Abstract
Aims/hypothesisTo determine the extent to which gestational fasting and postload levels of glucose explain differences in infant fat mass between UK-born Pakistani and white British infants.MethodsAnalyses were undertaken in a prospective pregnancy cohort study of 1,415 women and their singleton live-born infants (629 white British and 786 Pakistani). Infant fat mass was assessed by cord-blood leptin levels and fetal insulin secretion by cord-blood insulin levels. Maternal OGTTs were completed at 26–28 weeks of gestation.ResultsPakistani women had higher fasting and postload glucose levels and greater incidence of gestational diabetes than white British women. Higher fasting and postload glucose levels were associated with higher cord-blood levels of insulin and leptin in all participants, irrespective of ethnicity. Cord-blood leptin levels were 16% (95% CI 6, 26) higher in Pakistani than in white British infants. After adjustment for fasting glucose levels, this difference attenuated to 7% (−3, 16), and with additional adjustment for cord-blood insulin levels it attenuated further to 5% (−4, 14). Path analyses supported the hypothesis that fasting glucose levels mediate the relationship of Pakistani ethnicity to greater fat mass at birth, as measured by cord-blood leptin levels; on average, 19% of this mediation involved fetal insulin secretion. Postload glucose levels did not act as an important mediator of ethnic differences in cord-blood leptin levels. Results were very similar when 130 women with gestational diabetes were removed.Conclusions/interpretationThese novel findings suggest a role of maternal pregnancy glycaemia in mediating differences in fat mass between Pakistani and white British infants.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-014-3386-6) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
Highlights
For a given BMI, South Asian compared with white European adults have greater fat mass, leading to the suggestion that they have a ‘thin-fat’ insulin-resistant phenotype that underlies their increased type 2 diabetes risk [1,2,3]
Path analyses supported the hypothesis that fasting glucose levels mediate the relationship of Pakistani ethnicity to greater fat mass at birth, as measured by cord-blood leptin levels; on average, 19% of this mediation involved fetal insulin secretion
For a 1 unit increase in logged cord-blood leptin level, birthweight increased by 311 g in white British women and 263 g in Pakistani women
Summary
For a given BMI, South Asian compared with white European adults have greater fat mass, leading to the suggestion that they have a ‘thin-fat’ insulin-resistant phenotype that underlies their increased type 2 diabetes risk [1,2,3]. South Asian babies born in India have been found to be fatter (as measured by subscapular and triceps skinfolds or cord-blood leptin levels) than white European babies born in Europe or the USA [7,8,9]. These differences may reflect different socioeconomic, lifestyle and healthcare characteristics between people living in India compared with those in Western countries. Greater gestational hyperglycaemia amongst South Asian women [11,12,13,14] is a plausible exposure that could contribute to greater fat mass at birth in South Asian infants because (1) greater circulating pregnancy fasting and postload glucose concentrations promote fetal insulin secretion and fat accretion in a linear dose–response fashion [15,16,17,18,19]; and (2) an increased risk of gestational diabetes mellitus (GDM), hyperglycaemia and type 2 diabetes in people of South Asian origin is well established [1, 11,12,13,14, 20,21,22,23,24,25]
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