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Bulut EC, Erol Kutucu D, Üstünova S, Ağırbaşlı M, Dedeakayoğulları H, Tarhan Ç, Kapucu A, Yeğen BÇ, Demirci Tansel C, Gürel Gürevin E. Synbiotic supplementation ameliorates anxiety and myocardial ischaemia-reperfusion injury in hyperglycaemic rats by modulating gut microbiota. Exp Physiol 2024; 109:1882-1895. [PMID: 39264256 PMCID: PMC11522816 DOI: 10.1113/ep092052] [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: 05/22/2024] [Accepted: 08/09/2024] [Indexed: 09/13/2024]
Abstract
Hyperglycaemia, hyperlipidaemia, hypertension and obesity are the main risk factors affecting the development and prognosis of ischaemic heart disease, which is still an important cause of death today. In our study, male Sprague-Dawley rats were fed either a standard diet (SD) or a high fat and high carbohydrate diet (HF-HCD) for 8 weeks and streptozotocin (STZ) was injected at the seventh week of the feeding period. In one set of rats, a mixture of a prebiotic and probiotics (synbiotic, SYN) was administered by gavage starting from the beginning of the feeding period. Experimental myocardial ischaemia-reperfusion (30 min/60 min) was induced at the end of 8 weeks. Hyperglycaemia, hypertension and increased serum low-density lipoprotein levels occurred in SD- and HF-HCD-fed and STZ-treated rats followed for 8 weeks. Increased density of the Proteobacteria phylum was observed in rats with increased blood glucose levels, indicating intestinal dysbiosis. The severity of cardiac damage was highest in the dysbiotic HF-HCD-fed hyperglycaemic rats, which was evident with increased serum creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), tumour necrosis factor-α, and interleukin-6 levels, along with a decrease in ST-segment resolution index. SYN supplementation to either a normal or a high-fat high-carbohydrate diet improved gut dysbiosis, reduced anxiety, decreased CK-MB and cTnI levels, and alleviated myocardial ischaemia-reperfusion injury in hyperglycaemic rats.
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Affiliation(s)
- Erman Caner Bulut
- Department of Biology, Institute of Graduate Studies in SciencesIstanbul UniversityIstanbulTurkey
| | - Deniz Erol Kutucu
- Department of Biology, Faculty of ScienceIstanbul UniversityIstanbulTurkey
| | - Savaş Üstünova
- Department of Physiology, School of MedicineBezmialem Vakıf UniversityIstanbulTurkey
| | - Mehmet Ağırbaşlı
- Department of Cardiology, School of MedicineIstanbul Medeniyet UniversityIstanbulTurkey
| | - Huri Dedeakayoğulları
- Department of Medical Biochemistry, Faculty of MedicineBiruni UniversityIstanbulTurkey
| | - Çağatay Tarhan
- Department of Molecular Biology and Genetics, Faculty of ScienceIstanbul UniversityIstanbulTurkey
| | - Ayşegül Kapucu
- Department of Biology, Faculty of ScienceIstanbul UniversityIstanbulTurkey
| | - Berrak Ç. Yeğen
- Department of Physiology, School of MedicineMarmara UniversityIstanbulTurkey
| | | | - Ebru Gürel Gürevin
- Department of Biology, Faculty of ScienceIstanbul UniversityIstanbulTurkey
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Shea EV, Yu S, Schumacher KR, Lowery R, Doman T, Rocchini AP. Insulin Resistance after Fontan Palliation. Pediatr Cardiol 2024:10.1007/s00246-024-03663-x. [PMID: 39375212 DOI: 10.1007/s00246-024-03663-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: 06/18/2024] [Accepted: 09/23/2024] [Indexed: 10/09/2024]
Abstract
Patients with a single ventricle heart who had Fontan palliation (S/P Fontan) are at increased risk for acquired morbidity. Insulin resistance (IR) is a predictor of cardiac morbidity and mortality. A single-center, cross-sectional study using S/P Fontan and controls was designed to assess IR S/P Fontan. Group comparisons were made in IR via the Quantitative Insulin Index (QUICKI) and the natural log-transformed homeostasis model assessment, ln (HOMA-IR), without/with adjusting for age. A total of 89 patients (59 Fontan and 30 controls) were included. Fontan patients showed a significant decrease in QUICKI (0.34 ± 0.03 vs 0.37 ± 0.02) and an elevation of ln (HOMA-IR) (0.82 ± 0.62 vs 0.24 ± 0.44) compared to controls (both p < 0.0001); this remained significant even adjusting for age. With older age, there was a significant, progressive decrease in QUICKI (p = 0.01) and an increase in ln (HOMA-IR) (p = 0.02) S/P Fontan. Analysis excluding Fontan patients with obesity still showed a significant reduction of QUICKI and an elevation of ln (HOMA-IR) in Fontan patients compared to controls when adjusting for age (both p < 0.05). Using QUICKI, IR was present in 41 (69.5%) Fontan patients vs. 3 (10%) controls (p < 0.0001) and using HOMA-IR, IR was present in 32 (54.2%) vs 5 (16.7%) controls (p = 0.001). Fontan patients had significantly more IR compared to controls and the prevalence of IR increases with age. Since IR is known to correlate with long-term morbidity and mortality and can be ameliorated by therapies, we believe it is critical that IR be identified as early as possible in Fontan patients.
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Affiliation(s)
- Erin V Shea
- Pediatric Cardiology, Duke University Medical Center, Durham, NC, USA
| | - Sunkyung Yu
- Division of Pediatric Cardiology, University of Michigan Congenital Heart Center, C.S. Mott Children's Hospital, 1540 East Medical Center Drive, Ann Arbor, MI, 48109-420, USA
| | - Kurt R Schumacher
- Division of Pediatric Cardiology, University of Michigan Congenital Heart Center, C.S. Mott Children's Hospital, 1540 East Medical Center Drive, Ann Arbor, MI, 48109-420, USA
| | - Ray Lowery
- Division of Pediatric Cardiology, University of Michigan Congenital Heart Center, C.S. Mott Children's Hospital, 1540 East Medical Center Drive, Ann Arbor, MI, 48109-420, USA
| | - Tammy Doman
- Division of Pediatric Cardiology, University of Michigan Congenital Heart Center, C.S. Mott Children's Hospital, 1540 East Medical Center Drive, Ann Arbor, MI, 48109-420, USA
| | - Albert P Rocchini
- Division of Pediatric Cardiology, University of Michigan Congenital Heart Center, C.S. Mott Children's Hospital, 1540 East Medical Center Drive, Ann Arbor, MI, 48109-420, USA.
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Sotiropoulos C, Giormezis N, Pertsas V, Tsirkas T. Biomarkers and Data Visualization of Insulin Resistance and Metabolic Syndrome: An Applicable Approach. Life (Basel) 2024; 14:1197. [PMID: 39337979 PMCID: PMC11433343 DOI: 10.3390/life14091197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Revised: 09/06/2024] [Accepted: 09/19/2024] [Indexed: 09/30/2024] Open
Abstract
Type 2 diabetes, prediabetes, and insulin resistance (IR) are widespread yet often undetected in their early stages, contributing to a silent epidemic. Metabolic Syndrome (MetS) is also highly prevalent, increasing the chronic disease burden. Annual check-ups are inadequate for early detection due to conventional result formats that lack specific markers and comprehensive visualization. The aim of this study was to evaluate low-budget biochemical and hematological parameters, with data visualization, for identifying IR and MetS in a community-based laboratory. In a cross-sectional study with 1870 participants in Patras, Greece, blood samples were analyzed for key cardiovascular and inflammatory markers. IR diagnostic markers (TyG-Index, TyG-BMI, Triglycerides/HDL ratio, NLR) were compared with HOMA-IR. Innovative data visualization techniques were used to present metabolic profiles. Notable differences in parameters of cardiovascular risk and inflammation were observed between normal-weight and obese people, highlighting BMI as a significant risk factor. Also, the inflammation marker NHR (Neutrophils to HDL-Cholesterol Ratio) Index was successful at distinguishing the obese individuals and those with MetS from normal individuals. Additionally, a new diagnostic index of IR, combining BMI (Body Mass Index) and NHR Index, demonstrated better performance than other well-known indices. Lastly, data visualization significantly helped individuals understand their metabolic health patterns more clearly. BMI and NHR Index could play an essential role in assessing metabolic health patterns. Integrating specific markers and data visualization in routine check-ups enhances the early detection of IR and MetS, aiding in better patient awareness and adherence.
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Affiliation(s)
- Christos Sotiropoulos
- Department of Microbiology, School of Medicine, University of Patras, 26504 Patras, Greece;
| | - Nikolaos Giormezis
- Department of Microbiology, School of Medicine, University of Patras, 26504 Patras, Greece;
| | - Vayianos Pertsas
- Informatics Department, University of Economics and Business, 10434 Athens, Greece;
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Mo X, Wang C, Pu Q, Zhang Z, Wu D. Revealing genetic causality between blood-based biomarkers and major depression in east Asian ancestry. Front Psychiatry 2024; 15:1424958. [PMID: 39323965 PMCID: PMC11423294 DOI: 10.3389/fpsyt.2024.1424958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Accepted: 08/26/2024] [Indexed: 09/27/2024] Open
Abstract
Introduction Major Depression (MD) is a common mental disorder. In East Asian ancestry, the association, causality, and shared genetic basis between blood-based biomarkers and MD remain unclear. Methods We investigated the relationships between blood-based biomarkers and MD through a cross-sectional study and Mendelian randomization (MR) analysis. Cross-trait analysis and enrichment analyses were used to highlight the shared genetic determinants and biological pathways. We conducted summary data-based MR to identify shared genes, which were then validated using a transcriptome dataset from drug-naïve patients with MD. Results In the cross-sectional study, C-Reactive Protein showed the significantly positive correlation with depressive symptoms, while hematocrit, hemoglobin, and uric acid exhibited significantly negative correlations. In MR analysis, basophil count (BASO) and low-density lipoprotein cholesterol (LDLc) had a significant causal effect on MD. The enrichment analysis indicated a significant role of inflammatory cytokines and oxidative stress. The shared genes MFN2, FAM55C, GCC2, and SCAPER were validated, with MFN2 identified as a pleiotropic gene involved in MD, BASO, and LDLc. Discussion This study highlighted that BASO and LDLc have a causal effect on MD in East Asian ancestry. The pathological mechanisms of MD are related not only to inflammatory cytokines and oxidative stress but also to down regulation of MFN2 expression and mitochondrial dysfunction.
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Affiliation(s)
- Xiaoxiao Mo
- Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
- Department of Environmental Genomics, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Chao Wang
- Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
- Department of Environmental Genomics, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Qiuyi Pu
- Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
- Department of Environmental Genomics, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Zhengdong Zhang
- Department of Environmental Genomics, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Dongmei Wu
- Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
- Department of Environmental Genomics, School of Public Health, Nanjing Medical University, Nanjing, China
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Stefkovich M, Titchenell PM. Location Matters: Mitochondrial Arginase 2 as a Treatment for Metabolic Disease? Cell Mol Gastroenterol Hepatol 2024; 17:883-884. [PMID: 38471656 PMCID: PMC11103180 DOI: 10.1016/j.jcmgh.2024.02.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Revised: 02/14/2024] [Accepted: 02/20/2024] [Indexed: 03/14/2024]
Affiliation(s)
- Megan Stefkovich
- Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Paul M Titchenell
- Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
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Singh N, Al-Naamani N, Brown MB, Long GM, Thenappan T, Umar S, Ventetuolo CE, Lahm T. Extrapulmonary manifestations of pulmonary arterial hypertension. Expert Rev Respir Med 2024; 18:189-205. [PMID: 38801029 PMCID: PMC11713041 DOI: 10.1080/17476348.2024.2361037] [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: 12/05/2023] [Accepted: 05/24/2024] [Indexed: 05/29/2024]
Abstract
INTRODUCTION Extrapulmonary manifestations of pulmonary arterial hypertension (PAH) may play a critical pathobiological role and a deeper understanding will advance insight into mechanisms and novel therapeutic targets. This manuscript reviews our understanding of extrapulmonary manifestations of PAH. AREAS COVERED A group of experts was assembled and a complimentary PubMed search performed (October 2023 - March 2024). Inflammation is observed throughout the central nervous system and attempts at manipulation are an encouraging step toward novel therapeutics. Retinal vascular imaging holds promise as a noninvasive method of detecting early disease and monitoring treatment responses. PAH patients have gut flora alterations and dysbiosis likely plays a role in systemic inflammation. Despite inconsistent observations, the roles of obesity, insulin resistance and dysregulated metabolism may be illuminated by deep phenotyping of body composition. Skeletal muscle dysfunction is perpetuated by metabolic dysfunction, inflammation, and hypoperfusion, but exercise training shows benefit. Renal, hepatic, and bone marrow abnormalities are observed in PAH and may represent both end-organ damage and disease modifiers. EXPERT OPINION Insights into systemic manifestations of PAH will illuminate disease mechanisms and novel therapeutic targets. Additional study is needed to understand whether extrapulmonary manifestations are a cause or effect of PAH and how manipulation may affect outcomes.
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Affiliation(s)
- Navneet Singh
- Department of Medicine, Warren Alpert School of Medicine at Brown University, Providence, RI
| | - Nadine Al-Naamani
- Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
| | - Mary Beth Brown
- Department of Rehabilitation Medicine, University of Washington School of Medicine, Seattle, WA
| | - Gary Marshall Long
- Department of Kinesiology, Health and Sport Sciences, University of Indianapolis, Indianapolis, IN
| | - Thenappan Thenappan
- Section of Advanced Heart Failure and Pulmonary Hypertension, Cardiovascular Division, University of Minnesota, Minneapolis, MN
| | - Soban Umar
- Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA
| | - Corey E. Ventetuolo
- Department of Medicine, Warren Alpert School of Medicine at Brown University, Providence, RI
- Department of Health Services, Policy and Practice, Brown University, Providence, RI
| | - Tim Lahm
- Department of Medicine, National Jewish Health, Denver, CO
- Department of Medicine, University of Colorado, Aurora, CO
- Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, CO
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Almuraikhy S, Doudin A, Domling A, Althani AAJF, Elrayess MA. Molecular regulators of exercise-mediated insulin sensitivity in non-obese individuals. J Cell Mol Med 2024; 28:e18015. [PMID: 37938877 PMCID: PMC10805515 DOI: 10.1111/jcmm.18015] [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: 03/08/2023] [Revised: 10/16/2023] [Accepted: 10/18/2023] [Indexed: 11/10/2023] Open
Abstract
Insulin resistance is a significant contributor to the development of type 2 diabetes (T2D) and is associated with obesity, physical inactivity, and low maximal oxygen uptake. While intense and prolonged exercise may have negative effects, physical activity can have a positive influence on cellular metabolism and the immune system. Moderate exercise has been shown to reduce oxidative stress and improve antioxidant status, whereas intense exercise can increase oxidative stress in the short term. The impact of exercise on pro-inflammatory cytokine production is complex and varies depending on intensity and duration. Exercise can also counteract the harmful effects of ageing and inflamm-ageing. This review aims to examine the molecular pathways altered by exercise in non-obese individuals at higher risk of developing T2D, including glucose utilization, lipid metabolism, mitochondrial function, inflammation and oxidative stress, with the potential to improve insulin sensitivity. The focus is on understanding the potential benefits of exercise for improving insulin sensitivity and providing insights for future targeted interventions before onset of disease.
