Introduction: Low carbohydrate ketogenic diets have received renewed interest for the treatment of obesity and type 2 diabetes. These diets promote weight loss, improve glycemic control, and reduce insulin resistance. However, whether the improvements in glycemic control and insulin sensitivity are secondary to the weight loss or result from a direct effect of hyperketonemia is controversial. Research design and methods: 29 overweight obese subjects were randomized to one of three dietary interventions for 10 days: (1) Weight-maintaining standard diet; (2) Weight-maintaining ketogenic diet; (3) Weight-maintaining ketogenic diet plus supplementation with the ketone ester of beta-hydroxybutyrate (β-OH-B), 8 g every 8 hours. At baseline, all subjects had oral glucose tolerance test, 2-step euglycemic insulin clamp (20 mU/m².min and 60 mU/m².min) with titrated glucose and indirect calorimetry. Results: Body weight, fat content, and per cent body fat (DEXA) remained constant over the 10-day dietary intervention period in all three groups. Plasma β-OH-B concentration increased twofold, while carbohydrate oxidation decreased, and lipid oxidation increased demonstrating the expected shifts in substrate metabolism with institution of the ketogenic diet. Glucose tolerance either decreased slightly or remained unchanged in the two ketogenic diet groups. Whole body (muscle), liver, and adipose tissue sensitivity to insulin remained unchanged in all 3 groups, as did the plasma lipid profile and blood pressure. Conclusion: In the absence of weight loss, a low carbohydrate ketogenic diet has no beneficial effect on glucose tolerance, insulin sensitivity, or other metabolic parameters.

Cardiogenic shock (CS) remains crucial in mortality rates for heart failure (HF) patients. However, contemporary data on long-term mortality trends related to CS are limited. This study investigates demographic patterns and trends in CS mortality among HF patients over 25 years. Data from the Centers for Disease Control and Prevention’s Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) database (1999–2023) included adults aged ≥25 diagnosed with HF and CS. Age-adjusted mortality rates (AAMRs) per 100,000 population and trends were analyzed using Joinpoint regression to find the average annual percent change (AAPC) and annual percent change (APC). Between 1999 and 2023, there were 108,514 deaths linked to cardiogenic shock among heart failure patients, with AAMRs increasing from 1.2 to 4.6 per 100,000 (AAPC: 5.90). The most significant increases occurred from 2009 to 2021 (APC: 14.17), followed by a sustained rise from 2021 to 2023 (APC: 7.83). Men consistently exhibited higher AAMRs than women (2.4 vs. 1.3), and Black individuals had the highest mortality rates across all racial and ethnic groups. Furthermore, mortality rates were notably higher in rural areas compared to urban settings (1.7 vs. 1.5). In the past 25 years, CS-related mortality in HF patients has increased nearly fourfold. This trend highlights the need to investigate its causes, including potential deteriorating health outcomes or improved healthcare access. Special focus should be on high-risk groups like men, Black individuals, and rural residents, as targeted interventions could mitigate disparities and enhance outcomes.

Stroke associated with atrial fibrillation (AF) is a significant cause of mortality. This study analyzed demographic trends and disparities in mortality rates due to stroke in AF patients aged ≥25 years. A retrospective analysis was conducted to acquire death data using the Centers for Disease Control and Prevention database from 1999 to 2020. Age-adjusted mortality rates (AAMRs) were calculated per 100,000 persons, and trends were assessed using Average Annual Percentage Change (AAPC) and annual percent change (APC). Data were stratified by year, sex, race/ethnicity, and geographical regions. Between 1999 and 2020, AF-associated stroke contributed to 331,106 deaths among adults in this study population. Deaths occurred predominantly in medical facilities (43.2 %). The overall AAMR for AF-associated stroke decreased from 7.4 in 1999 to 6.4 in 2020, with an APC of −1.02 (p-value = 0.004). Additionally, AAMR showed a significant decline from 2015 to 2018 with an APC of −7.22 (p-value <0.000001), followed by a striking rise from 2018 to 2020 (APC: 4.98) (p-value = 0.0008). Women had slightly higher AAMR than men (men: 6.6; women: 7.1) (p value = 0.02). AAMRs varied among racial/ethnic groups, with Whites having the highest AAMR (7.4), followed by Blacks (5.4), American Indian or Alaska Natives (4.6), Asian or Pacific Islanders (4.5), and Hispanics (4.1). AAMRs decreased for all races except Blacks. Geographically, AAMRs ranged from 4.3 in Nevada to 11.9 in Vermont, with the Western region showing the highest mortality (AAMR: 7.9). Nonmetropolitan areas had slightly higher AAMRs than metropolitan areas, with both experiencing a decrease over the study period. This analysis depicts significant demographic and geographic disparities in mortality rates attributed to stroke associated with AF. Targeted interventions and equitable healthcare access are crucial to mitigate these disparities and improve outcomes for this population.

The timely management of asymptomatic severe aortic stenosis (AS) presents an important clinical dilemma. This meta-analysis aims to investigate whether early intervention can lead to improved clinical outcomes compared with conservative management in asymptomatic severe AS. We conducted a literature search of major databases to identify randomized controlled trials that compared an early intervention (either early surgical aortic valve replacement or early transcatheter aortic valve replacement) with conservative management in patients with asymptomatic severe AS. Data for clinical outcomes were extracted, and risk ratios (RRs) were calculated for all end points with corresponding 95% confidence intervals (CIs). The meta-analysis included 4 randomized controlled trials with 1427 patients. Compared with conservative management, early intervention was associated with no significant difference in all-cause [RR, 0.52 (95% CI, 0.23–1.19)] or cardiovascular death [RR, 0.41 (95% CI, 0.10–1.64)]. A statistically significant reduction was observed in the risk of stroke [RR, 0.60 (95% CI, 0.38–0.94)] and unplanned hospitalizations [RR, 0.49 (95% CI, 0.40–0.60)] with an early intervention. The risk of myocardial infarction remained comparable [RR, 0.67 (95% CI, 0.13–3.54)]. Early intervention can be a suitable treatment option for patients with asymptomatic severe AS who prefer proactive management of their condition.