Pathophysiology of postprandial hyperglycaemia in women with type 1 diabetes during pregnancy

Aims/hypothesis: Although maternal hyperglycaemia is associated with increased risk of adverse pregnancy outcome, the mechanisms of postprandial hyperglycaemia during pregnancy are poorly understood. We aimed to describe glucose turnover in pregnant women with type 1 diabetes, according to stage of gestation (early vs late gestation). Methods: The rates of systemic glucose appearance (R a) and glucose disposal (R d) were measured in ten pregnant women with type 1 diabetes during early (12-16 weeks) and late (28-32 weeks) gestation. Women ate standardised meals-a starch-rich 80 g carbohydrate dinner and a sugar-rich 60 g carbohydrate breakfast-and fasted between meals and overnight. Stable-label isotope tracers ([6,6- 2H 2]glucose and [U- 13C]glucose) were used to determine R a, R d and glucose bioavailability. Closed-loop insulin delivery maintained stable glycaemic conditions. Results: There were no changes in fasting R a (10±2 vs 11±2 μmol kg -1 min -1; p=0.32) or fasting R d (11±2 vs 11±1 μmol kg -1 min -1; p=0.77) in early vs late gestation. There was increased hepatic insulin resistance (381±237 vs 540±242 μmol kg -1 min -1×pmol/l; p=0.04) and decreased peripheral insulin sensitivity (0.09±0.04 vs 0.05±0.02 μmol kg -1 min -1 per pmol/l dinner, 0.11±0.05 vs 0.07±0.03 μmol kg -1 min -1 per pmol/l breakfast; p=0.002) in late gestation. It also took longer for insulin levels to reach maximal concentrations (49 [37-55] vs 71 [52-108] min; p=0.004) with significantly delayed glucose disposal (108 [87-125] vs 135 [110-158] min; p=0.005) in late gestation. Conclusions/interpretation: Postprandial glucose control is impaired by significantly slower glucose disposal in late gestation. Early prandial insulin dosing may help to accelerate glucose disposal and potentially ameliorate postprandial hyperglycaemia in late pregnancy. Trial registration: ISRCTN 62568875 Funding: Diabetes UK Project Grant BDA 07/003551. H.R. Murphy is funded by a National Institute for Health Research (NIHR) research fellowship (PDF/08/01/036). Supported also by the Juvenile Diabetes Research Foundation (JDRF), Abbott Diabetes Care (Freestyle Navigator CGM and sensors free of charge), Medical Research Council Centre for Obesity and Related Metabolic Diseases and NIHR Cambridge Biomedical Research Centre.