Dysregulated growth hormone‐insulin‐like growth factor‐1 axis in adult type 1 diabetes with long duration

Kerstin Gutefeldt, Christina A. Hedman, Ingrid S.M. Thyberg, Margareta Bachrach‐Lindström, Anna Spångeus, Hans J. Arnqvist

In type 1 diabetes (T1D) dysregulation of the GH-IGF-1 axis has been reported. Whether this is related to upper extremity impairments (UEI) is unknown. Examine differences in GH-IGF-1 axis between T1D on subcutaneous insulin treatment and matched controls without diabetes and possible associations between GH-IGF-1 axis and UEI. Cross-sectional population-based study. T1D patients, onset <35 years, duration ≥ 20 years, <67 years old and controls were invited to answer questionnaires and take blood samples. 605 patients with T1D and 533 controls accepted to participate. Fasting levels of IGF-1, IGF-1 Z-score, IGFBP-1, IGFBP-3, C-peptide, GH and UEI. T1D patients had lower IGF-1 and IGFBP-3 and higher IGFBP-1 and GH than controls. The difference in IGF-1 persisted with age. Insulin dose was associated with increasing IGF-1 Z-score but even at a very high insulin dose (>1U/kg) IGF-1 Z-score was subnormal compared to controls. IGF-1 Z-score was unaffected by glycemic control (HbA1c) but increased with residual insulin secretion, (C-peptide 1-99 pmol/l). IGFBP-1 was associated with fasting blood glucose, negatively in controls and positively in T1D patients probably reflecting insulin resistance and insulin deficiency, respectively. There was no association between lower IGF-1 Z-score and UEI in T1D. In adult T1D with fair glycemic control the GH-IGF-1-axis is dysregulated exhibiting GH-resistance, low IGF-1 and elevated IGFBP-1. Subcutaneous insulin cannot normalize these changes while endogenous insulin secretion has marked effects on IGF-1 pointing to a role of portal insulin. This article is protected by copyright. All rights reserved.