title: Emergence of insulin resistance in juvenile baboon offspring of mothers exposed to moderate maternal nutrient reduction.
abstract: Developmental programming of postnatal pancreatic β-cell and peripheral insulin function by maternal nutrient reduction (MNR) has been extensively investigated in rodents and sheep, but no data exist from nonhuman primate offspring of MNR mothers. We hypothesized that moderate levels of MNR would result in developmental programming of postnatal β-cell function and peripheral insulin sensitivity that lead to emergence of a prediabetic state prior to puberty. Prepregnancy phenotype of 18 nonpregnant baboons was matched. During pregnancy and lactation 12 mothers ate chow ad libitum (controls), while six ate 70% of chow consumed by controls (weight-adjusted MNR). Weaned offspring ate normal chow. At 3.5 ± 0.18 yr (mean ± SE) in an intravenous glucose tolerance test, conscious, tethered MNR juvenile offspring (2 females and 4 males) showed increased fasting glucose (P < 0.04), fasting insulin (P < 0.04), and insulin area under the curve (AUC; P < 0.01) compared with controls (8 females and 4 males). Insulin AUC also increased following an arginine challenge (P < 0.02). Baseline homeostatic model assessment insulin β-cell sensitivity was greater in MNR offspring than controls (P < 0.03). In a hyperinsulinemic, euglycemic clamp, the glucose disposal rate decreased 26% in MNR offspring. Changes observed were not sex dependent. MNR in pregnancy and lactation programs offspring metabolic responses, increasing insulin resistance and β-cell responsiveness, resulting in emergence of an overall phenotype that would predispose to later life type-2 diabetes, especially, should other dietary challenges such as a Westernized diet be experienced.
authors.affiliation: Center for Pregnancy and Newborn Research, The University of Texas Health Science Center San Antonio, San Antonio, TX 78229-3900, USA.
authors.forename: Jaehyek
authors.initials: J
authors.lastname: Choi
authors.forename: Cun
authors.initials: C
authors.lastname: Li
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: McDonald
authors.forename: Anthony
authors.initials: A
authors.lastname: Comuzzie
authors.forename: Vicki
authors.initials: V
authors.lastname: Mattern
authors.forename: Peter W
authors.initials: PW
authors.lastname: Nathanielsz
mesh_terms: D000367:Age Factors; D000375:Aging; D000704:Analysis of Variance; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D005215:Fasting / Q000097:blood; D005260:Female; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006706:Homeostasis; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007774:Lactation; D008297:Male; D044342:Malnutrition / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D010215:Papio; D010641:Phenotype; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D039401:Prenatal Nutritional Physiological Phenomena; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D001786:Blood Glucose; D007328:Insulin