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden
- Antaros Medical AB, BioVenture Hub, Mölndal, Sweden
| | - Lars Lind
- Department of Medical Sciences, Clinical Epidemiology, Uppsala University, Uppsala, Sweden
| | - Fredrik Rosqvist
- Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden
- *Correspondence: Fredrik Rosqvist
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Gao M, Wang Q, Piernas C, Astbury NM, Jebb SA, Holmes MV, Aveyard P. Associations between body composition, fat distribution and metabolic consequences of excess adiposity with severe COVID-19 outcomes: observational study and Mendelian randomisation analysis. Int J Obes (Lond) 2022; 46:943-950. [PMID: 35031696 PMCID: PMC8758930 DOI: 10.1038/s41366-021-01054-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 11/26/2021] [Accepted: 12/16/2021] [Indexed: 12/21/2022]
Abstract
Background Higher body mass index (BMI) and metabolic consequences of excess weight are associated with increased risk of severe COVID-19, though their mediating pathway is unclear. Methods A prospective cohort study included 435,504 UK Biobank participants. A two-sample Mendelian randomisation (MR) study used the COVID-19 Host Genetics Initiative in 1.6 million participants. We examined associations of total adiposity, body composition, fat distribution and metabolic consequences of excess weight, particularly type 2 diabetes, with incidence and severity of COVID-19, assessed by test positivity, hospital admission, intensive care unit (ICU) admission and death. Results BMI and body fat were associated with COVID-19 in the observational and MR analyses but muscle mass was not. The observational study suggested the association with central fat distribution was stronger than for BMI, but there was little evidence from the MR analyses than this was causal. There was evidence that strong associations of metabolic consequences with COVID-19 outcomes in observational but not MR analyses. Type 2 diabetes was strongly associated with COVID-19 in observational but not MR analyses. In adjusted models, the observational analysis showed that the association of BMI with COVID-19 diminished, while central fat distribution and metabolic consequences of excess weight remained strongly associated. In contrast, MR showed the reverse, with only BMI retaining a direct effect on COVID-19. Conclusions Excess total adiposity is probably casually associated with severe COVID-19. Mendelian randomisation data do not support causality for the observed associations of central fat distribution or metabolic consequences of excess adiposity with COVID-19.
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Affiliation(s)
- Min Gao
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Observatory Quarter, Oxford, UK. .,NIHR Oxford Biomedical Research Centre, Oxford University Hospitals, NHS Foundation Trust, Oxford, UK.
| | - Qin Wang
- Nuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford, UK
| | - Carmen Piernas
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Observatory Quarter, Oxford, UK
| | - Nerys M Astbury
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Observatory Quarter, Oxford, UK.,NIHR Oxford Biomedical Research Centre, Oxford University Hospitals, NHS Foundation Trust, Oxford, UK
| | - Susan A Jebb
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Observatory Quarter, Oxford, UK.,NIHR Oxford Biomedical Research Centre, Oxford University Hospitals, NHS Foundation Trust, Oxford, UK
| | - Michael V Holmes
- NIHR Oxford Biomedical Research Centre, Oxford University Hospitals, NHS Foundation Trust, Oxford, UK.,Nuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford, UK.,Medical Research Council Population Health Research Unit, University of Oxford, Oxford, UK
| | - Paul Aveyard
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Observatory Quarter, Oxford, UK. .,NIHR Oxford Biomedical Research Centre, Oxford University Hospitals, NHS Foundation Trust, Oxford, UK.
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Martínez-Montoro JI, Damas-Fuentes M, Fernández-García JC, Tinahones FJ. Role of the Gut Microbiome in Beta Cell and Adipose Tissue Crosstalk: A Review. Front Endocrinol (Lausanne) 2022; 13:869951. [PMID: 35634505 PMCID: PMC9133559 DOI: 10.3389/fendo.2022.869951] [Citation(s) in RCA: 3] [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] [Received: 02/05/2022] [Accepted: 03/08/2022] [Indexed: 12/12/2022] Open
Abstract
In the last decades, obesity has reached epidemic proportions worldwide. Obesity is a chronic disease associated with a wide range of comorbidities, including insulin resistance and type 2 diabetes mellitus (T2D), which results in significant burden of disease and major consequences on health care systems. Of note, intricate interactions, including different signaling pathways, are necessary for the establishment and progression of these two closely related conditions. Altered cell-to-cell communication among the different players implicated in this equation leads to the perpetuation of a vicious circle associated with an increased risk for the development of obesity-related complications, such as T2D, which in turn contributes to the development of cardiovascular disease. In this regard, the dialogue between the adipocyte and pancreatic beta cells has been extensively studied, although some connections are yet to be fully elucidated. In this review, we explore the potential pathological mechanisms linking adipocyte dysfunction and pancreatic beta cell impairment/insulin resistance. In addition, we evaluate the role of emerging actors, such as the gut microbiome, in this complex crosstalk.
