title: A 5-day high-fat, high-calorie diet impairs insulin sensitivity in healthy, young South Asian men but not in Caucasian men.
abstract: South Asians (SAs) develop type 2 diabetes at a younger age and lower BMI compared with Caucasians (Cs). The underlying cause is still poorly understood but might result from an innate inability to adapt to the Westernized diet. This study aimed to compare the metabolic adaptation to a high-fat, high-calorie (HFHC) diet between both ethnicities. Twelve healthy, young lean male SAs and 12 matched Cs underwent a two-step hyperinsulinemic-euglycemic clamp with skeletal muscle biopsies and indirect calorimetry before and after a 5-day HFHC diet. Hepatic triglyceride content (HTG) and abdominal fat distribution were assessed using magnetic resonance imaging and spectroscopy. At baseline, SAs had higher insulin clamp levels than Cs, indicating reduced insulin clearance rate. Despite the higher insulin levels, endogenous glucose production was comparable between groups, suggesting lower hepatic insulin sensitivity in SAs. Furthermore, a 5-day HFHC diet decreased the insulin-stimulated (nonoxidative) glucose disposal rate only in SA. In skeletal muscle, no significant differences were found between groups in insulin/mammalian target of rapamycin signaling, metabolic gene expression, and mitochondrial respiratory chain content. Furthermore, no differences in (mobilization of) HTG and abdominal fat were detected. We conclude that HFHC feeding rapidly induces insulin resistance only in SAs. Thus, distinct adaptation to Western food may partly explain their propensity to develop type 2 diabetes.
authors.affiliation: Department of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Leontine E H
authors.initials: LE
authors.lastname: Bakker
authors.forename: Linda D
authors.initials: LD
authors.lastname: van Schinkel
authors.forename: Bruno
authors.initials: B
authors.lastname: Guigas
authors.forename: Trea C M
authors.initials: TC
authors.lastname: Streefland
authors.forename: Jacqueline T
authors.initials: JT
authors.lastname: Jonker
authors.forename: Jan B
authors.initials: JB
authors.lastname: van Klinken
authors.forename: Gerard C M
authors.initials: GC
authors.lastname: van der Zon
authors.forename: Hildo J
authors.initials: HJ
authors.lastname: Lamb
authors.forename: Johannes W A
authors.initials: JW
authors.lastname: Smit
authors.forename: Hanno
authors.initials: H
authors.lastname: Pijl
authors.forename: A Edo
authors.initials: AE
authors.lastname: Meinders
authors.forename: Ingrid M
authors.initials: IM
authors.lastname: Jazet
mesh_terms: D000328:Adult; D044466:Asian People; D001786:Blood Glucose / Q000378:metabolism; D004032:Diet / Q000208:ethnology*; D059305:Diet, High-Fat; D015309:Glucose Clamp Technique; D006801:Humans; D007333:Insulin Resistance / Q000208:ethnology* / Q000502:physiology; D050356:Lipid Metabolism / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D044465:White People
chemical_list: D001786:Blood Glucose; D014280:Triglycerides