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

Abstract

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. Patients with T1D, onset <35years, duration ≥ 20years, <67years old and controls were invited to answer questionnaires and take blood samples. A total of 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. Patients with T1D 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 glycaemic 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 patients with T1D 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 glycaemic 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.