Emergence of insulin resistance in juvenile baboon offspring of mothers exposed to moderate maternal nutrient reduction

Choi J, Li C, McDonald TJ, Comuzzie A, Mattern V, Nathanielsz PW. Emergence of insulin resistance in juvenile baboon offspring of mothers exposed to moderate maternal nutrient reduction. Am J Physiol Regul Integr Comp Physiol 301: R757-R762, 2011. First published June 8, 2011; doi:10.1152/ajpregu.00051.2011.-Developmental programming of postnatal pancreatic beta-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 beta-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 beta-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 beta-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.