Urinary uric acid clearance appears to decrease in proportion to increases in insulin resistance in normal volunteers, leading to an increase in serum uric acid concentration. Thus, it appears that modulation of serum uric concentration by insulin resistance is exerted at the level of the kidney.

No abstract

Fasting and postprandial plasma glucose, free fatty acid (FFA), lactate, and insulin concentrations were measured at hourly intervals for 24 h in 27 nonobese individuals-9 with normal glucose tolerance, 9 with mild non-insulin-dependent diabetes mellitus (NIDDM, fasting plasma glucose less than 175 mg/dl), and 9 with severe NIDDM (fasting plasma glucose greater than 250 mg/dl). In addition, hepatic glucose production (HGP) was measured from midnight to 0800 in normal individuals and patients with severe NIDDM. Plasma glucose concentration was highest in patients with severe NIDDM, lowest in those with normal glucose tolerance, and intermediate in those with mild NIDDM (two-way ANOVA, P less than .001). Variations in plasma FFA and lactate levels of the three groups were qualitatively similar, with lowest concentrations seen in normal individuals, intermediate levels in the group with mild NIDDM, and the highest concentration in those with severe NIDDM (two-way ANOVA, P less than .001). Of particular interest was the observation that plasma FFA concentrations were dramatically elevated from midnight to 0800 in patients with severe NIDDM. The 24-h insulin response was significantly increased in patients with mild NIDDM, with comparable values seen in the other two groups. Values for HGP fell progressively throughout the night in normal individuals and patients with severe NIDDM, despite a concomitant decline in plasma glucose and insulin levels. Although the magnitude of the fall in HGP was greater in NIDDM, the absolute value was significantly (P less than .001) greater than normal throughout the period of observation.(ABSTRACT TRUNCATED AT 250 WORDS)

Previous studies have demonstrated reduced in vivo insulin action in obese subjects compared with lean controls. However, little data is available on the relationship between degree of obesity and insulin action, and this relationship has not been shown to be independent of individual differences in maximal aerobic capacity. We studied 55 male Pima Indians and 35 male Caucasians with normal glucose tolerance. In vivo insulin action was measured using the hyperinsulinemic, euglycemic clamp technique at a plasma insulin concentration of approximately 100 microU/ml. Body composition was determined by densitometry, and maximal aerobic capacity was estimated using a graded exercise test. The results showed that degree of obesity was nonlinearly related to in vivo insulin action. In both Indians and Caucasians there was a significant decline in insulin action with increasing obesity up to a percent body fat of approximately 28-30%. Further increases in obesity in the Indians were not associated with significant changes in insulin action. Maximal aerobic capacity was positively linearly correlated with insulin action over the entire range of insulin action in both racial groups. Degree of obesity and maximal aerobic capacity were each independently associated with insulin action although these independent relationships were of marginal significance in the Caucasians. Surprisingly, individual differences in obesity and maximal aerobic capacity accounted for only half the variability observed in insulin action in these glucose tolerant subjects.

Measurements were made of both glucose disposal (M) during hyperinsulinemic clamp studies and plasma glucose and insulin responses to an oral glucose challenge in 100 individuals with normal glucose tolerance. The subjects were divided into 4 quartiles on the basis of M values, ranging from a low mean (+/- SEM) value of 140 +/- 3 mg/m2 X min (quartile 1) to a high of 349 mg/m2 X min (quartile 4). The plasma insulin response to oral glucose inversely correlated with the M value (r = -0.60; P less than 0.001), being highest in those with the lowest M (quartile 1) and lowest in those with the highest M (quartile 4). On the other hand, the plasma glucose responses of the 4 quartiles were virtually identical. These results document that insulin-stimulated glucose uptake varies widely in subjects with normal glucose tolerance, and that these differences are independent of any change in the plasma glucose response to oral glucose. Furthermore, the results indicate that insulin resistance in normal individuals is associated with hyperinsulinemia.