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Affiliation(s)
- José Ignacio Martínez-Montoro
- Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Instituto de Investigación Biomédica de Málaga (IBIMA), Faculty of Medicine, University of Málaga, Málaga, Spain
- *Correspondence: José Ignacio Martínez-Montoro, ; Francisco J. Tinahones,
| | - Miguel Damas-Fuentes
- Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Instituto de Investigación Biomédica de Málaga (IBIMA), Faculty of Medicine, University of Málaga, Málaga, Spain
- Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain
| | - José Carlos Fernández-García
- Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain
- Department of Endocrinology and Nutrition, Regional University Hospital of Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Faculty of Medicine, University of Málaga, Málaga, Spain
| | - Francisco J. Tinahones
- Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Instituto de Investigación Biomédica de Málaga (IBIMA), Faculty of Medicine, University of Málaga, Málaga, Spain
- Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain
- *Correspondence: José Ignacio Martínez-Montoro, ; Francisco J. Tinahones,
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Bhori M, Rastogi V, Tungare K, Marar T. A review on interplay between obesity, lipoprotein profile and nutrigenetics with selected candidate marker genes of type 2 diabetes mellitus. Mol Biol Rep 2021; 49:687-703. [PMID: 34669123 DOI: 10.1007/s11033-021-06837-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Accepted: 10/12/2021] [Indexed: 12/06/2022]
Abstract
BACKGROUND Type 2 diabetes mellitus, a rapidly growing epidemic, and its frequently related complications demand global attention. The two factors commonly attributed to the epidemic are genetic factors and environmental factors. Studies indicate that the genetic makeup at an individual level and the environmental aspects influence the occurrence of the disease. However, there is insufficiency in understanding the mechanisms through which the gene mutations and environmental components individually lead to T2DM. Also, discrepancies have often been noted in the association of gene variants and type 2 diabetes when the gene factor is examined as a sole attribute to the disease. STUDY In this review initially, we have focused on the proposed ways through which CAPN10, FABP2, GLUT2, TCF7L2, and ENPP1 variants lead to T2DM along with the inconsistencies observed in the gene-disease association. The article also emphasizes on obesity, lipoprotein profile, and nutrition as environmental factors and how they lead to T2DM. Finally, the main objective is explored, the environment-gene-disease association i.e. the influence of each environmental factor on the aforementioned specific gene-T2DM relationship to understand if the disease-causing capability of the gene variants is exacerbated by environmental influences. CONCLUSION We found that environmental factors may influence the gene-disease relationship. Reciprocally, the genetic factors may alter the environment-disease relationship. To precisely conclude that the two factors act synergistically to lead to T2DM, more attention has to be paid to the combined influence of the genetic variants and environmental factors on T2DM occurrence instead of studying the influence of the factors separately.
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Affiliation(s)
- Mustansir Bhori
- School of Biotechnology and Bioinformatics, D. Y. Patil Deemed To Be University, Navi Mumbai, 400614, India
| | - Varuni Rastogi
- School of Biotechnology and Bioinformatics, D. Y. Patil Deemed To Be University, Navi Mumbai, 400614, India
| | - Kanchanlata Tungare
- School of Biotechnology and Bioinformatics, D. Y. Patil Deemed To Be University, Navi Mumbai, 400614, India.
| | - Thankamani Marar
- School of Biotechnology and Bioinformatics, D. Y. Patil Deemed To Be University, Navi Mumbai, 400614, India
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Lu YW, Chang CC, Chou RH, Tsai YL, Liu LK, Chen LK, Huang PH, Lin SJ. Gender difference in the association between TyG index and subclinical atherosclerosis: results from the I-Lan Longitudinal Aging Study. Cardiovasc Diabetol 2021; 20:206. [PMID: 34645432 PMCID: PMC8515653 DOI: 10.1186/s12933-021-01391-7] [Citation(s) in RCA: 60] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Accepted: 09/22/2021] [Indexed: 02/08/2023] Open
Abstract
Background Insulin resistance (IR) is a known risk factor for cardiovascular disease (CVD) in non-diabetic patients through the association of hyperglycemia or associated metabolic factors. The triglyceride glucose (TyG) index, which was defined by incorporating serum glucose and insulin concentrations, was developed as a surrogate marker of insulin resistance. We aimed to investigate the association between the TyG index and the early phase of subclinical atherosclerosis (SA) between the sexes. Methods The I-Lan Longitudinal Aging Study (ILAS) enrolled 1457 subjects aged 50–80 years. For each subject, demographic data and the TyG index {ln[fasting triglyceride (mg/dL) × fasting plasma glucose (mg/dL)]/2} were obtained. Patients were further stratified according to sex and the 50th percentile of the TyG index (≥ 8.55 or < 8.55). SA was defined as the mean carotid intima-media thickness (cIMT) at the 75th percentile of the entire cohort. Demographic characteristics and the presence of SA were compared between the groups. Logistic regression analysis was performed to assess the relationship between TyG index and SA. Results Patients with a higher TyG index (≥ 8.55) had a higher body mass index (BMI), hypertension (HTN) and diabetes mellitus (DM). They had higher lipid profiles, including total cholesterol (T-Chol) and low-density lipoprotein (LDL), compared to those with a lower TyG index (< 8.55). Gender disparity was observed in non-diabetic women who had a significantly higher prevalence of SA in the high TyG index group than in the low TyG index group. In multivariate logistic regression analysis, a high TyG index was independently associated with SA in non-diabetic women after adjusting for traditional risk factors [adjusted odds ratio (OR): 1.510, 95% CI 1.010–2.257, p = 0.045] but not in non-diabetic men. The TyG index was not associated with the presence of SA in diabetic patients, irrespective of sex. Conclusion A high TyG index was significantly associated with SA and gender disparity in non-diabetic patients. This result may highlight the need for a sex-specific risk management strategy to prevent atherosclerosis. Supplementary Information The online version contains supplementary material available at 10.1186/s12933-021-01391-7.
