Insulin resistance seen in non-insulin dependent diabetes mellitus and hypertension.

Abstract

The characteristics of NIDDM seen in Japanese is coexistence of diminished insulin secretion and the impaired sensitivity to insulin in the target tissues. Thus, insulin resistance does not mean hyperinsulinemia. To investigate the organ-specific insulin action on glucose homeostasis, we developed an innovative non-invasive method, using an euglycemic hyperinsulinemic clamp combined with oral glucose load. With this procedure, we could reveal muscle glucose uptake and hepatic glucose uptake following oral glucose load, quantitatively, separately and simultaneously. The effect of strict glycemic control in non-obese NIDDM who were secondary failure to sulfonylurea with 3 times prandial regular insulin injections, on glucose disposals are investigated. Glucose disposal by peripheral tissues was not altered (clamped blood glucose and insulin concentration are, 90 mg/dl and 200 microU/ml, respectively). The ratio of splanchnic glucose disposal to the amount of ingested glucose, on the other hand, significantly increased to 33.1% from 14.5%. Therefore, short-term strict glycemic control appears to improve glucose handling by splanchnic tissues without affecting insulin sensitivity of peripheral tissues in NIDDM. This method would be feasible to investigate whether insulin resistance seen in hypertensive patients, is located only in peripheral tissues or is also in the liver. To find patients with asymptomatic atherosclerosis, we routinely apply a noninvasive maneuver using high resolution B-mode imaging of the carotid artery, to determine atherosclerosis quantitatively. Impaired glucose tolerance (IGT) male subjects showed significantly greater thickness of the intimal plus medial complex (IMT) than age-matched healthy males and showed no significant differences compared to age-matched NIDDM patients. Among IGT, those with exaggerated insulin secretion (average serum insulin concentration was 100 microU/ml at 1 and 2 h after), in other words, insulin resistant, showed thicker IMT. The characteristics of IGT groups with high insulin level were, BMI more than 25, diastolic blood pressure more than 83 mmHg, serum triglyceride more than 215 mg/dl. Thus, among mildly obese, mild hypertensive, mild glucose intolerant, slightly hypertriglyceridemic Japanese male subjects, there exist advanced atherosclerotic subjects.