INTENSIVE THERAPY AND PROGRESSION TO CLINICAL ALBUMINURIA IN PATIENTSWITH INSULIN-DEPENDENT DIABETES-MELLITUS AND MICROALBUMINURIA

Objective-To study the effect of intensive therapy of diabetes on the progression to clinical albuminuria in insulin dependent diabetic pati ents with microalbuminuria. Design-Randomised controlled clinical tria l of intensive versus conventional therapy of diabetes for a median of 5 years (range 2-8). Setting-Nine hospital based specialist diabetes centres in England and Wales. Subjects-70 European insulin dependent d iabetic patients aged 17-59 years with microalbuminuria (albumin excre tion 30-199 mu g/min), but without arterial hypertension, recruited fr om the nine hospital based specialist diabetes centres. Interventions- Intensive diabetic therapy was allocated to 36 patients (27 men, 9 wom en) and conventional diabetic therapy to 34 (24 men, 10 women). Main o utcome measures-Development of clinical albuminuria, defined as albumi n excretion greater than 200 mu g/min on at least two consecutive occa sions, and rate of change of albumin excretion. Results-Mean glycated haemoglobin concentration, similar at baseline in the two groups (inte nsive therapy group 10.3% (SEM 1.9%), conventional therapy group 9.8% (1.6%)), fell significantly (by 14%) in the intensive therapy group on ly. A significant glycaemic separation between the two groups was main tained for up to three years. Progression to clinical albuminuria occu rred in six patients in each group. Blood pressure, similar at baselin e, fell significantly by 1 mm Hg (95% confidence interval -4.20 to 1.4 3) per year in the conventional therapy group, but the difference in t he rate of blood pressure change between the groups was not significan t. Independent of treatment assignment, a mean blood pressure above th e group mean (93.6 mm Hg), but not the glycated haemoglobin concentrat ion, predicted progression to clinical albuminuria (relative risk 4.2, 95% confidence interval 1.3 to 13.0). Conclusions-Intensive therapy w ith improved glycaemic control for three years had no impact on the pr ogression of albuminuria in insulin dependent diabetic patients with m icroalbuminuria. The reduction in blood pressure in the conventional t herapy group may have affected outcome-in that arterial blood pressure rather than glycated haemoglobin concentration seemed to be the main predictor of progression from microalbuminuria to clinical albuminuria .