β-cell Lipotoxicity in Response to Free Fatty Acid Elevation in Youth: African American versus Caucasian Contrast

  1. Silva A. Arslanian, M.D.1,4
  1. 1Division of Weight Management, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center
  2. 2Division of Endocrinology and Metabolic Disease, University of Verona School of Medicine and Azienda Ospedaliera Universitaria Integrata, Verona, Italy
  3. 3Eunice Kennedy Shriver National Institute of Child Health & Human Development, NIH
  4. 4Division of Pediatric Endocrinology, Metabolism & Diabetes Mellitus, Children’s Hospital of Pittsburgh
  1. Corresponding author: Silva Arslanian, Silva.arslanian{at}chp.edu

Abstract

Prepubertal African American (AA) youth compared with their Caucasian (C) peers have higher insulin secretion which correlates positively with free fatty acid (FFA) concentration. In our continued efforts to explain the racial disparity in insulinemia, and because FFAs modulate insulin secretion, we hypothesized that AA youth would have a greater response to FFA-induced β-cell insulin secretion than C youth. We compared the short-term effects of FFA elevation on fasting and glucose-stimulated C-peptide-modeled insulin secretion in prepubertal normal-weight AA versus C peers during a 2-hour hyperglycemic clamp (12.5mmol/L) on two occasions: a) infusion of normal saline (NS) and b) infusion of 20% intralipid (IL). During IL infusion, insulin sensitivity (IS) declined comparably in AA and C youth. Glucose sensitivity of 1st and 2nd phase insulin secretion showed a significant condition x race interaction being higher in AA youth. Disposition index, β-cell function relative to IS, declined with IL infusion in both AA and C youth with a significantly greater decrease in Cs compared with AAs. In conclusion, both AA and C prepubertal youth demonstrated a decline in β-cell function relative to IS during IL infusion, indicative of acute lipotoxicity. The greater decline in C youth compared with AAs may suggest that either C youth are more susceptible to β-cell lipotoxicity than AA youth, or alternatively, AA youth are hypersensitive to FFA stimulation of β-cell insulin secretion consistent with our theory.

  • Received November 29, 2012.
  • Accepted March 23, 2013.

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