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OBJECTIVE: To validate AnthropoAge, a new metric of biological age (BA), for prediction of all-cause mortality and age-related outcomes and characterize population-specific aging patterns using multinational longitudinal cohorts. METHODS: We analyzed harmonized multinational data from the Gateway to Global Aging, including studies from the US, England, Mexico, Costa Rica, and China. We used body mass index and waist-to-height ratio to estimate AnthropoAge and AnthropoAgeAccel in participants aged 50-90 years old as proxies of BA and age acceleration, respectively. We compared the predictive capacity for all-cause mortality of AnthropoAge and chronological age (CA) using Cox models, described aging trends in all countries and explored the utility of longitudinal assessments of AnthropoAgeAccel to predict new-onset functional decline and age-related diseases using generalized estimating equations (GEE). FINDINGS: Using data from 55,628 participants, we found AnthropoAge (c-statistic 0.772) outperformed CA (0.76) for prediction of mortality independently of comorbidities, sex, race/ethnicity, education, and lifestyle; this result was replicated in most countries individually except for Mexico. Individuals with accelerated aging had a ~39% higher risk of death, and AnthropoAge also identified trends of faster biological aging per year. In longitudinal analyses, higher AnthropoAgeAccel values were independently predictive of self-reported health deterioration and new-onset deficits in basic/instrumental activities of daily living (ADL/IADL), diabetes, hypertension, cancer, chronic lung disease, myocardial infarction, and stroke. CONCLUSIONS: AnthropoAge is a robust and reproducible BA metric associated with age-related outcomes. Its implementation could facilitate modeling trends of biological aging acceleration in different populations, although recalibration may enhance its utility in underrepresented populations such as individuals from Latin America.

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BACKGROUND: Prediabetes has been associated with increased all-cause and cardiovascular mortality. However, no large-scale studies have been conducted in Mexico or Latin America examining these associations. METHODS: We analyzed data from 115,919 adults without diabetes (diagnosed or undiagnosed) aged 35-84 years who participated in the Mexico City Prospective Study between 1998 and 2004. Participants were followed until January 1st, 2021 for cause-specific mortality. We defined prediabetes according to the American Diabetes Association (ADA, HbA1c 5.7% to 6.4%) and the International Expert Committee (IEC, HbA1c 6.0-6.4%) definitions. Cox regression adjusted for confounders was used to estimate all-cause and cause-specific mortality rate ratios (RR) at ages 35-74 years associated with prediabetes. FINDINGS: During 2,085,392 person-years of follow-up (median in survivors 19 years), there were 6,810 deaths at ages 35-74, including 1,742 from cardiovascular disease, 892 from renal disease and 108 from acute diabetic crises. Of 110,405 participants aged 35-74 years at recruitment, 28,852 (26%) had ADA-defined prediabetes and 7,203 (7%) had IEC-defined prediabetes. Compared with those without prediabetes, individuals with prediabetes had higher risk of all-cause mortality at ages 35-74 years (RR 1.13, 95% CI 1.07-1.19 for ADA-defined prediabetes and RR 1.28, 1.18-1.39 for IEC-defined prediabetes), as well as increased risk of cardiovascular mortality (RR 1.22 [1.10-1.35] and 1.42 [1.22-1.65], respectively), renal mortality (RR 1.35 [1.08-1.68] and 1.69 [1.24-2.31], respectively), and death from an acute diabetic crisis (RR 2.63 [1.76-3.94] and 3.43 [2.09-5.62], respectively). RRs were larger at younger than at older ages, and similar for men compared to women. The absolute excess risk associated with ADA and IEC-defined prediabetes at ages 35-74 accounted for6% and 3% of cardiovascular deaths respectively, 10% and 5% of renal deaths respectively, and 31% and 14% of acute diabetic deaths respectively. INTERPRETATION: Prediabetes is a significant risk factor for all-cause, cardiovascular, renal, and acute diabetic deaths in Mexican adults. Identification and timely management of individuals with prediabetes for targeted risk reduction could contribute to reducing premature mortality from cardiometabolic causes in this population. FUNDING: Wellcome Trust, the Mexican Health Ministry, the National Council of Science and Technology for Mexico, Cancer Research UK, British Heart Foundation, UK Medical Research Council. Instituto Nacional de Geriatría (Mexico City).

