The use of the sleep‐promoting hormone melatonin is rapidly increasing as an assumed safe sleep aid. During the last decade, accumulating observations suggest that melatonin affects glucose homeostasis, but the precise role remains to be defined. We investigated the metabolic effects of long‐term melatonin treatment in patients with type 2 diabetes including determinations of insulin sensitivity and glucose‐stimulated insulin secretion. We used a double‐blinded, randomized, placebo‐controlled, crossover design. Seventeen male participants with type 2 diabetes completed (1) 3 months of daily melatonin treatment (10 mg) 1 h before bedtime (M) and (2) 3 months of placebo treatment 1 h before bedtime (P). At the end of each treatment period, insulin secretion was assessed by an intravenous glucose tolerance test (0.3 g/kg) (IVGTT) and insulin sensitivity was assessed by a hyperinsulinemic‐euglycemic clamp (insulin infusion rate 1.5 mU/kg/min) (primary endpoints). Insulin sensitivity decreased after melatonin (3.6 [2.9–4.4] vs. 4.1 [3.2–5.2] mg/(kg × min), p = .016). During the IVGTT, the second‐phase insulin response was increased after melatonin (p = .03). In conclusion, melatonin treatment of male patients with type 2 diabetes for 3 months decreased insulin sensitivity by 12%. Clinical use of melatonin treatment in dosages of 10 mg should be reserved for conditions where the benefits will outweigh the potential negative impact on insulin sensitivity.

BackgroundCongenital heart disease (CHD) is associated with risk factors for ischemic stroke including cardiac arrhythmias and heart failure. However, few long‐term follow‐up data exist on ischemic stroke risk and associated mortality in adults with CHD.Methods and ResultsUsing Danish nationwide registries, we identified individuals aged ≥18 years diagnosed with CHD, at any age, from 1963 to 2017 and a sex and birth year‐matched (1:10) general population comparison cohort. We computed risks, as well as sex and birth year‐adjusted hazard ratios (aHRs) for ischemic stroke and 30‐day post‐stroke mortality in CHD adults compared with the general population. Analyses were stratified according to age <60 years (young) and ≥60 years (older). We identified 16 836 adults with CHD. The risk of ischemic stroke at age 60 years was 7.4% in the CHD cohort and 2.9% in the general population cohort. The adjusted hazard ratios for ischemic stroke compared with the general population was 3.8 (95% CI: 3.3–4.3) in young CHD adults and 1.6 (95% CI: 1.4–1.9) in older CHD adults. The adjusted hazard ratios for post‐stroke mortality compared with the general population was 2.3 (95% CI: 1.2–4.4) in young CHD adults and 1.3 (95% CI: 0.9–1.9) in older CHD adults.ConclusionsBoth younger and older CHD adults have an increased risk of ischemic stroke and by 60 years of age 7.4% of CHD adults will have had an ischemic stroke. Post‐stroke mortality was also increased in CHD adults compared with the general population.

Background & aims: The connection between peripheral insulin resistance (IR) and coronary artery disease is well-established. Both are major risk factors for the development of ischemic cardiomyopathy potentially leading to heart failure (HF). Whether cardiac IR also impacts overall survival and morbidity is still debated. We therefore aimed to test if cardiac IR predicts mortality and major cardiovascular events (MACE) in patients with HF scheduled for cardiac viability testing before revascularization. Methods: This retrospective study included 131 patients with a clinical diagnosis of ischemic HF (114 (87%) male, 33 (25%) with diabetes) referred to a viability Rubidium-82 (perfusion) and dynamic 18 F-Fluorodeoxyglucose (metabolism) positron emission tomography combined with computed tomography prior to a potential revascularization procedure. Cardiac IR was assessed by myocardial glucose uptake (MGU) in a remote (non-scarred) area of the left ventricle during a hyperinsulinemic-euglycemic clamp (1mIE/kg/min). Results: MGU correlated with skeletal muscle glucose uptake (p < 0.001) and whole-body glucose uptake (M-value) (p < 0.001), whereas no association was observed for individuals with diabetes. MGU did not predict the risk of death or MACE. However, both overt diabetes and reduced coronary flow reserve predicted overall survival. Conclusion: Even though diabetes and related small-vessel disease is associated with increased mortality, cardiac IR per se does not predict cardiovascular morbidity and mortality.