title: Free fatty acid-mediated impairment of glucose-stimulated insulin secretion in nondiabetic Oji-Cree individuals from the Sandy Lake community of Ontario, Canada: a population at very high risk for developing type 2 diabetes.
abstract: The Oji-Cree population of the Sandy Lake region of Ontario, Canada, has the third highest prevalence of type 2 diabetes in the world. Changes in their diet and physical activity over the past half-century, particularly the marked increase in consumption of dietary fats, are felt to be important factors accounting for this epidemic. The aim of the present study was to examine the beta-cell response to a 48-h approximately twofold elevation of plasma free fatty acids (FFAs) (induced by Intralipid and heparin infusion) in members of the Sandy Lake Oji-Cree population (n = 12) and to compare the response to that in healthy age-matched nondiabetic Caucasian subjects (n = 16). The insulin secretion rate, insulin sensitivity index (S(I)), and disposition index (D(I)) (an index of insulin secretion that takes into account the ambient S(I)) were assessed in response to a 4-h graded intravenous glucose infusion followed by a 20 mmol/l 2-h hyperglycemic clamp. Total insulin secretory response to the graded glucose infusion did not change after a 48-h FFA elevation versus saline control in Caucasians and increased by approximately 30% in Oji-Cree individuals (P = 0.04 for difference between the two groups). Infusion of heparin-Intralipid reduced S(I) by approximately 40% in both groups (P = 0.002). Although D(I) was markedly reduced by heparin-Intralipid infusion in Caucasians (by approximately 40%), it was reduced by only 15% in Oji-Cree individuals (P = 0.03 for difference of response between the two groups). However, S(I) and D(I) in the Oji-Cree individuals were already much lower than in Caucasians at baseline, in keeping with the very high risk of type 2 diabetes in this population. It is concluded that Oji-Cree individuals from a community at very high risk for developing type 2 diabetes are not more susceptible to the FFA-induced desensitization of glucose-stimulated insulin secretion than healthy non-Natives and, in fact, appear to be less susceptible. Whether this reflects an inherent resistance to lipotoxicity or an already-present lipotoxic effect in this population will require further study.
authors.affiliation: Department of Medicine, University of Sherbrooke, Sherbrooke, Québec, Canada.
authors.forename: André
authors.initials: A
authors.lastname: Carpentier
authors.forename: Bernard
authors.initials: B
authors.lastname: Zinman
authors.forename: Nathalie
authors.initials: N
authors.lastname: Leung
authors.forename: Adria
authors.initials: A
authors.lastname: Giacca
authors.forename: Anthony J G
authors.initials: AJ
authors.lastname: Hanley
authors.forename: Stewart B
authors.initials: SB
authors.lastname: Harris
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hegele
authors.forename: Gary F
authors.initials: GF
authors.lastname: Lewis
mesh_terms: D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology*; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D005951:Glucose Tolerance Test; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000139:chemically induced; D007198:Indians, North American; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007700:Kinetics; D008297:Male; D009864:Ontario / Q000453:epidemiology; D012307:Risk Factors; D044465:White People
chemical_list: D001786:Blood Glucose; D005217:Fat Emulsions, Intravenous; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D006493:Heparin