Endocrine Abstracts

Background

Insulin resistance is associated with obesity, metabolic syndrome and hypertension. These risk factors for type 2 diabetes and cardiovascular may be programmed by the early diet. Here we assessed insulin sensitivity in pre- and postnatally nutritionally challenged offspring at 1 yr of age in sheep.

Methods

37 twin-bearing ewes were randomly allocated to receive either a control (C, n=24) or nutrient restricted diet (NR, 50% C intake, n=13) from days 30 to 80 of gestation. Thereafter all sheep were fed to 100% requirement to term (12–13 MJ/day). Offspring were delivered spontaneously and either ewe reared or bottle-fed (BF, n=8 from control group; 1–1.5 L/d Volac) until weaning (10–12 weeks). Thereafter to 1 yr offspring were reared indoors with restricted activity and increased food availability to promote fat deposition (Obese controls OC, n=8; Obese nutrient restricted ONR, n=13; Obese bottle-fed OBF, n=8) or pasture grazed with unrestricted activity (Lean controls LC, n=8). An insulin tolerance test was conducted and the fall in blood glucose recorded over 4–16 min after bolus injection of 0.75IU/kg insulin at time 0 (Novorapid).

Results

Baseline blood glucose was higher in obese relative to lean sheep (Obese, ∼3.9±0.1 vs. lean, 3.4±0.2). In addition, the negative slope (21±1 vs. −28±2 nM/min), ½ time (−36±3 vs. −26±2 min) and %decline (2.2±0.1 vs. 2.8±0.2%/min) of the fall in blood glucose all indicated insulin resistance in obese relative to lean sheep, respectively. There was no additive effect of prenatal undernutrition or bottle feeding. Of the obese sheep, the control group tended to have the poorest insulin sensitivity (e.g. slope and ½ time were −18±3 nM/min & 46±7 min, respectively).

Conclusions

This study has shown poor insulin sensitivity in obese relative to lean sheep. There appeared no programmed alteration in insulin-dependent glucose disposal in the short term but further study of plasma glucose and insulin responses to a glucose tolerance test incorporating both insulin-dependent and independent effects may highlight specific differences between groups.