Calvin Ke

Importance: Epidemiologic studies suggest that people who were exposed to famine during early life but now live in nutrient-abundant environments have an elevated risk of type 2 diabetes (T2D) and other cardiometabolic conditions. Although many individuals who were exposed to famine in early life have now immigrated to high-income countries, the association between early life famine exposure and cardiometabolic outcomes among immigrants is unknown. Objective: To investigate the associations of early life exposure to the Great Chinese Famine with the incidence of T2D, hypertension, and cardiovascular hospitalization among immigrants. Design, Setting, and Participants: This population-based cohort study in Ontario, Canada, used 3 cohorts (1 for each coprimary outcome of T2D, hypertension, and cardiovascular hospitalization) of adult Chinese immigrants aged 20 to 85 years living in Ontario from April 1, 1992, to March 31, 2019. Participants were followed up until 85 years of age, relocation from Ontario, or March 31, 2023 (whichever occurred first). Data were analyzed from April 22, 2024, to September 30, 2025. Exposure: Prenatal, childhood, and adolescent exposure to famine, classified by year of birth (1941-1952). Those born before 1941 or after 1962 served as the comparison group. Main Outcomes and Measures: Incident T2D, hypertension, and cardiovascular hospitalization were the coprimary outcomes. Results: The T2D cohort included 188 292 individuals (exposed: mean [SD] age, 52.6 [10.8] years; 53.3% female; unexposed: mean [SD] age, 37.4 [12.5] years; 54.9% female), the hypertension cohort included 180 510 individuals (exposed: mean [SD] age, 51.8 [10.6] years; 52.3% female; unexposed: mean [SD] age, 36.6 [11.5] years; 55.0% female), and the cardiovascular hospitalization cohort included 208 921 individuals (exposed: mean [SD] age, 50.5 [12.0] years; 51.5% female; comparison: mean [SD] age, 37.8 [13.1] years; 54.6% female). Event rates among the famine-exposed group were 13.6% for T2D, 29.8% for hypertension, and 1.6% for cardiovascular hospitalization. Early life famine exposure was associated with increased hazards of T2D (prenatal: hazard ratio [HR], 1.58 [95% CI, 1.49-1.68]; childhood: HR, 1.45 [95% CI, 1.38-1.54]; adolescent: HR, 1.37 [95% CI, 1.28-1.46]) and hypertension (prenatal: HR, 1.22 [95% CI, 1.17-1.27]; childhood: HR, 1.25 [95% CI, 1.21-1.30]; adolescent: HR, 1.25 [95% CI, 1.20-1.31]). Prenatal and childhood exposure to famine were not associated with risk of cardiovascular hospitalization (prenatal: HR, 0.92 [95% CI, 0.76-1.12]; childhood: HR, 0.98 [95% CI, 0.86-1.11]), but adolescent exposure to famine was associated with a 14% decrease in risk of cardiovascular hospitalization (HR, 0.86 [95% CI, 0.75-0.98]). Conclusions and Relevance: In this cohort study of Chinese immigrants, early life famine exposure was strongly associated with increased risks of incident T2D and hypertension, but not cardiovascular hospitalization. Early life undernutrition is a novel cardiometabolic risk factor among immigrants associated with the burden of T2D and hypertension in high-income countries.

It is unclear whether variation in covert cerebrovascular disease prevalence is attributable to ethnic differences or to other factors. We aimed to examine the associations of country of residence with covert vascular brain injury (VBI) and cognitive dysfunction among Chinese adults residing in Canada and China. This was a multisite cross-sectional study of Chinese adults aged 40-80 years in the Canadian Alliance for Healthy Hearts and Healthy Minds (CAHHM; January 1, 2014, to December 31, 2018) and Prospective Urban Rural Epidemiological-Mind (PURE-MIND; November 1, 2010, to July 31, 2015) cohorts living in Canada and China. The exposure was country of residence. The co-primary outcomes were covert VBI (defined as MRI findings of high white matter hyperintensities or covert brain infarct) and cognitive dysfunction (defined as a Montreal Cognitive Assessment [MoCA] score <26). We used generalized linear models to describe the association between country of residence and each outcome, adjusting for selected covariates. We included 884 adults living in Canada (mean age 57.3 years, 55.4% female) and 473 living in China (mean age 56.8 years, 60.3% female). Participants in Canada had a lower prevalence of covert VBI (age 65-79 years: male, 11.5%; female, 12.2%) than those living in China (age 65-79 years: male, 62.9%; female, 52.1%). Prevalence of MoCA score <26 was lower among men and women in Canada (age 65-79 years: 40.2% and 30.0%, respectively) than among men and women in China (age 65-79 years: 74.3% and 79.2%). Living in China was associated with a 6-fold increase in the odds of covert VBI (5.85, 4.06-8.45), which remained significant after covariate adjustment. Living in China was associated with a 7-fold increase in the odds of MoCA score <26 (6.98, 5.38-9.04), which was no longer significant after covariate adjustment. Despite sharing a similar ethnicity, the prevalence of covert VBI and cognitive dysfunction varied substantially by country of residence. Disparities in cognitive dysfunction were completely explained by differences in education and traditional cerebrovascular risk factors, whereas disparities in covert VBI prevalence were only partially explained by differences in such factors, suggesting a role for other environmental factors.