Reducing intergenerational obesity and diabetes risk

Abstract

To address the intergenerational transmission of obesity and diabetes, strategies promoting the health of women of reproductive age appear to be urgently needed. In this narrative review, we summarise what has been learned from many prenatal clinical trials, discuss the emerging evidence from preconception clinical trials and highlight persistent gaps and critical future directions. Most trials tested prenatal interventions that resulted in a limited gestational weight gain of~1 kg and reduced gestational diabetes by 20-30%. These interventions also reduced macrosomia by 20-40% but had little-to-no impact on other offspring outcomes at birth or beyond. Far fewer trials tested preconception interventions, with almost all designed to improve conception or live-birth rates in overweight or obese women with infertility rather than reduce intergenerational risks in diverse populations. Preconception trials have successfully reduced weight by 3-9 kg and improved markers of glucose homeostasis and insulin resistance by the end of the intervention but whether effects were sustained to conception is unclear. Very few studies have reported offspring outcomes at birth and beyond, with no evidence thus far of beneficial effects on offspring obesity or diabetes risks. Further efforts to develop effective and scalable strategies to reduce risk of obesity and diabetes before conception should be prioritised, especially for diverse and under-resourced populations at disparately high risk of obesity and diabetes. Future clinical trials should include interventions with high potential for dissemination, diverse populations, thorough maternal phenotyping from enrolment through to conception and pregnancy, and rigorous assessment of offspring obesity and diabetes risks from birth onwards, including into the third generation.

Prepregnancy weight change associated with high gestational weight gain

“…This is not only biologically plausible but clinically relevant. Our results join the accumulating evidence that prepregnancy health is an important determinant of pregnancy health (37,50,51).…”

“…Ameliorating excess GWG is important in order to reduce APOs such as preeclampsia, gestational diabetes, and severe maternal morbidity that have consequences for perinatal and long‐term health outcomes (1‐4,36). In addition, weight gain is progressive and cumulative in women during the reproductive years, and GWG contributes to these patterns (37‐39). Our data suggest that attention to the preconception patterns of gain is important for pregnancy health and its lifelong contribution to risk for obesity.…”

The Relationship between Fetal Abdominal Wall Thickness and Intrapartum Complications amongst Mothers with Pregestational Type 2 Diabetes

“…The relationship between fetal AWT and long-term health of offspring remains unknown. With evidence to support increasing prevalence and disease severity of type 2 diabetes with each successive generation affected [46][47][48], there is question as to whether or not a thicker fetal subcutaneous fat layer might represent an early marker of future metabolic disease. Overall, fetuses in our study had thicker subcutaneous fat layers than described in other studies (8.2 mm at 35 to 36 weeks versus 5.4 mm at 35 to 39 weeks in the Higgins study) [25]: this difference may be related to the restriction of our study population to only those mothers with confirmed pregestational type 2 diabetes or it may be a consequence of a poorer underlying maternal metabolic environment of mothers in our cohort including higher rates of morbid obesity.…”

The life course perspective of gestational diabetes: An opportunity for the prevention of diabetes and heart disease in women

“… 13 , 14 , 15 This propensity for metabolic dysfunction that links mother and child may be the consequence of multiple elements including (i) shared genetic factors, (ii) the home environment and associated lifestyle, and (iii) fetal exposure to the altered intrauterine environment of the GDM pregnancy, which potentially may program adverse developmental pathways as per the Developmental Origins of Health and Disease (DOHaD) paradigm. 16 , 17 , 18 , 19 , 20 Moreover, evidence to date suggests that current antepartum treatment of GDM does not reduce these future risks in the offspring 21 , 22 and it remains uncertain whether non-insulin pharmacologic therapy for GDM (such as glyburide or metformin) could even have deleterious effects on the offspring that might emerge during childhood. 23 …”