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Background: Results from the COORDINATE-Diabetes trial (Coordinating Cardiology Clinics Randomized Trial of Interventions to Improve Outcomes - Diabetes) demonstrated that a multifaceted, clinic-based intervention increased prescription of evidence-based medical therapies to participants with type 2 diabetes and atherosclerotic cardiovascular disease. This secondary analysis assessed whether intervention success was consistent across sex, race, and ethnicity., Methods: COORDINATE-Diabetes, a cluster randomized trial, recruited participants from 43 US cardiology clinics (20 randomized to intervention and 23 randomized to usual care). The primary outcome was the proportion of participants prescribed all 3 groups of evidence-based therapy (high-intensity statin, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, and sodium-glucose cotransporter-2 inhibitor or glucagon-like peptide 1 receptor agonist) at last trial assessment (6 to 12 months). In this prespecified analysis, mixed-effects logistic regression models were used to assess the outcome by self-reported sex, race, and ethnicity in the intervention and usual care groups, with adjustment for baseline characteristics, medications, comorbidities, and site location., Results: Among 1045 participants with type 2 diabetes and atherosclerotic cardiovascular disease, the median age was 70 years, 32% were female, 16% were Black, and 9% were Hispanic. At the last trial assessment, there was an absolute increase in the proportion of participants prescribed all 3 groups of evidence-based therapy in women (36% versus 15%), Black participants (41% versus 18%), and Hispanic participants (46% versus 18%) with the intervention compared with usual care, with consistent benefit across sex (male versus female; P interaction =0.44), race (Black versus White; P interaction =0.59), and ethnicity (Hispanic versus Non-Hispanic; P interaction = 0.78)., Conclusions: The COORDINATE-Diabetes intervention successfully improved delivery of evidence-based care, regardless of sex, race, or ethnicity. Widespread dissemination of this intervention could improve equitable health care quality, particularly among women and minority communities who are frequently underrepresented in clinical trials., Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03936660., Competing Interests: Dr Tannu has received funding from the National Institutes of Health (T32HL069749). Dr Pagidipati reported receiving personal fees from Boehringer Ingelheim, Lilly, AstraZeneca, Novartis, Novo Nordisk, Merck, and CRISPR Therapeutics and receiving grants from Amgen, Novartis, Novo Nordisk, and Eggland’s Best. Dr Nelson reported receiving personal fees from Boehringer Ingelheim, AstraZeneca, Amgen, Novartis, and Sanofi. Dr McGuire reported receiving personal fees from Duke Clinical Research Institute, AstraZeneca, Novo Nordisk, Esperion Therapeutics, Lilly, CSL Behring, Afimmune, Boehringer Ingelheim, Merck, Pfizer, Bayer, Lexicon Pharmaceuticals, Altimmune, Intercept Pharmaceuticals, and Applied Therapeutics. Dr Pop-Busui reported receiving personal fees from Boehringer Ingelheim, Roche, Procter & Gamble, and Lexicon Pharmaceuticals; receiving grants from JDRF (formerly the Juvenile Diabetes Research Foundation), Novo Nordisk, and Medtronic; and being on the board of directors and president of medicine and science for the American Diabetes Association. Dr Cavender reported receiving personal fees from Duke Clinical Research Institute, Novo Nordisk, Bayer, Medtronic, Boehringer Ingleheim, Zoll, Merck, Amgen, and Edwards Lifesciences and receiving grants from AstraZeneca, Novartis, Amgen, CSL Behring, and Boehringer-Ingelheim. Dr Aroda reported receiving personal fees from Duke Clinical Research Institute, Applied Therapeutics, Pfizer, Fractyl Health, Lilly, Novo Nordisk, and Sanofi and that her spouse is an employee of Janssen Pharmaceuticals and receives salary and employee benefits. Dr Richardson reported receiving grants from Blue Cross Blue Shield of Michigan and the Nielsen Foundation and receiving personal fees from the Annals of Family Medicine for serving as a diabetes editor. Dr Lingvay reported receiving grants from Novo Nordisk, Boehringer Ingelheim, Sanofi, Structure Therapeutics, Merck, Pfizer, and Mylan and receiving personal fees from Novo Nordisk, Boehringer Ingelheim, Lilly, Sanofi, Zealand Pharma, Target RWE, Shionogi & Co, Pfizer, Johnson & Johnson, Carmot Therapeutics, Altimmune, Merck, Valeritas, Intercept Pharmaceuticals, and Bayer. Dr Al-Khalidi reported receiving personal fees from Medpace Holdings Inc and CSL Behring. T. Gaynor reported being an employee of Boehringer Ingelheim Pharmaceuticals, Inc. Dr Pak reported being an employee of Eli Lilly and Co. Dr Lopes reported receiving personal fees from Bayer, Boehringer Ingleheim, Bristol Myers Squibb, Daiichi Sankyo, GSK (formerly GlaxoSmithKline), Medtronic, Merck, Pfizer, Portola Pharmaceuticals, and Sanofi and receiving grants from Bristol Myers Squibb, GSK, Medtronic, Pfizer, and Sanofi. Dr Green reported receiving personal fees from Boehringer Ingelheim, Lilly, Bayer, Novo Nordisk, Pfizer, AstraZeneca, Sanofi, Hawthorne Effect, Omada Health, Vertex Pharmaceuticals, Valo Therapeutics, and Anji Pharmaceuticals and receiving grants from Merck, Roche, Sanofi, and Lexicon Pharmaceuticals. Dr Granger reported receiving personal fees from AbbVie, Abiomed, Alnylam Pharmaceuticals, Anthos Therapeutics, Bayer, Boston Scientific, Bristol Myers Squibb, Cardionomic, CeleCor Therapeutics, Cadrenal Therapeutics, Janssen Pharmaceuticals, Medscape, Medtronic, Merck, Novo Nordisk, Novartis, PLx Pharma, Pfizer, Philips, Reata Pharmaceuticals, and NephroSynergy; receiving grants from Bristol Myers Squibb, Janssen Pharmaceuticals, Novartis, Pfizer, and Philips; and having equity in Tenac.io. The other authors reported no conflicts. This research was made possible in part by a collaborative grant with Boehringer Ingelheim Pharmaceuticals, Inc and Lilly USA, LLC, which provided financial support for the study. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors and were fully responsible for all aspects of the trial and publication development.

Objectives: To evaluate the impact of intubation timing, guided by severity criteria, on mortality in critically ill COVID-19 patients, amidst existing uncertainties regarding optimal intubation practices., Design: Prospective, multicenter, observational study conducted from February 1, 2020, to November 1, 2022., Setting: Ten academic institutions in the United States and Europe., Patients: Adults (≥ 18 yr old) confirmed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and hospitalized specifically for COVID-19, requiring intubation postadmission. Exclusion criteria included patients hospitalized for non-COVID-19 reasons despite a positive SARS-CoV-2 test., Interventions: Early invasive mechanical ventilation (EIMV) was defined as intubation in patients with less severe organ dysfunction (Sequential Organ Failure Assessment [SOFA] < 7 or Pa o2 /F io2 ratio > 250), whereas late invasive mechanical ventilation (LIMV) was defined as intubation in patients with SOFA greater than or equal to 7 and Pa o2 /F io2 ratio less than or equal to 250., Measurements and Main Results: The primary outcome was mortality within 30 days of hospital admission. Among 4464 patients, 854 (19.1%) required mechanical ventilation (mean age 60 yr, 61.7% male, 19.3% Black). Of those, 621 (72.7%) were categorized in the EIMV group and 233 (27.3%) in the LIMV group. Death within 30 days after admission occurred in 278 patients (42.2%) in the EIMV and 88 patients (46.6%) in the LIMV group ( p = 0.28). An inverse probability-of-treatment weighting analysis revealed a statistically significant association with mortality, with patients in the EIMV group being 32% less likely to die either within 30 days of admission (adjusted hazard ratio [HR] 0.68; 95% CI, 0.52-0.90; p = 0.008) or within 30 days after intubation irrespective of its timing from admission (adjusted HR 0.70; 95% CI, 0.51-0.90; p = 0.006)., Conclusions: In severe COVID-19 cases, an early intubation strategy, guided by specific severity criteria, is associated with a reduced risk of death. These findings underscore the importance of timely intervention based on objective severity assessments., Competing Interests: Dr. Hayek is funded by the National Heart, Lung, and Blood Institute 1R01HL153384-01, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 1R01DK12801201A1, U01-DK119083-03S1, and the Frankel Cardiovascular Center COVID-19: Impact Research Ignitor (U-M G024231) award. Dr. Pop-Busui is supported by the National Institutes of Health (NIH)/NIDDK-1-R01-DK-107956-01, NIH U01 DK119083, the Juvenile Diabetes Research Foundation 5-COE-2019-861-S-B, and by a Pilot and Feasibility