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Affiliation(s)
- Ya-Wen Lu
- Division of Interventional Cardiology, Cardiovascular Center, Taichung Veterans General Hospital, 1650 Taiwan Boulevard Sect. 4, Taichung, Taiwan.,Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Institute of Clinical Medicine, Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chun-Chin Chang
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. .,Institute of Clinical Medicine, Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.
| | - Ruey-Hsing Chou
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Institute of Clinical Medicine, Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Department of Critical Care Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yi-Lin Tsai
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Institute of Clinical Medicine, Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Li-Kuo Liu
- Center for Geriatrics and Gerontology, Taipei Veterans General Hospital, Taipei, Taiwan.,Aging and Health Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Liang-Kung Chen
- Center for Geriatrics and Gerontology, Taipei Veterans General Hospital, Taipei, Taiwan.,Aging and Health Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Institute of Public Health, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Taipei Municipal Gan-Dau Hospital, Taipei, Taiwan
| | - Po-Hsun Huang
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. .,Institute of Clinical Medicine, Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan. .,Department of Critical Care Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
| | - Shing-Jong Lin
- Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Institute of Clinical Medicine, Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Department of Critical Care Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Taipei Heart Institute, Taipei Medical University, Taipei, Taiwan.,Division of Cardiology, Heart Center, Cheng-Hsin General Hospital, Taipei, Taiwan
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Htun KT, Pan J, Pasanta D, Tungjai M, Udomtanakunchai C, Petcharoen T, Chamta N, Kosicharoen S, Chukua K, Lai C, Kothan S. Advanced Molecular Imaging (MRI/MRS/ 1H NMR) for Metabolic Information in Young Adults with Health Risk Obesity. Life (Basel) 2021; 11:1035. [PMID: 34685406 PMCID: PMC8541404 DOI: 10.3390/life11101035] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2021] [Revised: 08/31/2021] [Accepted: 09/03/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Obesity or being overweight is a medical condition of abnormal body fat accumulation which is associated with a higher risk of developing metabolic syndrome. The distinct body fat depots on specific parts of the anatomy have unique metabolic properties and different types of regional excessive fat distribution can be a disease hazard. The aim of this study was to identify the metabolome and molecular imaging phenotypes among a young adult population. METHODS The amount and distribution of fat and lipid metabolites profile in the abdomen, liver, and calf muscles of 46 normal weight, 17 overweight, and 13 obese participants were acquired using MRI and MR spectroscopy (MRS), respectively. The serum metabolic profile was obtained using proton NMR spectroscopy. NMR spectra were integrated into seven integration regions, which reflect relative metabolites. RESULTS A significant metabolic disorder symptom appeared in the overweight and obese group, and increased lipid deposition occurred in the abdomen, hepatocytes, and muscles that were statistically significant. Overall, the visceral fat depots had a marked influence on dyslipidemia biomarkers, blood triglyceride (r = 0.592, p < 0.001), and high-density lipoprotein cholesterol (r = -0.484, p < 0.001). Intrahepatocellular lipid was associated with diabetes predictors for hemoglobin (HbA1c%; r = 0.379, p < 0.001) and for fasting blood sugar (r = 0.333, p < 0.05). The lipid signals in serum triglyceride and glucose signals gave similar correspondence to biochemical lipid profiles. CONCLUSIONS This study proves the association between alteration in metabolome in young adults, which is the key population for early prevention of obesity and metabolic syndrome. This study suggests that dyslipidemia prevalence is influenced mainly by the visceral fat depot, and liver fat depot is a key determinant for glucose metabolism and hyperglycemia. Moreover, noninvasive advanced molecular imaging completely elucidated the impact of fat distribution on the anthropometric and laboratory parameters, especially indices of the metabolic syndrome biomarkers in young adults.
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Affiliation(s)
- Khin Thandar Htun
- Center of Radiation Research and Medical Imaging, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (K.T.H.); (D.P.); (M.T.); (C.U.); (T.P.); (N.C.); (S.K.); (K.C.)
| | - Jie Pan
- Center of Radiation Research and Medical Imaging, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (K.T.H.); (D.P.); (M.T.); (C.U.); (T.P.); (N.C.); (S.K.); (K.C.)
- Shandong Provincial Key Laboratory of Animal Resistant Biology, College of Life Sciences, Shandong Normal University, Jinan 250014, China
| | - Duanghathai Pasanta
- Center of Radiation Research and Medical Imaging, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (K.T.H.); (D.P.); (M.T.); (C.U.); (T.P.); (N.C.); (S.K.); (K.C.)
| | - Montree Tungjai
- Center of Radiation Research and Medical Imaging, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (K.T.H.); (D.P.); (M.T.); (C.U.); (T.P.); (N.C.); (S.K.); (K.C.)
| | - Chatchanok Udomtanakunchai
- Center of Radiation Research and Medical Imaging, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (K.T.H.); (D.P.); (M.T.); (C.U.); (T.P.); (N.C.); (S.K.); (K.C.)
| | - Thanaporn Petcharoen
- Center of Radiation Research and Medical Imaging, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (K.T.H.); (D.P.); (M.T.); (C.U.); (T.P.); (N.C.); (S.K.); (K.C.)
| | - Nattacha Chamta
- Center of Radiation Research and Medical Imaging, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (K.T.H.); (D.P.); (M.T.); (C.U.); (T.P.); (N.C.); (S.K.); (K.C.)
| | - Supak Kosicharoen
- Center of Radiation Research and Medical Imaging, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (K.T.H.); (D.P.); (M.T.); (C.U.); (T.P.); (N.C.); (S.K.); (K.C.)
| | - Kiattisak Chukua
- Center of Radiation Research and Medical Imaging, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (K.T.H.); (D.P.); (M.T.); (C.U.); (T.P.); (N.C.); (S.K.); (K.C.)
| | - Christopher Lai
- Health and Social Sciences, Singapore Institute of Technology, 10 Dover Drive, Singapore 138683, Singapore;
| | - Suchart Kothan
- Center of Radiation Research and Medical Imaging, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand; (K.T.H.); (D.P.); (M.T.); (C.U.); (T.P.); (N.C.); (S.K.); (K.C.)
