Background: Excess gestational weight gain (GWG) is associated with the development of gestational diabetes mellitus (GDM). In the DALI study, significant limitation in GWG through a combined lifestyle intervention was not associated with reduced GDM development (1). We have now compared the effect of higher and lower GWG on the insulin-glucose axis to investigate possible reasons for the limited impact of lifestyle interventions on preventing GDM.
Methods: Pregnant women at risk of GDM with a BMI≥29 (kg/m2) undertook a 75g oral glucose tolerance test (OGTT) before 20 weeks gestation. Those without GDM (n=437) at baseline received different structured lifestyle interventions (healthy eating and/or physical activity). Comparisons were made between women above and below the median GWG at 24-28 weeks and 35-37 weeks (excluding GDM):approximately 7kg GWG difference by 24-28 weeks gestation.
Findings: Women achieving above the median GWG at 24-28/40 (≥5.65kg, vs below), had a lower baseline body mass index (BMI: 33.0±3.5 vs 34.6±4.2 kg/m2, respectively p<0.001) and were more likely to smoke (20.8% vs 9.9% p<0.01), developing a higher fasting glucose (4.64±0.03 vs 4.56±0.03 mmol/l, p<0.05) and HOMA-IS (371.5±28.9 vs 253.3±28.9, p<0.01) by 24-28 weeks gestation. Women above the median GWG at 35-37 weeks (≥9.5kg) without GDM at 24-28 weeks, had a lower baseline 2 hour glucose (6.32±0.10 vs 6.60±0.11 mmol/l, p<0.05) but developed a higher HOMA-IR (4.30±0.19 vs 3.11±0.20, p<0.01) and HOMA-IS (460.8±28.3 vs 394.5±29.7, p<0.01) at 24-28 weeks, delivering babies who were more likely to be large for gestational age (LGA) 21.2 vs 8.6% p<0.01). GDM rates were non-significantly higher among women with the highest GWG at 24-28 and 35-37 weeks gestation (odds ratio 1.43 (0.79-2.60), 1.26(0.67-2.42)) respectively
Interpretation: Among overweight/obese women, more GWG is associated with an increase in insulin resistance and insulin secretion. Lifestyle interventions appear insufficient to overcome this increase in insulin resistance.