title: Endogenous glucose production, insulin sensitivity, and insulin secretion in normal glucose-tolerant Pima Indians with low birth weight.
abstract: Individuals with low birth weight (LBW) are at increased risk of developing type 2 diabetes in later life. Whether impairments in endogenous glucose production (EGP), insulin action, insulin secretion, or a combination thereof account for this association is unclear. We, therefore, examined these parameters in Pima Indians with normal glucose tolerance. Body composition, glucose and insulin responses during a 75-g oral glucose tolerance test (OGTT), EGP, insulin-stimulated glucose disposal during low- and high-dose insulin infusion (M-low and M-high, hyperinsulinemic glucose clamp), and acute insulin response (AIR) to a 25-g intravenous glucose challenge were measured in 230 Pima Indians (147 men and 83 women, aged 25 +/- 0.4 years [mean +/- SE; range, 18 to 44]) with normal glucose tolerance. A subgroup of 63 subjects additionally underwent biopsies of subcutaneous adipose tissue for determination of adipocyte cell size and lipolysis. Subjects in the lowest quartile of birth weight (birth weight: 2,891 +/- 33 g, LBW, n = 58) were compared to those whose birth weight was in the upper 3 quartiles (birth weight: 3,657 +/- 28 g, NBW, n = 172). Age- and sex-adjusted body mass index (BMI), percent body fat, and waist-to-thigh ratio (WTR) were similar in LBW and NBW subjects. Suppression of EGP during the clamp was less in LBW than in NBW subjects before (P = .002) and after adjustment for age, sex, percent body fat, and M-low (P = .02). M-low and M-high were less in LBW than in NBW subjects before (P = .05 and P = .01) and after adjustment for age, sex, percent body fat, and WTR (P = .04 and P = .05). AIR was not different in LBW compared to NBW subjects before adjustments (P = .06), but it was lower in LBW than in NBW subjects after adjustment for age, sex, percent body fat, and M-low (P = .02), suggesting that AIR did not increase appropriately for the decrease in insulin-stimulated glucose disposal (M). In addition, average adipocyte cell size (P = .08) and basal lipolysis (P = .02) were higher in the LBW than in the NBW group. These results show that Pima Indians with LBW manifest a variety of impairments in metabolism in adulthood. Among these, a lesser insulin-stimulated suppression of EGP and a lesser insulin secretory capacity are the predominant ones. We conclude that interaction of multiple defects may contribute to increased susceptibility to type 2 diabetes among individuals with LBW.
authors.affiliation: The Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, USA.
authors.forename: Norbert
authors.initials: N
authors.lastname: Stefan
authors.forename: Christian
authors.initials: C
authors.lastname: Weyer
authors.forename: Claire
authors.initials: C
authors.lastname: Levy-Marchal
authors.forename: Michael
authors.initials: M
authors.lastname: Stumvoll
authors.forename: William C
authors.initials: WC
authors.lastname: Knowler
authors.forename: P Antonio
authors.initials: PA
authors.lastname: Tataranni
authors.forename: Clifton
authors.initials: C
authors.lastname: Bogardus
authors.forename: Richard E
authors.initials: RE
authors.lastname: Pratley
mesh_terms: D017667:Adipocytes / Q000502:physiology / Q000648:ultrastructure; D000328:Adult; D001823:Body Composition / Q000502:physiology; D015992:Body Mass Index; D003920:Diabetes Mellitus / Q000097:blood / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005947:Glucose / Q000096:biosynthesis*; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance / Q000097:blood / Q000453:epidemiology*; D006801:Humans; D007198:Indians, North American; D007230:Infant, Low Birth Weight / Q000097:blood*; D007231:Infant, Newborn; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D008066:Lipolysis / Q000502:physiology; D008297:Male; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
chemical_list: D007328:Insulin; D005947:Glucose