Evaluation of risk factors for the development of nephropathy in patients with IDDM: Insertion/deletion angiotensin converting enzyme gene polymorphism, hypertension and metabolic control

Diabetic nephropathy represents a major complication in patients with insulin-dependent diabetes mellitus (IDDM), Intervention trials using angiotensin-converting enzyme (ACE) inhibitors have pointed towards the important pathogenetic role of the renin-angiotensin system. Recently an insertion/deletion (I/D) polymorphism for the gene encoding the ACE has been described, the deletion type being associated with higher plasma ACE levels. As the intrarenal renin-angiotensin system might also be activated in this setting, we determined the ACE genotype together with other risk factors for the development of diabetic nephropathy in 122 patients with IDDM from a single centre with (n = 63) and without (n = 59) nephropathy. Long-term glycaemic control was evaluated using mean HbA(1c) values from the last 10 years. The two patient group were comparable with regard to duration of diabetes and glycaemic control as assessed by current HbA(1c) values. However, mean long-term HbA(1c) values were significantly higher in patients with diabetic nephropathy as was systemic blood pressure, The DD genotype was more prevalent in patients with renal disease. In the subgroup of patients who had had diabetes for more than 20 years (n = 90), the DD genotype was even more frequent in patients with nephropathy, and blood pressure and long-term HbA(1c) values were also higher in patients with renal disease. Logistic regression analysis revealed long-term glycaemic control, blood pressure and the ACE genotype to be independent risk factors for the prevalence of diabetic nephropathy.