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Affiliation(s)
- Shamma Almuraikhy
- Biomedical Research CenterQatar UniversityDohaQatar
- Groningen Research Institute of Pharmacy, Drug DesignGroningen UniversityGroningenThe Netherlands
| | - Asmaa Doudin
- Biomedical Research CenterQatar UniversityDohaQatar
| | - Alexander Domling
- Groningen Research Institute of Pharmacy, Drug DesignGroningen UniversityGroningenThe Netherlands
| | - Asmaa Ali J. F. Althani
- Biomedical Research CenterQatar UniversityDohaQatar
- Department of Biomedical Sciences, College of Health Science, QU HealthQatar UniversityDohaQatar
| | - Mohamed A. Elrayess
- Biomedical Research CenterQatar UniversityDohaQatar
- College of Pharmacy, QU HealthQatar UniversityDohaQatar
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Li K, Cao B, Wang X, Chai T, Ke J, Zhao D. Sex differences in the non-linear association between BMI and LDL cholesterol in type 2 diabetes. Front Endocrinol (Lausanne) 2023; 14:1180012. [PMID: 37484947 PMCID: PMC10360932 DOI: 10.3389/fendo.2023.1180012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2023] [Accepted: 06/26/2023] [Indexed: 07/25/2023] Open
Abstract
Background A data-based study reported the linear relationship between body mass index (BMI) and low-density lipoprotein cholesterol (LDL-C) in a normal population. However, there were no studies giving the suggestion for diabetes patients limited by sample size. This study aimed to investigate the non-linear dose-response relationship between BMI and LDL-C in type 2 diabetes mellitus (T2DM). Method The study participants registered at the National Metabolic Management Center (MMC) of Beijing Luhe hospital from June 2017 to June 2021. T2DM was diagnosed according to the 1999 World Organization criteria. The generalized additive models (GAMs) were used to investigate the non-linear association between BMI and LDL-C. The relationship between BMI and LDL-C was visualized via the smooth splines function plot by sex. Segmented regressions were fitted to calculate the slopes with different estimated breakpoints. Results After data cleaning, a total of 2500 participants with T2DM aged 30 to 70 years were included in this study. Compared with females, the spline between BMI and LDL-C showed an Inverted U shape in males. In males, the slopes below and above the breakpoint (26.08. 95% CI: 24.13 to 28.03) were 2.38 (95%CI: 1.06, 3.70) and -0.36 (95%CI: -1.20, 0.48), respectively. Conclusion There was an Inverted U shape association between BMI and LDL-C in male participants with T2DM, for which the LDL-C was increased with BMI in the lean population, while LDL-C gradually tended to be flat or even decreased in the obese population. However, the Inverted U-shape between BMI and LDL-C was not found in female patients with T2DM.
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Affiliation(s)
- Kun Li
- Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Diabetes Research and Care, Capital Medical University, Beijing, China
| | - Bin Cao
- Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Diabetes Research and Care, Capital Medical University, Beijing, China
| | - Xiaojing Wang
- Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Diabetes Research and Care, Capital Medical University, Beijing, China
| | - Tao Chai
- Physical Examination Center, Beijing Luhe Hospital, Capital Medical University, Beijing, China
| | - Jing Ke
- Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Diabetes Research and Care, Capital Medical University, Beijing, China
| | - Dong Zhao
- Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Diabetes Research and Care, Capital Medical University, Beijing, China
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Boyer W, Toth L, Brenton M, Augé R, Churilla J, Fitzhugh E. The role of resistance training in influencing insulin resistance among adults living with obesity/overweight without diabetes: A systematic review and meta-analysis. Obes Res Clin Pract 2023; 17:279-287. [PMID: 37331899 DOI: 10.1016/j.orcp.2023.06.002] [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: 07/21/2022] [Revised: 05/24/2023] [Accepted: 06/09/2023] [Indexed: 06/20/2023]
Abstract
The purpose of this study was to systematically examine the independent effect of resistance training (RT) on markers of insulin resistance (IR) (fasting insulin and HOMA-IR) among individuals with overweight/obesity without diabetes. PubMed, SPORTdiscus, SCOPUS, Prospero, and clinicaltrials.gov were searched through December 19, 2022. Article screening was conducted in three phases: title screen (n = 5020), abstract screen (n = 202), and full text screen (n = 73). A total of 27 studies with 402 individual data points were used for the meta-analysis. Comprehensive Meta-Analysis software version 3.0 was used to interpret pre- and post-IR measurements with a random-effects model. Exploratory sub-analyses were conducted on studies for only females, only males, and age (< 40 and ≥ 40 years). RT had a significant effect on fasting insulin (- 1.03, 95 % CI - 1.03, - 0.75 p < 0.001) and HOMA-IR (- 1.05, 95 % CI - 1.33, - 0.76, p < 0.001). Sub-analyses revealed that males had a more pronounced effect compared to females and those < 40 years of age had a more pronounced effect compared to those ≥ 40 years. The results of this meta-analysis illustrate that RT plays an independent role in improving IR among adults with overweight/obesity. RT should continue to be recommended as part of preventive measures among these populations. Future studies examining the effect of RT on IR should consider dose centered on the current U.S. physical activity guidelines.
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Affiliation(s)
- William Boyer
- California Baptist University, Department of Kinesiology, 8432 Magnolia Ave., Riverside, CA 92504, United States of America.
| | - Lindsay Toth
- University of North Florida, Department of Clinical and Applied Movement Sciences, 1 UNF Dr., Jacksonville, FL 32224, United States of America
| | - Madison Brenton
- California Baptist University, Department of Kinesiology, 8432 Magnolia Ave., Riverside, CA 92504, United States of America
| | - Robert Augé
- University of Tennessee, Department of Plant Sciences, 2505 E J. Chapman Dr., Knoxville, TN 37919, United States of America
| | - James Churilla
- University of North Florida, Department of Clinical and Applied Movement Sciences, 1 UNF Dr., Jacksonville, FL 32224, United States of America
| | - Eugene Fitzhugh
- University of Tennessee, Department of Kinesiology, Recreation and Sports Studies, 1914 Andy Holt Ave, Knoxville, TN 37996, United States of America
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Castro-Sepulveda M, Fernández-Verdejo R, Zbinden-Foncea H, Rieusset J. Mitochondria-SR interaction and mitochondrial fusion/fission in the regulation of skeletal muscle metabolism. Metabolism 2023; 144:155578. [PMID: 37164310 DOI: 10.1016/j.metabol.2023.155578] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Revised: 03/20/2023] [Accepted: 04/22/2023] [Indexed: 05/12/2023]
Abstract
Mitochondria-endoplasmic/sarcoplasmic reticulum (ER/SR) interaction and mitochondrial fusion/fission are critical processes that influence substrate oxidation. This narrative review summarizes the evidence on the effects of substrate availability on mitochondrial-SR interaction and mitochondria fusion/fission dynamics to modulate substrate oxidation in human skeletal muscle. Evidence shows that an increase in mitochondria-SR interaction and mitochondrial fusion are associated with elevated fatty acid oxidation. In contrast, a decrease in mitochondria-SR interaction and an increase in mitochondrial fission are associated with an elevated glycolytic activity. Based on the evidence reviewed, we postulate two hypotheses for the link between mitochondrial dynamics and insulin resistance in human skeletal muscle. First, glucose and fatty acid availability modifies mitochondria-SR interaction and mitochondrial fusion/fission to help the cell to adapt substrate oxidation appropriately. Individuals with an impaired response to these substrate challenges will accumulate lipid species and develop insulin resistance in skeletal muscle. Second, a chronically elevated substrate availability (e.g. overfeeding) increases mitochondrial production of reactive oxygen species and induced mitochondrial fission. This decreases fatty acid oxidation, thus leading to the accumulation of lipid species and insulin resistance in skeletal muscle. Altogether, we propose mitochondrial dynamics as a potential target for disturbances associated with low fatty acid oxidation.
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Affiliation(s)
- Mauricio Castro-Sepulveda
- Laboratorio de Fisiología del Ejercicio y Metabolismo (LABFEM), Escuela de Kinesiologia, Facultad de Medicina, Universidad Finis Terrae, Santiago, Chile.
| | - Rodrigo Fernández-Verdejo
- Laboratorio de Fisiología del Ejercicio y Metabolismo (LABFEM), Escuela de Kinesiologia, Facultad de Medicina, Universidad Finis Terrae, Santiago, Chile
| | - Hermann Zbinden-Foncea
- Laboratorio de Fisiología del Ejercicio y Metabolismo (LABFEM), Escuela de Kinesiologia, Facultad de Medicina, Universidad Finis Terrae, Santiago, Chile; Centro de Salud Deportiva, Clinica Santa Maria, Santiago, Chile
| | - Jennifer Rieusset
- CarMeN Laboratory, UMR INSERM U1060/INRA U1397, Université Claude Bernard Lyon 1, Pierre-Bénite, France
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Almuraikhy S, Anwardeen N, Doudin A, Sellami M, Domling A, Agouni A, Al Thani AA, Elrayess MA. The Metabolic Switch of Physical Activity in Non-Obese Insulin Resistant Individuals. Int J Mol Sci 2023; 24:ijms24097816. [PMID: 37175541 PMCID: PMC10178125 DOI: 10.3390/ijms24097816] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 04/20/2023] [Accepted: 04/21/2023] [Indexed: 05/15/2023] Open
Abstract
Healthy non-obese insulin resistant (IR) individuals are at higher risk of metabolic syndrome. The metabolic signature of the increased risk was previously determined. Physical activity can lower the risk of insulin resistance, but the underlying metabolic pathways remain to be determined. In this study, the common and unique metabolic signatures of insulin sensitive (IS) and IR individuals in active and sedentary individuals were determined. Data from 305 young, aged 20-30, non-obese participants from Qatar biobank, were analyzed. The homeostatic model assessment of insulin resistance (HOMA-IR) and physical activity questionnaires were utilized to classify participants into four groups: Active Insulin Sensitive (ISA, n = 30), Active Insulin Resistant (IRA, n = 20), Sedentary Insulin Sensitive (ISS, n = 21) and Sedentary Insulin Resistant (SIR, n = 23). Differences in the levels of 1000 metabolites between insulin sensitive and insulin resistant individuals in both active and sedentary groups were compared using orthogonal partial least square discriminate analysis (OPLS-DA) and linear models. The study indicated significant differences in fatty acids between individuals with insulin sensitivity and insulin resistance who engaged in physical activity, including monohydroxy, dicarboxylate, medium and long chain, mono and polyunsaturated fatty acids. On the other hand, the sedentary group showed changes in carbohydrates, specifically glucose and pyruvate. Both groups exhibited alterations in 1-carboxyethylphenylalanine. The study revealed different metabolic signature in insulin resistant individuals depending on their physical activity status. Specifically, the active group showed changes in lipid metabolism, while the sedentary group showed alterations in glucose metabolism. These metabolic discrepancies demonstrate the beneficial impact of moderate physical activity on high risk insulin resistant healthy non-obese individuals by flipping their metabolic pathways from glucose based to fat based, ultimately leading to improved health outcomes. The results of this study carry significant implications for the prevention and treatment of metabolic syndrome in non-obese individuals.
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Affiliation(s)
- Shamma Almuraikhy
- Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar
- Groningen Research Institute of Pharmacy, Drug Design, Groningen University, 9713 AV Groningen, The Netherlands
| | - Najeha Anwardeen
- Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar
| | - Asmma Doudin
- Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar
| | - Maha Sellami
- Physical Education Department (PE), College of Education, Qatar University, Doha P.O. Box 2713, Qatar
| | - Alexander Domling
- Groningen Research Institute of Pharmacy, Drug Design, Groningen University, 9713 AV Groningen, The Netherlands
| | - Abdelali Agouni
- College of Pharmacy, QU Health, Qatar University, Doha P.O. Box 2713, Qatar
| | - Asmaa A Al Thani
- Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar
- Department of Biomedical Sciences, College of Health Science, QU Health, Qatar University, Doha P.O. Box 2713, Qatar
| | - Mohamed A Elrayess
- Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar
- College of Pharmacy, QU Health, Qatar University, Doha P.O. Box 2713, Qatar
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12
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Valderrábano RJ, Badour S, Ferri-Guerra J, Barb D, Garg R. Body Fat Distribution in Lean Individuals with Metabolic Abnormalities. Metab Syndr Relat Disord 2023; 21:79-84. [PMID: 36448994 DOI: 10.1089/met.2022.0026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
Objective: Obesity, defined as body mass index (BMI) >30 kilogram/m2 is associated with metabolic derangements, but lean individuals with BMI <25 kilogram/m2 may also have metabolic abnormalities. This study was conducted to evaluate fat distribution in metabolically unhealthy lean (MUL) individuals. Methods: Adults with BMI 18.5-24.9 kilogram/m2 had their body composition evaluated with dual-energy X-ray absorptiometry. Metabolic data were obtained from their medical records. Patients with ≥2 components of the metabolic syndrome (MetS) were considered MUL and those with ≤1 component metabolically healthy lean (MHL). Multivariable logistic regression was used to analyze the association between metabolic abnormalities and anthropometric indexes. Results: The study includes 119 subjects; 69 in MHL and 50 in the MUL group. Two groups had comparable total body fat, fat mass index, and appendicular lean mass. Indices of visceral fat were associated with increased odds of being MUL (odds ratio with 95% confidence interval): visceral adipose tissue 1.75 (1.13-2.73), trunk-to-legs fat ratio 2.28 (1.30-4.00), trunk-to-limb fat ratio 2.43 (1.37-4.32), android-to-gynoid fat ratio 1.80 (1.07-3.03), and visceral-to-total fat percentage 1.80 (1.07-3.05). Conclusion: Metabolically unhealthy subjects had increased truncal distribution of body fat without an increase in total body fat. Body morphometry in MUL was similar to that of obese individuals with MetS.
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Affiliation(s)
- Rodrigo J Valderrábano
- Section in Men's Health and Aging, Clinical Research Unit, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Sanaa Badour
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida, USA
| | - Juliana Ferri-Guerra
- Department of Internal Medicine, Mount Sinai Medical Center, Miami Beach, Florida, USA
| | - Diana Barb
- Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida, USA
| | - Rajesh Garg
- Division of Endocrinology, University of Miami, Miller School of Medicine, Miami, Florida, USA
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13
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Martínez-Colón GJ, Ratnasiri K, Chen H, Jiang S, Zanley E, Rustagi A, Verma R, Chen H, Andrews JR, Mertz KD, Tzankov A, Azagury D, Boyd J, Nolan GP, Schürch CM, Matter MS, Blish CA, McLaughlin TL. SARS-CoV-2 infection drives an inflammatory response in human adipose tissue through infection of adipocytes and macrophages. Sci Transl Med 2022; 14:eabm9151. [PMID: 36137009 PMCID: PMC9529056 DOI: 10.1126/scitranslmed.abm9151] [Citation(s) in RCA: 68] [Impact Index Per Article: 22.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Accepted: 09/09/2022] [Indexed: 01/11/2023]
Abstract
Obesity, characterized by chronic low-grade inflammation of the adipose tissue, is associated with adverse coronavirus disease 2019 (COVID-19) outcomes, yet the underlying mechanism is unknown. To explore whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of adipose tissue contributes to pathogenesis, we evaluated COVID-19 autopsy cases and deeply profiled the response of adipose tissue to SARS-CoV-2 infection in vitro. In COVID-19 autopsy cases, we identified SARS-CoV-2 RNA in adipocytes with an associated inflammatory infiltrate. We identified two distinct cellular targets of infection: adipocytes and a subset of inflammatory adipose tissue-resident macrophages. Mature adipocytes were permissive to SARS-CoV-2 infection; although macrophages were abortively infected, SARS-CoV-2 initiated inflammatory responses within both the infected macrophages and bystander preadipocytes. These data suggest that SARS-CoV-2 infection of adipose tissue could contribute to COVID-19 severity through replication of virus within adipocytes and through induction of local and systemic inflammation driven by infection of adipose tissue-resident macrophages.
