Abstract
BACKGROUND: Ischemic heart disease (IHD) and type 2 diabetes mellitus (T2DM) are leading causes of disability-adjusted life years globally among adults aged 55 years and older. Although both diseases share common risk factors and pathophysiological pathways, previous research has predominantly addressed these conditions in isolation. The co-occurrence patterns and regional variations of IHD and T2DM burden remain poorly understood. We aimed to characterize the global co-occurrence patterns of IHD and T2DM from a spatial perspective and to identify the corresponding risk factors distinguishing different burden regions. METHODS: Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 database, we extracted age-standardized disability-adjusted life year (DALY) rates for IHD and T2DM among individuals aged 55 years and older from 204 countries and territories. Based on quartile distributions of global DALY rates for both diseases, we classified countries into four distinct burden regions: Low-Burden Regions (56 countries), T2DM-Dominant Regions (46 countries), IHD-Dominant Regions (46 countries), and Dual-Burden Regions (56 countries). We examined temporal trends from 1990-2021, computed population attributable fractions for major risk factors, and used machine learning-based SHAP (Shapley Additive Explanations) analysis to screen and quantify the effects of corresponding risk factors distinguishing regional classifications. RESULTS: Dual-Burden Regions were distributed across multiple geographic areas including the Caribbean and Central America, Persian Gulf states, Balkan Peninsula, Southeast Asia, West Africa, Eastern Mediterranean, and Northern Europe. The spatial distribution revealed distinct geographic clustering, with higher IHD rates in Eastern Europe and Central Asia, and elevated T2DM rates in Pacific Island nations and parts of the Middle East. Countries and territories with the highest burden for both diseases included North African countries (eg, Morocco: IHD 25,193.1/100,000 and T2DM 32,197.24/100,000) and Pacific Island nations such as Fiji exhibiting IHD burden of 24,758.17 per 100,000 and T2DM burden of 32,197.24 per 100,000. Marshall Islands showed IHD burden of 25,107.72/100,000 and T2DM burden of 22,122.46/100,000, while Nauru demonstrated the highest IHD burden (39,483.92/100,000). High systolic blood pressure contributed most to IHD burden globally (49.79%), while high body-mass index dominated T2DM burden (51.89%). Environmental factors demonstrated clear regional gradients, with household air pollution ranging from 4·58% in Low-Burden to 14.43% in Dual-Burden Regions for IHD. High body-mass index contributed 51.89% to T2DM burden globally, with regional variation from 40.61% in IHD-Dominant to 51.36% in Low-Burden Regions. SHAP analysis identified sociodemographic index (SDI2021) as the primary factor distinguishing Low-Burden from Dual-Burden Regions for both IHD (mean |SHAP| = 1.245) and T2DM (mean |SHAP| = 1.317). Diet high in processed meat consistently showed strong discriminatory power across multiple regional comparisons for T2DM (SHAP values 0.923-1.721), while secondhand smoke emerged as a critical differentiator with SHAP values exceeding 1.0 across various regional distinctions. Diet low in vegetables served as a primary differentiator between Low-Burden and T2DM-Dominant Regions (mean |SHAP| = 1.188). CONCLUSION: The co-occurrence of IHD and T2DM exhibits pronounced global heterogeneity, with Pacific Island nations and multiple geographic regions including Gulf states, North Africa, and other areas bearing disproportionate dual-burden. Socioeconomic development level fundamentally characterizes dual-burden status, while dietary and environmental factors serve as key regional differentiators. Intervening in modifiable risk factors, particularly processed meat consumption, vegetable intake, and environmental exposures, can fundamentally reduce the global burden of these co-occurring diseases.