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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.

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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.

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Background: Post-acute sequelae after SARS-CoV-2 infection (PASC) remains a concerning long-term complication of COVID-19. Here, we aimed to characterize the epidemiology of PASC in Mexico during 2022 and identify potential associations of covariates with PASC prevalence using nationally representative data. Methods: We analyzed data from the 2022 Mexican National Health and Nutrition Survey (ENSANUT) from 24,434 participants, representing 85,521,661 adults ≥20 years. PASC was defined using both the National Institute for Health and Care Excellence (NICE) definition and a PASC score ≥12. Estimates of PASC prevalence were stratified by age, sex, rural vs. urban setting, social lag quartiles, number of reinfections, vaccination status and periods of predominance of SARS-CoV-2 circulating variants. Determinants of PASC were assessed using log-binomial regression models adjusted by survey weights. Findings: Persistent symptoms after SARS-CoV-2 infection were reported by 12.44% (95% CI 11.89-12.99) of adults ≥20 years in Mexico in 2022. The most common persistent symptoms were fatigue, musculoskeletal pain, headache, cough, loss of smell or taste, fever, post-exertional malaise, brain fog, anxiety, and chest pain. PASC was present in 21.21% (95% CI 19.74-22.68) of subjects with previously diagnosed COVID-19. Over 28.6% of patients with PASC reported symptoms persistence ≥6 months and 14.05% reported incapacitating symptoms. Higher PASC prevalence was associated with SARS-CoV-2 reinfections, depressive symptoms and living in states with high social lag. PASC prevalence, particularly its more severe forms, decreased with COVID-19 vaccination and for infections during periods of Omicron variant predominance. Interpretation: PASC remains a significant public health burden in Mexico as the COVID-19 pandemic transitions into endemic. Promoting SARS-CoV-2 reinfection prevention and booster vaccination may be useful in reducing PASC burden. Funding: This research was supported by Instituto Nacional de Geriatría in Mexico.

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Background: Characterizing prediabetes phenotypes may be useful in guiding diabetes prevention efforts; however, heterogeneous criteria to define prediabetes have led to inconsistent prevalence estimates, particularly in low- and middle-income countries. Here, we estimated trends in prediabetes prevalence in Mexico across different prediabetes definitions and their association with prevalent cardiometabolic conditions. Methods: We conducted a serial cross-sectional analysis of National Health and Nutrition Surveys in Mexico (2016-2022), totalling 22 081 Mexican adults. After excluding individuals with diagnosed or undiagnosed diabetes, we defined prediabetes using ADA (impaired fasting glucose [IFG] 100-125 mg/dL and/or HbA1c 5.7-6.4%), WHO (IFG 110-125 mg/dL), and IEC criteria (HbA1c 6.0-6.4%). Prevalence trends of prediabetes over time were evaluated using weighted Poisson regression and its association with prevalent cardiometabolic conditions with weighted logistic regression. Findings: The prevalence of prediabetes (either IFG or high HbA1c [ADA]) in Mexico was 20.9% in 2022. Despite an overall downward trend in prediabetes (RR 0.973, 95% CI 0.957-0.988), this was primarily driven by decreases in prediabetes by ADA-IFG (RR 0.898, 95% CI 0.880-0.917) and WHO-IFG criteria (RR 0.919, 95% CI 0.886-0.953), while prediabetes by ADA-HbA1c (RR 1.055, 95% CI 1.033-1.077) and IEC-HbA1C criteria (RR 1.085, 95% CI 1.045-1.126) increased over time. Prediabetes prevalence increased over time in adults >40 years, with central obesity, self-identified as indigenous or living in urban areas. For all definitions, prediabetes was associated with an increased risk of cardiometabolic conditions. Interpretation: Prediabetes rates in Mexico from 2016 to 2022 varied based on defining criteria but consistently increased for HbA1c-based definitions and high-risk subgroups. Funding: This research was supported by Instituto Nacional de Geriatría in Mexico. JAS was supported by NIH/NIDDK Grant# K23DK135798.