Grant from the Michigan Diabetes Research Center (NIH Grant P30-DK020572). Dr. Huang disclosed work for hire. Dr. Giamarellos-Bourboulis’ institution received funding from Abbott Products Operations AG, BioMerieux, and MSD; they received funding from Abbott CH, BioMérieux, Brahms GmbH, GSK, InflaRx GmbH, Sobi, XBiotech, AbbVie, Johnson & Johnson, MSD, Novartis, UCB, and from the Horizon2020 Marie-Curie Project European Sepsis Academy, the Horizon 2020 European Grants ImmunoSep and RISKinCOVID, and from the Horizon Europe project EPIC-CROWN-2. Drs. Reiser and Banerjee received support for article research from the NIH. Dr. Reiser disclosed they are a co-founder and co-chair of the Scientific Advisory Board of Walden Biosciences; they received support for article research from Rush University Medical Center. Dr. Banerjee’s institution received funding from the NIDDK; they received funding from Novo Nordisk, Roche, and Lexicon Pharmaceuticals. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: Preexisting cardiovascular disease (CVD) is perceived as a risk factor for poor outcomes in patients with COVID-19. We sought to determine whether CVD is associated with in-hospital death and cardiovascular events in critically ill patients with COVID-19., Methods: This study used data from a multicenter cohort of adults with laboratory-confirmed COVID-19 admitted to intensive care units at 68 centers across the United States from March 1 to July 1, 2020. The primary exposure was CVD, defined as preexisting coronary artery disease, congestive heart failure, or atrial fibrillation/flutter. Myocardial injury on intensive care unit admission defined as a troponin I or T level above the 99th percentile upper reference limit of normal was a secondary exposure. The primary outcome was 28-day in-hospital mortality. Secondary outcomes included cardiovascular events (cardiac arrest, new-onset arrhythmias, new-onset heart failure, myocarditis, pericarditis, or stroke) within 14 days., Results: Among 5133 patients (3231 male [62.9%]; mean age 61 years [SD, 15]), 1174 (22.9%) had preexisting CVD. A total of 1178 (34.6%) died, and 920 (17.9%) had a cardiovascular event. After adjusting for age, sex, race, body mass index, history of smoking, and comorbidities, preexisting CVD was associated with a 1.15 (95% CI, 0.98-1.34) higher odds of death. No independent association was observed between preexisting CVD and cardiovascular events. Myocardial injury on intensive care unit admission was associated with higher odds of death (adjusted odds ratio, 1.93 [95% CI, 1.61-2.31]) and cardiovascular events (adjusted odds ratio, 1.82 [95% CI, 1.47-2.24]), regardless of the presence of CVD., Conclusions: CVD risk factors, rather than CVD itself, were the major contributors to outcomes in critically ill patients with COVID-19. The occurrence of myocardial injury, regardless of CVD, and its association with outcomes suggests it is likely due to multiorgan injury related to acute inflammation rather than exacerbation of preexisting CVD., Registration: NCT04343898; https://clinicaltrials.gov/ct2/show/NCT04343898.

Multiple sodium glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have been shown to impart significant cardiovascular and kidney benefits, but are underused in clinical practice. Both SGLT-2i and GLP-1RA were first studied as glucose-lowering drugs, which may have impeded uptake by cardiologists in the wake of proven cardiovascular efficacy. Their significant effect on cardiovascular and kidney outcomes, which are largely independent of glucose-lowering effects, must drive a broader use of these drugs. Cardiologists are 3 times more likely than endocrinologists to see patients with both type 2 diabetes and cardiovascular disease, thus they are ideally positioned to share responsibility for SGLT-2i and GLP-1RA treatment with primary care providers. In order to increase adoption, SGLT-2i and GLP-1RA must be reframed as primarily cardiovascular and kidney disease risk-reducing agents with a side effect of glucose-lowering. Coordinated and multifaceted interventions engaging clinicians, patients, payers, professional societies, and health systems must be implemented to incentivize the adoption of these medications as part of routine cardiovascular and kidney care. Greater use of SGLT-2i and GLP-1RA will improve outcomes for patients with type 2 diabetes at high risk for cardiovascular and kidney disease.