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Hakim O, Bello O, Ladwa M, Shojaee-Moradie F, Jackson N, Peacock JL, Umpleby AM, Charles-Edwards G, Amiel SA, Goff LM. Adiponectin is associated with insulin sensitivity in white European men but not black African men. Diabet Med 2021; 38:e14571. [PMID: 33783876 DOI: 10.1111/dme.14571] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Revised: 03/15/2021] [Accepted: 03/27/2021] [Indexed: 02/06/2023]
Abstract
AIMS We aimed to assess ethnic differences in inflammatory markers and their relationships with insulin sensitivity and regional adiposity between white European and black African men. METHODS A total of 53 white European and 53 black African men underwent assessment of inflammatory markers alongside Dixon-magnetic resonance imaging to quantify subcutaneous and visceral adipose tissue and intrahepatic lipid. A hyperinsulinaemic-euglycaemic clamp was used to measure whole-body and adipose tissue insulin sensitivity. To assess ethnic differences in relationships, the statistical significance of an interaction term between adipokines and ethnic group was tested in multivariable regression models. RESULTS The black African men exhibited significantly lower adiponectin and tumour necrosis factor-α (TNF-α) and greater interleukin-10 (IL-10) compared to white European men (all p < 0.05). There were no statistically significant ethnic differences in leptin, resistin, IL-6, interferon-γ, IL-13, IL-1β, IL-8 and vascular endothelial growth factor. Several relationships differed significantly by ethnicity such that they were stronger in white European than black African men including IL-6 with visceral adipose tissue; adiponectin with subcutaneous adipose tissue; leptin with intrahepatic lipid; adiponectin, IL-6 and TNF-α with whole-body insulin sensitivity and TNF-α with adipose tissue insulin sensitivity (all pinteraction <0.05). Leptin significantly predicted whole-body insulin sensitivity in white European (R2 = 0.51) and black African (R2 = 0.29) men; however, adiponectin was a statistically significant predictor in only white European men (R2 = 0.22). CONCLUSIONS While adiponectin is lower in black African men, its insulin sensitising effects may be greater in white men suggesting that the role of adipokines in the development of type 2 diabetes may differ by ethnicity.
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Affiliation(s)
- Olah Hakim
- Department of Diabetes, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK
| | - Oluwatoyosi Bello
- Department of Diabetes, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK
| | - Meera Ladwa
- Department of Diabetes, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK
| | | | - Nicola Jackson
- Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
| | - Janet L Peacock
- Department of Epidemiology Geisel, School of Medicine at Dartmouth, Dartmouth, NH, USA
- School of Population Health and Environmental Sciences, King's College London, London, UK
| | - A Margot Umpleby
- Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
| | - Geoffrey Charles-Edwards
- Medical Physics, Guy's and St Thomas, NHS Foundation Trust, London, UK
- School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK
| | - Stephanie A Amiel
- Department of Diabetes, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK
| | - Louise M Goff
- Department of Diabetes, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK
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Wheatley SD, Deakin TA, Arjomandkhah NC, Hollinrake PB, Reeves TE. Low Carbohydrate Dietary Approaches for People With Type 2 Diabetes-A Narrative Review. Front Nutr 2021; 8:687658. [PMID: 34336909 PMCID: PMC8319397 DOI: 10.3389/fnut.2021.687658] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 06/14/2021] [Indexed: 01/02/2023] Open
Abstract
Although carbohydrate restriction is not a new approach for the management of Type 2 diabetes, interest in its safety and efficacy has increased significantly in recent years. The purpose of the current narrative review is to summarise the key relevant research and practical considerations in this area, as well as to explore some of the common concerns expressed in relation to the use of such approaches. There is a strong physiological rationale supporting the role of carbohydrate restriction for the management of Type 2 diabetes, and available evidence suggests that low carbohydrate dietary approaches (LCDs) are as effective as, or superior to, other dietary approaches for its management. Importantly, LCDs appear to be more effective than other dietary approaches for facilitating a reduction in the requirement for certain medications, which leads to their effects on other health markers being underestimated. LCDs have also been demonstrated to be an effective method for achieving remission of Type 2 diabetes for some people. The available evidence does not support concerns that LCDs increase the risk of cardiovascular disease, that such approaches increase the risk of nutrient deficiencies, or that they are more difficult to adhere to than other dietary approaches. A growing number of organisations support the use of LCDs as a suitable choice for individuals with Type 2 diabetes.
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Affiliation(s)
| | | | - Nicola C Arjomandkhah
- School of Social and Health Sciences, Leeds Trinity University, Leeds, United Kingdom
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Viurcos-Sanabria R, Escobedo G. Immunometabolic bases of type 2 diabetes in the severity of COVID-19. World J Diabetes 2021; 12:1026-1041. [PMID: 34326952 PMCID: PMC8311488 DOI: 10.4239/wjd.v12.i7.1026] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 04/16/2021] [Accepted: 06/16/2021] [Indexed: 02/06/2023] Open
Abstract
The outbreak of coronavirus disease 2019 (COVID-19) is caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). COVID-19 and type 2 diabetes (T2D) have now merged into an ongoing global syndemic that is threatening the lives of millions of people around the globe. For this reason, there is a deep need to understand the immunometabolic bases of the main etiological factors of T2D that affect the severity of COVID-19. Here, we discuss how hyperglycemia contributes to the cytokine storm commonly associated with COVID-19 by stimulating monocytes and macrophages to produce interleukin IL-1β, IL-6, and TNF-α in the airway epithelium. The main mechanisms through which hyperglycemia promotes reactive oxygen species release, inhibition of T cell activation, and neutrophil extracellular traps in the lungs of patients with severe SARS-CoV-2 infection are also studied. We further examine the molecular mechanisms by which proinflammatory cytokines induce insulin resistance, and their deleterious effects on pancreatic β-cell exhaustion in T2D patients critically ill with COVID-19. We address the effect of excess glucose on advanced glycation end product (AGE) formation and the role of AGEs in perpetuating pneumonia and acute respiratory distress syndrome. Finally, we discuss the contribution of preexisting endothelial dysfunction secondary to diabetes in the development of neutrophil trafficking, vascular leaking, and thrombotic events in patients with severe SARS-CoV-2 infection. As we outline here, T2D acts in synergy with SARS-CoV-2 infection to increase the progression, severity, and mortality of COVID-19. We think a better understanding of the T2D-related immunometabolic factors that contribute to exacerbate the severity of COVID-19 will improve our ability to identify patients with high mortality risk and prevent adverse outcomes.
