Delayed β-cell response and glucose intolerance in young women with Turner syndrome

Abstract

Background: To investigate glucose homeostasis in detail in Turner syndrome (TS), where impaired glucose tolerance (IGT) and type 2 diabetes are frequent.

Methods: Cross sectional study of women with Turner syndrome (TS)(n = 13) and age and body mass index matched controls (C) (n = 13), evaluated by glucose tolerance (oral and intravenous glucose tolerance test (OGTT and IVGTT)), insulin sensitivity (hyperinsulinemic, euglycemic clamp), beta-cell function (hyperglycaemic clamp, arginine and GLP-1 stimulation) and insulin pulsatility.

Results: Fasting glucose and insulin levels were similar. Higher glucose responses was seen in TS during OGTT and IVGTT, persisting after correction for body weight or muscle mass, while insulin responses were similar in TS and C, despite the higher glucose level in TS, leading to an insufficient increase in insulin response during dynamic testing. Insulin sensitivity was comparable in the two groups (TS vs. control: 8.6 ± 1.8 vs. 8.9 ± 1.8 mg/kg*30 min; p = 0.6), and the insulin responses to dynamic β-cell function tests were similar. Insulin secretion patterns examined by deconvolution analysis, approximate entropy, spectral analysis and autocorrelation analysis were similar. In addition we found low IGF-I, higher levels of cortisol and norepinephrine and an increased waist-hip ratio in TS.

Conclusions: Young normal weight TS women show significant glucose intolerance in spite of normal insulin secretion during hyperglycaemic clamping and normal insulin sensitivity. We recommend regularly testing for diabetes in TS.

Trial registration: Registered with http://clinicaltrials.com, ID nr: NCT00419107.

Figure 1

Study design of day 1, 2 and 3. On day 1 an oral glucose tolerance test (OGTT), as well as DEXA scan and exercise test was performed. On day 2, we did the intravenous glucose tolerance test, followed by a hyperinsulinemic euglycemic clamp. Energy expenditure was assessed in fasting condition and during the steady state period of the clamp. On day 3, we performed insulin pulsatility testing followed by a graded hyperglycaemic clamp with arginine bolus and finally GLP-1 bolus to stress the β-cell maximally (for details - see Materials and Method section).

Figure 2

Levels of glucose, insulin, glucagon-like. peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP); free fatty acids (FFA), triglycerides, Insulin-like growth factor 1(IGF-1) and growth hormone (GH) during the 2-hour oral glucose tolerance test. P-values are based on differences between TS and controls based on AUC and given in the figure. All mean ± SD.

Figure 3

Glucose and insulin levels (mean ± SD) during the hyperglycemic clamp (60-240 minutes) (A), arginine (240-270 minutes) (B) and GLP-1 stimulation (270-300 minutes) (C). P-values are given in the figure.

Figure 4

Growth hormone (GH) and free fatty acid (FFA) during the hyperinsulinemic clamp period (60-240 minutes). Glucagon levels during the arginine and GLP-1 stimulation (240-300 minutes), and GLP-1 levels during the GLP-1 infusion period (270-300 minutes). All numbers are presented as mean ± SD. P-values are given in the figure.