Gut hormone activity of children born to women with and without gestational diabetes.

Children exposed to gestational diabetes mellitus (GDM) in utero have greater risk for obesity and comorbid health problems as compared to children from non-diabetic mothers (1-3). This effect is believed to be at least partially attributable to altered intrauterine programming of metabolism and body weight regulation. Gut hormones play an important role in the regulation of body weight homeostasis via signaling of hunger and satiety. To date, however, there are no published studies that have examined the concentrations and activity of gut hormones among offspring of women with gestational diabetes (OGD) versus those from a non-diabetic intrauterine environment (CTRL). Ghrelin is a hormone secreted in the stomach and to date, is the only peripheral signal that is known to stimulate food intake (4). Secretion of ghrelin increases prior to a meal and is suppressed following a meal (5). Among obese adults, fasting concentrations of ghrelin tend to be lower, and the post-prandial suppression of ghrelin is blunted (6; 7). Although it appears paradoxical for obese individuals to have lower fasting ghrelin, it has been hypothesized that this pattern is consequent to increased insulin, which is inversely associated with ghrelin, or is an adaptive response to positive energy balance in obese adults (6). Despite consistent findings in studies of adults, studies of lean versus obese children, have yielded less consistent results (8; 9). Glucagon-like peptide 1 (GLP-1) and peptide-tyrosine-tyrosine (PYY) are anorectic hormones that are secreted from L-cells in the ileum of the small intestine in response to feeding. Circulating concentrations of GLP-1 tend to be lower among obese adults and children (10; 11), and the acute increase in GLP-1 following meal consumption may be suppressed in obese states (12). There are two endogenous forms of PYY: 1-36 and 3-36; the latter of these has been more strongly implicated in feeding. Some, but not all (9), studies have shown lower fasting concentrations of PYY3-36 among obese individuals (13; 14). Furthermore, obesity has been consistently associated with suppression of the usual increase in PYY3-36 concentration that occurs following a meal (9; 13; 14). Previous research has not examined whether the response of GLP-1 and PYY to a meal challenge is perturbed among children of women with GDM. The main objective of this study was to compare fasting and postprandial concentrations of ghrelin, GLP-1 and PYY3-36 among children with and without intrauterine exposure to maternal GDM. The secondary objective was to examine whether associations of these hormones with children’s usual food intake differed by group. Differences in body composition, energy intake, physical activity, insulin sensitivity and secretion among OGD versus CTRL from this cohort have been reported previously (2). We hypothesized that, similar to obese individuals, OGD would have lower fasting concentrations of ghrelin, GLP-1, and PYY3-36, and an attenuated postprandial response of these gut hormones. These hypotheses were tested among 5-10 year-old children with and without intrauterine exposure to GDM.