title: Pancreatic lipid content is not associated with beta cell dysfunction in youth-onset type 2 diabetes.
abstract: 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.
authors.affiliation: Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada; University of Manitoba, Department of Pediatrics and Child Health, Faculty of Medicine, Winnipeg, Manitoba, Canada. Electronic address: bwicklow@hsc.mb.ca.
authors.forename: Brandy A
authors.initials: BA
authors.lastname: Wicklow
authors.affiliation: Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada.
authors.forename: Angella T
authors.initials: AT
authors.lastname: Griffith
authors.affiliation: Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada.
authors.forename: Jacqueline N
authors.initials: JN
authors.lastname: Dumontet
authors.affiliation: National Research Council Canada Institute for Biodiagnostics, Winnipeg, Manitoba, Canada.
authors.forename: Niranjan
authors.initials: N
authors.lastname: Venugopal
authors.affiliation: National Research Council Canada Institute for Biodiagnostics, Winnipeg, Manitoba, Canada.
authors.forename: Lawrence N
authors.initials: LN
authors.lastname: Ryner
authors.affiliation: Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada; University of Manitoba, Department of Pediatrics and Child Health, Faculty of Medicine, Winnipeg, Manitoba, Canada.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: McGavock
mesh_terms: D000293:Adolescent; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D005260:Female; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics; D006801:Humans; D050417:Insulin-Secreting Cells / Q000502:physiology*; D050356:Lipid Metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D010179:Pancreas / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D051538:Hepatocyte Nuclear Factor 1-alpha; D014280:Triglycerides
keywords: adolescent; diabète de type 2; lipotoxicity; lipotoxicité; nuclear magnetic resonance (NMR) spectroscopy; pancreas; pancréas; spectroscopie par résonance magnétique nucléaire (RMN); steatosis; stéatose; type 2 diabetes