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.

Keywords: Clinical trials; Diabetes; Intergenerational; Obesity; Offspring; Preconception; Pregnancy; Review.

Fig. 1

Approaches needed in clinical trials investigating risk of intergenerational transmission of obesity and diabetes. Prior clinical trials investigating risk of intergenerational transmission of obesity and diabetes have been: (1) restricted to women of predominately non-Hispanic, white race/ethnicity; (2) expensive to implement; (3) focused on mid- and late-prenatal assessments; and (4) limited to offspring assessments at birth, and mainly from medical records. Further efforts to develop effective and scalable strategies to reduce obesity and diabetes risks before conception should be prioritised, including approaches that: (1) include diverse, under-resourced, and high-risk populations; (2) have cost-effective interventions, while reporting resources needed for widespread implementation; (3) rigorously assess weight and blood glucose levels before and around conception; and (4) evaluate offspring outcomes and the postnatal environment from birth to adulthood. This figure is available as a downloadable slide