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Affiliation(s)
| | - Galileo Escobedo
- Laboratorio de Proteómica, Dirección de Investigación, Hospital General de Mexico “Dr. Eduardo Liceaga”, Mexico City 06720, Mexico
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41
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Manyara AM. Optimal cut-offs of five anthropometric indices and their predictive ability of type 2 diabetes in a nationally representative Kenyan study. AIMS Public Health 2021; 8:507-518. [PMID: 34395701 PMCID: PMC8334637 DOI: 10.3934/publichealth.2021041] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 07/06/2021] [Indexed: 11/18/2022] Open
Abstract
Background Type 2 diabetes (T2D) is one of the top non-communicable diseases in Kenya and prevention strategies are urgently needed. Intervening to reduce obesity is the most common prevention strategy. However, black populations develop T2D at lower obesity levels and it is unclear which anthropometric cut-offs could provide the best predictive ability for T2D risk. This study, therefore, aimed to determine the optimal anthropometric cut-offs and their predictive ability of T2D in Kenya. Methods The study included 2159 participants (59% women) aged 35-70 years from the Kenya STEPwise survey conducted in 2014. Five anthropometric indices were used-body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR), waist to height ratio (WHtR) and waist divided by height0.5(WHt.5R). Diabetes was defined as a fasting blood glucose of ≥7.0 mmol/l or a previous diagnosis by a health worker. Optimal anthropometric cut-offs and their receiver operating characteristics, such as the area under the curve (AUC), were computed. Results Overall, the optimal cut-off for BMI, WC, WHR, WHtR and WHt.5R were 24.8 kg.m-2, 90 cm, 0.88, 0.54 and 6.9. On disaggregation by sex, the optimal cut-off for BMI, WC, WHR WHtR and WHt.5R was 27.1 kg.m-2, 87 cm, 0.85, 0.55 and 6.9 in women, and 24.8 kg.m-2, 91 cm, 0.88, 0.54 and 6.9 in men. Overall, WC (AUC 0.71 (95% confidence interval 0.65, 0.76)) WHtR (AUC 0.71 (0.66, 0.76)) and WHt.5R (AUC 0.70 (0.65,0.75)) had a better predictive ability for T2D than BMI (AUC 0.68 (0.62, 0.73)). Conclusions WC, WHtR and WHt.5R were better predictors of T2D than BMI and should be used for risk stratification in Kenya. A WC cut-off of 87cm in women and 91cm in men, a WHtR cut-off of 0.54 or a WHt.5R of 6.9 in both men and women should be used to identify individuals at an elevated risk of T2D.
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Affiliation(s)
- Anthony Muchai Manyara
- Social and Political Sciences, Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
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Brito MDF, Torre C, Silva-Lima B. Scientific Advances in Diabetes: The Impact of the Innovative Medicines Initiative. Front Med (Lausanne) 2021; 8:688438. [PMID: 34295913 PMCID: PMC8290522 DOI: 10.3389/fmed.2021.688438] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Accepted: 06/02/2021] [Indexed: 12/16/2022] Open
Abstract
Diabetes Mellitus is one of the World Health Organization's priority diseases under research by the first and second programmes of Innovative Medicines Initiative, with the acronyms IMI1 and IMI2, respectively. Up to October of 2019, 13 projects were funded by IMI for Diabetes & Metabolic disorders, namely SUMMIT, IMIDIA, DIRECT, StemBANCC, EMIF, EBiSC, INNODIA, RHAPSODY, BEAT-DKD, LITMUS, Hypo-RESOLVE, IM2PACT, and CARDIATEAM. In general, a total of €447 249 438 was spent by IMI in the area of Diabetes. In order to prompt a better integration of achievements between the different projects, we perform a literature review and used three data sources, namely the official project's websites, the contact with the project's coordinators and co-coordinator, and the CORDIS database. From the 662 citations identified, 185 were included. The data collected were integrated into the objectives proposed for the four IMI2 program research axes: (1) target and biomarker identification, (2) innovative clinical trials paradigms, (3) innovative medicines, and (4) patient-tailored adherence programmes. The IMI funded projects identified new biomarkers, medical and research tools, determinants of inter-individual variability, relevant pathways, clinical trial designs, clinical endpoints, therapeutic targets and concepts, pharmacologic agents, large-scale production strategies, and patient-centered predictive models for diabetes and its complications. Taking into account the scientific data produced, we provided a joint vision with strategies for integrating personalized medicine into healthcare practice. The major limitations of this article were the large gap of data in the libraries on the official project websites and even the Cordis database was not complete and up to date.