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Affiliation(s)
| | - Kalani Ratnasiri
- Program in Immunology, Stanford University School of Medicine, Stanford, CA, 94305, USA
| | - Heping Chen
- Department of Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA
| | - Sizun Jiang
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305, USA
- Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, 02215, USA
| | - Elizabeth Zanley
- Department of Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA
| | - Arjun Rustagi
- Department of Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA
| | - Renu Verma
- Department of Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA
| | - Han Chen
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305, USA
| | - Jason R. Andrews
- Department of Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA
| | - Kirsten D. Mertz
- Institute of Pathology, Cantonal Hospital Baselland, 4410, Liestal, Switzerland
| | - Alexandar Tzankov
- Institute of Medical Genetics and Pathology, University Hospital of Basel, University of Basel, 4056, Basel, Switzerland
| | - Dan Azagury
- Department of Surgery, Stanford University School of Medicine, Stanford, CA, 94305, USA
| | - Jack Boyd
- Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA, 94305, USA
| | - Garry P. Nolan
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, 94305, USA
| | - Christian M. Schürch
- Department of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tübingen, 72070, Tübingen, Germany
| | - Matthias S. Matter
- Institute of Medical Genetics and Pathology, University Hospital of Basel, University of Basel, 4056, Basel, Switzerland
| | - Catherine A. Blish
- Department of Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA
- Program in Immunology, Stanford University School of Medicine, Stanford, CA, 94305, USA
- Chan Zuckerberg Biohub, San Francisco, CA, 94158, USA
| | - Tracey L. McLaughlin
- Department of Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA
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14
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High-fat diet consumption by male rat offspring of obese mothers exacerbates adipose tissue hypertrophy and metabolic alterations in adult life. Br J Nutr 2022:1-10. [PMID: 36412162 DOI: 10.1017/s0007114522003737] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Obese mothers' offspring develop obesity and metabolic alterations in adulthood. Poor postnatal dietary patterns also contribute to obesity and its comorbidities. We aimed to determine whether in obese mothers' offspring an adverse postnatal environment, such as high-fat diet (HFD) consumption (second hit) exacerbates body fat accumulation, metabolic alterations and adipocyte size distribution. Female Wistar rats ate chow (C-5 %-fat) or HFD (maternal obesity (MO)-25 %-fat) from weaning until the end of lactation. Male offspring were weaned on either control (C/C and MO/C, maternal diet/offspring diet) or HFD (C/HF and MO/HF) diet. At 110 postnatal days, offspring were killed. Fat depots were excised to estimate adiposity index (AI). Serum glucose, triglyceride, leptin, insulin, insulin resistance index (HOMA-IR), corticosterone and dehydroepiandrosterone (DHEA) were determined. Adipocyte size distribution was evaluated in retroperitoneal fat. Body weight was similar in C/C and MO/C but higher in C/HF and MO/HF. AI, leptin, insulin and HOMA-IR were higher in MO/C and C/HF v. C/C but lower than MO/HF. Glucose increased in MO/HF v. MO/C. C/HF and MO/C had higher triglyceride and corticosterone than C/C, but lower corticosterone than MO/HF. DHEA and the DHEA/corticosterone ratio were lower in C/HF and MO/C v. C/C, but higher than MO/HF. Small adipocyte proportion decreased while large adipocyte proportions increased in MO/C and C/HF v. C/C and exacerbated in MO/HF v. C/HF. Postnatal consumption of a HFD by the offspring of obese mothers exacerbates body fat accumulation as well as the decrease of small and the increase of large adipocytes, which leads to larger metabolic abnormalities.
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Oost LJ, Tack CJ, de Baaij JHF. Hypomagnesemia and Cardiovascular Risk in Type 2 Diabetes. Endocr Rev 2022; 44:357-378. [PMID: 36346820 PMCID: PMC10166267 DOI: 10.1210/endrev/bnac028] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 08/22/2022] [Accepted: 11/04/2022] [Indexed: 11/11/2022]
Abstract
Hypomagnesemia is tenfold more common in individuals with type 2 diabetes (T2D), compared to the healthy population. Factors that are involved in this high prevalence are low Mg2+ intake, gut microbiome composition, medication use and presumably genetics. Hypomagnesemia is associated with insulin resistance, which subsequently increases the risk to develop T2D or deteriorates glycaemic control in existing diabetes. Mg2+ supplementation decreases T2D associated features like dyslipidaemia and inflammation; which are important risk factors for cardiovascular disease (CVD). Epidemiological studies have shown an inverse association between serum Mg2+ and the risk to develop heart failure (HF), atrial fibrillation (AF) and microvascular disease in T2D. The potential protective effect of Mg2+ on HF and AF may be explained by reduced oxidative stress, fibrosis and electrical remodeling in the heart. In microvascular disease, Mg2+ reduces the detrimental effects of hyperglycemia and improves endothelial dysfunction. Though, clinical studies assessing the effect of long-term Mg2+ supplementation on CVD incidents are lacking and gaps remain on how Mg2+ may reduce CVD risk in T2D. Despite the high prevalence of hypomagnesemia in people with T2D, routine screening of Mg2+ deficiency to provide Mg2+ supplementation when needed is not implemented in clinical care as sufficient clinical evidence is lacking. In conclusion, hypomagnesemia is common in people with T2D and is both involved as cause, probably through molecular mechanisms leading to insulin resistance, and consequence and is prospectively associated with development of HF, AF and microvascular complications. Whether long-term supplementation of Mg2+ is beneficial, however, remains to be determined.
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Affiliation(s)
- Lynette J Oost
- Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Cees J Tack
- Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Jeroen H F de Baaij
- Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
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16
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Jeans MR, Ghaddar R, Vandyousefi S, Landry MJ, Gray MJ, Leidy HJ, Whittaker TA, Bray MS, Davis JN. Distinct racial and ethnic metabolic syndrome characteristics: A comparative assessment in low-income children 7-10 years of age. Pediatr Obes 2022; 17:e12925. [PMID: 35560860 DOI: 10.1111/ijpo.12925] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Revised: 02/28/2022] [Accepted: 04/13/2022] [Indexed: 01/19/2023]
Abstract
BACKGROUND Pediatric MetS prevalence varies due to lack of consensus on evaluative criteria and associated thresholds, with most not recommending a diagnosis <10 years. However, MetS risk components are becoming evident earlier in life and affect races and ethnicities disproportionately. OBJECTIVES To compare the prevalence of MetS based on existing definitions and elucidate racial- and ethnic-specific characteristics associated with MetS prevalence. METHODS The baseline and follow-up samples included 900 and 557 children 7-10 years, respectively. Waist circumference, BMI percentile, blood pressure, fasting plasma glucose (FPG), insulin, triglycerides, and high-density lipoprotein cholesterol (HDL-C) were measured. Agreement between MetS definitions was quantified via kappa statistics. MetS and risk factor prevalence and the predictability of metabolic parameters on MetS eight months later was evaluated via logistic regression. McFadden pseudo-R2 was reported as a measure of predictive ability, and the Akaike information criterion evaluated fit of each model. RESULTS The baseline sample was 55.0% male and 71.6% Hispanic, followed by non-Hispanic White (NHW) (17.3%) and non-Hispanic Black (NHB) (11.1%), with an average age of 9.2 years. MetS prevalence ranged from 7.6% to 21.4%, highest in Hispanic (9.0%-24.0%) and lowest in NHB children (4.0%-14.0%). Highest agreement was between Ford et al. and Cook et al. definitions (K = 0.88) and lowest agreements were consistently with the International Diabetes Federation criteria (K ≤ 0.57). Compared to NHW children, Hispanic children had higher odds for MetS (OR: 1.7; p = 0.03) and waist circumference, HDL-C, and FPG risk factors (p < 0.05), while NHB children had higher odds for the FPG risk factor (p ≤ 0.007) and lower odds for the plasma triglycerides risk factor (p = 0.002), across multiple MetS definitions. In longitudinal analyses, HDL-C was the strongest independent predictor of MetS in Hispanic and NHW children (p < 0.001 and p < 0.01, respectively), while plasma triglycerides was the strongest independent predictor of MetS in NHB children (p < 0.05). CONCLUSIONS MetS prevalence was high in children ≤10 years, and proposed criteria are susceptible to racial and ethnic bias, diagnosing some populations more than other populations with high cardiovascular risk. Earlier preventative measures should be imposed in clinical settings, accounting for racial and ethnic differences, to mitigate disease onset.
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Affiliation(s)
- Matthew R Jeans
- Department of Nutritional Sciences, College of Natural Sciences, The University of Texas at Austin, Austin, Texas, USA
| | - Reem Ghaddar
- Department of Nutritional Sciences, College of Natural Sciences, The University of Texas at Austin, Austin, Texas, USA
| | - Sarvenaz Vandyousefi
- Department of Medicine, New York University Grossman Medical Center, New York, New York, USA
| | - Matthew J Landry
- Stanford University, School of Medicine, Stanford Prevention Research Center, Palo Alto, California, USA
| | - Megan J Gray
- Department of Pediatrics, Dell Medical Center, The University of Texas at Austin, Austin, Texas, USA
| | - Heather J Leidy
- Department of Nutritional Sciences, College of Natural Sciences, The University of Texas at Austin, Austin, Texas, USA.,Department of Pediatrics, Dell Medical Center, The University of Texas at Austin, Austin, Texas, USA
| | - Tiffany A Whittaker
- Department of Educational Psychology, College of Education, The University of Texas at Austin, Austin, Texas, USA
| | - Molly S Bray
- Department of Nutritional Sciences, College of Natural Sciences, The University of Texas at Austin, Austin, Texas, USA
| | - Jaimie N Davis
- Department of Nutritional Sciences, College of Natural Sciences, The University of Texas at Austin, Austin, Texas, USA
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AlMuraikhy S, Anwardeen N, Naeem A, Sellami M, Domling A, Agouni A, Elrayess MA. Comparing the Metabolic Profiles Associated with Fitness Status between Insulin-Sensitive and Insulin-Resistant Non-Obese Individuals. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph191912169. [PMID: 36231474 PMCID: PMC9564877 DOI: 10.3390/ijerph191912169] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Revised: 09/17/2022] [Accepted: 09/19/2022] [Indexed: 05/27/2023]
Abstract
(1) Background: Young non-obese insulin-resistant (IR) individuals could be at risk of developing metabolic diseases including type 2 diabetes mellitus. The protective effect of physical activity in this apparently healthy group is expected but not well characterized. In this study, clinically relevant metabolic profiles were determined and compared among active and sedentary insulin-sensitive (IS) and IR young non-obese individuals. (2) Methods: Data obtained from Qatar Biobank for 2110 young (20-30 years old) non-obese (BMI ≤ 30) healthy participants were divided into four groups, insulin-sensitive active (ISA, 30.7%), insulin-sensitive sedentary (ISS, 21.4%), insulin-resistant active (IRA, 20%), and insulin-resistant sedentary (IRS, 23.3%), using the homeostatic model assessment of insulin resistance (HOMA-IR) and physical activity questionnaires. The effect of physical activity on 66 clinically relevant biochemical tests was compared among the four groups using linear models. (3) Results: Overall, non-obese IR participants had significantly (p ≤ 0.001) worse vital signs, blood sugar profiles, inflammatory markers, liver function, lipid profiles, and vitamin D levels than their IS counterparts. Physical activity was positively associated with left handgrip (p ≤ 0.01) and levels of creatine kinase (p ≤ 0.001) and creatine kinase-2 (p ≤ 0.001) in both IS and IR subjects. Furthermore, physical activity was positively associated with levels of creatinine (p ≤ 0.01) and total vitamin D (p = 0.006) in the IR group and AST (p = 0.001), folate (p = 0.001), and hematocrit (p = 0.007) in the IS group. Conversely, physical inactivity was negatively associated with the white blood cell count (p = 0.001) and an absolute number of lymphocytes (p = 0.003) in the IR subjects and with triglycerides (p = 0.005) and GGT-2 (p ≤ 0.001) in the IS counterparts. (4) Conclusions: An independent effect of moderate physical activity was observed in non-obese apparently healthy individuals a with different HOMA-IR index. The effect was marked by an improved health profile including higher vitamin D and lower inflammatory markers in IRA compared to IRS, and a higher oxygen carrying capacity and lipid profile in ISA compared to the ISS counterparts.
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Affiliation(s)
- Shamma AlMuraikhy
- Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar
- Groningen Research Institute of Pharmacy, Drug Design, Groningen University, 9712 CP Groningen, The Netherlands
| | - Najeha Anwardeen
- Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar
| | - Aisha Naeem
- Ministry of Public Health, Doha P.O. Box 42, Qatar
- Department of Oncology and Pathology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, 3800 Reservoir Rd., NW, Washington, DC 20007, USA
| | - Maha Sellami
- Physical Education Department (PE), College of Education, Qatar University, Doha P.O. Box 2713, Qatar
| | - Alexander Domling
- Groningen Research Institute of Pharmacy, Drug Design, Groningen University, 9712 CP Groningen, The Netherlands
| | - Abdelali Agouni
- College of Pharmacy, QU Health, Qatar University, Doha P.O. Box 2713, Qatar
| | - Mohamed A. Elrayess
- Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar
- College of Pharmacy, QU Health, Qatar University, Doha P.O. Box 2713, Qatar
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18
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Khalafi M, Symonds M. Impact of exercise training plus caloric restriction on cardiometabolic health in menopausal women who are overweight or obese: A meta-analysis. Sci Sports 2022. [DOI: 10.1016/j.scispo.2022.01.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
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19
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Insulin resistance in children. Curr Opin Pediatr 2022; 34:400-406. [PMID: 35796641 DOI: 10.1097/mop.0000000000001151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE OF REVIEW Insulin resistance (IR) is a clinical condition due to the decline in the efficiency of insulin promoting glucose uptake and utilization. The aim of this review is to provide an overview of the current knowledge on IR in children, focusing on its physiopathology, the most appropriate methods of measurement of IR, the assessment of risk factors, the effects of IR in children, and finally giving indications on screening and treatment. RECENT FINDINGS IR has evolved more and more to be a global public health problem associated with several chronic metabolic diseases. SUMMARY Detecting a correct measurement method and specific risk predictors, in order to reduce the incidence of IR, represents a challenging goal.
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20
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Ong SL, Abbasi F, Watson K, Robakis T, Myoraku A, Rasgon N. Family history of diabetes moderates metabolic depression endophenotypes in overweight/obese adults. J Psychiatr Res 2022; 151:583-589. [PMID: 35636036 DOI: 10.1016/j.jpsychires.2022.05.018] [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: 02/27/2022] [Revised: 05/12/2022] [Accepted: 05/19/2022] [Indexed: 11/19/2022]
Abstract
OBJECTIVE Insulin resistance (IR) is linked to depressive disorders, and there is growing evidence that targeting IR may be beneficial in treating them. We examine the association between depressive symptoms and a direct measure of IR, and whether family history of type 2 diabetes (FHx-T2DM) or major depressive disorder (FHx-MDD) moderate this relationship. METHODS Cross-sectional data were collected from 96 primarily overweight/obese adults ages 25-50 without diabetes or clinical depression. Multiple regression and correlation analyses were used to assess the association between depressive symptoms and a direct measure of IR (steady-state plasma glucose) as well as moderating effects of FHx-T2DM or FHx-MDD. RESULTS In the total sample, elevated depressive symptoms were positively associated with IR (p = 0.005). IR was associated with depressive symptoms in subjects with FHx-T2DM (p = 0.002) or FHx-MDD (p = 0.009) whereas BMI was associated with depressive symptoms in subjects without FHx-T2DM (p = 0.049) or FHx-MDD (p = 0.029). The odds of being in the top tertile of IR increased with elevated depressive symptoms alone (OR, 4.22; 95%CI, 1.15 to 17.33), presence of FHx-T2DM alone (OR, 3.42; 95%CI, 1.26 to 10.00), and presence of both FHx-T2DM and elevated depressive symptoms (OR, 10.08; 95%CI, 1.94 to 96.96). CONCLUSIONS Our findings indicate that depressive symptoms are positively associated with a direct measure of IR in overweight/obese individuals without diabetes or clinical depression. This association is moderated by FHx-T2DM. Early identification of groups vulnerable to IR related to depressive symptomatology may be useful for determining personalized interventions that have the potential to reduce morbidity in later years.