Purpose: To investigate the relationship between central corneal thickness (CCT) and diabetes disease severity among patients with diabetic peripheral neuropathy (DPN) compared with controls., Methods: In this cross-sectional study, 34 participants were examined. DPN status was assessed by clinical examination, nerve conduction studies, and quantitative sensory testing. All participants underwent comprehensive eye examination that included intraocular pressure measured by Goldmann applanation tonometry. CCT was measured by ultrasound pachymetry, and the thickness of corneal layers was assessed by corneal confocal microscopy. Association of CCT and DPN was examined using ANOVA., Results: Among the 34 participants, there were 9 controls, 16 patients with mild DPN, and 9 patients with severe DPN. CCT was significantly increased in the DPN groups compared with controls (P = 0.0003). Mean CCT among controls was 552.7 ± 29.2 μm compared with 583.4 ± 25.0 μm in the mild DPN group and 613.3 ± 28.8 μm in the severe DPN group. In addition, stromal thickness differed significantly between the 3 study groups (P = 0.045). Mean stromal thickness among controls was 439.5 ± 23.5 μm compared with 478.9 ± 37.5 μm in the mild DPN group and 494.5 ± 39.1 μm in the severe DPN group., Conclusions: This study demonstrates that CCT increases with DPN severity because of an increase in stromal thickness. CCT increase associated with DPN has important clinical implications including glaucoma progression, keratoconus susceptibility, and intraocular pressure assessment and should be accounted for when evaluating patients with diabetes.

Background: Rosiglitazone improves glycemic control for patients with type 2 diabetes mellitus, but there remains controversy regarding an observed association with cardiovascular hazard. The cardiovascular effects of rosiglitazone for patients with coronary artery disease remain unknown., Methods and Results: To examine any association between rosiglitazone use and cardiovascular events among patients with diabetes mellitus and coronary artery disease, we analyzed events among 2368 patients with type 2 diabetes mellitus and coronary artery disease in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. Total mortality, composite death, myocardial infarction, and stroke, and the individual incidence of death, myocardial infarction, stroke, congestive heart failure, and fractures, were compared during 4.5 years of follow-up among patients treated with rosiglitazone versus patients not receiving a thiazolidinedione by use of Cox proportional hazards and Kaplan-Meier analyses that included propensity matching. After multivariable adjustment, among patients treated with rosiglitazone, mortality was similar (hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.58-1.18), whereas there was a lower incidence of composite death, myocardial infarction, and stroke (HR, 0.72; 95% CI, 0.55-0.93) and stroke (HR, 0.36; 95% CI, 0.16-0.86) and a higher incidence of fractures (HR, 1.62; 95% CI, 1.05-2.51); the incidence of myocardial infarction (HR, 0.77; 95% CI, 0.54-1.10) and congestive heart failure (HR, 1.22; 95% CI, 0.84-1.82) did not differ significantly. Among propensity-matched patients, rates of major ischemic cardiovascular events and congestive heart failure were not significantly different., Conclusions: Among patients with type 2 diabetes mellitus and coronary artery disease in the BARI 2D trial, neither on-treatment nor propensity-matched analysis supported an association of rosiglitazone treatment with an increase in major ischemic cardiovascular events., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00006305.

Background: The Epidemiology of Diabetes Interventions and Complications (EDIC) study, a prospective observational follow-up of the Diabetes Control and Complications Trial (DCCT) cohort, reported persistent benefit of prior intensive therapy on retinopathy and nephropathy in type 1 diabetes mellitus. We evaluated the effects of prior intensive insulin therapy on the prevalence and incidence of cardiac autonomic neuropathy (CAN) in former DCCT intensive and conventional therapy subjects 13 to 14 years after DCCT closeout., Methods and Results: DCCT autonomic measures (R-R variation with paced breathing, Valsalva ratio, postural blood pressure changes, and autonomic symptoms) were repeated in 1226 EDIC subjects in EDIC year 13/14. Logistic regression models were used to calculate the odds of incident CAN by DCCT treatment group after adjustment for DCCT baseline covariates, duration in the DCCT, and quantitative autonomic measures at DCCT closeout. In EDIC year 13/14, the prevalence of CAN using the DCCT composite definition was significantly lower in the former intensive group versus the former conventional group (28.9% versus 35.2%; P=0.018). Adjusted R-R variation was significantly greater in the former DCCT intensive versus the former conventional group (29.9 versus 25.9; P<0.001). Prior DCCT intensive therapy reduced the risks of incident CAN by 31% (odds ratio, 0.69; 95% confidence interval, 0.51 to 0.93) and of incident abnormal R-R variation by 30% (odds ratio, 0.70; 95% confidence interval, 0.51 to 0.96) in EDIC year 13/14., Conclusions: Although CAN prevalence increased in both groups, the incidence was significantly lower in the former intensive group compared with the former conventional group. The benefits of former intensive therapy extend to measures of CAN up to 14 years after DCCT closeout.