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Affiliation(s)
| | - Carla Torre
- Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal.,Laboratory of Systems Integration Pharmacology, Clinical & Regulatory Science-Research Institute for Medicines (iMED.ULisboa), Lisbon, Portugal
| | - Beatriz Silva-Lima
- Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal.,Laboratory of Systems Integration Pharmacology, Clinical & Regulatory Science-Research Institute for Medicines (iMED.ULisboa), Lisbon, Portugal
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Gujral UP, Kanaya AM. Epidemiology of diabetes among South Asians in the United States: lessons from the MASALA study. Ann N Y Acad Sci 2021; 1495:24-39. [PMID: 33216378 PMCID: PMC8134616 DOI: 10.1111/nyas.14530] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Revised: 10/19/2020] [Accepted: 10/21/2020] [Indexed: 02/06/2023]
Abstract
South Asian individuals in the United States are at an increased risk of type 2 diabetes (T2DM); however, the mechanisms behind this are not well understood. The Mediators of Atherosclerosis in South Asians Living in America (MASALA) study is the only longitudinal cohort of South Asians in the United States and provides key insights as to the epidemiology of T2DM in South Asians. Evidence from the MASALA study suggests that South Asians experience a disproportionately high burden of prevalent and incident T2DM compared with members of other race/ethnic groups. Higher insulin resistance in South Asians, even with low body mass index (BMI), more impairment in insulin secretion, and greater deposition of ectopic fat likely play a role in T2DM etiology. Furthermore, South Asian migrants to the United States experience a range of factors related to acculturation, social networks, and religious beliefs, which may impact physical activity and dietary practices. Interventions to prevent T2DM in South Asians should include a focus on cultural factors related to health and should consider the complete mechanistic pathway and the relative contributions of insulin resistance, β cell dysfunction, and ectopic fat deposition on T2DM development in South Asians, particularly in those with lower BMI.
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Affiliation(s)
- Unjali P. Gujral
- Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA
| | - Alka M. Kanaya
- Division of General Internal Medicine, University of California, San Francisco, San Francisco, CA
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44
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Gezginci-Oktayoglu S, Sancar S, Karatug-Kacar A, Bolkent S. miR-375 induces adipogenesis through targeting Erk1 in pancreatic duct cells under the influence of sodium palmitate. J Cell Physiol 2021; 236:3881-3895. [PMID: 33107061 DOI: 10.1002/jcp.30129] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 10/13/2020] [Accepted: 10/15/2020] [Indexed: 12/16/2022]
Abstract
The goal of this study was to research long-term saturated fatty acid overexposure that can induce differentiation of pancreatic duct cells into adipocytes and also into β-cells. The important findings can be summarized as follows: (i) adipogenesis and early stage β-cell differentiation were stimulated in duct cells under lipotoxicity and glucolipotoxicity conditions, (ii) miR-375 expression was upregulated while its target Erk1 was downregulated and miR-375 inhibitor upregulated Erk1 while expression of adipogenesis markers was downregulated in duct cells under both conditions, (iii) apoptosis was induced in β and duct cells under both conditions, (iv) lipotoxicity induced proliferation of co-cultured β-cells. These findings suggest that long-term saturated fatty acid overexposure may cause intrapancreatic fat accumulation by inducing differentiation of duct cells into adipocytes and it may contributes to β-cell compensation by stimulating the early stage of β-cell differentiation in duct cells. In addition, miR-375 may have the potential to be a new target in the treatment of Type 2 diabetes, and NAFPD due to its role in the adipogenesis of duct cells.
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Affiliation(s)
- Selda Gezginci-Oktayoglu
- Biology Department, Molecular Biology Section, Faculty of Science, Istanbul University, Vezneciler, Istanbul, Turkey
| | - Serap Sancar
- Biology Department, Molecular Biology Section, Faculty of Science, Istanbul University, Vezneciler, Istanbul, Turkey
| | - Ayse Karatug-Kacar
- Biology Department, Molecular Biology Section, Faculty of Science, Istanbul University, Vezneciler, Istanbul, Turkey
| | - Sehnaz Bolkent
- Biology Department, Molecular Biology Section, Faculty of Science, Istanbul University, Vezneciler, Istanbul, Turkey
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45
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Biradar RA, Singh DP, Prasad JB. Burden of increased blood glucose due to modifiable risk factors among men in India. Diabetes Metab Syndr 2021; 15:725-732. [PMID: 33813248 DOI: 10.1016/j.dsx.2021.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Revised: 03/04/2021] [Accepted: 03/07/2021] [Indexed: 11/23/2022]
Abstract
BACKGROUND AND AIMS Worldwide, many diabetes cases are occurring mainly due to lifestyle risk factors. Hence, to quantify and compare the attributable burden of key modifiable risk factors associated with increased Blood Glucose (BG) among Indian states and districts. METHODS The study used the National Family Health Survey (2015-16) data to estimate Population Attributable Risk (PAR) for increased BG (>140 mg/dl) among men aged 15-54 years in 640 districts of 36 States/Union Territories (UTs), India. We have considered three key modifiable factors such as high Body Mass Index (BMI), use of tobacco and alcohol. Population Attributable Risk techniques were employed to address the attributable burden of increased blood glucose due to modifiable risk factors. RESULTS Substantial variations were found in the burden of increased BG due to high BMI, alcohol and tobacco use in India. The overall burden of increased BG due to high BMI, tobacco and alcohol in India was 28.5%, 2.1% and 6.4%, respectively. Regional variations in BG were found in high BMI, tobacco and alcohol consumption groups. The high burden of increased BG related to the above key modifiable risk factors mostly seen in North-Eastern' districts due to alcohol, Southern and Northern' districts was due to high BMI. However, the higher burden due to tobacco was reported in Central, Eastern and North-Eastern' districts. CONCLUSION Three modifiable risk factors are contributing significantly to increased BG among men. Since there are regional differences in their contributions, state/district, specific targeted interventions may be necessary to control increased BG among men in India.
