Pancreatic Triglyceride Content is Not Associated with Beta Cell Dysfunction in Youth-Onset Type 2 Diabetes

Abstract

To determine if pancreatic triglyceride content is a characteristic feature of type 2 diabetes (T2D) in adolescents and if it is associated with beta-cell function. This was a cross-sectional study comparing 1H-magnetic resonance spectroscopy-derived pancreatic triglyceride content between adolescents 13 and 18 years with T2D (n=20) and BMI-matched normoglycemic controls (n=34). Beta-cell function was determined from the acute insulin response and disposition index derived from a frequently sampled intravenous glucose tolerance test. Despite similar BMI Z scores (1.72±0.67 vs. 1.99±0.45), youth with T2D displayed a 96% lower acute insulin response and 81% lower disposition index (p<0.001) compared to normoglycemic youth. Pancreatic triglyceride content was not significantly different between youth with T2D and normoglycemic peers (2.41 [95% CI: 0.63, 5.60] vs. 1.22 [0.08, 5.93], p=0.27). Within the entire cohort, and stratified by glucose tolerance, pancreatic triglyceride was not associated with beta-cell function. Pancreatic triglyceride content was ∼4 fold higher in youth with T2D that were carriers of the G319S polymorphism in the HNF1α gene (7.45 [2.85, 26.8] vs. 2.20 [0.350, 3.30] %F/W, p=0.032). Pancreatic triglyceride content is not elevated in youth with T2D nor is it associated with beta-cell function among overweight adolescents. The presence of the G319S mutation in the HNF1α gene in youth with T2D may be associated with higher pancreatic triglyceride content. Further research is needed to understand the mechanisms of beta cell failure in youth with type 2 diabetes.