ESPE Yearbook of Paediatric Endocrinology

Diabetes Care. 2021 May;44(5):1185–1193. 10.2337/dc20-3006. https://pubmed.ncbi.nlm.nih.gov/33827804/

Luo et al. performed a retrospective cohort study of 159 children (age 7–11 years), including undertaking a food cue task while in the MRI scanner, to investigate whether brain reward systems are altered by in utero exposure to gestational diabetes mellitus (GDM) or maternal obesity, and whether these changes lead to increased food intake and obesity. Exposure to GDM in utero was independently associated with enhanced orbital frontal cortex food cue reactivity, increased energy intake, and increased waist to hip ratio, thereby contributing to the risk for development of obesity.

Notably, GDM exposure before 26 weeks gestation was associated with these offspring outcomes, suggesting that the early timing of GDM exposure may have a crucial effect on fetal programming and the development of the child’s brain reward system. Interestingly, maternal prepregnancy BMI was not associated with offspring daily energy intake or food cue reactivity within brain reward areas.

In utero exposure to GDM or maternal obesity contributes to higher risks for childhood obesity, insulin resistance and metabolic syndrome (1, 2). However, little is known regarding the underlying neural mechanisms. Accumulating evidence suggests that altered hypothalamic structure and function as well as altered responses to palatable food or food cues potentiated by the brain’s reward system are implicated in the pathogenesis of obesity. Animal and human studies show that in utero exposure to maternal obesity or GDM disrupts the development of the hypothalamus, leading offspring to overeating and obesity (3, 4). To the best of our knowledge, this is the first imaging study that investigated the possible effects of in utero GDM exposure to brain reward regions in the offspring. Future studies including a larger sample with/or a longitudinal follow-up are necessary to assess these findings. In addition, potential sex differences in the effects of GDM exposure on feeding behavior on offspring should be considered. The better understanding of biological pathways linking in utero exposures, such as GDM, to adverse health outcomes later in life will help us design future targets for early identification and prevention.

References: 1. Dabelea D, Hanson RL, Lindsay RS, Pettitt DJ, Imperatore G, Gabir MM, et al. Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity: a study of discordant sibships. Diabetes. 2000 Dec;49(12):2208–11.2. Kim SY, England JL, Sharma JA, Njoroge T. Gestational Diabetes Mellitus and Risk of Childhood Overweight and Obesity in Offspring: A Systematic Review. Experimental Diabetes Research. 2011 2011/09/22;2011:541308.3. Page KA, Luo S, Wang X, Chow T, Alves J, Buchanan TA, et al. Children Exposed to Maternal Obesity or Gestational Diabetes Mellitus During Early Fetal Development Have Hypothalamic Alterations That Predict Future Weight Gain. Diabetes Care. 2019 Aug;42(8):1473–80.4. Morris MJ, Chen H. Established maternal obesity in the rat reprograms hypothalamic appetite regulators and leptin signaling at birth. Int J Obes (Lond). 2009 Jan;33(1):115–22.