Diabetic Dead-in-Bed Syndrome: A Possible Link to a Cardiac Ion Channelopathy

Sudden unexpected nocturnal death among patients with diabetes occurs approximately ten times more commonly than in the general population. Malignant ventricular arrhythmia due to Brugada syndrome has been postulated as a cause, since a glucose-insulin bolus can unmask the Brugada electrocardiographic signature in genetically predisposed individuals. In this report we present a 16-year-old male with insulin-dependent diabetes who died suddenly at night. His diabetes had been well controlled, without significant hypoglycaemia. At autopsy, he had a full stomach and a glucose level of 7 mmol/L in vitreous humor, excluding hypoglycaemia. Genetic analysis of autopsy DNA revealed a missense mutation, c.370A>G (p.Ile124Val), in the GPD1L gene. A parent carried the same mutation and has QT prolongation. Mutations in this gene have been linked to Brugada syndrome and sudden infant death. The patient may have died from a ventricular arrhythmia, secondary to occult Brugada syndrome, triggered by a full stomach and insulin. The data suggest that molecular autopsies are warranted to investigate other cases of the diabetic dead-in-bed syndrome

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Ethnic inequity in diabetes outcomes-inaction in the face of need

Evaluation of a longstanding primary care audit and diabetes care support service (DCSS) programme was reported in a paper published in Lancet Global Health on 15 October 2020. The paper showed 24 years of health outcome inequity among people with type 2 diabetes in South, East and West Auckland.1 Mortality decreased and hospital admissions increased across European, Māori and Pacific ethnic groups over the period. However, Māori and Pacific had consistently higher hospitalisation rates than European patients. After adjusting for sex, age, socio-economic status, smoking, obesity, birth-cohort and period effects, Māori but not Pacific patients had higher all-cause mortality (adjusted incidence rates ratio (IRR): 1.96 [95% confidence interval 1.8–2.14), cardiovascular mortality (1.93 [1.63–2.29]), and cancer mortality (1.64 [1.40–1.93]) compared with European patients. The excess mortality for Māori occurred at a young age affecting people in their most productive years. Most of this excess mortality can be attributed to diabetes and its complications

Does a diabetes annual review make a difference?

Aims To determine whether a diabetes annual review, independently of other care processes, is followed by improved patient clinical measurements. Methods Audits conducted independently of the diabetes annual review were analysed for a time-trend in patient clinical measures. An interaction variable between the review and the year of audit was used to test for a change in gradient before and after a diabetes annual review. Each patient formed their own control. Results The data included 9471 audits on 3397 patients from 92 practices, and diabetes annual reviews from 2003 to mid-2008. Percentages of patients with raised HbA1c, systolic blood pressure and lipids improved from first to last audit. Predicted means after a diabetes annual review for HbA1c decreased by 0.13% (1.0mmol/mol), for HDL cholesterol increased by 0.04mmol/L and for triglyceride decreased by 0.2mmol/L. Predicted systolic and diastolic blood pressure, total cholesterol and urinary albumin:creatinine ratio did not change significantly. Conclusions Metabolic control improved over time but this was largely independently of the diabetes annual review, which appears to add little clinical value to existing New Zealand general practice care processes. Currently, general practitioners are paid to undertake a diabetes annual review and report the measurements collected. We would argue that payment needs to be directed to demonstrating appropriate changes in clinical management or achieving meaningful clinical goals, and that the annual review results should be part of systematic feedback to general practitioners, particularly directed at clinical inertia

Child obesity prevalence across communities in New Zealand: 2010–2016

&copy; 2019 The Authors Objective: To assess community-level differences in four-year-old obesity prevalence in New Zealand (NZ), trends over time, and the extent to which differences can be explained by ethnicity, deprivation and urbanicity. Methods: Obesity measures from the Ministry of Health&rsquo;s B4 School Check were available for 72&ndash;92% of NZ four-year-olds for fiscal years 2010/11&ndash;2015/16. Ethnicity, deprivation and urbanicity data for the 78 communities were obtained by linking to administrative records. Growth models were used to examine variability in obesity levels and trends over time, and the extent to which ethnicity, deprivation and urbanicity contributed to differences between communities. Results: There were large variations in obesity across communities (range 8.4% to 28.8%). A decline in the prevalence of childhood obesity was observed in most (48 of 78) communities from 2010/11 to 2015/16 (average change=0.2%, range=-2.0% to 1.9%). Around 50% of the variance in obesity between territorial authorities could be explained by differences in socioeconomic deprivation and ethnic composition. Conclusions: Child obesity varies between NZ communities, but most territorial authorities have experienced a decrease in obesity over the period 2010/11&ndash;2015/16. Implications for public health: Addressing deprivation and ethnic inequalities in obesity could substantially reduce community-level differences in obesity in NZ

Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes

BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo