Role of glycaemic control in development of microalbuminuria in patients with insulin dependent diabetes

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Abstract
Objective: To ascertain which factors determine the progression from very low rates of albumin excretion to persistent microalbuminuria in patients with insulin dependent diabetes mellitus. Design: A 10 year prospective study of a cohort of diabetic patients. Setting: Outpatient department of the Portsmouth District Hospitals. Subjects—97 patients with insulin dependent diabetes mellitus who were initially free of microalbuminuria and hypertension. Main outcome measure—Urinary albumin: creatinine ratio. Results: Eight of the 97 patients had developed microalbuminuria (urinary albumin:creatinine ratio > 3 mg/mmol in three consecutive early morning samples) by the 10 year follow up. The group who developed microalbuminuria had higher baseline log 10 plasma glucose concentrations (mean (SD), 1.210 (0.122) (upsilon) 0.984 (0.196) mmol/l, P < 0.001) and glycated haemoglobin concentrations (1.112% (0.069%) (upsilon) 0.997% (0.076%), P < 0.001) and a younger age at onset of diabetes (10.0 (5.5) (upsilon) 15.6 (7.8) years, P < 0.05). There was no difference in baseline duration of diabetes, smoking, sex, insulin dose, body mass index, serum creatinine concentration, or systolic, diastolic, or mean arterial blood pressure between the two groups. Multiple linear regression analysis showed that urinary albumin:creatinine ratio at 10 years was influenced by initial albumin: creatinine ratio (P = 0.006), initial glycated haemoglobin concentration (P = 0.002), and duration of diabetes (P = 0.045). Genotype for angiotensin converting enzyme was not related to the development of microalbuminuria nor, in a larger group of patients, the presence of any degree of diabetic nephropathy. Conclusion: In patients with insulin dependent diabetes mellitus the progression of minimal albuminuria and the development of microalbuminuria is determined primarily by poor long term glycaemic control. There is a weaker relation with longer duration of disease and younger age at onset of diabetes, but blood pressure does not seem to be implicated. Gene polymorphism for angiotensin converting enzyme is not linked to the development of microalbuminuria or established diabetic nephropathy.