Prediabetes as a risk factor for all-cause and cause-specific mortality: a prospective analysis of 115,919 adults without diabetes in Mexico City
Authors: Fermín-Martínez Carlos A. , Bello-Chavolla Omar Yaxmehen , Paz-Cabrera César Daniel , Ramírez-García Daniel , Perezalonso-Espinosa Jerónimo , Fernández-Chirino Luisa , Vargas-Vázquez Arsenio , Díaz-Sánchez Juan Pablo , Méndez-Labra Padme Nailea , Núñez-Luna Alejandra , Basile-Alvarez Martín Roberto , Sánchez-Castro Paulina , Bragg Fiona , Friedrichs Louisa Gnatiuc , Aguilar-Ramírez Diego , Emberson Jonathan R. , Berumen-Campos Jaime , Kuri-Morales Pablo , Tapia-Conyer Roberto , Alegre-Díaz Jesus , Seiglie Jacqueline A. , Antonio-Villa Neftali Eduardo 
Published: April 2024

ABSTRACTBACKGROUNDPrediabetes 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.METHODSWe 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, HbA1c5.7% to 6.4%) and the International Expert Committee (IEC, HbA1c6.0-6.4%) 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.FINDINGSDuring 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.INTERPRETATIONPrediabetes 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.FUNDINGWellcome 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).RESEARCH IN CONTEXTEvidence before this studyWe conducted a literature search in PubMed to identify articles published in English before February 27th, 2024 that reported on prospective studies examining the association between prediabetes with all-cause or cause-specific mortality or progression to diabetes in a Mexican or Latin American population, using the terms (“prediabetes” OR “impaired fasting glucose” OR “impaired glucose tolerance”) AND (“mortality” OR “death”) AND (“Mexico” OR “Mexican” OR “Latin America” OR “Latin American”). There were no studies examining risk associated with prediabetes definitions and mortality among adults in Mexico. We identified one study from Peru that included 988 participants and investigated only all-cause mortality for impaired fasting glucose and HbA1c-based definitions of prediabetes from ADA and IEC; this study reported increased mortality risk related to ADA-defined prediabetes based on HbA1cmeasures. Generalizability of these findings to other Latin American countries and regions with distinct cardiometabolic profiles in unclear.Added value of this studyOur study included 115,919 participants without diabetes from Mexico City, of whom (26%) had ADA-defined prediabetes and 7,203 (7%) had IEC-defined prediabetes. We found that prediabetes is associated with higher risks of all-cause and cause-specific mortality (cardiovascular, renal, and acute diabetic causes) than among participants without prediabetes. We found RRs to be larger at younger than at older ages, and largely similar for men compared to women. Among those without previously diagnosed diabetes, we found that the excess risk associated with ADA- and IEC-defined prediabetes at ages 35-74 years accounted for 6% and 3% of cardiovascular deaths, 10% and 5% of renal deaths, and 31% and 14% of acute diabetic deaths, respectively. .Implications of all the available evidenceOur results show that prediabetes is a significant risk factor for cardiovascular, kidney, and acute diabetic deaths among Mexican adults and accounts for a notable fraction of such deaths. Identification of individuals with prediabetes should be prioritized for optimized management to improve cardiometabolic outcomes in Mexican adults.