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Affiliation(s)
- Rajeshwari A Biradar
- School of Development Studies, Tata Institute of Social Sciences, Mumbai, India.
| | - Dharmendra P Singh
- School of Research Methodology, Tata Institute of Social Sciences, Mumbai, India.
| | - Jang Bahadur Prasad
- Department of Epidemiology and Biostatistics, KLE University, Belgaum, 590010, Karnataka, India.
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Ferguson LD, Linge J, Dahlqvist Leinhard O, Woodward R, Hall Barrientos P, Roditi G, Radjenovic A, McInnes IB, Siebert S, Sattar N. Psoriatic arthritis is associated with adverse body composition predictive of greater coronary heart disease and type 2 diabetes propensity - a cross-sectional study. Rheumatology (Oxford) 2021; 60:1858-1862. [PMID: 33147607 PMCID: PMC8024001 DOI: 10.1093/rheumatology/keaa604] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2020] [Accepted: 08/14/2020] [Indexed: 12/21/2022] Open
Abstract
OBJECTIVES To compare body composition in PsA with metabolic disease free (MDF) controls and type 2 diabetes and assess body-composition predicted propensity for cardiometabolic disease. METHODS Detailed MRI body composition profiles of 26 PsA participants from the IMAPA study were compared with 130 age, sex and BMI-matched MDF controls and 454 individuals with type 2 diabetes from UK Biobank. The body-composition predicted propensity for coronary heart disease (CHD) and type 2 diabetes was compared between PsA and matched MDF controls. RESULTS PsA participants had a significantly greater visceral adipose tissue (VAT) volume [mean 5.89 l (s.d. 2.10 l)] compared with matched-MDF controls [mean 4.34 l (s.d. 1.83 l)] (P <0.001) and liver fat percentage [median 8.88% (interquartile range 4.42-13.18%)] compared with MDF controls [3.29% (1.98-7.25%)] (P <0.001). These differences remained significant after adjustment for age, sex and BMI. There were no statistically significant differences in VAT, liver fat or muscle fat infiltration (MFI) between PsA and type 2 diabetes. PsA participants had a lower thigh muscle volume than MDF controls and those with type 2 diabetes. Body composition-predicted propensity for CHD and type 2 diabetes was 1.27 and 1.83 times higher, respectively, for PsA compared with matched-MDF controls. CONCLUSION Individuals with PsA have an adverse body composition phenotype with greater visceral and ectopic liver fat and lower thigh muscle volume than matched MDF controls. Body fat distribution in PsA is more in keeping with the pattern observed in type 2 diabetes and is associated with greater propensity to cardiometabolic disease. These data support the need for greater emphasis on weight loss in PsA management to lessen CHD and type 2 diabetes risk.
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Affiliation(s)
- Lyn D Ferguson
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Jennifer Linge
- AMRA Medical, Linköping, Sweden
- Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
| | - Olof Dahlqvist Leinhard
- AMRA Medical, Linköping, Sweden
- Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
| | - Rosemary Woodward
- Glasgow Clinical Research Imaging Facility, Queen Elizabeth University Hospital, Glasgow, UK
| | - Pauline Hall Barrientos
- Glasgow Clinical Research Imaging Facility, Queen Elizabeth University Hospital, Glasgow, UK
| | - Giles Roditi
- Glasgow Clinical Research Imaging Facility, Queen Elizabeth University Hospital, Glasgow, UK
| | - Aleksandra Radjenovic
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Iain B McInnes
- Institute of Infection, Immunity, and Inflammation, University of Glasgow, Glasgow, UK
| | - Stefan Siebert
- Institute of Infection, Immunity, and Inflammation, University of Glasgow, Glasgow, UK
| | - Naveed Sattar
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
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Halpern B, Mancini MC. Type 2 diabetes and metabolic surgery guidelines and recommendations should urgently be unified. Acta Diabetol 2021; 58:531-536. [PMID: 32930887 PMCID: PMC7491361 DOI: 10.1007/s00592-020-01603-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Accepted: 09/03/2020] [Indexed: 10/26/2022]
Abstract
Metabolic surgery has been studied in the last decades as an effective and safe treatment for type 2 diabetes (T2D), and randomized controlled trials generally found surgery superior when compared with medical treatment. In 2016, the DSS-II Joint Statement recognized the importance of metabolic surgery in the treatment of T2D and urged clinicians to discuss, recommend, or at least consider this procedure for their patients. Diabetes societies also cogitate metabolic surgery as an option for T2D patients in their guidelines. However, there are some differences in recommendations that could lead a careful reader to some confusion. This was potentialized in a recent document published by the same DSS-II group concerning prioritization for surgery after the COVID-19 pandemic, in which the criteria suggested for an expedited recommendation that is not exactly evidence-based, and collided substantially with several clinical guidelines worldwide, especially with regard to secondary prevention of cardiovascular disease. A more harmonious discussion and unified guidelines between clinicians and surgeons are needed in order to provide the same message for those who read different articles.
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Affiliation(s)
- Bruno Halpern
- Obesity Group, Department of Endocrinology, Hospital das Clinicas Universidade de São Paulo, São Paulo, Brazil.
