Pancreatic lipid content is not associated with beta cell dysfunction in youth-onset type 2 diabetes.

OBJECTIVE: To determine whether pancreatic lipid content is associated with type 2 diabetes and beta cell function in Indigenous and Caucasian adolescents. METHODS: This was a cross-sectional study comparing (1)H-magnetic resonance spectroscopy-derived pancreatic triglyceride content in adolescents 13 to 18 years of age with type 2 diabetes (n=20) and body mass index-matched normoglycemic controls (n=34). Beta cell function was measured by the acute insulin response and disposition index derived from intravenous glucose tolerance tests. RESULTS: Pancreatic lipid content was not significantly different in youth with type 2 diabetes and their normoglycemic body mass index-matched peers (2.41 [95% CI: 0.63, 5.60] vs. 1.22 [0.08, 5.93]; p=0.27). Pancreatic triglyceride levels were not associated with measures of beta cell function in the cohort. In subgroup analyses, pancreatic lipid content was ∼4-fold higher in youth with type 2 diabetes who were carriers of the G319S mutation in the HNF-1alpha gene (7.45 [2.85, 26.8] vs. 2.20 [0.350, 3.30] % Fat to Water Ratio F/W; p=0.032). CONCLUSIONS: Pancreatic lipid content is not elevated in Indigenous or Caucasian youth with type 2 diabetes compared to normoglycemic youth, nor is it associated with beta cell function. The presence of the G319S mutation in the HNF-1alpha gene in Indigenous youth with type 2 diabetes is associated with higher pancreatic lipid content. Further research is needed to understand the mechanisms that explain beta cell failure in overweight youth with type 2 diabetes.