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Affiliation(s)
- Stacie L Ong
- Stanford University School of Medicine, Stanford, CA, 94305, USA
| | - Fahim Abbasi
- Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA
| | - Kathleen Watson
- Department of Psychiatry, Stanford University School of Medicine, Stanford, CA, 94305, USA
| | - Thalia Robakis
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
| | - Alison Myoraku
- Department of Psychiatry, Stanford University School of Medicine, Stanford, CA, 94305, USA
| | - Natalie Rasgon
- Department of Psychiatry, Stanford University School of Medicine, Stanford, CA, 94305, USA.
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A retrospective real-world observational pilot analysis of Waya: a self-monitoring fitness app in Germany. Cardiovasc Endocrinol Metab 2022; 11:e0266. [PMID: 35755420 PMCID: PMC9213173 DOI: 10.1097/xce.0000000000000266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Accepted: 05/23/2022] [Indexed: 11/25/2022]
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22
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Šebeková K, Gurecká R, Csongová M, Koborová I, Repiská G, Podracká Ľ. Lean insulin-resistant young adults display increased cardiometabolic risk: A retrospective cross-sectional study. Diabetes Res Clin Pract 2022; 185:109217. [PMID: 35114297 DOI: 10.1016/j.diabres.2022.109217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Revised: 11/01/2021] [Accepted: 01/24/2022] [Indexed: 11/17/2022]
Abstract
AIM We investigated whether lean insulin-resistant individuals manifest increased cardiometabolic risk. METHODS 2,341 (51.8% females) healthy 16-23-year-old subjects were categorized as lean or overweight/obese; and insulin-sensitive or insulin-resistant, and compared. RESULTS In both sexes, lean insulin-sensitive and insulin-resistant subjects displayed similar measures of obesity (e.g., males, waist-to-height ratio: lean insulin-sensitive: 0.42 ± 0.03, lean insulin-resistant: 0.43 ± 0.03, overweight/obese insulin-sensitive: 0.49 ± 0.05, overweight/obese insulin-resistant: 0.53 ± 0.06). Lean insulin-sensitive individuals were more insulin-sensitive compared with their overweight/obese peers; insulin-resistant groups presented similar insulin-sensitivity (males, the Quantitative insulin-sensitivity check index (QUICKI): lean insulin-sensitive: 0.354 ± 0.022, lean insulin-resistant: 0.304 ± 0.013, overweight/obese insulin-sensitive: 0.343 ± 0.019, overweight/obese insulin-resistant: 0.299 ± 0.015). The two-factor analysis of variance indicated an independent effect of insulin sensitivity, overweight/obesity, and their interaction on the continuous metabolic syndrome score (p < 0.001, all; males, lean insulin-sensitive: 1.87 ± 0.35, lean insulin-resistant: 2.14 ± 0.42, overweight/obese insulin-sensitive: 2.15 ± 0.40, overweight/obese insulin-resistant: 2.75 ± 0.69). C-reactive protein, leukocyte count, and glomerular filtration rate in both sexes; uric acid, asymmetric dimethyl-arginine, and soluble vascular adhesion protein-1 in males; and soluble receptor for advanced glycation end-products in females were independently associated with insulin resistance. Among phenotypes associated with low QUICKI, the distribution of insulin-resistant individuals was random. CONCLUSION Later clinical consequences of insulin resistance in lean subjects remain to be elucidated in longitudinal studies.
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Affiliation(s)
- Katarína Šebeková
- Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia.
| | - Radana Gurecká
- Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia; Institute of Medical Physics, Biophysics, Informatics and Telemedicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia
| | - Melinda Csongová
- Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia
| | - Ivana Koborová
- Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia
| | - Gabriela Repiská
- Institute of Physiology, Comenius University, Bratislava, Slovakia
| | - Ľudmila Podracká
- Department of Pediatrics of the Faculty of Medicine, Comenius University, and of The National Institute of Children's Health, Bratislava, Slovakia
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Cruz-Pineda WD, Garibay-Cerdenares OL, Rodríguez-Ruíz HA, Matia-García I, Marino-Ortega LA, Espinoza-Rojo M, Reyes-Castillo Z, Castro-Alarcón N, Castañeda-Saucedo E, Illades-Aguiar B, Parra-Rojas I. Changes in the Expression of Insulin Pathway, Neutrophil Elastase and Alpha 1 Antitrypsin Genes from Leukocytes of Young Individuals with Insulin Resistance. Diabetes Metab Syndr Obes 2022; 15:1865-1876. [PMID: 35757193 PMCID: PMC9215908 DOI: 10.2147/dmso.s362881] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Accepted: 05/19/2022] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Chronic hyperinsulinemia is a hallmark of insulin resistance that affects a diversity of cells, including leukocytes modifying the expression of some genes involved in insulin signaling. PURPOSE The aim of this study was to evaluate how hyperinsulinemia affects the expression of genes involved in the proximal insulin signaling pathway in leukocytes from 45 young individuals grouped: normal weight with not insulin resistance (NIR), with insulin resistance (IR) and with obesity (OB-IR). METHODS qPCR was performed to analyze the expression of insulin receptor (INSR), insulin receptor substrate 1 and 2 (IRS-1 and IRS-2), neutrophil elastase (NE), alpha 1 antitrypsin (A1AT), glucose transporters 1, 3 and 4 (GLUT-1, GLUT-3 and GLUT-4) by the 2-ΔCt method, and the correlation between the genes was determined by Spearman's test. RESULTS The mRNA expression analysis of all genes between NIR and IR individuals revealed no differences. However, when comparing NIR and IR individuals with OB-IR, an increase in NE and A1AT expression and a clear trend towards a decrease in IRS-2 expression was observed, whereas the comparison of IR and OB-IR showed a decrease in GLUT-3 expression. Overall, the correlation analysis showed that in the IR group there was a positive correlation only between NE with IRS-1 (r = 0.72, p = 0.003), while in the OB-IR group, there was a positive correlation between the NE and A1AT with INSR (r = 0.62, p = 0.01 and r = 0.74, p = 0.002, respectively) and with IRS-2 (r = 0.74, p = 0.002 and r = 0.76, p = 0.001, respectively). CONCLUSION These results suggest that hyperinsulinemia and obesity are associated with changes in the expression of genes in leukocytes involved in the insulin pathway that are related to NE and A1AT.
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Affiliation(s)
- Walter David Cruz-Pineda
- Laboratorio de Investigación en Obesidad y Diabetes, Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, México
| | - Olga Lilia Garibay-Cerdenares
- CONACyT-Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, México
- Laboratorio de Biomedicina Molecular, Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, México
- Olga Lilia Garibay-Cerdenares, CONACyT-Universidad Autónoma de Guerrero, Avenida Lázaro Cárdenas S/N, Ciudad Universitaria, Chilpancingo, Guerrero, CP 39090, México, Tel/Fax +52 7474710901, Email
| | - Hugo Alberto Rodríguez-Ruíz
- Laboratorio de Investigación en Obesidad y Diabetes, Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, México
- Laboratorio de Biomedicina Molecular, Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, México
| | - Inés Matia-García
- Laboratorio de Investigación en Obesidad y Diabetes, Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, México
| | - Linda Anahí Marino-Ortega
- Laboratorio de Investigación en Obesidad y Diabetes, Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, México
| | - Mónica Espinoza-Rojo
- Laboratorio de Biología Molecular y Genómica, Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, México
| | - Zyanya Reyes-Castillo
- Instituto de Investigaciones en Comportamiento Alimentario y Nutrición, Centro Universitario del Sur, Universidad de Guadalajara, Ciudad Guzmán, Jalisco, México
| | - Natividad Castro-Alarcón
- Laboratorio de Investigación en Microbiología, Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, México
| | - Eduardo Castañeda-Saucedo
- Laboratorio de Investigación en Biología Celular del Cáncer, Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, México
| | - Berenice Illades-Aguiar
- Laboratorio de Biomedicina Molecular, Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, México
| | - Isela Parra-Rojas
- Laboratorio de Investigación en Obesidad y Diabetes, Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, México
- Correspondence: Isela Parra-Rojas, Laboratorio de Investigación en Obesidad y Diabetes, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Avenida Lázaro Cárdenas S/N, Ciudad Universitaria, Chilpancingo, Guerrero, CP 39090, México, Tel/Fax +52 7474719310, Email
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Shen L, Wang D, Huang Y, Ye L, Zhu C, Zhang S, Cai S, Wang Z, Chen H. Longitudinal trends in lipid profiles during pregnancy: Association with gestational diabetes mellitus and longitudinal trends in insulin indices. Front Endocrinol (Lausanne) 2022; 13:1080633. [PMID: 36714591 PMCID: PMC9880552 DOI: 10.3389/fendo.2022.1080633] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Accepted: 12/28/2022] [Indexed: 01/15/2023] Open
Abstract
OBJECTIVE To investigate the correlation of trends in lipid profiles from first to second trimester with trends in insulin indices and gestational diabetes mellitus (GDM). METHODS Secondary analysis of an ongoing prospective cohort study was conducted on 1234 pregnant women in a single center. Lipid profiles, glucose metabolism and insulin indices were collected in the first and second trimesters. Trends in lipid profiles were divided into four subgroups: low-to-low, high-to-high, high-to-low and low-to-high group. Insulin indices including homeostasis model assessment of insulin resistance and quantitative insulin sensitivity check index were calculated to evaluate insulin resistance (IR). Trends in insulin indices were described as: no IR, persistent IR, first-trimester IR alone and second-trimester IR alone. Pearson correlation analysis and multivariate logistic regression were performed to assess the associations of lipid profiles subgroups with insulin indices and GDM. RESULTS First- and second-trimester total cholesterol (TC), triglycerides (TG) and high-density lipoprotein cholesterol were strongly correlated to first- and second-trimester insulin indices. Only TG had a sustained correlation with glucose metabolism indices. High-to-high low-density lipoprotein cholesterol (LDL-c) was an independent risk factor for GDM. High-to-high TG and high-to-low TG groups were independent risk factors for persistent IR. High-to-high TG and low-to-high TG groups were independent risk factors for second-trimester IR alone. CONCLUSION TG has a sustained correlation with insulin indices and glucose metabolism indices. Persistently high TG is an independent risk factor for persistent IR and second-trimester IR alone. Regardless of whether pregnant women have first-trimester IR, lower TG levels help reduce the risk for persistent IR or subsequent development of IR. These results highlight the benefit of lowering TG levels in early and middle pregnancy to prevent the development of IR.
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Affiliation(s)
| | | | | | | | | | | | | | - Zilian Wang
- *Correspondence: Haitian Chen, ; Zilian Wang,
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Simental-Mendía LE, Gómez-Díaz R, Wacher NH, Guerrero-Romero F. The Triglycerides and Glucose Index is Negatively Associated with Insulin Secretion in Young Adults with Normal Weight. Horm Metab Res 2022; 54:33-36. [PMID: 34986498 DOI: 10.1055/a-1713-7821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Several studies have supported the usefulness of the triglycerides and glucose (TyG) index as a surrogate measure of insulin resistance; however, it has not been evaluated in insulin secretion. The aim of this study was to assess the association between the TyG index and insulin secretion in young adults with normal weight. Apparently healthy non-pregnant women and men, aged 18 to 23 years, were enrolled in a cross-sectional study. Overweight, obesity, pregnancy, smoking, alcohol consumption, diabetes, liver disease, renal disease, cardiovascular disease, and neoplasia were the exclusion criteria. Normal weight was defined by a body mass index (BMI)≥18.5<25.0 kg/m2 and the TyG index was calculated as the Ln [fasting triglycerides (mg/dl) x fasting glucose (mg/dl)]/2. A total of 1676 young adults with normal-weight, 1141 (68%) women, and 535 (32%) men were enrolled. Of them, 269 (16%) individuals exhibited insulin resistance; 213 (12.7%) women and 56 (3.3%) men. The linear regression analysis adjusted by gender, BMI, and waist circumference showed a significant association between the TyG index and HOMA-B (B=-35.90; 95% CI:-68.25 to-3.54, p=0.03) in the overall population. An additional analysis adjusted by BMI and waist circumference revealed that the TyG index is significantly associated with HOMA-B in subjects with and without insulin resistance (B=-104.73; 95% CI:-204.28 to-5.18, p=0.03 and B=-74.72; 95% CI:-108.04 to-41.40, p<0.001). The results of this study showed that the TyG index is negatively associated with insulin secretion in young adults with normal weight.
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Affiliation(s)
- Luis E Simental-Mendía
- Unidad de Investigación Biomédica, Instituto Mexicano del Seguro Social, Durango, Dgo., México
| | - Rita Gómez-Díaz
- Unidad de Investigación Médica en Epidemiología Clínica, Centro Médico Nacional "Siglo XXI", Instituto Mexicano del Seguro Social, México
| | - Niels H Wacher
- Unidad de Investigación Médica en Epidemiología Clínica, Centro Médico Nacional "Siglo XXI", Instituto Mexicano del Seguro Social, México
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Puzziferri N, Friedman AN, Wolfe BM. Bariatric surgery and kidney disease. NUTRITIONAL MANAGEMENT OF RENAL DISEASE 2022:793-804. [DOI: 10.1016/b978-0-12-818540-7.00022-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Ezemaduka Okoli CB, Woldu HG, Peterson CA. Low Urinary Iodine Concentration Is Associated with Increased Risk for Elevated Plasma Glucose in Females: An Analysis of NHANES 2011-12. Nutrients 2021; 13:4523. [PMID: 34960073 PMCID: PMC8708116 DOI: 10.3390/nu13124523] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 12/13/2021] [Accepted: 12/15/2021] [Indexed: 12/17/2022] Open
Abstract
Iodine intake in the US has declined in recent years. Iodine insufficiency increases the risk for inadequate thyroid hormone production and there is growing evidence that sub-clinical hypothyroidism may be disruptive to metabolic health, including insulin resistance (IR). We investigated the association between urinary iodine concentrations (UIC), a measurement of iodine status, and IR in adults. Data from 1286 US adults (≥20 years) in the NHANES 2011-2012 were analyzed. Two subgroups (low = UIC < 100 µg/L and normal = UIC ≥ 100 µg/L) were compared for markers of IR, including fasting plasma glucose (FPG) and insulin, homeostatic model assessment of insulin resistance (HOMA-IR), and glycated hemoglobin (HbA1C). Chi-square test, both linear and logistic regression models were used. In males, there were no significant associations between UIC and markers of IR; however, females with normal UIC had greater risks for elevated HOMA-IR (AOR = 0.56, 95% CI= 0.32-0.99) and HbA1C (AOR = 0.56, 95% CI = 0.34-0.90), while females with low UIC had a greater risk for FPG ≥ 5.6 mmol/L (AOR = 1.73, 95% CI = 1.09-2.72). Results only partially support our hypothesis that UIC is associated with the odds of IR in adults. The finding of an increased risk for elevated FPG, a marker of prediabetes, in female adults with low iodine status requires further investigation.
