RELATIVE EFFECTS OF CALORIE RESTRICTION AND WEIGHT-LOSS IN NONINSULIN-DEPENDENT DIABETES-MELLITUS

In obese patients with noninsulin-dependent diabetes mellitus (NIDDM), reducing calorie intake improves glycemic control, often more rapidly than weight loss. Conversely, after weight loss has been achieved, me tabolic control can deteriorate once calorie intake is increased, even if there is no regaining of weight. The current study, therefore, tes ted the hypothesis that restricting calorie consumption has an importa nt role, independent of weight loss, in metabolic regulation of NIDDM patients. Isotopic determinations of hepatic glucose production (HGP), post-absorptively and after ingestion of 75 g glucose (dual glucose i sotope method), were made in conjunction with measurement of insulin s ecretion and insulin sensitivity in seven obese NIDDM volunteers after four periods of controlled calorie intake: 1) 7 days of a baseline we ight maintenance diet, 2) followed immediately by 7 days of calorie re striction (800 Cal/day); 3) followed by a weight loss program that con sisted of 2 months of a very low calorie diet (400 Cal/day) and then 4 weeks of gradual refeeding and 7 days on a weight maintenance diet; a nd 4) a final week of calorie restriction (800 Cal/day). The initial b rief interval of calorie restriction produced substantial decreases in fasting plasma glucose, HGP, and fasting plasma triglyceride and incr eases in insulin sensitivity and secretion. After a substantial weight loss (12.7 +/- 2 kg), each parameter improved further, with the effec t of weight loss approximately equal to that obtained with initial cal orie restriction. Reimposing calorie restriction after weight loss had little effect, except that fasting plasma glucose and HGP improved sl ightly further. In obese NIDDM subjects, a 7-day period of calorie res triction produces approximately half of the overall improvement in HGP , insulin sensitivity, and insulin secretion that is obtained after a substantial loss of weight. These findings indicate that calorie restr iction has an important regulatory effect on the metabolism of obese p atients with NIDDM that is independent of weight loss.