Circulating triacylglycerols but not pancreatic fat associate with insulin secretion in healthy humans

Background: Loss of adequate insulin secretion for the prevailing insulin resistance is critical for the development of type 2 diabetes and has been suggested to result from circulating lipids (triacylglycerols [TG] or free fatty acids) and/or adipocytokines or from ectopic lipid storage in the pancreas. This study aimed to address whether circulating lipids, adipocytokines or pancreatic fat primarily associates with lower insulin secretion.

Subjects/methods: Nondiabetic persons (n=73), recruited from the general population, underwent clinical examinations, fasting blood drawing to measure TG and adipocytokines and oral glucose tolerance testing (OGTT) to assess basal and dynamic insulin secretion and sensitivity indices. Magnetic resonance imaging and ¹H-magnetic resonance spectroscopy were used to measure body fat distribution and ectopic fat content in liver and pancreas.

Results: In age-, sex- and BMI-adjusted analyses, total and high-molecular-weight adiponectin were the strongest negative predictors of fasting beta-cell function (BCF; β=-0.403, p=0.0003 and β=-0.237, p=0.01, respectively) and adaptation index (AI; β=-0.210, p=0.006 and β=-0.133, p=0.02, respectively). Circulating TG, but not pancreatic fat content, related positively to BCF (β=0.375, p<0.0001) and AI (β=0.192, p=0.003). Similar results were obtained for the disposition index (DI).

Conclusions: The association of serum lipids and adiponectin with beta-cell function may represent a compensatory response to adapt for lower insulin sensitivity in nondiabetic humans.