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

Abstract

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 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 wildtype 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 (PZ0.03). 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.European Journal of Endocrinology 156 83-90

Aging phenotype and its relationship with IGF-I gene promoter polymorphisms in elderly people living in Catalonia

“…lower IGF-I levels in homozygous than heterozygous and non-carriers [27,28], as similar levels have also been reported [29]. The discrepancy of these observations might be due to chance, unknown confounders, variations in patterns of linkage disequilibrium between populations, different study designs and methods to measure IGF-I [30,31].…”

What is the mechanism of microalbuminuria in diabetes: a role for the glomerular endothelium?

“…Somatostatin analogues ameliorate the increase in IGF-1 and renal hypertrophy and reduce AER [ 85 ]. In human type 1 diabetes, serum growth hormone levels and urinary IGF-1 levels are elevated and correlate with microalbuminuria, while an IGF-1 gene polymorphism modifies the risk of development of microalbuminuria [ 86 ]. The somatostatin analogue octreotide reduces macroalbuminuria and endothelial dysfunction in type 2 diabetes [ 87 ].Taken together, this evidence points to a role for the growth hormone/IGF system early in human diabetic nephropathy.…”

Farmacogenética do tratamento do hormônio de crescimento em pacientes com síndrome de Turner

“…Inúmeros estudos avaliaram a influência desse microssatélite sobre as concentrações séricas de IGF-1 em adultos (93,96,97) e sobre diversas variáveis relacionadas às ações desse hormônio, tais como: comprimento e peso ao nascer (97,98) , estatura adulta (95,99) , densidade mineral óssea (100) , distribuição de gordura corporal (101) , risco de câncer (102,103) , risco de diabetes (104) e risco de microalbuminúria em diabéticos tipo 1 (105) .…”