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Residual ß-Cell Function More than Glycemic Control Determines Abnormalities of the Insulin-Like Growth Factor System in Type 1 Diabetes

Division of Internal Medicine (C.A.H., T.L., H.J.A.), Department of Medicine and Care and Division of Cell Biology (H.J.A.), Department of Biomedicine and Surgery, Diabetes Research Centre, Faculty of Health Sciences, Linkoping University, S-581 83 Linkoping, Sweden; and Medical Research Laboratories, Aarhus University Hospital (J.F., J.-W.C., A.F., H.Ø.), DK-8000 Aarhus, Denmark

Address all correspondence and requests for reprints to: Dr. Christina Hedman, Division of Internal Medicine, Department of Medicine and Care, Linkoping University, S-581 83 Linkoping, Sweden. E-mail: christina.hedman{at}lio.se.

The GH-IGF-I axis is disturbed in patients with type 1 diabetes. Our aim was to investigate whether abnormalities are found in patients in very good glycemic control and, if so, to estimate the role of residual ß-cell function. Patients with hemoglobin A_1c (HbA_1c) less than 6% (reference range, 3.6–5.4%) were selected for the study. Twenty-two men and 24 women, aged 41.3 ± 13.8 yr (mean ± SD), with a diabetes duration of 17.8 ± 14.6 yr participated. Healthy controls (15 women and nine men), aged 41.3 ± 13.0 yr, were also studied. Overnight fasting serum samples were analyzed for HbA_1c, C peptide, free and total IGFs, IGF-binding proteins (IGFBPs), GH-binding protein, and IGFBP-3 proteolysis. HbA_1c was 5.6 ± 0.5% in patients and 4.4 ± 0.3% in controls. Total IGF-I was 148 ± 7 µg/liter in patients and 178 ± 9 µg/liter in controls (P < 0.001). Free IGF-I, total IGF-II, IGFBP-3, and GH-binding protein were lower, whereas IGFBP-1, IGFBP-1-bound IGF-I, and IGFBP-2 were elevated compared with control values. Patients with detectable C peptide (100 pmol/liter) had higher levels of total IGF-I, free IGF-I, and total IGF-II and lower levels of IGFBP-1 and IGFBP-2 than those with an undetectable C peptide level despite having identical average HbA_1c. IGFBP-3 proteolysis did not differ between patients and controls. Despite very good glycemic control, patients with type 1 diabetes and no endogenous insulin production have low free and total IGF-I. Residual ß-cell function, therefore, seems more important for the disturbances in the IGF system than good metabolic control per se, suggesting that portal insulin delivery is needed to normalize the IGF system.

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