Eight-Month Correction of Hyperglycemia in Insulin-dependent Diabetes Mellitus Is Associated with a Significant and Sustained Reduction of Urinary Albumin Excretion Rates in Patients with Microalbuminuria

Abstract

Persistent Albustix-positive proteinuria and subsequent chronic renal failure are frequently encountered in insulin- dependent diabetes mellitus (IDDM). Rates of decline of renal function may be modified by treatment of accompanying hypertension, but studies of the effects of long-term continuous subcutaneous insulin infusion (CSII) on deterioration of renal function provide no statistically significant evidence of benefit of near-normoglycemia. However, short-term studies in IDDM subjects with negative Albustix tests but subclinically raised levels of albumin excretion rate (AER) have shown that treatment with CSII significantly reduces this microalbuminuria. The prospective, controlled 8-mo Kroc Collaborative Study therefore offered the opportunity of examining more protracted effects of CSIIinduced metabolic correction upon microalbuminuria. Twenty-four-hour urine collections obtained at baseline, 4, and 8 mo were available from 59 Albustix-negative patients. β2-microglobulin excretion was normal. The 39 normoalbuminuric (AER < 12 μ/min) patients did not differ from the 20 microalbuminuric (AER elevated between 13.2 and 192.6 μg/min) with respect to distributions of age, sex, and duration of diabetes. In both the normoalbuminuric and the microalbuminuric groups studied at 4 and 8 mo, percent glycosylated hemoglobin (%HbA1) and mean blood glucose were significantly decreased during CSII compared with baseline values, whereas no change occurred in the group continuing their conventional insulin therapy (CIT). AER did not differ between CIT and CSII treatments in the normoalbuminuric group. AER fell significantly in the CSII-treated microalbuminuric patients at 4 (P < 0.05) and 8 (P < 0.01) mo but showed no consistent change in the CIT microalbuminuric group. With respect to responses of patients at particularly high risk of progression to clinical nephropathy (i.e., AER > 30 μ/min), four of four improved during CSII, but only two of six during CIT. These observations demonstrate a sustained reduction of abnormal rates of urinary albumin excretion during therapy designed to achieve near-normoglycemia in IDDM.