Dear Sir, Insulin resistance is commonly seen in patients with impaired glucose tolerance or non-insulin-dependent diabetes mellitus NIDDM, normoglycaemic first-degree relatives of patients with NIDDM, patients with high blood pressure and their normotensive first-degree relatives, dyslipidaemic individuals with high plasma triglyeeride and low HDL cholesterol concentrations, and both microvascular angina and conventional coronary heart disease [1-8]. Given these observations, it is not surprising that this phenomenon has received, and continues to receive considerable attention. In this context, plasma insulin concentration is often used as a surrogate marker for insulin-mediated glucose uptake. Although the relationship between plasma insulin concentration and insulin resistance is statistically significant in non-diabetic subjects [9], measurement of the plasma insulin level is not identical to the direct determination of insulin resistance, either quantitatively or conceptually. For approximately 20 years we have used a simple infusion procedure (insulin suppression test) to directly measure insulinmediated glucose uptake based upon the suppression of endogenous insulin secretion and the constant infusion of glucose and exogenous insulin [1-8]. Under these conditions, similar steady-state plasma insulin (SSPI) concentrations are reached in all individuals, and the steady-state plasma glucose (SSPG) concentration provides a direct estimate of insulin-mediated glucose uptake. More recently we have used somatostatin to suppress endogenous insulin secretion as initially suggested by Harano et al.[10]. Although this approach is satisfactory, it suffers from some practical drawbacks. For example, in the United States the use of somatostatin requires tiling for an investigative new drug number at the Food and Drug Administration. A specific grade of good manufacturing practice of this material must be purchased in bulk and prepared in aliquots for intravenous infusion. Furthermore, it is necessary to prove lack of pyrogenicity for these preparations. The present study was initiated in an effort to overcome these practical hurdles, and to simplify the use of the insulin suppression test to directly assess insulin resistance. Specifically, we compared the results of measuring insulin resistance with the commercially available somatostatin analogue, octreotide, and somatostatin.

The study population consisted of 29 normal volunteers, 13 males and 16 females in good general health, taking no medication known to influence carbohydrate or lipid metabolism. They had a mean age of 46years (range 22-69) and a mean body mass index of 26.1 kg/mZ (range 18.6-35.4). Criteria for inclusion into the study included a normal medical history, physical examination, haemogram, and chemical screening battery. In addition, all subjects had a normal oral glucose tolerance test. This study was approved by the Stanford Human Subjects Committee, and each subject gave written informed consent.