A longitudinal study of serum insulin-like growth factor-I levels over 6 years in a large cohort of children and adolescents with type 1 diabetes mellitus: A marker reflecting diabetic retinopathy.

OBJECTIVE: To evaluate longitudinal serum insulin-like growth factor-I (IGF-I) in a large cohort of children and adolescents with type 1 diabetes in relation to hemoglobin A1c (HbA1c), age, diabetes duration, and body mass index (BMI), its association to height and retinopathy, and in comparison with healthy subject references. METHODS: A total of 2683 serum IGF-I values were obtained from 806 children and adolescents with T1DM, from annual blood samples for up to 6 consecutive years. RESULTS: In a multiple regression analysis IGF-I values were negatively correlated to HbA1c and diabetes duration, and positively correlated to BMI (P < .001, P < .001, and P < .001, respectively, adjusted r2 = 0.102). Children and adolescents with T1DM had lower mean IGF-I levels and reference interval limits compared to healthy subjects. In boys, mean (SD) IGF-I SD score (SDS) levels were -1.04 (±1.3) calculated from the healthy reference. IGF-I peaked at 15 years of age, similarly to healthy controls, but with markedly lower levels in late puberty. Girls were more affected at later stages of puberty but with a slightly less depressed overall mean IGF-I SDS of -0.69 (±1.2). In a subgroup of 746 subjects with fundus photography, a negative correlation was seen between individual mean IGF-I SDS and preproliferative retinopathy (P = .004, adjusted r2 = 0.021). In another subgroup of 84 adolescents, no correlation was seen between individual mean IGF-I SDS and target height SDS or distance to target height SDS. CONCLUSION: Poor metabolic control and diabetes duration impact negatively on serum IGF-I levels. A low individual mean IGF-I level was associated with progression of retinopathy independently of HbA1c, age, gender, and diabetes duration. Disease, sex and age related IGF-I SDS may become clinical helpful as a supplement to HbA1c in predicting the long-term outcome for children and adolescents with T1DM.

Lower HbA1c after 1 year, in children with type 1 diabetes treated with insulin glargine vs. NPH insulin from diagnosis: a retrospective study.

OBJECTIVE: Insulin glargine offers sustained insulin delivery for 24 h. Change to glargine treatment consistently results in lower fasting glucose and fewer hypoglycemic episodes in children with type 1 diabetes compared to continuation of NPH, although glargine has not been shown to improve HbA1c in randomized trials. Studies comparing glargine and NPH in multiple injection therapy in children treated from diagnosis of type 1 diabetes are lacking. METHODS: HbA1c and insulin requirement were compared in a retrospective study of children (7-17 yr of age) with type 1 diabetes treated from diagnosis with basal insulin glargine (n = 49) or NPH (n = 49) in a multiple injection therapy (MIT) regimen with a rapid-acting insulin analogue. Patients were followed every third month for 1 yr. HbA1c, insulin dose, and weight data were retrieved. RESULTS: HbA1c (mean ± SD) was lower at 3-5 months (5.5 ± 0.89 vs. 6.2 ± 0.89%, p < 0.05) and 6-9 months (5.6 ± 1.14 vs. 6.6 ± 0.99%; p < 0.001) in glargine treated. After 12 months, HbA1c was significantly lower in glargine treated (6.3 ± 1.56 vs. 7.1 ± 1.28; p < 0.01). Reported total insulin doses were similar at nadir (0.5 U/kg BW × 24 h), but significantly lower at 12 months in glargine treated (0.64 ± 0.23 vs. 0.86 ± 0.3 U/kg BW × 24 h; p < 0.001). CONCLUSIONS: HbA1c 1 yr from diagnosis was lower in children treated with glargine from start as compared with those on NPH. This observation should be viewed in the light of a significantly lower dose of total daily insulin in the glargine group.

Normalization of the IGF-IGFBP axis by sustained nightly insulinization in type 1 diabetes.

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 (-1.8 +/- 0.4) rapidly increased and remained 54 +/- 9% elevated (P < 0.001) after 12 weeks on glargine. A1C decreased from 8.3 +/- 0.6% to a nadir of 6.9 +/- 0.3% (P = 0.002) at 6 weeks and correlated with changes in IGF-I (r = -0.64, P < 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 = 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.