Failure of Maternal Glucose-Insulin Adjustments in Pregnancy Might Contribute to Poor Fetal Growth in India

Background: In the well-nourished Western populations maternal insulin concentrations (and insulin resistance) progressively increase during gestation to support fetal growth. Information in undernourished women from LMICs is scarce. We investigated serial glucose-insulin and lipid concentrations from early to late pregnancy in rural and urban Indian women, and studied their association with offspring birth weight.

Methods: Women from antenatal clinics were enrolled in early pregnancy. Fasting glucose, insulin, cholesterol and triglyceride concentrations were measured at 16, 28 and 33 weeks gestation and a75gm OGTT was performed at 28 weeks gestation. GDM was diagnosed using the prevalent WHO 1999/ IADPSG 2011 criteria. Demographic and anthropometric measurements were obtained, and babies were measured at birth.

Results: A total of 256 (161 rural, 95 urban) women were enrolled: they were 23 y old, 153 cm tall, and had a BMI 20.7 kg/m²at ∼16 weeks gestation. Thirty nine GDM women (22 rural) were excluded from further analysis. In 217 normal glucose tolerant women, fasting plasma glucose progressively fell with increasing gestation, insulin concentrations and HOMA-IR remained similar (51% showed a fall); total and HDL cholesterol and triglyceride concentrations increased. Urban women were older, taller and heavier, and had significantly higher glucose, insulin and HOMA-IR compared to rural women; they gained 7kg and rural women 6kg between early and late visits. Mean birth weight was 2.8kg, 39% babies were SGA and 1% LGA (INTERGROWTH). Birth weight was positively associated with maternal size (height, weight, BMI) and fasting plasma glucose concentrations. HOMA-IR was not independently associated.

Conclusion: The short and undernourished women from India failed to increase their insulin resistance with increasing gestation. This may be a novel explanation for fetal growth restriction in India and for its short term and long term sequele, including risk of diabetes.