Smoking, all-cause, and cause-specific mortality in individuals with diabetes in Mexico: an analysis of the Mexico city prospective study.

OBJECTIVE: Evidence from low- and middle-income countries regarding the effect of smoking in people with diabetes is lacking. Here, we report the association of smoking with mortality in a large cohort of Mexican adults with diabetes. METHODS: Participants with diabetes mellitus (self-reported diagnosis, use of antidiabetic medications or HbA1c ≥ 6.5%) aged 35-74 years when recruited into the Mexico City Prospective Study were included. Cox regression confounder-adjusted mortality rate ratios (RRs) associated with baseline smoking status were estimated. RESULTS: Among 15,975 women and 8225 men aged 35-74 years with diabetes but no other comorbidities at recruitment, 2498 (16%) women and 2875 (35%) men reported former smoking and 2753 (17%) women, and 3796 (46%) men reported current smoking. During a median of 17 years of follow-up there were 5087 deaths at ages 35-74 years. Compared with never smoking, all-cause mortality RR was 1.08 (95%CI 1.01-1.17) for former smoking, 1.11 (95%CI 1.03-1.20) for current smoking, 1.09 (95%CI 0.99-1.20) for non-daily smoking, 1.06 (95%CI 0.96-1.16) for smoking < 10 cigarettes/day (median during follow-up 4 cigarettes/day), and 1.28 (95% CI 1.14-1.43) for smoking ≥ 10 cigarettes/day (median during follow-up 15 cigarettes/day). Mortality risk among daily smokers was greatest for COPD, lung cancer, cardiovascular diseases, and acute diabetic complications. CONCLUSION: In this cohort of Mexican adults with diabetes, low-intensity daily smoking was associated with increased mortality, despite observing smoking patterns which are different from other populations, and over 5% of total deaths were associated with smoking.

Metabolomic Profile Alterations Associated with the SLC16A11 Risk Haplotype Following a Lifestyle Intervention in People With Prediabetes.

Background: A risk haplotype in SLC16A11 characterized by alterations in fatty acid metabolism emerged as a genetic risk factor associated with increased susceptibility to type 2 diabetes (T2D) in Mexican population. Its role on treatment responses is not well understood. Objectives: We aimed to determine the impact of the risk haplotype on the metabolomic profile during a lifestyle intervention (LSI). Methods: We recruited Mexican-mestizo individuals with ≥1 prediabetes criteria according to the American Diabetes Association with a body mass index between 25 and 45 kg/m2. We conducted a 24-wk quasiexperimental LSI study for diabetes prevention. Here, we compared longitudinal plasma liquid chromatography/mass spectrometry metabolomic changes between carriers and noncarriers. We analyzed the association of risk haplotype with metabolites leveraging repeated assessments using multivariable-adjusted linear mixed models. Results: Before the intervention, carriers (N = 21) showed higher concentrations of hippurate, C16 carnitine, glycine, and cinnamoylglycine. After 24 wk of LSI, carriers exhibited a deleterious metabolomic profile. This profile was characterized by increased concentrations of hippurate, cinnamoglycine, xanthosine, N-acetylputrescine, L-acetylcarnitine, ceramide (d18:1/24:1), and decreased concentrations of citrulline and phosphatidylethanolamine. These metabolites were associated with higher concentrations of total cholesterol, triglycerides, and low density lipoprotein cholesterol. The effect of LSI on the risk haplotype was notably more pronounced in its impact on 2 metabolites: methylmalonylcarnitine (ß: -0.56; P-interaction = 0.014) and betaine (ß: -0.64; P-interaction = 0.017). Interestingly, lower consumption across visits of polyunsaturated (ß: -0.038; P = 0.017) fatty acids were associated with higher concentrations of methylmalonylcarnitine. Covariates for adjustment across models included age, sex, genetic ancestry principal components, and body mass index. Conclusions: Our study highlights the persistence of deleterious metabolomic patterns associated with the risk haplotype before and during a 24-wk LSI. We also emphasize the potential regulatory role of polyunsaturated fatty acids on methylmalonylcarnitine concentrations suggesting a route for improving interventions for individuals with high-genetic risk.

Prediabetes as a risk factor for all-cause and cause-specific mortality: a prospective analysis of 115,919 adults without diabetes in Mexico City.

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).

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.

Prevalence and determinants of post-acute sequelae after SARS-CoV-2 infection (Long COVID) among adults in Mexico during 2022: a retrospective analysis of nationally representative data.

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.

Prevalence of prediabetes in Mexico: a retrospective analysis of nationally representative surveys spanning 2016-2022.

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.

