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).

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.

Transformation of a long-standing phosphaturic tumor-inducing osteomalacia into malignancy.

Key Clinical Message: Tumor-induced osteomalacia is a paraneoplastic syndrome characterized by renal phosphate wasting and deranged bone turnover. Clinicians should consider tumor-induced osteomalacia in unexplained hypophosphatemia and investigate for underlying tumors. Abstract: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by renal phosphate wasting, which leads to deranged bone turnover. TIO is usually associated with benign mesenchymal tumors, although it has also been reported in malignant tumors. We present the case of a 56-year-old individual who experienced a protracted 6-year clinical course characterized by hypophosphatemia, weakness, and kyphosis, alongside the presence of a foot tumor. Subsequently, this lesion displayed malignant behavior and was ultimately diagnosed as a high-grade sarcoma. To date, this case is among the 10 reported cases in the literature of a mesenchymal tumor associated with TIO undergoing malignant transformation. This report underscores the importance of a comprehensive evaluation of patients with unexplained hypophosphatemia and highlights the need for diligent follow-up to detect possible malignant transformation of the underlying tumor. Clinicians should consider TIO in the differential diagnosis of hypophosphatemia and promptly investigate for the presence of an underlying tumor, as early detection may improve the patient's prognosis.

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.

A novel mutation c.457C > T p.Q153 in the HMBS gene in a Mexican woman with acute intermittent porphyria.

Key Clinical Message: The detection of a novel HMBS gene mutation (c.457C > T) in a Mexican woman with acute intermittent porphyria underscores the importance of expanding genetic analyses in diverse populations to improve diagnosis, management, and knowledge of the disease's clinical implications. Abstract: Acute intermittent porphyria (AIP) is an autosomal dominant disorder caused by a deficiency in the enzymatic activity of porphobilinogen deaminase (HMBS), resulting in the accumulation of toxic heme metabolites. In this report, we present the case of a Mexican woman with AIP who experienced recurrent episodes of severe abdominal pain, weakness, vomiting, and insomnia. Despite the challenges in diagnosis and treatment, genetic analysis revealed a novel HMBS mutation, c.457C > T (p.Q153X), located in exon 9. This mutation induces a premature translational stop codon and had not been previously reported in medical literature among individuals with AIP. Remarkably, the patient exhibited a positive response to RNA interference therapy. We hypothesize that this novel HMBS mutation may potentially account for the more severe clinical presentation observed in this case. However, further research is necessary to establish a definitive link between this specific mutation and disease severity. The prevalence and genetic variants of AIP in Mexico remain largely unknown, underscoring the importance of conducting additional research and expanding genetic analyses to gain a better understanding of the clinical implications associated with these mutations.

Positron emission tomography and its role in the assessment of vulnerable plaques in comparison to other imaging modalities.

The diagnosis and management of vulnerable plaques are topics of high interest in the cardiovascular field. Although imaging techniques like computed tomography angiography (MCTA) and ultrasonography (USG) can structurally evaluate atherosclerotic plaques, they are limited in examining internal cellular processes. Positron emission tomography (PET) molecular imaging, on the other hand, can highlight these cellular processes, including inflammation, angiogenesis, and lipid oxidation. Magnetic resonance imaging (MRI) is also a valuable non-invasive imaging technique that can provide detailed anatomical and functional information on the cardiovascular system. In this review, we compare the advantages and drawbacks of MCTA, USG and MRI imaging techniques with PET molecular imaging in evaluating vulnerable plaques. PET imaging allows physicians to measure different pathophysiological events within the plaque using intravenous radiotracers, of which 18F-fluorodeoxyglucose (18F-FDG) is the most validated one. By using 18F-FDG, physicians can understand the formation of the plaque, assess the accumulation of macrophages, and predict major cardiovascular events. However, some limitations exist in using 18F-FDG, including myocardial uptake and low sensitivity in imaging coronary arteries. We also mention other radiotracers that can help in evaluating vulnerable plaques, including 18F-NaF. Although PET imaging is still challenging, it has shown promise in evaluating vulnerable plaques and could be used to intervene in high-risk patients before major cardiovascular events occur.

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.