INSULIN-RESISTANCE DURING EUGLYCEMIC CLAMP STUDIES IN CHRONICALLY UNDERNOURISHED RATS WITH MILD STREPTOZOCIN DIABETES

Malnutrition has been shown to impair insulin sensitivity, but it is n ot known whether this effect has any impact on coexisting diabetes. In sulin sensitivity was therefore studied using the glucose clamp techni que in rats with chronic nutritional deprivation superimposed on mild streptozocin (STZ) diabetes mellitus. In pair-feeding experiments, 4 w eek-old littermate rats were either allowed ad libitum access to food or restricted to 50% of ad libitum intake for 8 weeks, and were inject ed with STZ 40 mg/kg intraperitoneally halfway through the experiment. Fasting plasma glucose (FPG) was similar in both groups of rats, but fasting plasma insulin (FPI) was lower in the undernourished group (P =.016). Undernourished rats were significantly more insulin resistant during euglycemic hyperinsulinemia of the same degree, with glucose di sposal rate being impaired by 50% as compared with that in ad libitum- fed diabetic littermates (24.4 +/- 2.8 v 51.5 +/- 4.4 mu mol/kg/min, P =.0008). The insulin sensitivity index was significantly lower in the undernourished group (3.03 +/- 0.32 v 5.67 +/- 0.6, P =.0057). The re sults show that chronic undernutrition markedly reduces insulin sensit ivity in rats with mild STZ diabetes. This is further evidence that ch ronic undernutrition is a deleterious modifying influence on coexistin g diabetes mellitus. It suggests that the insulin resistance of malnut rition-related diabetes mellitus (MRDM) could potentially he an acquir ed defect mediated by the coexistent undernutrition, rather than a ''d istinctive'' feature that is intrinsically unique to this diabetic syn drome. Copyright (C) 1995 by W.B. Saunders Company