Justine Davies

OBJECTIVE Despite the importance of diabetes for global health, the future economic consequences of the disease remain opaque. We forecast the full global costs of diabetes in adults through the year 2030 and predict the economic consequences of diabetes if global targets under the Sustainable Development Goals (SDG) and World Health Organization Global Action Plan for the Prevention and Control of Noncommunicable Diseases 2013–2020 are met. RESEARCH DESIGN AND METHODS We modeled the absolute and gross domestic product (GDP)-relative economic burden of diabetes in individuals aged 20–79 years using epidemiological and demographic data, as well as recent GDP forecasts for 180 countries. We assumed three scenarios: prevalence and mortality 1) increased only with urbanization and population aging (baseline scenario), 2) increased in line with previous trends (past trends scenario), and 3) achieved global targets (target scenario). RESULTS The absolute global economic burden will increase from U.S. $1.3 trillion (95% CI 1.3–1.4) in 2015 to $2.2 trillion (2.2–2.3) in the baseline, $2.5 trillion (2.4–2.6) in the past trends, and $2.1 trillion (2.1–2.2) in the target scenarios by 2030. This translates to an increase in costs as a share of global GDP from 1.8% (1.7–1.9) in 2015 to a maximum of 2.2% (2.1–2.2). CONCLUSIONS The global costs of diabetes and its consequences are large and will substantially increase by 2030. Even if countries meet international targets, the global economic burden will not decrease. Policy makers need to take urgent action to prepare health and social security systems to mitigate the effects of diabetes.

BACKGROUND: Allopurinol has been shown to improve endothelial function in chronic heart failure. This study aimed to establish its mechanism of action and to construct a dose-response curve for the effect of allopurinol. METHODS AND RESULTS: Two randomized, placebo-controlled, double-blind, crossover studies were performed for 1 month on patients with New York Heart Association Class II-III chronic heart failure, comparing 300 mg allopurinol, 600 mg allopurinol, and placebo for the first study and 1000 mg probenecid versus placebo in the second study. Endothelial function was assessed by standard forearm venous occlusion plethysmography. Allopurinol 600 mg/d significantly increased forearm blood flow response to acetylcholine compared with both allopurinol 300 mg/d and placebo (% change in forearm blood flow [mean+/-SEM]: 240.31+/-38.19% versus 152.10+/-18.21% versus 73.96+/-10.29%, P<0.001). For similar levels of urate lowering, the uricosuric agent probenecid had no effect on endothelial function. Sodium nitroprusside response was unchanged by all treatments. Vitamin C and acetylcholine coinfusion data showed that 600 mg/d allopurinol completely abolished the oxidative stress that was sensitive to high-dose vitamin C. CONCLUSIONS: For the first time, we have shown that a steep dose-response relationship exists between allopurinol and its effect on endothelial function. We also showed that the mechanism of improvement in endothelial function with allopurinol lies in its ability to reduce vascular oxidative stress and not in urate reduction. The reduction in vascular oxidative stress was profound because high-dose allopurinol totally abolished the oxidative stress that was sensitive to the high-dose vitamin C that was used in this study.

AIMS: To test whether a single large dose of vitamin D2 can improve endothelial function in patients with Type 2 diabetes mellitus and low serum 25-hydroxyvitamin D levels. METHODS: Double-blind, parallel group, placebo-controlled randomized trial. A single dose of 100,000 IU vitamin D2 or placebo was administered to patients with Type 2 diabetes over the winter, when levels of circulating 25-hydroxyvitamin D were likely to be lowest. Patients were enrolled if their baseline 25-hydroxyvitamin D level was < 50 nmol/l. Endothelial function and blood pressure were measured and fasting blood samples were taken at baseline and 8 weeks after administration of vitamin D. RESULTS: Forty-nine per cent of subjects screened had 25-hydroxyvitamin D levels < 50 nmol/l. Thirty-four subjects completed the study, with a mean age of 64 years and a baseline 25-hydroxyvitamin D level of 38.3 nmol/l. Vitamin D supplementation increased 25-hydroxyvitamin D levels by 15.3 nmol/l relative to placebo and significantly improved flow mediated vasodilatation (FMD) of the brachial artery by 2.3%. The improvement in FMD remained significant after adjusting for changes in blood pressure. Vitamin D supplementation significantly decreased systolic blood pressure by 14 mmHg compared with placebo; this did not correlate with change in FMD. CONCLUSIONS: Vitamin D insufficiency is common in patients with Type 2 diabetes during winter in Scotland. A single large dose of oral vitamin D2 improves endothelial function in patients with Type 2 diabetes and vitamin D insufficiency.