An IGF-I gene polymorphism modifies the risk of developing persistent microalbuminuria in type 1 diabetes.
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.


METHODS
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 patient 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 HbA(1c) 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.
Hovind
Peter
P
Steno Diabetes Center, Gentofte, Denmark.
Lamberts
Steven
S
Hop
Wim
W
Deinum
Jaap
J
Tarnow
Lise
L
Parving
Hans-Henrik
HH
Janssen
Joop A M J L
JA
D000293:Adolescent; D000328:Adult; D000419:Albuminuria / Q000453:epidemiology / Q000235:genetics*; D000483:Alleles; D001794:Blood Pressure / Q000502:physiology; D002096:C-Peptide / Q000097:blood; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics; D048909:Diabetes Complications / Q000235:genetics* / Q000652:urine*; D003922:Diabetes Mellitus, Type 1 / Q000652:urine*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007223:Infant; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012306:Risk
D002096:C-Peptide; D007334:Insulin-Like Growth Factor I; D004247:DNA