Long-term follow-up after early protein-calorie malnutrition in young rats: Sex difference in glucose tolerance and serum insulin levels

Abstract

Acute protein-calorie malnutrition impairs both glucose tolerance and insulin secretion, and long-term pancreatic damage leading to malnutrition diabetes has been postulated. The present study has investigated this association in rats weaned onto 5% protein (LP) or 18% protein (normal, N) diet from age 3 weeks to 6 weeks. From 6 weeks both LP and N rats were fed N diet for the remainder of the experiment. LP rats did not grow while on the LP diet and remained significantly lighter for several weeks. Nose to tail tip length was identical for the two groups in both sexes at both 24 and 48 weeks, and mean body weight was not significantly less in LP than N after 18 weeks in either sex. Protein/DNA ratios in LP (an index of cell size) remained lower than N in heart, skeletal muscle, and lung at 24 and 48 weeks, but not in gut, liver, or kidney tissues. Thus, skeletal growth was apparently not impaired by the early malnutrition, but muscle tissue did not catch up. The similarity in final body weight implies greater adipose stores in older LP rats. At 12 weeks there was no difference in glucose tolerance tests (GTT) either between males and females within a dietary group or between N and LP, despite impaired insulin secretion in LP. Both fasting glucose levels and GTT deteriorated markedly between 12 and 48 weeks in all rats, but especially in LP males. Serum insulin levels following glucose injection were lower at 48 weeks than 12 weeks. At 48 weeks glucose levels were lower at all time points in female than male LP, and insulin levels were lower in N females than N males. Similar trends in N glucose and LP insulin levels were not significant. This sex difference in GTT in older rats has not previously been described. Thus, although short-term protein-calorie malnutrition leads to persistent alterations in growth and metabolism into early adult life, it does not alone cause overt diabetes mellitus in rats up to one year of age. Following the nutritional deficit, insulin levels in relation to glucose homeostasis recovered slowly but were comparable with those of normal older rats.