Development of GDM is characterized by impaired fasting insulin sensitivity and β-cell dysfunction at early gestation

Objectives:

The pathophysiological components of impaired glucose metabolism (mainly impaired insulin action and β-cell dysfunction) could be quantified by advanced clinical examinations including clamp examinations as well as oral and intravenous glucose tolerance tests. However, also simple approximations from fasting measurements are available, which might be useful to provide an early and cheap identification of women with high risk for the later development of GDM.

Methods:

112 pregnant women were included in this study and received a broad metabolic characterisation at early gestation (before 15+6 weeks of gestation) including fasting measurements of glucose, insulin and C-peptide to provide information on insulin sensitivity by using the homeostatic model assessment of insulin resistance (HOMA-IR) and insulin secretion (HOMA-β). The disposition index (DI) was calculated as the product of HOMA-IR and HOMA-β to provide an estimation of β-cell function (i.e. the ability of the β-cells to adapt for insulin resistance). The amount of insulin action was additionally estimated by the quantitative insulin sensitivity check index from C-peptide (QUICKIc) to provide an estimate of insulin sensitivity from prehepatic measurements.

Results:

GDM was diagnosed in 29 women, whereas 82 remained normal glucose tolerant (NGT) until end of gestation. Already at early pregnancy fasting surrogate measures of insulin action were considerably impaired in women who developed GDM as compared to those who remained NGT (HOMA-IR: 2.30 [IQR: 1.45 – 3.93] vs. 1.42 [IQR: 0.98 – 1.96], p < 0.001). Moreover, a lower DI indicated β-cell dysfunction in subjects with later development of GDM (76 [IQR: 58 – 97] vs. 115 [IQR: 88 – 158], p < 0.001). In particular, QUICKIc (ROC-AUC: 0.79, 95% CI: 0.68 – 0.90) as well as DI (ROC-AUC: 0.77, 95% CI: 0.65 – 0.87) were closely related to the later development of GDM.

Conclusion:

Later development of GDM is characterized by fasting surrogate measures of impaired g lucose disposal already at early gestation. These approximations if insulin resistance and β-cell dysfunction might be useful to identify those women with particularly high risk for developing GDM.

No conflict of interest has been declared by the author(s).