- Department of Epidemiology and Prevention, Brazilian Association for the Study of Obesity (ABESO), São Paulo, Brazil.
| | - Marcio C Mancini
- Obesity Group, Department of Endocrinology, Hospital das Clinicas Universidade de São Paulo, São Paulo, Brazil
- Brazilian Society of Endocrinology and Metabolism (SBEM), Rio de Janeiro, Brazil
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Dietary Management of Type 2 Diabetes in the MENA Region: A Review of the Evidence. Nutrients 2021; 13:nu13041060. [PMID: 33805161 PMCID: PMC8064070 DOI: 10.3390/nu13041060] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 03/21/2021] [Accepted: 03/21/2021] [Indexed: 12/11/2022] Open
Abstract
The alarmingly rising trend of type 2 diabetes constitutes a major global public health challenge particularly in the Middle Eastern and North African (MENA) region where the prevalence is among the highest in the world with a projection to increase by 96% by 2045. The economic boom in the MENA region over the past decades has brought exceptionally rapid shifts in eating habits characterized by divergence from the traditional Mediterranean diet towards a more westernized unhealthy dietary pattern, thought to be leading to the dramatic rises in obesity and non-communicable diseases. Research efforts have brought a greater understanding of the different pathways through which diet and obesity may affect diabetes clinical outcomes, emphasizing the crucial role of dietary interventions and weight loss in the prevention and management of diabetes. The purpose of this review is to explore the mechanistic pathways linking obesity with diabetes and to summarize the most recent evidence on the association of the intake of different macronutrients and food groups with the risk of type 2 diabetes. We also summarize the most recent evidence on the effectiveness of different macronutrient manipulations in the prevention and management of diabetes while highlighting the possible underlying mechanisms of action and latest evidence-based recommendations. We finally discuss the need to adequately integrate dietetic services in diabetes care specific to the MENA region and conclude with recommendations to improve dietetic care for diabetes in the region.
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Kozawa J, Shimomura I. Ectopic Fat Accumulation in Pancreas and Heart. J Clin Med 2021; 10:1326. [PMID: 33806978 PMCID: PMC8004936 DOI: 10.3390/jcm10061326] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 03/14/2021] [Accepted: 03/22/2021] [Indexed: 12/15/2022] Open
Abstract
Ectopic fat is found in liver, muscle, and kidney and is known to accumulate as visceral fat. In recent years, ectopic fat has also been observed in the pancreas, and it has been said that pancreatic fat accumulation is related to the pathophysiology of diabetes and the onset of diabetes, but the relationship has not yet been determined. In the heart, epicardium fat is another ectopic fat, which is associated with the development of coronary artery disease. Ectopic fat is also observed in the myocardium, and diabetic patients have more fat accumulation in this tissue than nondiabetic patients. Myocardium fat is reported to be related to diastolic cardiac dysfunction, which is one of the characteristics of the complications observed in diabetic patients. We recently reported that ectopic fat accumulation was observed in coronary arteries of a type 2 diabetic patient with intractable coronary artery disease, and coronary artery is attracting attention as a new tissue of ectopic fat accumulation. Here, we summarize the latest findings focusing on the relationship between ectopic fat accumulation in these organs and diabetic pathophysiology and complications, then describe the possibility of future treatments targeting these ectopic fat accumulations.
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Affiliation(s)
- Junji Kozawa
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan;
- Department of Diabetes Care Medicine, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan
| | - Iichiro Shimomura
- Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan;
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Suri S, Mitra P, Abhilasha A, Saxena I, Garg MK, Bohra GK, Sharma P. Role of interleukin-2 and interleukin-18 in newly diagnosed type 2 diabetes mellitus. J Basic Clin Physiol Pharmacol 2021; 33:185-190. [PMID: 33711216 DOI: 10.1515/jbcpp-2020-0272] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2020] [Accepted: 11/09/2020] [Indexed: 11/15/2022]
Abstract
OBJECTIVES The study aimed to compare the levels of anti-inflammatory interleukin-2 (IL-2) and proinflammatory interleukin-18 (IL-18) among newly diagnosed type 2 diabetes mellitus (T2DM) and nondiabetic volunteers, to predict their roles as markers in the diagnosis of newly diagnosed T2DM. METHODS In the study, 60 subjects were enrolled (30 T2DM cases and 30 non-diabetic controls). Biochemical parameters such as fasting plasma glucose (FBS), glycated haemoglobin (HbA1c), high sensitivity C-reactive protein (hs-CRP) and lipid profile were estimated in auto-analyser. Serum IL-2 and IL-18 levels were assessed by enzyme-linked immune sorbent assay (ELISA). RESULTS Significant differences were observed in the levels of interleukins among study groups. The median (95% confidence interval) of IL-2 in cases and controls were 8.55 (6.07-47.23) and 45.87 (12.81-145.4) (p=0.02). The median (95% CI) of IL-18 on the other hand in cases and controls were 691.6 (580.3-872.6) and 511.1 (452.6-557.5) (p=0.0014). CONCLUSIONS Our study is the first to correlate IL-2 and IL-18 in newly diagnosed T2DM patients. Findings from this study highlight the anti-inflammatory role of IL-2 and proinflammatory role of IL-18 in T2DM. ROC analysis helped predict their role as markers in T2DM diagnosis.
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Affiliation(s)
- Smriti Suri
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India
| | - Prasenjit Mitra
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India
| | - Abhilasha Abhilasha
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India
| | - Indu Saxena
- Department of Biochemistry, All India Institute of Medical Sciences, Gorakhpur, India
| | - Mahendra K Garg
- Department of General Medicine, All India Institute of Medical Sciences, Jodhpur, India
| | - Gopal Krishna Bohra
- Department of General Medicine, All India Institute of Medical Sciences, Jodhpur, India
| | - Praveen Sharma
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India
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