Performance of the enhanced Sampson-NIH equation for VLDL-C and LDL-C in a population with familial combined hyperlipidemia.

INTRODUCTION: Low-density cholesterol (LDL-C) has long been estimated by the Friedewald formula (F-LDL-C); however, this method underestimates LDL-C in patients with hypertriglyceridemia (HTG) or low LDL-C levels. The Martin (M-LDL-C) and Sampson (S-LDL-C) formulas partially resolve these limitations. Recently, Sampson et al. developed a new equation (eS-VLDL-C) that includes ApoB. This new equation could be particularly useful in FCHL, which is characterized by the predominance of triglyceride-rich VLDL and a discordance between LDL-C and ApoB. METHODS: Very low-density lipoproteins (VLDL-C) was measured in 336 patients with FCHL by sequential ultracentrifugation. LDL-C was estimated by subtracting VLDL-C, estimated by the different equations, from non-HDL cholesterol. Spearman correlations, R2, mean squared error (RMSE), and bias were used to compare the accuracy of the different equations. Concordance of the estimated LDL-C values with LDL-C thresholds and ApoB was also assessed by their kappa coefficients and ROC analysis. RESULTS: Overall population had a mean age of 47 years, and 61.5% were women. 19.5% had type 2 diabetes, hypertension was present in 20.8%, and only 12.2% were on statin treatment. Both S-LDL-C and eS-LDL-C performed similarly, and better than M-LDL-C and F-LDL-C. In Bland-Altman analysis, eS-LDL-C showed the lowest bias, better performance in HTG, and better concordance with LDL-C treatment goals compared to other formulas (e.g. ρ: 0.87, 95% CI 0.84-0.89). CONCLUSIONS: LDL-S and LDL-eS equations estimate the concentration of LDL-C with greater accuracy than other formulas. The LDL-eS has best performance in estimating LDL-C with lower RMSE than other formulas.

Protection of hybrid immunity against SARS-CoV-2 reinfection and severe COVID-19 during periods of Omicron variant predominance in Mexico.

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.

Effectiveness of a nationwide COVID-19 vaccination program in Mexico against symptomatic COVID-19, hospitalizations, and death: a retrospective analysis of national surveillance data.

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.

Diagnostic performance of questionnaires to identify individuals with impaired fasting glucose in Mexican adult population.

AIMS: To evaluate the diagnostic performance of five questionnaires to identify impaired fasting glucose (IFG) in Mexican adult population. METHODS: The study included 23,311 subjects from five cohorts, three composed of individuals who sought medical advice in their first level clinics or participated in research studies and two representative surveys of the Mexican population. The reference standard was IFG which was defined as a fasting glucose ≥ 100 mg/dL. Diagnostic performance was evaluated with specificity, sensitivity, positive and negative predictive values, area under the curve, and the proportion of correctly classified individuals. RESULTS: The prevalence of IFG ranged from 14.4 to 48.1 % across the cohorts. Diagnostic performance of the questionnaires varied in each cohort depending on IFG prevalence. The questionnaires designed by Rojas, American Diabetes Association and International Diabetes Federation had the best performance considering the correct classification (>66.0 %) of subjects in all cohorts. However, Rojas' questionnaire had the best balance between sensitivity and specificity across the cohorts. CONCLUSION: In the Mexican population, considering different scenarios, the Rojas' questionnaire had the best diagnostic performance. The implementation of questionnaires for the identification of prediabetes and undiagnosed diabetes requires further study in specific populations.

AnthropoAge, a novel approach to integrate body composition into the estimation of biological age.

Aging is believed to occur across multiple domains, one of which is body composition; however, attempts to integrate it into biological age (BA) have been limited. Here, we consider the sex-dependent role of anthropometry for the prediction of 10-year all-cause mortality using data from 18,794 NHANES participants to generate and validate a new BA metric. Our data-driven approach pointed to sex-specific contributors for BA estimation: WHtR, arm and thigh circumferences for men; weight, WHtR, thigh circumference, subscapular and triceps skinfolds for women. We used these measurements to generate AnthropoAge, which predicted all-cause mortality (AUROC 0.876, 95%CI 0.864-0.887) and cause-specific mortality independently of ethnicity, sex, and comorbidities; AnthropoAge was a better predictor than PhenoAge for cerebrovascular, Alzheimer, and COPD mortality. A metric of age acceleration was also derived and used to assess sexual dimorphisms linked to accelerated aging, where women had an increase in overall body mass plus an important subcutaneous to visceral fat redistribution, and men displayed a marked decrease in fat and muscle mass. Finally, we showed that consideration of multiple BA metrics may identify unique aging trajectories with increased mortality (HR for multidomain acceleration 2.43, 95%CI 2.25-2.62) and comorbidity profiles. A simplified version of AnthropoAge (S-AnthropoAge) was generated using only BMI and WHtR, all results were preserved using this metric. In conclusion, AnthropoAge is a useful proxy of BA that captures cause-specific mortality and sex dimorphisms in body composition, and it could be used for future multidomain assessments of aging to better characterize the heterogeneity of this phenomenon.

