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

Abstract

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. 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. 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 A_1c , 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. 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.