Gutefeldt Kerstin, Hedman Christina A, Thyberg Ingrid S M, Bachrach-Lindström Margareta, Spångeus Anna, Arnqvist Hans J
Department of Endocrinology, Linköping University, Linköping, Sweden.
Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
Clin Endocrinol (Oxf). 2018 Jul 10. doi: 10.1111/cen.13810.
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 <35 years, duration ≥ 20 years, <67 years 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.
在1型糖尿病（T1D）中，已报道生长激素-胰岛素样生长因子-1（GH-IGF-1）轴失调。这是否与上肢功能障碍（UEI）有关尚不清楚。
研究接受皮下胰岛素治疗的T1D患者与匹配的非糖尿病对照组之间GH-IGF-1轴的差异，以及GH-IGF-1轴与UEI之间可能的关联。
基于人群的横断面研究。邀请发病年龄<35岁、病程≥20年、年龄<67岁的T1D患者和对照组填写问卷并采集血样。
共有605例T1D患者和533例对照者接受参与研究。
空腹胰岛素样生长因子-1（IGF-1）水平、IGF-1 Z评分、胰岛素样生长因子结合蛋白-1（IGFBP-1）、胰岛素样生长因子结合蛋白-3（IGFBP-3）、C肽、生长激素（GH）和UEI。
T1D患者的IGF-1和IGFBP-3低于对照组，IGFBP-1和GH高于对照组。IGF-1的差异随年龄持续存在。胰岛素剂量与IGF-1 Z评分增加相关，但即使在非常高的胰岛素剂量（>1U/kg）下，IGF-1 Z评分与对照组相比仍低于正常水平。IGF-1 Z评分不受血糖控制（糖化血红蛋白HbA1c）影响，但随残余胰岛素分泌（C肽1-99 pmol/L）增加。IGFBP-1与空腹血糖相关，在对照组中呈负相关，在T1D患者中呈正相关，可能分别反映胰岛素抵抗和胰岛素缺乏。T1D患者中较低的IGF-1 Z评分与UEI之间无关联。
在血糖控制良好的成年T1D患者中，GH-IGF-1轴失调，表现为GH抵抗、低IGF-1和IGFBP-1升高。皮下胰岛素不能使这些变化正常化，而内源性胰岛素分泌对IGF-1有显著影响，提示门静脉胰岛素的作用。