Diabetes-Related Excess Mortality in Mexico: A Comparative Analysis of National Death Registries Between 2017-2019 and 2020.

OBJECTIVE: To estimate diabetes-related mortality in Mexico in 2020 compared with 2017-2019 after the onset of the coronavirus disease 2019 (COVID-19) pandemic. RESEARCH DESIGN AND METHODS: This retrospective, state-level study used national death registries of Mexican adults aged ≥20 years for the 2017-2020 period. Diabetes-related death was defined using ICD-10 codes listing diabetes as the primary cause of death, excluding certificates with COVID-19 as the primary cause of death. Spatial and negative binomial regression models were used to characterize the geographic distribution and sociodemographic and epidemiologic correlates of diabetes-related excess mortality, estimated as increases in diabetes-related mortality in 2020 compared with average 2017-2019 rates. RESULTS: We identified 148,437 diabetes-related deaths in 2020 (177 per 100,000 inhabitants) vs. an average of 101,496 deaths in 2017-2019 (125 per 100,000 inhabitants). In-hospital diabetes-related deaths decreased by 17.8% in 2020 versus 2017-2019, whereas out-of-hospital deaths increased by 89.4%. Most deaths were attributable to type 2 diabetes (130 per 100,000 inhabitants). Compared with 2018-2019 data, hyperglycemic hyperosmolar state and diabetic ketoacidosis were the two contributing causes with the highest increase in mortality (128% and 116% increase, respectively). Diabetes-related excess mortality clustered in southern Mexico and was highest in states with higher social lag, rates of COVID-19 hospitalization, and prevalence of HbA1c ≥7.5%. CONCLUSIONS: Diabetes-related deaths increased among Mexican adults by 41.6% in 2020 after the onset of the COVID-19 pandemic, occurred disproportionately outside the hospital, and were largely attributable to type 2 diabetes and hyperglycemic emergencies. Disruptions in diabetes care and strained hospital capacity may have contributed to diabetes-related excess mortality in Mexico during 2020.

Arterial Stiffness and HbA1c: Association Mediated by Insulin Resistance in Hispanic Adults.

Arterial stiffness may be associated with glucose metabolism parameters, such as HbA1c, mainly via insulin resistance. We aimed to investigate the association between arterial stiffness and HbA1c and explore the mediator effect of insulin resistance. In this cross-sectional study, arterial stiffness (pulse-wave velocity; PWV), HbA1c, and insulin resistance (METS-IR) were determined in Hispanic adults. In addition to sex and age, various biochemical measurements (glucose, lipid profile, etc.) and adipose tissue (fat mass and visceral fat mass) were considered as potential confounding variables. A multivariate regression analysis shows that HbA1c is associated with PWV, even after adjusting for several confounding variables. Importantly, the results show that insulin resistance mediated 17.9% of the effect of HbA1c over PWV. In conclusion, HbA1c may be a potential resource for predicting arterial stiffness due to the influence of insulin resistance in Hispanic subjects.

Socio-demographic inequalities and excess non-COVID-19 mortality during the COVID-19 pandemic: a data-driven analysis of 1 069 174 death certificates in Mexico.

BACKGROUND: In 2020, Mexico experienced one of the highest rates of excess mortality globally. However, the extent of non-COVID deaths on excess mortality, its regional distribution and the association between socio-demographic inequalities have not been characterized. METHODS: We conducted a retrospective municipal and individual-level study using 1 069 174 death certificates to analyse COVID-19 and non-COVID-19 deaths classified by ICD-10 codes. Excess mortality was estimated as the increase in cause-specific mortality in 2020 compared with the average of 2015-2019, disaggregated by primary cause of death, death setting (in-hospital and out-of-hospital) and geographical location. Correlates of individual and municipal non-COVID-19 mortality were assessed using mixed effects logistic regression and negative binomial regression models, respectively. RESULTS: We identified a 51% higher mortality rate (276.11 deaths per 100 000 inhabitants) compared with the 2015-2019 average period, largely attributable to COVID-19. Non-COVID-19 causes comprised one-fifth of excess deaths, with acute myocardial infarction and type 2 diabetes as the two leading non-COVID-19 causes of excess mortality. COVID-19 deaths occurred primarily in-hospital, whereas excess non-COVID-19 deaths occurred in out-of-hospital settings. Municipal-level predictors of non-COVID-19 excess mortality included levels of social security coverage, higher rates of COVID-19 hospitalization and social marginalization. At the individual level, lower educational attainment, blue-collar employment and lack of medical care assistance prior to death were associated with non-COVID-19 deaths. CONCLUSION: Non-COVID-19 causes of death, largely chronic cardiometabolic conditions, comprised up to one-fifth of excess deaths in Mexico during 2020. Non-COVID-19 excess deaths occurred disproportionately out-of-hospital and were associated with both individual- and municipal-level socio-demographic inequalities.