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Affiliation(s)
| | - Henok G. Woldu
- Department of Health Management and Informatics, School of Medicine, University of Missouri, Columbia, MO 65211, USA;
| | - Catherine A. Peterson
- Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211, USA
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Kovačević S, Brkljačić J, Vojnović Milutinović D, Gligorovska L, Bursać B, Elaković I, Djordjevic A. Fructose Induces Visceral Adipose Tissue Inflammation and Insulin Resistance Even Without Development of Obesity in Adult Female but Not in Male Rats. Front Nutr 2021; 8:749328. [PMID: 34869524 PMCID: PMC8632624 DOI: 10.3389/fnut.2021.749328] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Accepted: 10/08/2021] [Indexed: 12/15/2022] Open
Abstract
Introduction: Obesity and related metabolic disturbances are frequently related to modern lifestyle and are characterized by excessive fructose intake. Visceral adipose tissue (VAT) inflammation has a central role in the development of insulin resistance, type 2 diabetes (T2D), and metabolic syndrome. Since sex-related differences in susceptibility and progression of metabolic disorders are not yet fully understood, our aim was to examine inflammation and insulin signaling in VAT of fructose-fed female and male adult rats. Methods: We analyzed effects of 9-week 10% fructose-enriched diet on energy intake, VAT mass and histology, and systemic insulin sensitivity. VAT insulin signaling and markers of VAT inflammation, and antioxidative defense status were also evaluated. Results: The fructose diet had no effect on VAT mass and systemic insulin signaling in the female and male rats, while it raised plasma uric acid, increased PPARγ level in the VAT, and initiated the development of a distinctive population of small adipocytes in the females. Also, adipose tissue insulin resistance, evidenced by increased PTP1B and insulin receptor substrate 1 (IRS1) inhibitory phosphorylation and decreased Akt activity, was detected. In addition, fructose stimulated the nuclear accumulation of NFκB, increased expression of proinflammatory cytokines (IL-1β, IL-6, and TNFα), and protein level of macrophage marker F4/80, superoxide dismutase 1, and glutathione reductase. In contrast to the females, the fructose diet had no effect on plasma uric acid and VAT inflammation in the male rats, but less prominent alterations in VAT insulin signaling were observed. Conclusion: Even though dietary fructose did not elicit changes in energy intake and led to obesity in the females, it initiated the proliferation of small-sized adipocytes capable of storing fats further. In contrast to the males, this state of VAT was accompanied with enhanced inflammation, which most likely contributed to the development of insulin resistance. The observed distinction could possibly originate from sex-related differences in uric acid metabolism. Our results suggest that VAT inflammation could precede obesity and start even before the measurable increase in VAT mass, making it a silent risk factor for the development of T2D. Our results emphasize that adipose tissue dysfunction, rather than its simple enlargement, could significantly contribute to the onset and development of obesity and related metabolic disorders.
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Affiliation(s)
- Sanja Kovačević
- Department of Biochemistry, Institute for Biological Research "Siniša Stanković"-National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Jelena Brkljačić
- Department of Biochemistry, Institute for Biological Research "Siniša Stanković"-National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Danijela Vojnović Milutinović
- Department of Biochemistry, Institute for Biological Research "Siniša Stanković"-National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Ljupka Gligorovska
- Department of Biochemistry, Institute for Biological Research "Siniša Stanković"-National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Biljana Bursać
- Department of Biochemistry, Institute for Biological Research "Siniša Stanković"-National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Ivana Elaković
- Department of Biochemistry, Institute for Biological Research "Siniša Stanković"-National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia
| | - Ana Djordjevic
- Department of Biochemistry, Institute for Biological Research "Siniša Stanković"-National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia
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Karczewska-Kupczewska M, Nikołajuk A, Stefanowicz M, Matulewicz N, Arnoriaga-Rodriguez M, Fernandez-Real JM, Strączkowski M. Novel Laboratory Index, Based on Fasting Blood Parameters, Accurately Reflects Insulin Sensitivity. J Clin Endocrinol Metab 2021; 106:e5208-e5221. [PMID: 34228124 DOI: 10.1210/clinem/dgab489] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Indexed: 01/02/2023]
Abstract
CONTEXT Simple and reliable measurement of insulin sensitivity may be important for the prevention of insulin-resistance-related diseases. Surrogate indices of insulin sensitivity are of limited utility in population without signs of metabolic syndrome. OBJECTIVE The aim of our study was to provide simple and accurate index of insulin sensitivity. DESIGN The study group comprised 150 young healthy participants. Hyperinsulinemic-euglycemic clamp was performed. Regression models with different laboratory parameters were constructed. Validation cohort 1 comprised independent group of 110 subjects, including individuals with prediabetes and newly diagnosed type 2 diabetes. Validation cohort 2 comprised 38 obese subjects before and after diet-induced weight loss. Validation cohort 3 comprised 60 nondiabetic subjects from an independent center. RESULTS The supervised principal component model established optimal set of variables correlated with insulin sensitivity. This model (Fasting Laboratory Assessment of Insulin Sensitivity [FLAIS]) used red blood cell count, alanine aminotransferase activity, serum C-peptide, SHBG, IGF-binding protein 1, and adiponectin concentrations. FLAIS exhibited strong correlation with clamp-derived insulin sensitivity. The sensitivity of the model was 90% and the specificity was 68%. In validation cohort 1, differences in FLAIS among the groups paralleled those observed with the clamp, with the lowest values in prediabetes and diabetes. In validation cohort 2, FLAIS reflected the change in insulin sensitivity after weight loss. The main findings were confirmed in validation cohort 3. CONCLUSION We provide simple and accurate method of assessing insulin sensitivity, which allows to identify insulin resistance even in the population without overt metabolic disturbances.
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Affiliation(s)
- Monika Karczewska-Kupczewska
- Department of Internal Medicine and Metabolic Diseases, Medical University of Białystok, 15-276 Białystok, Poland
| | - Agnieszka Nikołajuk
- Department of Prophylaxis of Metabolic Diseases, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland
| | - Magdalena Stefanowicz
- Department of Metabolic Diseases, Medical University of Białystok, Białystok, Poland
| | - Natalia Matulewicz
- Department of Metabolic Diseases, Medical University of Białystok, Białystok, Poland
| | - Maria Arnoriaga-Rodriguez
- Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta University Hospital; Department of Medical Sciences, Faculty of Medicine, University of Girona; and CIBERobn Pathophysiology of Obesity and Nutrition, Girona, Spain
| | - Jose Manuel Fernandez-Real
- Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta University Hospital; Department of Medical Sciences, Faculty of Medicine, University of Girona; and CIBERobn Pathophysiology of Obesity and Nutrition, Girona, Spain
| | - Marek Strączkowski
- Department of Prophylaxis of Metabolic Diseases, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland
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Li H, Ma J, Zheng D, Li X, Guo X, Wang J, Su P. Sex differences in the non-linear association between BMI and LDL cholesterol in middle-aged and older adults: findings from two nationally representative surveys in China. Lipids Health Dis 2021; 20:162. [PMID: 34774059 PMCID: PMC8590757 DOI: 10.1186/s12944-021-01591-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 10/29/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The relationship between body mass index (BMI) and low-density lipoprotein cholesterol (LDL-C) has not been clearly elucidated in middle-aged and older adults. This study aimed to evaluate the non-linear dose-response relationship between BMI and LDL-C in males and females. METHODS Data was obtained from two nationally representative surveys in China-the China Health and Nutrition Survey (CHNS, 2009) and China Health and Retirement Longitudinal Study (CHARLS, 2011-2012). To evaluate the sex differences in the association between BMI and LDL-C, the generalized additive models with a smooth function for continuous BMI and smooth-factor interaction for sexes with BMI were used. Segmented regressions were fitted to calculate the slopes with different estimated breakpoints among females and males. RESULTS A total of 12,273 participants (47.1% male) aged 45 to 75 years were included. The generalized additive models revealed that a non-linear relationship between BMI and LDL-C level in both sexes after adjustment for age, residence, education levels, marital status, drinking, smoking status, and cohort (CHNS or CHARLS). Slopes of the association between BMI and LDL-C association changed at BMI 20.3 kg/m2 (95% CI: 18.8 to 21.8) in females and 27.1 kg/m2 (95% CI: 25. 8 to 28.4) in males. Below these BMI breakpoints, LDL-C levels increased 1.84 (95% CI: 1.45 to 2.31) in males and 3.49 (95% CI: 1.54 to 5.45) mg/dL per kg/m2 in females. However, LDL-C levels declined - 1.50 (95% CI: - 2.92 to - 0.09) mg/dL per kg/m2 above BMI of 27.1 kg/m2 in males. The non-linear association BMI and LDL-C in males and females was varied by cohort source, age groups, and the number of metabolic syndrome criteria. CONCLUSIONS In the Chinese middle aged and older adults, the BMI and LDL-C relationship was inverted U-shaped with a high level of LDL-C at a BMI of 27.1 kg/m2 in males, and an approximately linear association was observed in females.
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Affiliation(s)
- Haibin Li
- Department of Cardiac Surgery, Heart Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Jiahui Ma
- Department of Anesthesiology and Critical Care Medicine, Peking University First Hospital, Beijing, China
| | - Deqiang Zheng
- Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China
| | - Xia Li
- Department of Mathematics and Statistics, La Trobe University, Melbourne, Victoria, Australia
| | - Xiuhua Guo
- Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China
| | - Jing Wang
- Department of Clinical Laboratory, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
| | - Pixiong Su
- Department of Cardiac Surgery, Heart Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
- Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
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Sears B, Saha AK. Dietary Control of Inflammation and Resolution. Front Nutr 2021; 8:709435. [PMID: 34447777 PMCID: PMC8382877 DOI: 10.3389/fnut.2021.709435] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Accepted: 07/13/2021] [Indexed: 12/18/2022] Open
Abstract
The healing of any injury requires a dynamic balance of initiation and resolution of inflammation. This hypothesis-generating review presents an overview of the various nutrients that can act as signaling agents to modify the metabolic responses essential for the optimal healing of injury-induced inflammation. In this hypothesis-generating review, we describe a defined nutritional program consisting of an integrated interaction of a calorie-restricted anti-inflammatory diet coupled with adequate levels of omega-3 fatty acids and sufficient levels of dietary polyphenols that can be used in clinical trials to treat conditions associated with insulin resistance. Each dietary intervention works in an orchestrated systems-based approach to reduce, resolve, and repair the tissue damage caused by any inflammation-inducing injury. The orchestration of these specific nutrients and their signaling metabolites to facilitate healing is termed the Resolution Response. The final stage of the Resolution Response is the activation of intracellular 5' adenosine monophosphate-activated protein kinase (AMPK), which is necessary to repair tissue damaged by the initial injury-induced inflammation. The dietary optimization of the Resolution Response can be personalized to the individual by using standard blood markers. Once each of those markers is in their appropriate ranges, activation of intracellular AMPK will be facilitated. Finally, we outline how the resulting activation of AMPK will affect a diverse number of other intercellular signaling systems leading to an extended healthspan.
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Affiliation(s)
- Barry Sears
- Inflammation Research Foundation, Peabody, MA, United States
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Sweatt AJ, Reddy R, Rahaghi FN, Al-Naamani N, on behalf of the American Thoracic Society Pulmonary Circulation Assembly Early Career Working Group. What's new in pulmonary hypertension clinical research: lessons from the best abstracts at the 2020 American Thoracic Society International Conference. Pulm Circ 2021; 11:20458940211040713. [PMID: 34471517 PMCID: PMC8404658 DOI: 10.1177/20458940211040713] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2021] [Accepted: 07/26/2021] [Indexed: 12/23/2022] Open
Abstract
In this conference paper, we review the 2020 American Thoracic Society International Conference session titled, "What's New in Pulmonary Hypertension Clinical Research: Lessons from the Best Abstracts". This virtual mini-symposium took place on 21 October 2020, in lieu of the annual in-person ATS International Conference which was cancelled due to the COVID-19 pandemic. Seven clinical research abstracts were selected for presentation in the session, which encompassed five major themes: (1) standardizing diagnosis and management of pulmonary hypertension, (2) improving risk assessment in pulmonary arterial hypertension, (3) evaluating biomarkers of disease activity, (4) understanding metabolic dysregulation across the spectrum of pulmonary hypertension, and (5) advancing knowledge in chronic thromboembolic pulmonary hypertension. Focusing on these five thematic contexts, we review the current state of knowledge, summarize presented research abstracts, appraise their significance and limitations, and then discuss relevant future directions in pulmonary hypertension clinical research.
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Affiliation(s)
- Andrew J. Sweatt
- Division of Pulmonary, Allergy and Critical Care Medicine, Stanford University, Stanford, CA, USA
- Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford, CA, USA
| | - Raju Reddy
- Division of Pulmonary and Critical Care Medicine, Oregon Health and Science University, Portland, OR, USA
| | - Farbod N. Rahaghi
- Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Boston, MA, USA
| | - Nadine Al-Naamani
- Division of Pulmonary and Critical Care Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - on behalf of the American Thoracic Society Pulmonary Circulation Assembly Early Career Working Group
- Division of Pulmonary, Allergy and Critical Care Medicine, Stanford University, Stanford, CA, USA
- Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford, CA, USA
- Division of Pulmonary and Critical Care Medicine, Oregon Health and Science University, Portland, OR, USA
- Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Boston, MA, USA
- Division of Pulmonary and Critical Care Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
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Huang J, Peng X, Dong K, Tao J, Yang Y. The Association Between Insulin Resistance, Leptin, and Resistin and Diabetic Nephropathy in Type 2 Diabetes Mellitus Patients with Different Body Mass Indexes. Diabetes Metab Syndr Obes 2021; 14:2357-2365. [PMID: 34079314 PMCID: PMC8163637 DOI: 10.2147/dmso.s305054] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 04/15/2021] [Indexed: 02/01/2023] Open
Abstract
AIM This study aimed to compare HOMA-IR, leptin, and resistin as the risk factors for diabetic nephropathy in the type 2 diabetes mellitus (T2DM) patients with different BMI classifications. MATERIALS AND METHODS A total of 309 patients with T2DM were enrolled in this cross-sectional study. All participants were divided into three groups according to BMI: the normal weight group (18.5 kg/m2≤BMI<24 kg/m2), the overweight group (24kg/m2≤BMI<28 kg/m2) and the obesity group (BMI≥28 kg/m2). The clinical information and laboratory examinations were recorded in detail. Leptin and resistin levels were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS Higher HOMA-IR, leptin and resistin levels were found to be the risk factors for diabetic nephropathy when we made comparisons in the total population (P<0.05). In the normal weight group, logistic regression analysis showed that T2DM patients with higher HOMA-IR (OR=4.210, P=0.001), leptin (OR=2.474, P=0.031) and resistin levels (OR=8.299, P<0.001) had nearly 4-fold, 2-fold and 8-fold risk for diabetic nephropathy, respectively, after adjustments. The receiver operating characteristic (ROC) curves indicated that the area under the curves (AUCs) of HOMA-IR and resistin were 0.699 (95% CI 0.617-0.772) and 0.790 (95% CI 0.715-0.854), respectively, which were significantly larger than the AUC of 0.5 (all P<0.001). However, no significant association was observed between HOMA-IR, leptin, and resistin and renal complications (all P>0.05) in the overweight and obesity groups in both logistic regression and AUC analysis. CONCLUSION Higher insulin resistance, leptin and resistin levels were observed as risk factors for diabetic nephropathy in T2DM patients with lower BMI. These were not obvious in the overweight and obese patients.
