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Visceral Adiposity and Glucoregulatory Peptides are Associated with Susceptibility to Type 2 Diabetes: The TOFI_Asia Study.

Human Nutrition Unit, School of Biological Sciences, Faculty of Science, University of Auckland, Auckland, New Zealand. High Value Nutrition, National Science Challenge, New Zealand. Department of Statistics, Faculty of Science, University of Auckland, Auckland, New Zealand. Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. Auckland District Health Board, Auckland, New Zealand. Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland, New Zealand. Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. School of Biological Sciences, Faculty of Science, University of Auckland, Auckland, New Zealand. Centre for Advanced Discovery and Experimental Therapeutics, Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK. Department of Pharmacology, Division of Medical Sciences, University of Oxford, Oxford, UK. Riddet Centre of Research Excellence for Food and Nutrition, Palmerston North, New Zealand.

Obesity (Silver Spring, Md.). 2020;(12):2368-2378
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Abstract

OBJECTIVE Ethnic differences in fat deposition contribute to type 2 diabetes (T2D). Identification of biomarkers that underpin dysglycemia are needed for better-targeted prevention and treatment. METHODS The cross-sectional thin-on-the-outside-fat-on-the-inside (TOFI)_Asia study investigated adipose depots and clinical biomarkers as predictors of fasting plasma glucose (FPG) and insulin resistance (IR; assessed using the updated homeostatic model assessment of IR) in lean and overweight normo- and dysglycemic Chinese (n = 199) and Caucasian (n = 158) individuals. Multivariate least-angle regression models were used to identify predictors of FPG and IR. RESULTS At similar age and BMI, Chinese individuals had lower body weight but had a greater percentage of total abdominal adipose tissue and a greater percentage of total visceral adipose tissue (VAT) (all P < 0.005). In Chinese individuals, FPG, hemoglobin A1c , fasting insulin, and triglycerides were higher, whereas HDL cholesterol and total and high-molecular-weight adiponectin levels were lower (all P < 0.0001). Raised liver enzyme and peptide concentrations (P < 0.02) were consistent with increased T2D risk. Lean Chinese women (<25 kg/m2 ) had greater total abdominal adipose tissue (kilograms) and VAT (kilograms) than Caucasian women, exhibiting the TOFI profile, with raised FPG (P < 0.001) and IR (P = 0.01). Risk factors for elevated FPG specific to Chinese individuals included male gender, VAT, and triglycerides (R2  = 0.33), and risk factors for IR specific to Chinese individuals included amylin, C-peptide, and glucagon (R2  = 0.49). VAT, amylin, and C-peptide were predictors in Caucasian individuals. CONCLUSIONS VAT contributed to dysglycemia in both ethnicities, particularly in Chinese individuals characterized by the TOFI phenotype, as did the glucoregulatory peptides amylin and C-peptide, providing targets for T2D prevention.