Diabetes Risk Is Increased in First Nations and Non–First Nations Offspring of Mothers With Diabetes and Worsened Among Those Large for Gestational Age: Results From the DIP: ORRIIGENSS Project

Abstract

Objectives

Our aim in this study was to determine how birthweight and exposure to diabetes in pregnancy (DIP) contribute to early-onset diabetes mellitus (DM) in Saskatchewan First Nations (FN) and non-FN offspring.

Methods

Using Ministry of Health administrative databases, we conducted a retrospective cohort study of FN and non-FN children born between 1980 and 2009 and followed to March 31, 2013. Using Cox regression models and cumulative survival analysis, we determined DM risk by birthweight (small [SGA], normal [NGA], or large for gestational age [LGA]), maternal diabetes in pregnancy (DIP) (gestational diabetes [GDM], pre-existing diabetes [pre-Gest/DM], or no DIP), and ethnicity.

Results

Among 360,508 offspring, 763 of 52,818 (1.4%) FN and 2,143 of 307,696 (0.7%) non-FN developed DM. FN people were over twice as likely as non-FN to develop DM, but the strongest DM predictor in both populations was DIP exposure (hazard ratios [HRs] 4.1 for FN and 4.9 for non-FN exposed to pre-Gest/DM; HRs 3.1 and 1.6 for FN and non-FN exposed to GDM). SGA and LGA were independent DM predictors in the total population, but only LGA interacted with DIP exposure to amplify DM risk in offspring. By 34 years, 38% of LGA FN (9% of non-FN) people exposed to pre-Gest/DM and 22% of LGA FN (4% of non-FN) people exposed to GDM developed DM.

Conclusions

GDM is a key to the epidemic of T2DM among Indigenous peoples. It is the strongest predictor of T2DM among younger FN women and a precursor to their high rates of pre-Gest/DM. Offspring exposed to GDM and especially pre-Gest/DM are at high risk for early-onset T2DM, further worsened by being LGA.