Physiological Network Is Disrupted in Severe COVID-19.

The human body is a complex system maintained in homeostasis thanks to the interactions between multiple physiological regulation systems. When faced with physical or biological perturbations, this system must react by keeping a balance between adaptability and robustness. The SARS-COV-2 virus infection poses an immune system challenge that tests the organism's homeostatic response. Notably, the elderly and men are particularly vulnerable to severe disease, poor outcomes, and death. Mexico seems to have more infected young men than anywhere else. The goal of this study is to determine the differences in the relationships that link physiological variables that characterize the elderly and men, and those that characterize fatal outcomes in young men. To accomplish this, we examined a database of patients with moderate to severe COVID-19 (471 men and 277 women) registered at the "Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán" in March 2020. The sample was stratified by outcome, age, and sex. Physiological networks were built using 67 physiological variables (vital signs, anthropometric, hematic, biochemical, and tomographic variables) recorded upon hospital admission. Individual variables and system behavior were examined by descriptive statistics, differences between groups, principal component analysis, and network analysis. We show how topological network properties, particularly clustering coefficient, become disrupted in disease. Finally, anthropometric, metabolic, inflammatory, and pulmonary cluster interaction characterize the deceased young male group.

Serum Vitamin D Levels Are Associated With Increased COVID-19 Severity and Mortality Independent of Whole-Body and Visceral Adiposity.

INTRODUCTION: Coronavirus disease (COVID-19) is a global pandemic. Vitamin D deficiency has been associated with susceptibility to infectious disease. In this study, the association between COVID-19 outcomes and vitamin D levels in patients attending a COVID-19 reference center in Mexico City are examined. METHODS: Consecutive patients with confirmed COVID-19 were evaluated. All patients underwent clinical evaluation and follow-up, laboratory measurements and a thoracic computerized tomography, including the measurement of epicardial fat thickness. Low vitamin D was defined as levels <20 ng/ml (<50nmol/L) and deficient Vitamin D as a level ≤12 ng/ml (<30 nmol/L). RESULTS: Of the 551 patients included, low vitamin D levels were present in 45.6% and deficient levels in 10.9%. Deficient Vitamin D levels were associated with mortality (HR 2.11, 95%CI 1.24-3.58, p = 0.006) but not with critical COVID-19, adjusted for age, sex, body-mass index and epicardial fat. Using model-based causal mediation analyses the increased risk of COVID-19 mortality conferred by low vitamin D levels was partly mediated by its effect on D-dimer and cardiac ultrasensitive troponins. Notably, increased risk of COVID-19 mortality conferred by low vitamin D levels was independent of BMI and epicardial fat. CONCLUSION: Vitamin D deficiency (≤12 ng/ml or <30 nmol/L), is independently associated with COVID-19 mortality after adjustment for visceral fat (epicardial fat thickness). Low vitamin D may contribute to a pro-inflammatory and pro-thrombotic state, increasing the risk for adverse COVID-19 outcomes.

Elevated serum uric acid is a facilitating mechanism for insulin resistance mediated accumulation of visceral adipose tissue.

OBJECTIVE: Serum uric acid (SUA) has been associated with cardiometabolic conditions such as insulin resistance (IR) and visceral adipose tissue (VAT) accumulation. Here, we aimed to clarify a unifying mechanism linking elevated SUA to IR and VAT. METHODS: We conducted analyses in 226 subjects from the UIEM cohort with both euglycemic hyperinsulinemic clamp (EHC) and dual X-ray absorptiometry (DXA) measurements for IR and VAT accumulation and explored the role of SUA and adiponectin by developing a network of causal mediation analyses to assess their impact on IR and VAT. These models were then translated to two population-based cohorts comprising 6337 subjects from NHANES 2003-2004 and 2011-2012 cycles in the US and ENSANUT Medio Camino 2016 in Mexico, using HOMA2IR and adipoIR as indicators of peripheral and adipose tissue IR, and METS-VF as a surrogate for VAT accumulation. RESULTS: SUA has a mediating role inside a bidirectional relationship between IR and visceral obesity, which was similar using either gold standard measurements or surrogate measures for IR and VAT. Furthermore, adiponectin acts as a linking mediator between elevated SUA and both peripheral IR and VAT accumulation. The proportion of the mechanism for IR-mediated (in either peripheral or adipose tissue) VAT accumulation was greater, compared to VAT-mediated IR accumulation (10.53% [9.23%-12.00%] to 5.44% [3.78%-7.00%]). Normal-range SUA levels can be used to rule-out underlying cardio-metabolic abnormalities in both men and women. CONCLUSIONS: Elevated SUA acts as a mediator inside the bidirectional relationship between IR and VAT accumulation and these observations could be applicable at a phenotype scale.

