RELATIONSHIPS AMONG MICROALBUMINURIA, INSULIN-RESISTANCE AND RENAL-CARDIAC COMPLICATIONS IN INSULIN-DEPENDENT AND NON-INSULIN-DEPENDENT DIABETES

A rate of albumin excretion rate above 20 mu g/min is a predicting fac tor of overt nephropathy in Type I diabetes. It has not yet been estab lished whether this is the case also for Type II diabetes, where micro albuminuria is antecedent to general and cardiovascular mortality but not to end-stage renal disease. The reasons accounting for this discre pancy between Type I and Type IT diabetes have not been fully elucidat ed. In principle two different hypotheses can be postulated to explain these findings. Firstly it can be suggested that overt proteinuria is not detected with similar incidence rates in microalbuminuric patient s with the two types of diseases because Type II diabetics are older a nd more prone to develop cardiovascular events. Therefore these patien ts would die frequently before developing overt proteinuria not becaus e microalbuminuria is not a predicting factor of End-stage Renal Disea se, but rather because the follow-up period is not long enough to moni tor the patients till the very moment they develop renal complications . Alternatively it is possible that microalbuminuria reflect a systemi c, endothelial and vascular disorder rather than glomerular structural abnormalities in these patients. We have recently described a cluster ing of clinical features encompassing microalbuminuria, hypertension, peripheral extrahepatic insulin resistance, renal and cardiac hypertro phy and altered cation membrane transport systems, not in the overall Type II diabetic population, but only in a cohort of these patients. E vidences in keeping with a strict association between insulin resistan ce, hypertension and microalbuminuria in a subgroup of Type II diabeti c patients have been recently reported by several authors both in cros s-sectional and longitudinal studies. However the hypothesis that micr oalbuminuria reflects a systemic endothelial and vascular disorder in Type II diabetic patients, does not rule out the possibility that thes e systemic disturbances are also associated with histologic abnormalit ies of the kidney. With regard to the characteristics of renal histolo gy in Type II diabetic patients with and without microalbuminuria, pre liminary data from our laboratory demonstrate that there is no evidenc e of any renal disorder other than diabetes in microalbuminuric Type I I diabetic patients. More particularly in this subset of patients we o bserved typical features of diabetic nephropathology (glomerular, tubu lo-interstitial and arteriolar changes), while a substantial number of patients with increased albumin excretion rate exhibited either marke d tubulo-interstitial lesions or arteriolar hyalinosis or both, in abs ence of significant glomerular changes. These findings suggest that it is not true that Type II diabetic patients with microalbuminuria show quite often normal renal histology, but rather than hyperglycemia may cause different patterns of renal injury as compared to Type I Diabet es. Furthermore always with regard to renal histology, it has been poi nted out that in Type I diabetes glomerulopathy (especially mesangial) is the crucial change, whereas recent studies found considerable stru ctural heterogeneity amongst proteinuric Type II diabetic patients wit h relatively high incidence of renal diseases other than diabetes. How ever parallel studies in a small group of micromacroalbuminuric Type I I diabetic patients reported the typical glomerular changes, usually s hown by Type I diabetic patients with similar patterns of renal damage . The issue of the relationships between microalbuminuria, hypertensio n and the development of overt nephropathy in Type II diabetes has bee n also examined in Pima Indians. The clinical scenario found in these patients does closely resemble that of Caucasian Type I diabetic patie nts.