ADDITIVE EFFECTS OF OBESITY, HYPERTENSION, AND TYPE-2 DIABETES ON INSULIN-RESISTANCE

Resistance to insulin-mediated glucose disposal has been previously shown to be increased in association with obesity, high blood pressure, and non-insulin-dependent diabetes mellitus. We initiated the present study to quantify the separate effects of hypertension and non-insulin-dependent diabetes mellitus on insulin resistance in both nonobese and obese subjects. To accomplish this, 88 subjects were divided into the following five experimental groups: normal blood pressure, nonobese (n=17); normal blood pressure, obese (n=18); high blood pressure, nonobese (n=18); high blood pressure, obese (n=19); and high blood pressure, obese, noninsulin-dependent diabetes mellitus (n=16). Plasma glucose and insulin concentrations were measured before and after a 75-g oral glucose load. Resistance to insulin-mediated glucose disposal was estimated by determining the steady-state plasma insulin and glucose concentrations during the last 30 minutes of a continuous infusion of somatostatin (5 mu g/min), exogenous insulin (25 mU/m(2) per minute), and glucose (240 mg/m(2) per minute). Since the steady-state plasma insulin concentrations are similar in all subjects, the higher the steady-state plasma glucose, the more insulin resistant the individual. Nonobese subjects with normal blood pressure had the lowest plasma glucose and insulin responses and steady-state plasma glucose concentrations, and their values were significantly different from the other four groups. Obese or nonobese subjects with high blood pressure had significantly higher plasma glucose responses and steady-state plasma glucose concentrations than did their respective weight-matched control subjects. Finally, plasma glucose responses and steady-state plasma glucose concentrations were significantly higher in obese subjects with both high blood pressure and non-insulin-dependent diabetes mellitus. These results support the view that the effects of obesity, high blood pressure, and non-insulin-dependent diabetes mellitus on resistance to insulin-mediated glucose disposal are additive.