Objective Type 1 diabetes and obesity has increased in childhood. We therefore tested the hypothesis that type 1 diabetes HLA-DQ risk genotypes may be associated with an increased body mass index (BMI). Design The type 1 diabetes high risk HLA-DQ A1*05:01-B1*02:01/A1*03:01-B1*03:02 genotype along with lower risk DQ genotypes were determined at the time of clinical onset by PCR and hybridization with allele-specific probes. Body mass index was determined after diabetes was stabilized. Subjects A total of 2403 incident type 1 diabetes children below 18 years of age were ascertained in the Swedish national Better Diabetes Diagnosis (BDD) studybetween May 2005 to September 2009. All children classified with type 1 diabetes including positivity for at least one islet autoantibody were investigated. Results Overall, type 1 diabetes HLA-DQ risk was negatively associated with BMI (p<0.0008). The proportion of the highest risk A1*05:01-B1*02:01/A1*03:01-B1*03:02 genotype decreased with increasing BMI (p<0.0004). However, lower risk type 1 diabetes DQ genotypes were associated with an increased proportion of patients who were overweight or obese (p<0.0001). Indeed, the proportion of patients with the low risk A1*05:01-B1*02:01/A1*05:01-B1*02:01 genotype increased with increasing body mass index (p<0.003). The magnitude of association on the multiplicative scale between the A1*05:01-B1*02:01/A1*05:01-B1*02:01 genotype and increased body mass index was significant (p<0.006). The odds ratio in patients with this genotype of being obese was 1.80 (95% CI 1.21–2.61; p<0.006). The increased proportion of overweight type 1 diabetes children with the A1*05:01-B1*02:01 haplotype was most pronounced in children diagnosed between 5 and 9 years of age. Conclusions Susceptibility for childhood type 1 diabetes was unexpectedly found to be associated with the A1*05:01-B1*02:01/A1*05:01-B1*02:01 genotype and an increased BMI. These results support the hypothesis that overweight may contribute to the risk of type 1 diabetes in children positive for HLA-DQ A1*05:01-B1*02:01.

OBJECTIVE -We sought to test the hypothesis that start of insulin glargine with sustained nightly insulin action results in changes in circulating concentrations of IGF-I and IGF binding proteins (IGFBPs) in adolescents with type 1 diabetes-changes that may support improvement of A1C.RESEARCH DESIGN AND METHODS -Twelve pubertal adolescents with type 1 diabetes and initially on NPH insulin were studied during 12 weeks of intensified treatment with glargine.RESULTS -Subnormal IGF-I SD scores on NPH (Ϫ1.8 Ϯ 0.4) rapidly increased and remained 54 Ϯ 9% elevated (P Ͻ 0.001) after 12 weeks on glargine. A1C decreased from 8.3 Ϯ 0.6% to a nadir of 6.9 Ϯ 0.3% (P ϭ 0.002) at 6 weeks and correlated with changes in IGF-I (r ϭ Ϫ0.64, P Ͻ 0.05). The increase in IGF-I did not suppress the mean overnight growth hormone (GH) secretion at 6 weeks. The mean overnight IGFBP-1 levels decreased (P ϭ 0.035), supporting the hypothesis that the nightly hepatic insulin action was increased. Circulating IGF-I increased in the absence of changes in both GH secretion and GH receptor numbers (assessed by growth hormone binding protein), indicating that postreceptor mechanisms are involved. IGFBP-3 proteolysis was decreased.CONCLUSIONS -Increased hepatic insulin action after start of glargine was evident from a decrease in night time IGFBP-1 concentrations. This may improve GH postreceptor signaling, resulting in increased circulating IGF-I. We suggest that even in the absence of changes in GH, increased IGF-I and decreased IGFBP-1 support the improvement of metabolic control.

In a group of fairly well-controlled diabetic children, the normal increase in IGF-I during puberty is blunted. Despite decreased IGF-I levels, target final height was attained, probably because of adequate insulin compensation leading to normal IGFBP-l, thus adequate bioavailability of IGF-I. Our results point out the importance of sufficient exogenous insulin in the period of rapid linear growth.

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The aim of the present study was to investigate whether the diurnal variability of B‐Glucose is dependent on GH, IGF‐I and IGFBP‐I levels, apart from insulin, and if there is any difference between Tanner stages 3 and 5. Five boys in Tanner stage 3 and 6 boys in stage 5 with type 1 diabetes were included. Blood was continuously collected from a cubital vein for 24 h. S‐Insulin, S‐GH, S‐IGF‐I and S‐IGFBP‐1 were analysed. B‐Glucose was analysed hourly at bedside. One week before and 1 wk after the 24‐h study period the participants performed self‐monitoring of blood glucose (SMBG) during normal physiologic conditions. In the 24‐h profile of B‐Glucose, insulin, IGFBP‐I and GH, we found a significant positive correlation between B‐Glucose and log IGFBP‐1 (r=0.5, p= 0.005) and an inverse correlation to insulin (r=‐0.5, p= 0.004) but no correlation to logGH (r=‐0.04, p= 0.831). In multiple regression analysis, B‐Glucose was still significantly correlated to log IGFBP‐1, when adjusting for insulin and GH, in Tanner stage 5. We found a difference between Tanner stages 3 and 5 in the variability of B‐Glucose over a longer period during normal daily activity (p= 0.02), but not over the 24‐h study period. Conclusion: We have demonstrated in type 1 diabetes adolescent boys a relationship between simultaneously measured blood‐glucose and IGFBP‐1 levels independent of the insulin and GH levels, suggesting that the free fraction of IGF‐I influences the glucose metabolism.