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Maternal diabetes influences neonatal obesity-adiposity but not in later life

Wagle, S. S.; Deshpande-Joshi, S. S.; Deshmukh, M. K.; Damle, H. S.; Otiv, S. R.; Phatak, S. B.; Dhadge, S. N.; Ambardekar, S. S.; Bhat, D. S.; Raut, D. A.; Kamat, R. P.; Wadke, S. G.; Kumaran, K.; Chandak, G. R.; Yajnik, C. S.

2023-05-01 endocrinology
10.1101/2023.04.28.23289246 medRxiv
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BackgroundBased on studies in overweight-obese populations, it is tacitly assumed that maternal hyperglycemia is responsible for obesity-adiposity at birth and in later life. Study designTwo hospital based case control studies: 1) Neonatal outcomes, 2) Later life outcomes. MethodsWe studied associations of neonatal and later life obesity-adiposity [age and sex-adjusted BMI, waist circumference, skinfolds, and body fat percent by Dual energy X-ray Absorptiometry (DXA)] in offspring of mothers with diabetes (ODM) and those of mothers without diabetes (ONDM). Exposures were parental hyperglycemia and overweight-obesity. ResultsNeonatal study included 372 non-diabetic and 816 diabetic pregnancies [74 type 1 diabetes, 102 type 2 diabetes, 640 gestational diabetes (GDM)]. Mothers with type 1 diabetes were the youngest, thinnest, and with highest HbA1c. Maternal glycemia but not BMI was associated with neonatal obesity-adiposity. Thus, neonates of mothers with type 1 diabetes had highest ponderal index, abdominal circumference, and skinfolds. Later life study included 200 ODM (25 type 1 diabetes, 22 type 2 diabetes, 153 GDM) and 177 age, sex and socio-economic matched ONDM (2 to 26 y). Their obesity-adiposity was associated with bi-parental overweight-obesity in an additive manner, but not with parental diabetes. Offspring birth weight was also positively associated. Offspring of mothers with type 1 diabetes had the lowest and offspring of mothers with type 2 diabetes the highest obesity-adiposity. ConclusionNeonatal obesity-adiposity is driven by maternal glycemia while later life obesity-adiposity by bi-parental obesity. Our results provide a clear insight into pathogenesis of obesity-adiposity in the offspring. Article HighlightsIt is tacitly assumed that maternal diabetes is responsible for offspring obesity-adiposity. We examined the determinants of obesity-adiposity in intrauterine and in later life in children born to mothers with type 1, type 2 and GDM. Paternal influence was also investigated. Mothers with type 1 diabetes were the thinnest and most hyperglycemic. Their children were the most obese-adipose at birth but thinnest in later life. Later life obesity-adiposity was driven by bi-parental overweight-obesity, not by diabetes. Our findings suggest that strict maternal metabolic control during pregnancy will reduce macrosomia while targeting obesogenic family environment may reduce later life offspring obesity-adiposity.

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