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Background: With the widespread transmission of the Omicron SARS-CoV-2 variant, reinfections have become increasingly common. Here, we explored the role of immunity, primary infection severity, and variant predominance in the risk of reinfection and severe COVID-19 during Omicron predominance in Mexico. Methods: We analyzed reinfections in Mexico in individuals with a primary infection separated by at least 90 days from reinfection using a national surveillance registry of SARS-CoV-2 cases from March 3rd, 2020, to August 13th, 2022. Immunity-generating events included primary infection, partial or complete vaccination, and booster vaccines. Reinfections were matched by age and sex with controls with primary SARS-CoV-2 infection and negative RT-PCR or antigen test at least 90 days after primary infection to explore reinfection and severe disease risk factors. We also compared the protective efficacy of heterologous and homologous vaccine boosters against reinfection. Results: We detected 231,202 SARS-CoV-2 reinfections in Mexico, most occurring in unvaccinated individuals (41.55%). Over 207,623 reinfections occurred during periods of Omicron (89.8%), BA.1 (36.74%), and BA.5 (33.67%) subvariant predominance and a case-fatality rate of 0.22%. Vaccination protected against reinfection, without significant influence of the order of immunity-generating events and provided >90% protection against severe reinfections. Heterologous booster schedules were associated with ~11% and ~ 54% lower risk for reinfection and reinfection-associated severe COVID-19, respectively, modified by time-elapsed since the last immunity-generating event, when compared against complete primary schedules. Conclusion: SARS-CoV-2 reinfections increased during Omicron predominance. Hybrid immunity provides protection against reinfection and associated severe COVID-19, with potential benefit from heterologous booster schedules.

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OBJECTIVES: Vaccination has been effective in ameliorating the impact of COVID-19. Here, we report vaccine effectiveness (VE) of the nationally available COVID-19 vaccines in Mexico. METHODS: Retrospective analysis of a COVID-19 surveillance system to assess the VE of the BNT162b2, messenger RNA (mRNA)-12732, Gam-COVID-Vac, Ad5-nCoV, Ad26.COV2.S, ChAdOx1, and CoronaVac vaccines against SARS-CoV-2 infection, COVID-19 hospitalization, and death in Mexico. The VE was estimated using time-varying Cox proportional hazard models in vaccinated and unvaccinated adults, adjusted for age, sex, and comorbidities. VE was also estimated for adults with diabetes, aged ≥60 years, and comparing the predominance of SARS-CoV-2 variants B.1.1.519 and B.1.617.2. RESULTS: We assessed 793,487 vaccinated and 4,792,338 unvaccinated adults between December 24, 2020 and September 27, 2021. The VE against SARS-CoV-2 infection was the highest for fully vaccinated individuals with mRNA-12732 (91.5%, 95% confidence interval [CI] 90.3-92.4) and Ad26.COV2.S (82.2%, 95% CI 81.4-82.9); for COVID-19 hospitalization, BNT162b2 (84.3%, 95% CI 83.6-84.9) and Gam-COVID-Vac (81.4% 95% CI 79.5-83.1), and for mortality, BNT162b2 (89.8%, 95% CI 89.2-90.2) and mRNA-12732 (93.5%, 95% CI 86.0-97.0). The VE decreased for all vaccines in adults aged ≥60 years, people with diabetes, and periods of Delta variant predominance. CONCLUSION: All the vaccines implemented in Mexico were effective against SARS-CoV-2 infection, COVID-19 hospitalization, and death. Mass vaccination with multiple vaccines is useful to maximize vaccination coverage.

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Sandfly species (Diptera: Psychodidae) are suspected or proven vectors of Leishmania spp. in the American region. Understanding niche conservatism (NC) in insect vectors allows an understanding of constraints on adaptive responses, and thus implications for disease ecology. Therefore, in this study, the authors evaluated NC in three vector species of leishmaniasis (Lutzomyia gomezi, Psathyromyia shannoni and Pintomyia ovallesi) in Central and South America. For this, the authors performed niche identity and similarity testing through paired comparisons in ENMTools and niche overlap in Niche Analyst. The authors found that species niches were more similar to each other than if the points had been randomly extracted, and they also found extensive similarity between Pa. shannoni and Lu. gomezi niches and in Pa. shannoni niches over different timescales. The authors suggest Pa. shannoni as a priority species due to fundamental niche similarity with phylogenetically related species and also its extensive evolutionary history and ecological plasticity that could affect the emergence and resurgence of leishmaniasis in areas endemic by this vector.

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