The implementation of urban and rural sanitation programmes in Botswana

The implementation of urban and rural sanitation programmes in Botswan

<b>Clonal Hematopoiesis of Indeterminate Potential (CHIP) and incident type 2 diabetes (T2D) risk</b>

Objective: Clonal hematopoiesis of indeterminate potential (CHIP) is an aging-related accumulation of somatic mutations in hematopoietic stem cells, leading to clonal expansion. CHIP presence has been implicated in atherosclerotic coronary heart disease (CHD) and all-cause mortality, but its association with incident T2D is unknown. We hypothesized that CHIP is associated with elevated risk of T2D.Research Design and Methods: CHIP was derived from whole genome sequencing of blood DNA in NHLBI Trans-omics for Precision Medicine (TOPMed) prospective cohorts. We analyzed 17,637 participants from 6 cohorts, without prior T2D, cardiovascular disease, or cancer. We evaluated baseline CHIP vs. no CHIP prevalence with incident T2D, including associations with DNMT3A, TET2, ASXL1, JAK2, and TP53 variants. We estimated multivariable-adjusted hazard ratios and 95% confidence intervals (HR [CI]) adjusted for age, sex, body mass index, smoking, alcohol, education, self-reported race/ethnicity, and combined cohorts’ estimates via fixed effects meta-analysis.Results: Mean age was 63.4 years (SD=11.5), 76% were female, and CHIP prevalence was 6.0% (n=1,055) at baseline. T2D was diagnosed in n=2,467 over mean follow-up of 9.8 years. Participants with CHIP had a 23% (1.04, 1.45) higher risk of T2D than those with no CHIP. Specifically, TET2 (HR=1.48; 1.05, 2.08) and ASXL1 (HR=1.76; 1.03, 2.99) mutations were at higher T2D risk, and DNMT3A was non-significant (HR=1.15; 0.93, 1.43); statistical power was limited for JAK2 and TP53 analyses.Conclusions: CHIP was associated with higher incidence of T2D. CHIP mutations located on genes implicated in CHD and mortality were also related to T2D, suggesting shared aging-related pathology.</p

Effects of calcium, magnesium, and potassium concentrations on ventricular repolarization in unselected individuals.

Background: Subclinical changes on the electrocardiogram are risk factors for cardiovascular mortality. Recognition and knowledge of electrolyte associations in cardiac electrophysiology are based on only in vitro models and observations in patients with severe medical conditions.Objectives: This study sought to investigate associations between serum electrolyte concentrations and changes in cardiac electrophysiology in the general population.Methods: Summary results collected from 153,014 individuals (54.4% women; mean age 55.1 ± 12.1 years) from 33 studies (of 5 ancestries) were meta-analyzed. Linear regression analyses examining associations between electrolyte concentrations (mmol/l of calcium, potassium, sodium, and magnesium), and electrocardiographic intervals (RR, QT, QRS, JT, and PR intervals) were performed. The study adjusted for potential confounders and also stratified by ancestry, sex, and use of antihypertensive drugs.Results: Lower calcium was associated with longer QT intervals (-11.5 ms; 99.75% confidence interval [CI]: -13.7 to -9.3) and JT duration, with sex-specific effects. In contrast, higher magnesium was associated with longer QT intervals (7.2 ms; 99.75% CI: 1.3 to 13.1) and JT. Lower potassium was associated with longer QT intervals (-2.8 ms; 99.75% CI: -3.5 to -2.0), JT, QRS, and PR durations, but all potassium associations were driven by use of antihypertensive drugs. No physiologically relevant associations were observed for sodium or RR intervals.Conclusions: The study identified physiologically relevant associations between electrolytes and electrocardiographic intervals in a large-scale analysis combining cohorts from different settings. The results provide insights for further cardiac electrophysiology research and could potentially influence clinical practice, especially the association between calcium and QT duration, by which calcium levels at the bottom 2% of the population distribution led to clinically relevant QT prolongation by >5 ms.</p