INSULIN-RESISTANCE AND ABNORMAL ALBUMIN EXCRETION IN NONDIABETIC FIRST-DEGREE RELATIVES OF PATIENTS WITH NIDDM

Microalbuminuria has recently been associated with insulin resistance in both insulin-dependent and non-insulin-dependent (NIDDM) diabetes m ellitus. To establish whether microalbuminuria in non-diabetic subject s as well is associated with insulin resistance and associated abnorma lities in glucose and lipid metabolism, oral glucose tolerance tests w ere performed with measurement of urinary albumin excretion rate, lipi ds and lipoproteins in 582 male non-diabetic first-degree relatives of patients with NIDDM. In addition, insulin sensitivity was assessed in 20 of these subjects with the euglycaemic hyperinsulinaemic clamp tec hnique. Abnormal albumin excretion rate (AER), defined as AER 15-200 m u g/min, was associated with higher systolic blood pressure (p < 0.05) , higher fasting glucose values (p < 0.05), lower HDL-cholesterol (p < 0.05) and lower apolipoprotein A-I (p < 0.05) concentrations than obs erved in subjects with normal AER. The rate of glucose metabolism was lower in subjects with abnormal compared to subjects with normal album in excretion rate (38.0 +/- 2.8 vs 47.3 +/- 2.4 mu mol . kg lean body mass(-1). min(-1); p = 0.028). This difference was almost completely a ccounted for by a reduction in non-oxidative glucose metabolism (17.7 +/- 1.9 vs 27.4 +/- 2.7 mu mol . kg lean body mass(-1). min(-1); p = 0 .010), which correlated inversely with the AER (r = -0.543; p = 0.013) . These results suggest that in non-diabetic individuals genetically p redisposed to NIDDM, abnormal AER is associated with insulin resistanc e and abnormalities in glucose and lipid metabolism.