Insulin resistance potentiates the effect of remnant cholesterol on cardiovascular mortality in individuals without diabetes.

BACKGROUND AND AIMS: Remnant cholesterol (RC) and insulin resistance (IR) have been independently associated with cardiovascular risk. Here, we evaluated the role of IR and RC on cardiovascular disease (CVD) mortality. METHODS: We conducted an analysis of 16,113 individuals ≥20 years without diabetes from the National Health and Nutrition Examination Survey (NHANES-III/IV). RC levels were calculated using total cholesterol, non-HDL-c, and LDL-c; IR was defined as HOMA2-IR≥2.5 and CVD mortality as a composite of cardiovascular and cerebrovascular mortality. Multiple linear regression was used to assess the relationship between HOMA2-IR and RC and Cox regression models to assess their joint role in CVD mortality. Causally ordered mediation models were used to explore the mediating role of IR in RC-associated CVD mortality. RESULTS: We identified an association between higher HOMA2-IR and higher RC levels. The effect of IR on CVD mortality was predominant (HR 1.32, 95%CI 1.18-1.48) and decreased at older ages (HR 0.934, 95%CI 0.918-0.959) compared to RC (HR 0.983, 95%CI 0.952-1.014). Higher risk of CVD mortality was observed in individuals with IR but normal RC (HR 1.37, 95%CI 1.25-1.50) and subjects with IR and high RC (HR 1.24, 95%CI 1.13-1.37), but not in subjects without IR but high RC. In mediation models, HOMA2-IR accounted for 78.2% (95%CI 28.11-98.89) of the effect of RC levels on CVD mortality. CONCLUSIONS: Our findings suggest that RC potentiates the risk of CVD mortality through its effect on whole-body insulin sensitivity, particularly among younger individuals.

Diabetes subgroups and sociodemographic inequalities in Mexico: a cross-sectional analysis of nationally representative surveys from 2016 to 2022.

Background: Differences in the prevalence of four diabetes subgroups have been reported in Mexico compared to other populations, but factors that may contribute to these differences are poorly understood. Here, we estimate the prevalence of diabetes subgroups in Mexico and evaluate their correlates with indicators of social disadvantage using data from national representative surveys. Methods: We analyzed serial, cross-sectional Mexican National Health and Nutrition Surveys spanning 2016, 2018, 2020, 2021, and 2022, including 23,354 adults (>20 years). Diabetes subgroups (obesity-related [MOD], severe insulin-deficient [SIDD], severe insulin-resistant [SIRD], and age-related [MARD]) were classified using self-normalizing neural networks based on a previously validated algorithm. We used the density-independent social lag index (DISLI) as a proxy of state-level social disadvantage. Findings: We identified 4204 adults (median age: 57, IQR: 47-66, women: 64%) living with diabetes, yielding a pooled prevalence of 16.04% [95% CI: 14.92-17.17]. When stratified by diabetes subgroup, prevalence was 6.62% (5.69-7.55) for SIDD, 5.25% (4.52-5.97) for MOD, 2.39% (1.95-2.83) for MARD, and 1.27% (1.00-1.54) for SIRD. SIDD and MOD clustered in Southern Mexico, whereas MARD and SIRD clustered in Northern Mexico and Mexico City. Each standard deviation increase in DISLI was associated with higher odds of SIDD (OR: 1.12, 95% CI: 1.06-1.12) and lower odds of MOD (OR: 0.93, 0.88-0.99). Speaking an indigenous language was associated with higher odds of SIDD (OR: 1.35, 1.16-1.57) and lower odds of MARD (OR 0.58, 0.45-0.74). Interpretation: Diabetes prevalence in Mexico is rising in the context of regional and sociodemographic inequalities across distinct diabetes subgroups. SIDD is a subgroup of concern that may be associated with inadequate diabetes management, mainly in marginalized states. Funding: This research was supported by Instituto Nacional de Geriatría in Mexico.