Objective: Derangements of the GH–IGF-I axis have been associated with microalbuminuria (MA) in type 1 diabetes. The aim of this study was to investigate whether an IGF-I gene promoter polymorphism influenced the development of persistent MA in type 1 diabetes. Design: A prospective follow-up study of a cohort of 277 patients with newly diagnosed type 1 diabetes consecutively enrolled between September 1979 and August 1984. Methods: Urinary albumin excretion rate over 24 h was measured in each

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... atient at least once a year. Persistent MA was defined as a urinary albumin excretion rate between 30 and 300 mg/24 h. Results: During a median follow-up of 18.0 years (range 1.0–21.5), 79 of 277 patients developed persistent MA. IGF-I gene genotype was available for 216 subjects; in 73% of the subjects, the wild-type genotype of this IGF-I gene polymorphism was present, while 27% had the variant type. At baseline, there were no differences in IGF-I levels and HbA1c values between subjects with the wild type and subjects with variant type. By Kaplan–Meier analysis, subjects with the variant type of this polymorphism had during follow-up a higher risk of development of MA compared subjects with the wild type (P = 0.03). Conclusions: Subjects with the variant type of an IGF-I gene polymorphism had a significantly increased risk of developing MA. This risk was not mediated through changes in circulating IGF-I levels. Our study suggests that in type 1 diabetes, this IGF-I gene polymorphism is a risk factor of MA.