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).

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.

Asthma patients' and physicians' perspectives on the burden and management of asthma.

BACKGROUND: The 2021 Global Initiative for Asthma (GINA) report recommends as-needed inhaled corticosteroid (ICS)/formoterol irrespective of severity, and maintenance and reliever treatment (MART) from GINA Step 3 as part of Treatment Track 1, partly based on the SYGMA studies. We investigated how current clinical practice in Australia, Canada, China and the Philippines relates to latest GINA recommendations. METHODS: Patients and physicians were recruited from online panels between July and August 2020 and invited to complete an online survey. INCLUSION CRITERIA: age ≥18 years, current/past physician diagnosis of asthma (patients); primary care (Canada also included respirologists/respiratory therapists), treating ≥4 patients with asthma per month, ≥3 years in clinical practice (physicians). RESULTS: Overall, 1216/70,183 patients and 803/8376 physicians replied and were eligible for inclusion. Only 8-15% of patients were using MART; 66-81% used regular maintenance therapy with/without an as-needed reliever. Across the four countries, physicians classified 48-63% of their patients as mild (GINA Steps 1-2) and 28-36% as moderate (GINA Steps 3-4). Generally, physicians rated symptom control over exacerbation reduction as their main treatment goal; patients also ranked symptom relief as very important. Approximately 9-29% of patients and 24-45% of physicians were unaware of MART, and among those who prescribed MART, 80-95% prescribed an additional (non-ICS) as-needed reliever. INTERPRETATION: Most physicians prioritized managing asthma symptoms over exacerbations. A lack of awareness and understanding of MART dosing exists among physicians. Practical strategies are required to implement GINA recommendations effectively in real-world clinical practice and to identify appropriate patients for MART.

Central Nervous System Depressants and Risk of Hospitalization due to Community-Acquired Pneumonia in very Old Patients.

BACKGROUND: Central Nervous System (CNS) depressants like antipsychotics, opioids, benzodiazepines and zolpidem are frequently used by patients of a wide range of ages. Uncertainty remains about their effect in very old adults (>80 years old) and their potential for pharmacodynamic and pharmacokinetic drug-drug interactions in this population. OBJECTIVE: To assess if the use of CNS depressants is associated with a higher risk of hospitalization due to community-acquired pneumonia (CAP) in very old patients. METHODS: In this prospective study, 362 patients over 80 years of age who had been consequently admitted to the general ward of a teaching hospital were examined. Each patient was assessed, by our pharmacovigilance team within 24 hours of admission, to identify outpatient medication use and potential drug-drug interactions. RESULTS: The overall use of CNS depressants as a group was not associated with a higher risk of admission due to CAP in very old patients (55% vs. 49%; OR=1.28 [0.76-2.16], p=0.34). However, the use of antipsychotics was associated with a higher rate of admissions due to CAP in this population (OR=1.98 [1.10-3.57], p=0.02). No association was seen between opioids (p=0.27), zolpidem (p=0.83), or benzodiazepines (p=0.15) and the rate of admissions due to CAP in these patients. Moreover, pharmacodynamic or pharmacokinetic interactions leading to CNS depression were equally found in patients admitted for CAP and those admitted for other reasons. CONCLUSION: The use of antipsychotics in very old adults was associated with an increased risk of hospital admission due to CAP. This suggests that the use of these medications in this population should be done with caution. No association was observed with opioids, benzodiazepines and zolpidem with the latter outcome.

A Systematic Approach to Assess the Burden of Drug Interactions in Adult Kidney Transplant Patients.

AIM: Renal transplant patients are frequently subject to polypharmacy and drug-drug interactions. However, no previous study has systematically assessed the risk of drug interactions and Adverse Drug Reactions (ADRs) in this population. METHODS: A total of 138 consecutive adult kidney transplant recipients admitted to our hospital between August 2010 and February 2012 were prospectively and systematically assessed by our pharmacovigilance team, within 24 hours of admission, to identify potential drug-drug interactions and probable ADRs. RESULTS: As a consequence of the high number of medications per patient (7.8±0.2 drugs), a considerable number of drugdrug interactions were observed in this population, with an average of 5.6±0.4 drug interactions per patient. Moreover, a significant percentage of admissions (~10%) of kidney transplant patients were related to probable ADRs. Almost all these patients had at least one drug interaction that could have potentially contributed to the probable ADR. Of note, clinically significant (i.e. severe) drug interactions were more frequent among patients with ADRs (29% vs. 15%, p<0.01). Also, patients with ADRs were more likely to have started a medication 30 days before admission (38.5% vs. 10.4%, p < 0.01). Non-immunosuppressive drugs most commonly involved in severe interactions were omeprazole, magnesium sulphate, and statins. The most commonly observed interactions were: tacrolimus and omeprazole, mycophenolate and omeprazole, sirolimus and enalapril, mycophenolate and antivirals, and mycophenolate and magnesium sulphate. CONCLUSION: Drug interactions were extremely frequent among kidney transplant recipients, and responsible for potentially avoidable ADRs. They should be carefully considered when following kidney transplant recipients.