Epicardial adipose tissue thickness is associated with increased COVID-19 severity and mortality.

BACKGROUND: Increased adiposity and visceral obesity have been linked to adverse COVID-19 outcomes. The amount of epicardial adipose tissue (EAT) may have relevant implications given its proximity to the heart and lungs. Here, we explored the role of EAT in increasing the risk for COVID-19 adverse outcomes. METHODS: We included 748 patients with COVID-19 attending a reference center in Mexico City. EAT thickness, sub-thoracic and extra-pericardial fat were measured using thoracic CT scans. We explored the association of each thoracic adipose tissue compartment with COVID-19 mortality and severe COVID-19 (defined as mortality and need for invasive mechanical ventilation), according to the presence or absence of obesity. Mediation analyses evaluated the role of EAT in facilitating the effect of age, body mass index and cardiac troponin levels with COVID-19 outcomes. RESULTS: EAT thickness was associated with increased risk of COVID-19 mortality (HR 1.18, 95% CI 1.01-1.39) independent of age, gender, comorbid conditions and BMI. Increased EAT was associated with lower SpO2 and PaFi index and higher levels of cardiac troponins, D-dimer, fibrinogen, C-reactive protein, and 4 C severity score, independent of obesity. EAT mediated 13.1% (95% CI 3.67-28.0%) and 5.1% (95% CI 0.19-14.0%) of the effect of age and 19.4% (95% CI 4.67-63.0%) and 12.8% (95% CI 0.03-46.0%) of the effect of BMI on requirement for intubation and mortality, respectively. EAT also mediated the effect of increased cardiac troponins on myocardial infarction during COVID-19. CONCLUSION: EAT is an independent risk factor for severe COVID-19 and mortality independent of obesity. EAT partly mediates the effect of age and BMI and increased cardiac troponins on adverse COVID-19 outcomes.

Prevalence Trends of Diabetes Subgroups in the United States: A Data-driven Analysis Spanning Three Decades From NHANES (1988-2018).

CONTEXT: Data-driven diabetes subgroups were proposed as an alternative to address diabetes heterogeneity. However, changes in trends for these subgroups have not been reported. OBJECTIVE: Here, we analyzed trends of diabetes subgroups, stratified by sex, race, education level, age categories, and time since diabetes diagnosis in the United States. METHODS: We used data from consecutive NHANES cycles spanning the 1988-2018 period. Diabetes subgroups (mild obesity-related [MOD], severe insulin-deficient [SIDD], severe insulin-resistant [SIRD], and mild age-related diabetes [MARD]) were classified using validated self-normalizing neural networks. Severe autoimmune diabetes (SAID) was assessed for NHANES-III. Prevalence was estimated using examination sample weights considering bicyclic changes (BCs) to evaluate trends and changes over time. RESULTS: Diabetes prevalence in the United States increased from 7.5% (95% CI 7.1-7.9) in 1988-1989 to 13.9% (95% CI 13.4-14.4) in 2016-2018 (BC 1.09%, 95% CI 0.98-1.31, P < .001). Non-Hispanic Black people had the highest prevalence. Overall, MOD, MARD, and SIDD had an increase during the studied period. Particularly, non-Hispanic Black people had sharp increases in MARD and SIDD, Mexican Americans in SIDD, and non-Hispanic White people in MARD. Males, subjects with secondary/high school, and adults aged 40-64 years had the highest increase in MOD prevalence. Trends in diabetes subgroups sustained after stratifying time since diabetes diagnosis. CONCLUSION: Prevalence of diabetes and its subgroups in the United States has increased from 1988 to 2018. These trends were different across sex, ethnicities, education, and age categories, indicating significant heterogeneity in diabetes within the US obesity burden, population aging, socioeconomic disparities, and lifestyle aspects could be implicated in the increasing trends of diabetes in the United States.