Predictors of progression from normoalbuminuria to microalbuminuria in NIDDM

Our objective was to establish the clinical, genetic, metabolic, and immunologic risk factors for the progression of the albumin excretion rate (AER) in normoalbuminuric NIDDM patients.

We recruited 108 NIDDM patients with normal AER after a diabetes duration of 9 years to participate in a prospective 9-year follow-up. In addition to conventional clinical and metabolic variables, we assessed microvascular (retinopathy, nephropathy, neuropathy) and macrovascular (coronary heart disease, peripheral vascular disease) diabetic complications, genetic markers (HLA genotypes), and organ-specific autoimmune markers, including islet cell antibodies. Multiple logistic regression was used to determine independent predictors of progression of AER.

A total of 21 patients (19%) died during the 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 to micro- or macroalbuminuria versus those who did not progress. In addition, progressors had higher fasting plasma glucose (P = 0.002) and HbA1 (P = 0.0002) concentrations at baseline than did nonprogressors. Neuropathy was more often seen in progressors than in nonprogressors at baseline (53 vs. 16%; P = 0.0004). Frequency of HLA genotypes and autoimmune markers did not differ between progressors and nonprogressors. In a multiple logistic regression analysis, HbA1 (P = 0.0005) and a history of smoking (P = 0.011) were independent predictors of progression of AER.

This study reemphasizes the importance of poor glycemic control and smoking as independent risk factors for progression of AER. Furthermore, development of micro- or macroalbuminuria in NIDDM was associated with neuropathy and male sex.