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

Background Based 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 design Two hospital based case control studies: 1) Neonatal outcomes, 2) Later life outcomes. Methods We 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. Results Neonatal 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. Conclusion Neonatal 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 Highlights It 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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Later life follow-up in this study was part of the InDiaGDM study funded by the Department of Biotechnology, New Delhi, India (BT/IN/Denmark/02/CSY/2014). The International Atomic Energy Agency, Vienna, Austria, provided financial support for the IAEA-B12 study (15382/R0) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: All individual studies received approvals from KEMHRC Ethics Committee (DIP 2128/08-12-2021), IAEA-B12 (064/06-03-2006/15382/R0) and InDiaGDM (1333/1404/10-03-2014, (BT/IN/Denmark/02/CSY/2014)). InDiaGDM was also registered with [ClinicalTrials.gov][1] ([NCT03388723][2]). All adult participants signed an informed consent. For children below 18 years, we obtained parental consent, and children between 12 and 18 years also signed an informed assent. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data can be requested from Prof. C.S.Yajnik by applying with a 200 word plan of analysis, data sharing is subject to KEMHRC Ethics Committee approval and permission of Health Ministry Screening Committee of Govt. of India. [1]: http://ClinicalTrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03388723&atom=%2Fmedrxiv%2Fearly%2F2023%2F05%2F01%2F2023.04.28.23289246.atom