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Clinical Endocrinology

Insulin resistance and β-cell dysfunction in normoglycaemic European women with a history of gestational diabetes

Authors


Mark I. McCarthy, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Site, Headington, Oxford OX3 7LJ, UK. Tel: +44(0) 1865 857321; Fax: +44(0) 1865 857217. E-mail: mark.mccarthy@drl.ox.ac.uk

Summary

objective Women with previous gestational diabetes (GDM) are at increased risk of subsequent type 2 diabetes. To characterize early metabolic abnormalities associated with this increased risk, we studied normoglycaemic women with a history of GDM.

patients and measurements We performed an insulin-modified, frequently sampled intravenous glucose tolerance test (FSIVGTT) in 34 normoglycaemic European women with previous GDM and 44 European control women, deriving measures of insulin sensitivity, glucose effectiveness, glucose disappearance rate and acute insulin response to glucose.

results Post-GDM women were more obese than controls [body mass index (BMI), geometric mean (95% confidence interval); 25·3 kg/m2 (23·8–27·1 kg/m2) vs. 23·1 kg/m2 (21·9–24·3 kg/m2), P = 0·03]. Evidence of insulin resistance was provided by their lower insulin sensitivity as measured by FSIVGTT [0·6 × 10−4/min/pmol/l (0·3–1·2 × 10−4/min/pmol/l) vs. 1·5 × 10−4/min/pmol/l (1·2–1·8 × 10−4/min/pmol/l), P = 0·01] and by homeostatic model assessment [72% (49–107%) vs. 153% (113–206%), P = 0·004]; and by their higher fasting triglycerides [1·0 mmol/l (0·7–1·5 mmol/l) vs. 0·7 mmol/l (0·6–0·8 mmol/l), P = 0·001]. Though there was no difference between groups in fasting NEFA levels, acute NEFA suppression was diminished in the post-GDM group (P = 0·01). Concomitant β-cell dysfunction in the post-GDM women was revealed by their lower disposition index [0·05/min (0·02–0·10/min) vs. 0·11/min (0·09–0·14/min), P = 0·02] compared to controls. The differences in insulin sensitivity, but not those of β-cell function, were partly, though not completely, attributable to differences in regional and total adiposity.

conclusions European normoglycaemic women with previous GDM display both glucoregulatory and antilipolytic insulin resistance, reduced β-cell function and dyslipidaemia. These metabolic abnormalities are likely to contribute to their increased risk of future type 2 diabetes.

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