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 PARTICIPANTSThis 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 MEASURESThe primary outcome was incident type 2 diabetes in offspring by age 30 years. RESULTSIn 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.

Increased residual cardiovascular risk in patients with diabetes and high versus normal triglycerides despite statin‐controlled LDL cholesterol

“…We assessed the robustness of the reported rate ratios using the recently proposed E‐value, a measure of the minimum association that an unmeasured confounder must have with respect to both treatment and outcome to explain the significant associations . A large E‐value implies that a large amount of residual confounding would be needed to explain the effect estimate, and it is a sensitivity technique for observational data that has been used in recent studies . All analyses were conducted using SAS version 9.4 (Cary, North Carolina).…”

Prevalence, incidence and outcomes of diabetes in Ontario First Nations children: a longitudinal population-based cohort study

“…31 Early screening for diabetes in pregnancy and close follow-up of offspring of women with gestational or preexisting type 2 diabetes may help to mitigate the known increased risk of early-onset type 2 diabetes in those exposed to diabetes in utero. 6,7 Importantly, strategies to prevent gestational diabetes and type 2 diabetes in young women could subsequently reduce the risk of type 2 diabetes in their offspring. 6,7 Possible factors to explain the observed disparity in access to care and outcomes of diabetes in First Nations children include poverty, food insecurity and mental health challenges that make it difficult to access care and adopt behavioural lifestyle changes essential to the clinical management of type 2 diabetes.…”

A comparison between point‐of‐care testing and venous glucose determination for the diagnosis of diabetes mellitus 6–12 weeks after gestational diabetes

“…Early diagnosis of Type 2 diabetes has been recognized as a cost-effective healthcare strategy. Screening provides an opportunity for early disease detection [3][4][5][6]. During pregnancy, a unique opportunity emerges for the early diagnosis of diabetes in women.…”

“…Glucose elevation during pregnancy is a significant risk factor for future metabolic disease, and earmarks high-risk mothers and offspring. Screening provides an opportunity for early disease detection [3][4][5][6]. In South Africa, screening of asymptomatic, reproductive-aged women at high risk of Type 2 diabetes is mostly confined to pregnancy.…”