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Affiliation(s)
- Jiaojiao Huang
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China
| | - Xuemin Peng
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China
| | - Kun Dong
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China
| | - Jing Tao
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China
| | - Yan Yang
- Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China
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Diboun I, Al-Mansoori L, Al-Jaber H, Albagha O, Elrayess MA. Metabolomics of Lean/Overweight Insulin-Resistant Females Reveals Alterations in Steroids and Fatty Acids. J Clin Endocrinol Metab 2021; 106:e638-e649. [PMID: 33053159 DOI: 10.1210/clinem/dgaa732] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Accepted: 10/08/2020] [Indexed: 01/13/2023]
Abstract
BACKGROUND The global diabetes epidemic is largely attributed to obesity-triggered metabolic syndrome. However, the impact of insulin resistance (IR) prior to obesity on the high prevalence of diabetes and the molecular mediators remain largely unknown. This study aims to compare the metabolic profiling of apparently healthy lean/overweight participants with IR and insulin sensitivity (IS), and identify the metabolic pathways underlying IR. METHODS In this cross-sectional study, clinical and metabolic data for 200 seemingly healthy young female participants (100 IR and 100 IS) was collected from Qatar Biobank. Orthogonal partial least square analysis was performed to assess the extent of separation between individuals from the 2 groups based on measured metabolites. Classical linear models were used to identify the metabolic signature of IR, followed by elastic-net-regularized generalized linear model (GLMNET) and receiver operating characteristic (ROC) analysis to determine top metabolites associated with IR. RESULTS Compared to lean/overweight participants with IS, those with IR showed increased androgenic steroids, including androsterone glucuronide, in addition to various microbiota byproducts, such as the phenylalanine derivative carboxyethylphenylalanine. On the other hand, participants with IS had elevated levels of long-chain fatty acids. A ROC analysis suggested better discriminatory performance using 20 metabolites selected by GLMNET in comparison to the classical clinical traits (area under curve: 0.93 vs 0.73, respectively). CONCLUSION Our data confirm the multifactorial mechanism of IR with a diverse spectrum of emerging potential biomarkers, including steroids, long-chain fatty acids, and microbiota metabolites. Further studies are warranted to validate these markers for diagnostic and therapeutic applications.
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Affiliation(s)
- Ilhame Diboun
- College of Health and Life Sciences, Hamad Bin Khalifa University (HBKU), Doha, Qatar
| | | | - Hend Al-Jaber
- Biomedical Research Center (BRC), Qatar University, Doha, Qatar
| | - Omar Albagha
- College of Health and Life Sciences, Hamad Bin Khalifa University (HBKU), Doha, Qatar
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Martins VF, Dobson CR, Begur M, Parekh J, Ball ST, Gonzalez F, Hughes-Austin JM, Schenk S. Surgical site peptidylarginine deaminase 4 (PAD4), a biomarker of NETosis, correlates with insulin resistance in total joint arthroplasty patients: A preliminary report. PLoS One 2021; 16:e0245594. [PMID: 33481860 PMCID: PMC7822240 DOI: 10.1371/journal.pone.0245594] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2020] [Accepted: 01/04/2021] [Indexed: 01/12/2023] Open
Abstract
While obesity and insulin resistance are known risk factors for wound complications after total joint arthroplasty (TJA), the biologic causes remain to be elucidated. Recently, neutrophil extracellular trap formation (NETosis) was identified as a mediator of delayed wound healing in insulin resistant states. Herein, we explored the relationship between obesity, insulin resistance and biomarkers of NET formation in TJA subjects. We enrolled 14 obese (body mass index [BMI]≥30 kg/m2), and 15 lean (BMI<30 kg/m2) subjects undergoing primary knee or hip TJA. On the day of surgery, skeletal muscle proximal to the operated joint and plasma were collected. Protein abundance of NETosis biomarkers, peptidylarginine deaminase 4 (PAD4) and neutrophil elastase (NE) were assessed in skeletal muscle by immunoblotting and metabolic parameters (glucose, insulin, triglycerides, free fatty acids) and cell-free double-stranded DNA (cf-dsDNA) were assessed in plasma and were correlated with obesity and insulin resistance (as measured by the homeostatic model assessment for insulin resistance). When comparing lean and obese subjects, there were no significant differences in plasma cf-dsDNA or skeletal muscle NE or PAD4 abundance. In contrast, skeletal muscle PAD4 abundance, but not NE or plasma cf-dsDNA, was positively correlated with insulin resistance. Compared to insulin sensitive subjects, insulin resistant TJA subjects have higher expression of PAD4 at the surgical site and therefore may have higher rates of NET formation, which may lead to delayed surgical site wound healing.
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Affiliation(s)
- Vitor F. Martins
- Department of Orthopaedic Surgery, University of California San Diego, La Jolla, CA, United States of America
- Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, CA, United States of America
| | - Christopher R. Dobson
- Department of Orthopaedic Surgery, University of California San Diego, La Jolla, CA, United States of America
| | - Maedha Begur
- Department of Orthopaedic Surgery, University of California San Diego, La Jolla, CA, United States of America
| | - Jesal Parekh
- Department of Orthopaedic Surgery, University of California San Diego, La Jolla, CA, United States of America
| | - Scott T. Ball
- Department of Orthopaedic Surgery, University of California San Diego, La Jolla, CA, United States of America
| | - Francis Gonzalez
- Department of Orthopaedic Surgery, University of California San Diego, La Jolla, CA, United States of America
| | - Jan M. Hughes-Austin
- Department of Orthopaedic Surgery, University of California San Diego, La Jolla, CA, United States of America
| | - Simon Schenk
- Department of Orthopaedic Surgery, University of California San Diego, La Jolla, CA, United States of America
- Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, CA, United States of America
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Yang Y, Wang B, Yuan H, Li X. Triglycerides to High-Density Lipoprotein Cholesterol Ratio Is the Best Surrogate Marker for Insulin Resistance in Nonobese Middle-Aged and Elderly Population: A Cross-Sectional Study. Int J Endocrinol 2021; 2021:6676569. [PMID: 34007274 PMCID: PMC8110426 DOI: 10.1155/2021/6676569] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Revised: 04/18/2021] [Accepted: 04/24/2021] [Indexed: 12/01/2022] Open
Abstract
OBJECTIVE Insulin resistance (IR) is closely associated with metabolic profiles, including obesity and dyslipidemia. The aim of the present study was to examine how lipid profiles were associated with IR in nonobese middle-aged and elderly Chinese population. METHODS This cross-sectional study included 1608 subjects. IR was defined by homeostasis model assessment of insulin resistance (HOMA-IR) of at least 2.5. RESULTS In nonobese subjects (body mass index (BMI) < 25 kg/m2, n = 996), triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio (odds ratio (OR) = 1.43, 95% confidence interval (CI) 1.13-1.81, P=0.003) was an independent risk factor for IR. The best marker for predicting IR in nonobese subjects was TG/HDL-C ratio with the areas under the receiver operating characteristic curves (AUC) of 0.73 (P < 0.001). The optimal cut-off point to identifying IR for TG/HDL-C ratio was ≥1.50 in the nonobese population. Other markers like BMI, TG, and total cholesterol (TC)/HDL-C also had acceptable discriminatory power for predicting IR in nonobese population (AUC ≥ 0.7 and P < 0.001). BMI had the highest AUC of 0.647 (P < 0.001) after being adjusted, but it was not effective enough to predict IR in obese subjects (BMI ≥ 25.0, n = 612). CONCLUSIONS The TG/HDL-C ratio may be the best reliable marker for predicting IR in the nonobese middle-aged and elderly Chinese population.
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Affiliation(s)
- Yumei Yang
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai 200032, China
| | - Baomin Wang
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai 200032, China
| | - Haoyue Yuan
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai 200032, China
| | - Xiaomu Li
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai 200032, China
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Abstract
(1) Background: Myoinositol (MI) and D-chiro-inositol (DCI) are involved in a number of biochemical pathways within oocytes having a role in oocyte maturation, fertilization, implantation, and post-implantation development. Both inositols have a role in insulin signaling and hormonal synthesis in the ovaries. (2) Methods: Literature search (with key words: inositols, myo-inositol, d-chiro-inositol, PCOS) was done in PubMed until Sept. 2020 and 197 articles were identified, of which 47 were of clinical trials (35 randomized controlled trials). (3) Results: Many studies have demonstrated that in patients with polycystic ovarian syndrome (PCOS) MI treatment improved ovarian function and fertility, decreased the severity of hyperandrogenism including acne and hirsutism, positively affected metabolic aspects, and modulated various hormonal parameters deeply involved in the reproductive axis function and ovulation. Thus treating with MI has become a novel method to ameliorate PCOS symptoms, improve spontaneous ovulation, or induce ovulation. The current review is focused on the effects of MI and DCI alone or in combination with other agents on the pathological features of PCOS with focus on insulin resistance and adverse metabolic outcomes. (4) Conclusions: The available clinical data suggest that MI, DCI, and their combination in physiological ratio 40:1 with or without other compound could be beneficial for improving metabolic, hormonal, and reproductive aspects of PCOS.
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Affiliation(s)
- Zdravko Kamenov
- Department of Internal Medicine, Clinic of Endocrinology University Hospital Alexandrovska, Medical University—Sofia, 1431 Sofia, Bulgaria;
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Jamka M, Kaczmarek N, Mądry E, Krzyżanowska-Jankowska P, Bajerska J, Kręgielska-Narożna M, Bogdański P, Walkowiak J. Metabolic Health in Obese Subjects-Is There a Link to Lactoferrin and Lactoferrin Receptor-Related Gene Polymorphisms? Nutrients 2020; 12:2843. [PMID: 32957486 PMCID: PMC7551427 DOI: 10.3390/nu12092843] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Revised: 08/25/2020] [Accepted: 09/15/2020] [Indexed: 12/21/2022] Open
Abstract
This study aimed to evaluate the association of genetic variants in lactoferrin (LTF) metabolism-related genes with the prevalence of metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO). In total, 161 MHO and 291 MUHO subjects were recruited to the study. The following polymorphisms were genotyped: low-density lipoprotein receptor-related protein (LRP) 2 rs2544390, LRP1 rs4759277, LRP1 rs1799986, LTF rs1126477, LTF rs2239692 and LTF rs1126478. We found significant differences in the genotype frequencies of LTF rs2239692 between MHO and MUHO subjects, with the CT variant associated with lower odds of developing metabolic syndrome than the TT variant. In the total population, significant differences in body weight and waist circumference (WC) were identified between LTF rs1126477 gene variants. A similar association with WC was observed in MUHO subjects, while significant differences in body mass index and low-density lipoprotein cholesterol levels were discovered between LTF rs1126477 gene variants in MHO subjects. Besides, there were significant differences in diastolic blood pressure between LRP1 rs1799986 gene variants in MUHO subjects, as well as in WC and high-density lipoprotein cholesterol levels between LRP1 rs4759277 gene variants in MHO subjects. In conclusion, selected lactoferrin and lactoferrin receptor-related gene variants may be associated with the prevalence of metabolically healthy or metabolically unhealthy obesity.
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Affiliation(s)
- Małgorzata Jamka
- Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, Szpitalna Str. 27/33, 60-572 Poznań, Poland; (N.K.); (P.K.-J.); (J.W.)
| | - Nina Kaczmarek
- Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, Szpitalna Str. 27/33, 60-572 Poznań, Poland; (N.K.); (P.K.-J.); (J.W.)
| | - Edyta Mądry
- Department of Physiology, Poznan University of Medical Sciences, Święcickiego Str. 6, 60-781 Poznań, Poland;
| | - Patrycja Krzyżanowska-Jankowska
- Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, Szpitalna Str. 27/33, 60-572 Poznań, Poland; (N.K.); (P.K.-J.); (J.W.)
| | - Joanna Bajerska
- Institute of Human Nutrition and Dietetics, Poznan University of Life Sciences, Wojska Polskiego Str. 31, 60-624 Poznań, Poland;
| | - Matylda Kręgielska-Narożna
- Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, Szamarzewskiego Str. 84, 60-569 Poznań, Poland; (M.K.-N.); (P.B.)
| | - Paweł Bogdański
- Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, Szamarzewskiego Str. 84, 60-569 Poznań, Poland; (M.K.-N.); (P.B.)
| | - Jarosław Walkowiak
- Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, Szpitalna Str. 27/33, 60-572 Poznań, Poland; (N.K.); (P.K.-J.); (J.W.)
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Vinciguerra F, Tumminia A, Baratta R, Ferro A, Alaimo S, Hagnäs M, Graziano M, Vigneri R, Frittitta L. Prevalence and Clinical Characteristics of Children and Adolescents with Metabolically Healthy Obesity: Role of Insulin Sensitivity. Life (Basel) 2020; 10:life10080127. [PMID: 32731619 PMCID: PMC7459932 DOI: 10.3390/life10080127] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 07/24/2020] [Accepted: 07/27/2020] [Indexed: 02/06/2023] Open
Abstract
Obesity represents a major risk factor for metabolic disorders, but some individuals, "metabolically healthy" (MHO), show less clinical evidence of these complications, in contrast to "metabolically unhealthy" (MUO) individuals. The aim of this cross-sectional study is to assess the prevalence of the MHO phenotype in a cohort of 246 overweight/obese Italian children and adolescents, and to evaluate their characteristics and the role of insulin resistance. Homeostasis model assessment-insulin resistance (HOMA-IR), insulin sensitivity index (ISI), insulinogenic index (IGI) and disposition index (DI) were all calculated from the Oral Glucose Tolerance Test (OGTT). MHO was defined by either: (1) HOMA-IR < 2.5 (MHO-IRes), or (2) absence of the criteria for metabolic syndrome (MHO-MetS). The MHO prevalence, according to MHO-MetS or MHO-IRes criteria, was 37.4% and 15.8%, respectively. ISI was the strongest predictor of the MHO phenotype, independently associated with both MHO-IRes and MHO-MetS. The MHO-MetS group was further subdivided into insulin sensitive or insulin resistant on the basis of HOMA-IR (either < or ≥ 2.5). Insulin sensitive MHO-MetS patients had a better metabolic profile compared to both insulin resistant MHO-MetS and MUO-MetS individuals. These data underscore the relevance of insulin sensitivity to identifying, among young individuals with overweight/obesity, the ones who have a more favorable metabolic phenotype.
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Affiliation(s)
- Federica Vinciguerra
- Endocrinology, Department of Clinical and Experimental Medicine, University of Catania, 95122 Catania, Italy; (F.V.); (A.T.); (M.H.); (M.G.); (R.V.)
| | - Andrea Tumminia
- Endocrinology, Department of Clinical and Experimental Medicine, University of Catania, 95122 Catania, Italy; (F.V.); (A.T.); (M.H.); (M.G.); (R.V.)
| | - Roberto Baratta
- Diabetes, Obesity and Dietetic Center, Garibaldi-Nesima Medical Center, 95122 Catania, Italy;
| | - Alfredo Ferro
- Bionformatic Unit, Department of Clinical and Experimental Medicine, University of Catania, 95125 Catania, Italy; (A.F.); (S.A.)
| | - Salvatore Alaimo
- Bionformatic Unit, Department of Clinical and Experimental Medicine, University of Catania, 95125 Catania, Italy; (A.F.); (S.A.)
| | - Maria Hagnäs
- Endocrinology, Department of Clinical and Experimental Medicine, University of Catania, 95122 Catania, Italy; (F.V.); (A.T.); (M.H.); (M.G.); (R.V.)
