title: β-Cell lipotoxicity after an overnight intravenous lipid challenge and free fatty acid elevation in African American versus American white overweight/obese adolescents.
abstract: OBJECTIVE
  Overweight/obese (OW/OB) African American (AA) adolescents have a more diabetogenic insulin secretion/sensitivity pattern compared with their American white (AW) peers. The present study investigated β-cell lipotoxicity to test whether increased free fatty acid (FFA) levels result in greater β-cell dysfunction in AA vs AW OW/OB adolescents.
  
  
  METHODS
  Glucose-stimulated insulin secretion was modeled, from glucose and C-peptide concentrations during a 2-hour hyperglycemic (225 mg/dL) clamp in 22 AA and 24 AW OW/OB adolescents, on 2 occasions after a 12-hour overnight infusion of either normal saline or intralipid (IL) in a random sequence. β-Cell function relative to insulin sensitivity, the disposition index (DI), was examined during normal saline and IL conditions. Substrate oxidation was evaluated with indirect calorimetry and body composition and abdominal adiposity with dual-energy X-ray absorptiometry and magnetic resonance imaging at L4-L5, respectively.
  
  
  RESULTS
  Age, sex, body mass index, total and sc adiposity were similar between racial groups, but visceral adiposity was significantly lower in AAs. During IL infusion, FFAs and fat oxidation increased and insulin sensitivity decreased similarly in AAs and AWs. β-Cell glucose sensitivity of first- and second-phase insulin secretion did not change significantly during IL infusion in either group, but DI in each phase decreased significantly and similarly in AAs and AWs.
  
  
  CONCLUSIONS
  Overweight/obese AA and AW adolescents respond to an overnight fat infusion with significant declines in insulin sensitivity, DI, and β-cell function relative to insulin sensitivity, suggestive of β-cell lipotoxicity. However, contrary to our hypothesis, there does not seem to be a race differential in β-cell lipotoxicity. Longer durations of FFA elevation may unravel such race-related contrasts.
authors.affiliation: Division of Weight Management and Wellness, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15224, USA.
authors.forename: Kara S
authors.initials: KS
authors.lastname: Hughan
authors.forename: Riccardo C
authors.initials: RC
authors.lastname: Bonadonna
authors.forename: SoJung
authors.initials: S
authors.lastname: Lee
authors.forename: Sara F
authors.initials: SF
authors.lastname: Michaliszyn
authors.forename: Silva A
authors.initials: SA
authors.lastname: Arslanian
mesh_terms: D050154:Adiposity / Q000208:ethnology; D000293:Adolescent; D041923:Adolescent Development; D001741:Black or African American; D015992:Body Mass Index; D015331:Cohort Studies; D018592:Cross-Over Studies; D059305:Diet, High-Fat / Q000009:adverse effects*; D004655:Emulsions; D005230:Fatty Acids, Nonesterified / Q000097:blood* / Q000378:metabolism; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance / Q000208:ethnology; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D050152:Intra-Abdominal Fat / Q000473:pathology; D050356:Lipid Metabolism; D008297:Male; D009765:Obesity / Q000097:blood / Q000208:ethnology / Q000378:metabolism* / Q000473:pathology; D050177:Overweight / Q000097:blood / Q000208:ethnology / Q000378:metabolism* / Q000473:pathology; D010414:Pennsylvania; D010743:Phospholipids; D013024:Soybean Oil; D044465:White People
chemical_list: D004655:Emulsions; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D010743:Phospholipids; C545823:soybean oil, phospholipid emulsion; D013024:Soybean Oil