Association of gestational diabetes and type 2 diabetes exposure in utero with the development of type 2 diabetes in first nations and non-first nations offspring

Abstract

IMPORTANCE Type 2 diabetes is increasing worldwide, disproportionately affecting First Nations (FN) people. Identifying early-life determinants of type 2 diabetes is important to address the intergenerational burden of illness. OBJECTIVE To investigate the association of in utero exposure to gestational diabetes and type 2 diabetes, stratified by FN status, with the development of type 2 diabetes in offspring. DESIGN, SETTING, AND PARTICIPANTS This cohort study was derived from the linkage of a pediatric diabetes clinical database and a population-based research data repository in Manitoba, Canada. Mother-infant dyads with a hospital birth or midwifery report in the data repository between April 1, 1984, and April 1, 2008, were identified. The dates of analysis were August through December 2017. Children identified with type 1 diabetes, monogenic diabetes, or secondary diabetes were excluded. EXPOSURES Primary exposures included maternal gestational diabetes or type 2 diabetes and FN status. MAIN OUTCOMES AND MEASURES The primary outcome was incident type 2 diabetes in offspring by age 30 years. RESULTS In this cohort study of 467 850 offspring (mean follow-up, 17.7 years; 51.2% male), FN status and diabetes exposure were associated with incident type 2 diabetes in offspring after adjustment for sex, maternal age, socioeconomic status, birth size, and gestational age. Type 2 diabetes exposure conferred a greater risk to offspring compared with gestational diabetes exposure (3.19 vs 0.80 cases per 1000 person-years, P < .001). Compared with no diabetes exposure, any diabetes exposure accelerated the time to the development of type 2 diabetes in offspring by a factor of 0.74 (95% CI, 0.62-0.90) for gestational diabetes and a factor of 0.50 (95% CI, 0.45-0.57) for type 2 diabetes. First Nations offspring had a higher risk compared with non-FN offspring (0.96 vs 0.14 cases per 1000 person-years, P < .001). First Nations offspring had accelerated type 2 diabetes onset by a factor of 0.52 (95% CI, 0.49-0.55) compared with non-FN offspring. Neither interaction between FN and type 2 diabetes (0.92; 95% CI, 0.80-1.05) nor interaction between FN and gestational diabetes (0.97; 95% CI, 0.77-1.20) was significant (P = .21 and P = .75, respectively). CONCLUSIONS AND RELEVANCE Important differences exist in offspring risk based on type of diabetes exposure in utero. These findings have implications for future research and clinical practice guidelines, including early pregnancy screening and follow-up of the offspring.