PREDICTORS OF PROGRESSION FROM NORMOALBUMINURIA TO MICROALBUMINURIA IN NIDDM

OBJECTIVE - Our objective was to establish the clinical, genetic, meta bolic, and immunologic risk factors for the progression of the albumin excretion rate (AER) in normoalbuminuric NIDDM patients. RESEARCH DES IGN AND METHODS - We recruited 108 NIDDM patients with normal AER afte r a diabetes duration of 9 years to participate in a prospective 9-yea r follow-up. In addition to conventional clinical and metabolic variab les, we assessed microvascular (retinopathy, nephropathy, neuropathy) and macrovascular (coronary heart disease, peripheral vascular disease ) diabetic complications, genetic markers (HLA genotypes), and organ-s pecific autoimmune markers, including islet cell antibodies. Multiple logistic regression was used to determine independent predictors of pr ogression of AER. RESULTS - A total of 21 patients (19%) died during t he follow-up. There was an overrepresentation of men (61 vs. 39%; P = 0.044) and smokers (55 vs. 27%; P = 0.01) in patients who progressed t o micro- or macroalbuminuria versus those who did not progress. In add ition, progressors had higher fasting plasma glucose (P = 0.002) and H bA(1) (P = 0.0002) concentrations at baseline than did nonprogressors. Neuropathy was more often seen in progressors than in nonprogressors at baseline (51 vs. 16%; P = 0.0004). Frequency of HLA. genotypes and autoimmune markers did not differ between progressors and nonprogresso rs. In a multiple logistic regression analysis, HbA1 (P = 0.0005) and a history of smoking (P = 0.011) were independent predictors of progre ssion of AER. CONCLUSIONS - This study reemphasizes the importance of poor glycemic control and smoking as independent risk factors for prog ression of AER. Furthermore, development of micro- or macroalbuminuria in NIDDM was associated with neuropathy and male sex.