- Center for Life Course Health Research, University of Oulu, 90570 Oulu, Finland
- Rovaniemi Health Center, 96200 Rovaniemi, Finland
| | - Marco Graziano
- Endocrinology, Department of Clinical and Experimental Medicine, University of Catania, 95122 Catania, Italy; (F.V.); (A.T.); (M.H.); (M.G.); (R.V.)
| | - Riccardo Vigneri
- Endocrinology, Department of Clinical and Experimental Medicine, University of Catania, 95122 Catania, Italy; (F.V.); (A.T.); (M.H.); (M.G.); (R.V.)
- Institute of Crystallography, Structural Chemistry and Biosystems, CNR-ICCSB, Catania Section, 95126 Catania, Italy
| | - Lucia Frittitta
- Endocrinology, Department of Clinical and Experimental Medicine, University of Catania, 95122 Catania, Italy; (F.V.); (A.T.); (M.H.); (M.G.); (R.V.)
- Diabetes, Obesity and Dietetic Center, Garibaldi-Nesima Medical Center, 95122 Catania, Italy;
- Correspondence: ; Tel.: +39-0957598702; Fax: +39-095472988
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Elrayess MA, Rizk NM, Fadel AS, Kerkadi A. Prevalence and Predictors of Insulin Resistance in Non-Obese Healthy Young Females in Qatar. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17145088. [PMID: 32679640 PMCID: PMC7399794 DOI: 10.3390/ijerph17145088] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/26/2020] [Revised: 02/23/2020] [Accepted: 02/24/2020] [Indexed: 12/18/2022]
Abstract
The state of Qatar suffers from diabetes epidemic due to obesity-associated metabolic syndrome. However, the prevalence of insulin resistance prior to obesity, which could play an important role in the high prevalence of diabetes, has not yet been described. This study aims to compare the prevalence of insulin resistance in apparently healthy non-obese and obese participants from Qatar and identify the predictors of insulin resistance in different body mass index (BMI)-groups. In this cross-sectional study, 150 young healthy females from Qatar were dichotomized into four groups (underweight, normal weight, overweight and obese) based on their BMI. Anthropometric measures as well as fasting plasma levels of lipids, adipokines, blood glucose and insulin were recorded. The prevalence of insulin resistance as per homeostatic model assessment of insulin resistance (HOMA-IR) was estimated and differences between insulin sensitive and insulin resistant were compared. Linear models were used to identify predictors of insulin resistance in every BMI group. Prevalence of insulin resistance in non-obese healthy females from Qatar ranges between 7% and 37% and increases with BMI. Overall, predictors of insulin resistance in the Qatari population are triglycerides/high-density lipoprotein (HDL) ratio and free fat mass but vary according to the BMI group. The main predictors were triglycerides in normal weight, triglycerides/HDL in overweight and triglycerides/HDL and interleukin-6 (IL-6) in obese individuals. The high prevalence of insulin resistance in non-obese Qataris may partially explain diabetes epidemic. Larger studies are warranted to confirm these findings and identify underlying causes for insulin resistance in non-obese individuals in Qatar, aiming at targeted intervention before diabetes onset.
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Affiliation(s)
- Mohamed A. Elrayess
- Biomedical Research Center, Qatar University, Doha 2713, Qatar
- Correspondence: (M.A.E.); (A.K.)
| | - Nasser M. Rizk
- Department of Biomedical Science, College of Health Sciences, QU-Health, Qatar University, Doha 2713, Qatar; (N.M.R.); (A.S.F.)
- Physiology Department, Mansoura Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
| | - Amina S. Fadel
- Department of Biomedical Science, College of Health Sciences, QU-Health, Qatar University, Doha 2713, Qatar; (N.M.R.); (A.S.F.)
| | - Abdelhamid Kerkadi
- Human Nutrition Department, College of Health Science, QU-Health, Qatar University, Doha 2713, Qatar
- Correspondence: (M.A.E.); (A.K.)
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Hosseini Khorami SA, Mutalib MSA, Feili Shiraz M, Abdullah JA, Rejali Z, Ali RM, Khaza'ai H. Genetic determinants of obesity heterogeneity in type II diabetes. Nutr Metab (Lond) 2020; 17:55. [PMID: 32670384 PMCID: PMC7346329 DOI: 10.1186/s12986-020-00476-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2020] [Accepted: 07/01/2020] [Indexed: 11/23/2022] Open
Abstract
Background Although obesity is considered as the main cause of Type II diabetes (T2DM), non-obese individuals may still develop T2DM and obese individuals may not. Method The mRNA expression of PI3K/AKT axis from 100 non-obese and obese participants with insulin sensitivity and insulin resistance states were compared in this study toward the understanding of obesity heterogeneity molecular mechanism. Result In present study, there was no statistically significant difference in gene expression levels of IRS1 and PTEN between groups, whereas PI3K, AKT2 and GLUT4 genes were expressed at a lower level in obese diabetic group compared to other groups and were statistically significant. PDK1 gene was expressed at a higher level in non-obese diabetic group compared to obese diabetic and non-obese non-diabetics groups. No statistically significant difference was identified in gene expression pattern of PI3K/AKT pathway between obese non-diabetics and non-obese non-diabetics. Conclusion The components of PI3K/AKT pathway which is related to the fasting state, showed reduced expression in obese diabetic group due to the chronic over-nutrition which may induced insensitivity and reduced gene expression. The pathogenesis of insulin resistance in the absence of obesity in non-obese diabetic group could be due to disturbance in another pathway related to the non-fasting state like gluconeogenesis. Therefore, the molecular mechanism of insulin signalling in non-obese diabetic individuals is different from obese diabetics which more investigations are required to study insulin signalling pathways in greater depth, in order to assess nutritional factors, contribute to insulin resistance in obese diabetic and non-obese diabetic individuals.
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Affiliation(s)
| | - Mohd Sokhini Abd Mutalib
- Department of Nutrition and Dietetic, University Putra Malaysia, 43400 Serdang, Selangor Malaysia
| | - Mohammad Feili Shiraz
- Department of Artificial Intelligence and Computer Engineering, Faculty of Electrical Engineering, Computer and IT, Qazvin Branch, Islamic Azad University, Qazvin, Iran
| | | | - Zulida Rejali
- Department of Obstetrics and Gynaecology, University Putra Malaysia, 43400 Serdang, Selangor Malaysia
| | - Razana Mohd Ali
- Department of Pathology, University Putra Malaysia, 43400 Serdang, Selangor Malaysia
| | - Huzwah Khaza'ai
- Department of Biomedical Science, University Putra Malaysia, 43400 Serdang, Selangor Malaysia
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Zeng X, Chen Q, Gong G, Yuan F, Wang T, Zhang G, Li X, Wang D, Wang Q. A simple formula to correct for the effects of storage time and temperature on the insulin concentration. J Clin Lab Anal 2020; 34:e23255. [PMID: 32133679 PMCID: PMC7370719 DOI: 10.1002/jcla.23255] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Revised: 02/03/2020] [Accepted: 02/04/2020] [Indexed: 11/09/2022] Open
Abstract
OBJECTIVE To investigate the influence of storage time and temperature on plasma insulin levels and to establish a correction formula. METHODS Venous blood samples were taken from 20 volunteers and processed as follows: whole blood samples, centrifuged samples, and separated plasma samples were stored at 4°C or 25°C. Insulin levels were determined by direct chemiluminescence at 0, 0.5, 1, 2, 4, and 8 hours. According to the correlation between the insulin concentration ratio and storage time, correction formulas for the insulin concentration were established. To verify the test, the venous blood samples of another 33 volunteers were processed in the same way. The insulin levels of the samples were corrected after 3, 6, 12, and 24 hours and compared with the value at 0 hours to verify the feasibility of the corrected formula. RESULTS With the prolongation of storage time, the insulin levels of the whole blood samples at 4°C or 25°C and of the centrifuged samples at 25°C decreased gradually (P < .001), and the insulin level correction formulas were Ccorrection = Cdetermination /0.991e-0.069 x , Ccorrection = Cdetermination /1.048e-0.126 x , and Ccorrection = Cdetermination /[-0.068ln(x) + 0.9242]. There was no significant difference between the corrected insulin results and the original results at any time within 12 hours (P > .05). CONCLUSIONS The insulin levels of the whole blood samples at 4°C or 25°C and of the plasma samples at 25°C gradually decreased with storage time. The effect of storage time on the insulin level can be reduced with the correction formulas.
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Affiliation(s)
- Xiaoli Zeng
- Department of Laboratory MedicineAffiliated Hospital of North Sichuan Medical CollegeNanchongChina
- Faculty of Laboratory MedicineCenter for Translational MedicineNorth Sichuan Medical collegeNanchongChina
- Department of Clinical TransfusionAffiliated Hospital of North Sichuan Medical CollegeNanchongChina
| | - Qi Chen
- Department of Laboratory MedicineAffiliated Sichuan Ba‐Yi Rehabilitation Center of Chengdu University of TCMChengduChina
| | - Guozhong Gong
- Department of Laboratory MedicineSuining First People's HospitalSuiningChina
| | - Fangyuan Yuan
- Faculty of Laboratory MedicineCenter for Translational MedicineNorth Sichuan Medical collegeNanchongChina
| | - Ting Wang
- Faculty of Laboratory MedicineCenter for Translational MedicineNorth Sichuan Medical collegeNanchongChina
| | - Guoyuan Zhang
- Department of Laboratory MedicineAffiliated Hospital of North Sichuan Medical CollegeNanchongChina
| | - Xiaoping Li
- Department of Clinical TransfusionAffiliated Hospital of North Sichuan Medical CollegeNanchongChina
| | - Dongsheng Wang
- Department of Laboratory MedicineSichuan Cancer Hospital & InstituteChengduChina
| | - Qiang Wang
- Department of Laboratory MedicineAffiliated Hospital of North Sichuan Medical CollegeNanchongChina
- Faculty of Laboratory MedicineCenter for Translational MedicineNorth Sichuan Medical collegeNanchongChina
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Dzięgielewska-Gęsiak S, Stołtny D, Brożek A, Muc-Wierzgoń M, Wysocka E. Are insulin-resistance and oxidative stress cause or consequence of aging. Exp Biol Med (Maywood) 2020; 245:1260-1267. [PMID: 32469639 DOI: 10.1177/1535370220929621] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
IMPACT STATEMENT Insulin resistance is associated with oxidative stress leading to cardiovascular diseases. However, little research has been performed examining elderly individuals with or without insulin-resistance. We demonstrate that antioxidant defense systems alone is not able to abrogate insulin action in elderly individuals at high risk for atherosclerosis, whereas the combined oxidant-antioxidant markers (thiobarbituric acid-reacting substances (TBARS), Cu,Zn-superoxide dismutase (SOD-1), and total antioxidant status (TAS)) might be more efficient and perhaps produce better clinical outcome. In fact, a decrease in oxidative stress and strong interaction between antioxidant defense can be seen only among insulin-resistant elderly individuals. This is, in our opinion, valuable information for clinicians, since insulin-resistance is considered strong cardiovascular risk factor.
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Affiliation(s)
| | - Dorota Stołtny
- Department of Internal Medicine, Medical University of Silesia in Katowice, Bytom 41-902, Poland
| | - Alicja Brożek
- Department of Clinical Biochemistry and Laboratory Medicine, Poznan University of Medical Sciences, Poznan 60-806, Poland
| | - Małgorzata Muc-Wierzgoń
- Department of Internal Medicine, Medical University of Silesia in Katowice, Bytom 41-902, Poland
| | - Ewa Wysocka
- Chair and Department of Laboratory Diagnostics, Poznan University of Medical Sciences, Poznan 60-569, Poland
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44
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Becchetti C, Dirchwolf M, Banz V, Dufour JF. Medical management of metabolic and cardiovascular complications after liver transplantation. World J Gastroenterol 2020; 26:2138-2154. [PMID: 32476781 PMCID: PMC7235200 DOI: 10.3748/wjg.v26.i18.2138] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Revised: 03/26/2020] [Accepted: 04/28/2020] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation represents the only curative option for patients with end-stage liver disease, fulminant hepatitis and advanced hepatocellular carcinoma. Even though major advances in transplantation in the last decades have achieved excellent survival rates in the early post-transplantation period, long-term survival is hampered by the lack of improvement in survival in the late post transplantation period (over 5 years after transplantation). The main etiologies for late mortality are malignancies and cardiovascular complications. The latter are increasingly prevalent in liver transplant recipients due to the development or worsening of metabolic syndrome and all its components (arterial hypertension, dyslipidemia, obesity, renal injury, etc.). These comorbidities result from a combination of pre-liver transplant features, immunosuppressive agent side-effects, changes in metabolism and hemodynamics after liver transplantation and the adoption of a sedentary lifestyle. In this review we describe the most prevalent metabolic and cardiovascular complications present after liver transplantation, as well as proposing management strategies.
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Affiliation(s)
- Chiara Becchetti
- Hepatology, Department of Visceral Surgery and Medicine, Inselspital, University Hospital Bern, Bern CH-3008, Switzerland
- Department of Biomedical Research, University of Bern, Bern CH-3008, Switzerland
| | - Melisa Dirchwolf
- Hepatology, Department of Visceral Surgery and Medicine, Inselspital, University Hospital Bern, Bern CH-3008, Switzerland
- Department of Biomedical Research, University of Bern, Bern CH-3008, Switzerland
- Hepatology, Hepatobiliary Surgery and Liver Transplant Unit, Hospital Privado de Rosario, Rosario S2000GAP, Santa Fe, Argentina
| | - Vanessa Banz
- Department of Visceral Surgery and Medicine, Inselspital, University Hospital Bern, Bern CH-3008, Switzerland
- Department of Clinical Research, University of Bern, Bern CH-3008, Switzerland
| | - Jean-François Dufour
- Hepatology, Department of Visceral Surgery and Medicine, Inselspital, University Hospital Bern, Bern CH-3008, Switzerland
- Department of Biomedical Research, University of Bern, Bern CH-3008, Switzerland
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45
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Tagi VM, Giannini C, Chiarelli F. Insulin Resistance in Children. Front Endocrinol (Lausanne) 2019; 10:342. [PMID: 31214120 PMCID: PMC6558106 DOI: 10.3389/fendo.2019.00342] [Citation(s) in RCA: 112] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Accepted: 05/13/2019] [Indexed: 12/28/2022] Open
Abstract
Insulin resistance (IR) is a pathological condition strongly associated with obesity. However, corticosteroids or growth hormone therapy and genetic diseases may affect insulin sensitivity lifelong. In obese children and adolescents of any age there is an evident association between IR and an increased prevalence of type 2 diabetes (T2D) and other elements contributing to the metabolic syndrome, leading to a higher cardiovascular risk. Therefore, early diagnosis and interventions in the attempt to prevent T2D when glycemia values are still normal is fundamental. The gold standard technique used to evaluate IR is the hyperinsulinemic euglycemic clamp, however it is costly and difficult to perform in clinical and research sets. Therefore, several surrogate markers have been proposed. Although the treatment of insulin resistance in children is firstly targeted to lifestyle interventions, in selected cases the integration of a pharmacological intervention might be taken into consideration. The aim of this review is to present the current knowledge on IR in children, starting with an outline of the recent evidences about the congenital forms of deficiency in insulin functioning and therefore focusing on the physiopathology of IR, its appropriate measurement, consequences, treatment options and prevention strategies.
