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Objective IGF-I may be a marker of later metabolic and cardiovascular disease. The interactions between IGF-I and glucose metabolism are multifactorial, and there is potential confounding from several secondary effects. In this study, we examined the interaction between IGF-I and glucose metabolism in a large cohort of clinically well-characterized elderly twins. Design A total of 303 twin pairs of the same gender (606 twins) were included in the study; 125 monozygotic and 178 dizygotic twin pairs. Methods A clinical examination including a standard oral glucose tolerance test (OGTT) and anthropometric measurements was performed. Results The heritability estimates were high for IGF-I and IGFBP-3 (h2: 0.65 (95% CI: 0.55–0.74) and 0.71 (0.48–0.94), respectively) and for insulin secretion (h2 = 0.56, P 2 = 0.14, P = 0.11). In a multiple regression analysis (adjusting for age, gender and twin status), there was a negative association between IGF-I and insulin sensitivity (B: −0.13, SE 0.03, P P Conclusions There was a high heritability for IGF-I and IGFBP-3, but a low heritability for insulin secretion and insulin sensitivity in a group of elderly twins. In addition, we found a strong negative relationship between IGF-I and insulin sensitivity, which did not seem to be strongly genetically determined.

BackgroundShort children born small for gestational age (SGA) are treated with a GH dose based on body size, but treatment may lead to high levels of IGF1. The objective was to evaluate IGF1 titration of GH dose in contrast to current dosing strategies.MethodsIn the North European Small-for-Gestational-Age Study (NESGAS), 92 short pre-pubertal children born SGA were randomised after 1 year of high-dose GH treatment (67 μg/kg per day) to three different regimens: high dose (67 μg/kg per day), low dose (35 μg/kg per day) or IGF1 titration.ResultsThe average dose during the second year of the randomised trial did not differ between the IGF1 titration group (38 μg/kg per day,s.d.0.019) and the low-dose group (35 μg/kg per day,s.d.0.002;P=0.46), but there was a wide variation in the IGF1 titration group (range 10–80 μg/kg per day). The IGF1 titration group had significantly lower height gain (0.17 SDS,s.d.0.18) during the second year of the randomised trial compared with the high-dose group (0.46 SDS,s.d.0.25), but not significantly lower than the low-dose group (0.23 SDS,s.d.0.15;P=0.17). The IGF1 titration group had lower IGF1 levels after 2 years of the trial (mean 1.16,s.d.1.24) compared with both the low-dose (mean 1.76,s.d.1.48) and the high-dose (mean 2.97,s.d.1.63) groups.ConclusionIGF1 titration of GH dose in SGA children proved less effective than current dosing strategies. IGF1 titration resulted in physiological IGF1 levels with a wide range of GH dose and a poorer growth response, which indicates the role of IGF1 resistance and highlights the heterogeneity of short SGA children.