1218-P: A Critique of Defective Insulin Secretion and Insulin Sensitivity as a Precision Approach to Gestational Diabetes

Introduction: Precision medicine approaches to gestational diabetes mellitus (GDM) have categorised patients according to disease pathophysiology (insulin resistance, insulin insufficiency, both) and demonstrated associations with clinical outcomes. We assessed if this approach is analytically robust, reproducible in a different population and useful diagnostically, prognostically or therapeutically in clinical practice.

Methods: 1308 pregnant women with >1 risk factor having an oral glucose tolerance test were recruited. Specimens were collected for analysis of glucose (standard and enhanced procedures), HbA1c and insulin. We categorised women into pathophysiological subtypes: insulin-resistant GDM (HOMA-2S<25^th centile of normal glucose tolerance (NGT) population); insulin-insufficient GDM (HOMA-2B <25^th centile); both or neither. We assessed associations with pregnancy outcomes using logistic regression.

Results: Using optimal specimen handling, 1027/1308 (78.5%) women had NGT, 135/1308 (10.3%) had insulin-resistant GDM, 73/1308 (5.6%) had insulin-insufficient GDM and 2/1308 (0.2%) had both insulin-resistant and insulin-insufficient GDM. Unexpectedly, 71/1308 (5.4%) had GDM with HOMA-2S and HOMA-2B both >25^th centile (GDM-neither). This novel subgroup appeared insulin-sensitive in the fasting state but developed marked post-load hyperglycaemia and hyperinsulinemia suggesting an isolated postprandial defect in insulin sensitivity, not captured by HOMA-2B or HOMA-2S. Women within most GDM subgroups had comparable pregnancy outcomes to normoglycaemic women. Similar findings were evident using different indices and standard specimen handling techniques.

Conclusions: Precision categorisation of GDM using HOMA-2S and HOMA-2B does not provide useful diagnostic, prognostic or therapeutic information, but distinguished a novel subgroup of GDM, characterised by an isolated postprandial defect in insulin sensitivity.