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46
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Chaos, mitochondria and type 2 diabetes; does type 2 diabetes arise from a metabolic dysrhythmia? Med Hypotheses 2019; 127:71-75. [PMID: 31088652 DOI: 10.1016/j.mehy.2019.03.032] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2019] [Revised: 03/23/2019] [Accepted: 03/27/2019] [Indexed: 12/15/2022]
Abstract
The increasing incidence of type 2 diabetes transcends all cultures, largely due to populations transitioning from traditional diets and manual occupations, to sedentary, calorific lifestyles. Excess calorie intake leads to intramuscular fat accumulation and insulin resistance. Physical inactivity causes underutilization of mitochondria causing dysfunction and inflammation. Both insulin resistance and mitochondrial dysfunction mechanisms are known to be closely related and to antagonise one another, although the precise nature of the relationship has eluded characterization. It is poorly understood why this mutual dysfunction progresses on to clinical diabetes in only some patients, why progression is often stepwise and why diabetes control only weakly predicts future cardiovascular disease in individuals. Clinical prediction in patients is therefore currently unsatisfactory and current linear assumptions require challenging. Cells contain networks of oscillating ionic fluxes. Cellular activity is characterised by complex patterns of fluctuation with sudden transitions between patterns. The non-linear nature of these oscillations is well characterised in neuronal activity, cardiac impulses and more recently mitochondria, but not previously in relation to diabetes. Cells under metabolic stress demonstrate complex fluctuations of mitochondrial distribution, coupling strength and synchronisation resulting in periodic or chaotic oscillations of function, causing accumulation of intracellular fat and excess reactive oxygen species (ROS), which exacerbates insulin resistance. Glucose, insulin and HbA1c in patients are also known to oscillate in complex patterns but the mechanisms and significance are largely unknown. Drawing on existing evidence and models from other diseases, a nonlinear, dynamical hypothesis of diabetes onset and progression is proposed. Insulin receptor pathways and mitochondria are treated as two populations of coupled, phase oscillators. Health or disease states depend on system stability or instability and reflect the balance of substrate supply and energy demand. The implication of this novel mechanism is that diabetes and the complications are not the consequence of a distinct pathological agent or pathway, but more an evolving dysrhythmia of normal cellular energetics systems, resulting from accumulated adverse lifestyle conditions. This hypothesis is proposed with the intention of stimulating research into non-linear dynamical constructs as an alternative to current linear models, to improve risk prediction and trajectory analysis in type 2 diabetes.
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47
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McLaughlin T, Abbasi F, Lamendola C, Yee G, Carter S, Cushman SW. Dietary weight loss in insulin-resistant non-obese humans: Metabolic benefits and relationship to adipose cell size. Nutr Metab Cardiovasc Dis 2019; 29:62-68. [PMID: 30497926 PMCID: PMC6410738 DOI: 10.1016/j.numecd.2018.09.014] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Revised: 09/27/2018] [Accepted: 09/28/2018] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIMS Overweight and obesity increase risk for diabetes and cardiovascular disease, largely through development of insulin resistance. Benefits of dietary weight loss are documented for obese individuals with insulin resistance. Similar benefits have not been shown in overweight individuals. We sought to quantify whether dietary weight loss improves metabolic risk profile in overweight insulin-resistant individuals, and evaluated potential mediators between weight loss and metabolic response. METHODS AND RESULTS Healthy volunteers with BMI 25-29.9 kg/m2 underwent detailed metabolic phenotyping including insulin-mediated-glucose disposal, fasting/daylong glucose, insulin, triglycerides, FFA, and cholesterol. Subcutaneous fat biopsies were performed for measurement of adipose cell size. After 14 weeks of hypocaloric diet and 2 weeks of weight maintenance, cardiometabolic measures and biopsies were repeated. Changes in weight, % body fat, waist circumference, adipose cell size and FFA were evaluated as predictors of change in insulin resistance. Weight loss (4.3 kg) yielded significant improvements in insulin resistance and all cardiovascular risk markers except glucose, HDL-C, and LDL-C. Improvement in insulin sensitivity was greater among those with <2 vs >2 cardiovascular risk factors at baseline. Decrease in adipose cell size and waist circumference, but not weight or body fat, independently predicted improvement in insulin resistance. CONCLUSIONS Weight loss yields metabolic health benefits in insulin-resistant overweight adults, even in the absence of classic cardiovascular risk factors. Weight loss-related improvement in insulin sensitivity may be mediated through changes in adipose cell size and/or central distribution of body fat. The insulin-resistant subgroup of overweight individuals should be identified and targeted for dietary weight loss. CLINICAL TRIALS IDENTIFIER NCT00186459.
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Affiliation(s)
- T McLaughlin
- Department of Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA.
| | - F Abbasi
- Department of Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA
| | - C Lamendola
- Department of Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA
| | - G Yee
- Department of Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA
| | - S Carter
- Department of Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA
| | - S W Cushman
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA
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Ibáñez CA, Vázquez-Martínez M, León-Contreras JC, Reyes-Castro LA, Rodríguez-González GL, Bautista CJ, Nathanielsz PW, Zambrano E. Different Statistical Approaches to Characterization of Adipocyte Size in Offspring of Obese Rats: Effects of Maternal or Offspring Exercise Intervention. Front Physiol 2018; 9:1571. [PMID: 30524294 PMCID: PMC6262415 DOI: 10.3389/fphys.2018.01571] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2018] [Accepted: 10/19/2018] [Indexed: 01/03/2023] Open
Abstract
Adipocyte size (AS) shows asymmetric distribution related to current metabolic state, e.g., adipogenesis or lipolysis. We profiled AS distribution using different statistical approaches in offspring (F1) of control (C) and obese (MO) mothers (F0) with and without F0 or F1 exercise. Offspring from F0 exercise were designated CF0ex and MOF0ex. Exercised F1 of sedentary mothers were designated CF1ex and MOF1ex. F1 retroperitoneal fat cross-sectional AS was measured by median, cumulative distributions, data dispersion and extreme values based on gamma distribution modeling. F1 metabolic parameters: body weight, retroperitoneal fat, adiposity index (AI), serum leptin, triglycerides (TG) and insulin resistance index (IRI) were measured. Male and female F1 AS showed different cumulative distribution between C and MO (p < 0.0001) therefore comparisons were performed among C, CF0ex and CF1ex groups and MO, MOF0ex and MOF1ex groups. MO AI was higher than C (p < 0.05) and male MOF1ex AI lower than MO (p < 0.05). Median AS was higher in male and female MO vs. C (p < 0.05). Male and female MOF0ex and MOF1ex reduced median AS (p < 0.05). Lower AS dispersion was observed in male CF1ex and MOF1ex vs. CF0ex and MOF0ex, respectively. MO reduced small and increased large adipocyte proportions vs. C (p < 0.05); MOF0ex increased small and MOF1ex the proportion of large adipocytes vs. MO (p < 0.05). MOF0ex reduced male IRI and female TG vs. MO (p < 0.05). MOF1ex reduced male and female leptin (p < 0.05); CF1ex reduced male leptin (p < 0.05). Conclusions: several factors, diet, physical activity and gender modify AS distribution. Conventional AS distribution methods normally do not include analyzes of extreme, large and small adipocytes, which characterize different phenotypes. Maternal high fat diet affects F1 AS distribution, which was programmed during development. F0ex and F1ex have gender specific F1 beneficial effects. AS distribution characterization helps explain adipose tissue metabolic changes in different physiological conditions and will aid design of efficacious interventions to prevent and/or recuperate adverse developmental programming outcomes. Finally, precise identification of effects of specific interventions as exercise of F0 and/or F1 are needed to improve outcomes in obese women and their obesity prone offspring.
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Affiliation(s)
- Carlos A Ibáñez
- Reproductive Biology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Magaly Vázquez-Martínez
- Reproductive Biology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - J Carlos León-Contreras
- Experimental Patology Section, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Luis A Reyes-Castro
- Reproductive Biology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Guadalupe L Rodríguez-González
- Reproductive Biology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Claudia J Bautista
- Reproductive Biology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Peter W Nathanielsz
- Department of Animal Science, University of Wyoming, Laramie WY, United States
| | - Elena Zambrano
- Reproductive Biology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
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Harada K, Suzuki H, Matsunaga S, Onishi T, Nishikawa Y, Funakubo H, Mamiya K, Nagao T, Shinoda N, Sakai S, Kato M, Marui N, Ishii H, Amano T, Matsubara T, Murohara T. Clinical Characteristics of Nonobese Patients with Acute Coronary Syndrome and Increased Epicardial Fat Volume. J Atheroscler Thromb 2018; 25:1044-1052. [PMID: 29386421 PMCID: PMC6193182 DOI: 10.5551/jat.42663] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
Abstract
Aim: Increased epicardial fat volume (EFV) is an independent risk factor for acute coronary syndrome (ACS). Although EFV increases with body mass index (BMI), some ACS patients have an increased EFV but normal BMI. We here investigated the clinical characteristics of nonobese ACS patients with an increased EFV. Methods: A total of 197 Japanese patients hospitalized for ACS was evaluated for EFV, abdominal visceral fat area (VFA), and lipid and glucose profiles. Control subjects comprised 141 individuals who were suspected of having ACS but whose coronary computed tomography findings were normal. Results: EFV was increased in ACS patients compared with control subjects (120 ± 47 versus 95 ± 45 mL, P < 0.01). ACS patients were divided into four groups based on average EFV (120 mL) and a BMI obesity cutoff of 25 kg/m2. For the 30 nonobese ACS patients with an above-average EFV, EFV was positively correlated with VFA (r = 0.23, P = 0.031). These individuals were significantly older (74 ± 10 years) and tended to have a higher homeostasis model assessment–insulin resistance value (5.5 ± 3.8) compared with other ACS patients. Among nonobese study subjects, EFV was independently associated with ACS (odds ratio= 2.01, P = 0.021) and correlated with abdominal circumference (r = 0.26, P = 0.017). Conclusion: Nonobese ACS patients with an increased EFV were elderly and tended to manifest insulin resistance. Measurement of EFV may prove informative for evaluation of ACS risk among elderly nonobese individuals with an increased abdominal girth.
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Affiliation(s)
- Ken Harada
- Department of Cardiology, Chubu Rosai Hospital
| | | | | | | | | | | | | | | | | | | | | | | | - Hideki Ishii
- Department of Cardiology, Nagoya University Graduate School of Medicine
| | - Tetsuya Amano
- Department of Cardiology, Aichi Medical University Hospital
| | | | - Toyoaki Murohara
- Department of Cardiology, Nagoya University Graduate School of Medicine
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50
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Laclaustra M, Lopez-Garcia E, Civeira F, Garcia-Esquinas E, Graciani A, Guallar-Castillon P, Banegas JR, Rodriguez-Artalejo F. LDL Cholesterol Rises With BMI Only in Lean Individuals: Cross-sectional U.S. and Spanish Representative Data. Diabetes Care 2018; 41:2195-2201. [PMID: 30061315 DOI: 10.2337/dc18-0372] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2018] [Accepted: 06/28/2018] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Elevated LDL cholesterol (LDLc) is not strongly associated with obesity or metabolic syndrome (MS), but this relationship repeatedly has been examined assuming a linear association. This study aimed to assess the dose-response relationship between body mass index (BMI) or waist circumference (WC) and LDLc and to evaluate its link to metabolic impairment. RESEARCH DESIGN AND METHODS Participants in the continuous National Health and Nutrition Examination Survey (NHANES, 1999-2010) (n = 12,383) and the Study on Nutrition and Cardiovascular Risk (ENRICA, 2008-2010) (n = 11,765), representative samples of U.S. and Spanish noninstitutionalized populations, were cross-sectionally investigated. LDLc was modeled with age- and sex-adjusted regressions, with BMI and/or WC as explanatory variables included in models as two-segment linear and natural cubic splines. RESULTS In NHANES and ENRICA, slopes of the BMI-LDLc association changed (P < 0.001) at BMI 27.1 and 26.5 kg/m2, respectively, forming an inverted U shape. Below these BMI inflection points, LDLc rose 2.30 and 2.41 mg/dL per kg/m2 (both P < 0.001). However, above said points, LDLc declined -0.37 and -0.38 mg/dL per kg/m2 (both P < 0.001). The WC-LDLc relationship was similar to the BMI-LDLc relationship. Accumulation of MS traits was associated with a weakening of the positive BMI-LDLc association among lean participants (below the BMI inflection point). Aging shifted the inflection point of the BMI-LDLc relationship to lower BMI values. CONCLUSIONS The BMI- and WC-LDLc relationships have inverted U shapes. Diminishing associations between BMI and LDLc might indicate metabolic impairment as a result of aging or other metabolic diseases. In lean individuals, small weight losses might help to lower LDLc for cardiovascular prevention.
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Affiliation(s)
- Martin Laclaustra
- Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV) and Instituto de Investigación Sanitaria de Aragón (IIS Aragón), Translational Research Unit, Hospital Universitario Miguel Servet, Universidad de Zaragoza, Zaragoza, Spain .,Centro de Investigación Biomédica en Red Epidemiología y Salud Pública (CIBERESP), Department of Preventive Medicine and Public Health, School of Medicine, Universidad Autónoma de Madrid/Instituto de Investigación del Hospital La Paz (IDIPAZ), Madrid, Spain
| | - Esther Lopez-Garcia
- Centro de Investigación Biomédica en Red Epidemiología y Salud Pública (CIBERESP), Department of Preventive Medicine and Public Health, School of Medicine, Universidad Autónoma de Madrid/Instituto de Investigación del Hospital La Paz (IDIPAZ), Madrid, Spain.,Instituto Madrileño de Estudios Avanzados-Alimentación (IMDEA-Food), Centro de Excelencia International UAM+CSIC, Madrid, Spain
| | - Fernando Civeira
- Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV) and Instituto de Investigación Sanitaria de Aragón (IIS Aragón), Translational Research Unit, Hospital Universitario Miguel Servet, Universidad de Zaragoza, Zaragoza, Spain
| | - Esther Garcia-Esquinas
- Centro de Investigación Biomédica en Red Epidemiología y Salud Pública (CIBERESP), Department of Preventive Medicine and Public Health, School of Medicine, Universidad Autónoma de Madrid/Instituto de Investigación del Hospital La Paz (IDIPAZ), Madrid, Spain
| | - Auxiliadora Graciani
- Centro de Investigación Biomédica en Red Epidemiología y Salud Pública (CIBERESP), Department of Preventive Medicine and Public Health, School of Medicine, Universidad Autónoma de Madrid/Instituto de Investigación del Hospital La Paz (IDIPAZ), Madrid, Spain
| | - Pilar Guallar-Castillon
- Centro de Investigación Biomédica en Red Epidemiología y Salud Pública (CIBERESP), Department of Preventive Medicine and Public Health, School of Medicine, Universidad Autónoma de Madrid/Instituto de Investigación del Hospital La Paz (IDIPAZ), Madrid, Spain.,Instituto Madrileño de Estudios Avanzados-Alimentación (IMDEA-Food), Centro de Excelencia International UAM+CSIC, Madrid, Spain
| | - Jose R Banegas
- Centro de Investigación Biomédica en Red Epidemiología y Salud Pública (CIBERESP), Department of Preventive Medicine and Public Health, School of Medicine, Universidad Autónoma de Madrid/Instituto de Investigación del Hospital La Paz (IDIPAZ), Madrid, Spain
| | - Fernando Rodriguez-Artalejo
- Centro de Investigación Biomédica en Red Epidemiología y Salud Pública (CIBERESP), Department of Preventive Medicine and Public Health, School of Medicine, Universidad Autónoma de Madrid/Instituto de Investigación del Hospital La Paz (IDIPAZ), Madrid, Spain.,Instituto Madrileño de Estudios Avanzados-Alimentación (IMDEA-Food), Centro de Excelencia International UAM+CSIC, Madrid, Spain
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