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BackgroundThe sodium–glucose cotransporter 2 inhibitor, dapagliflozin, has been shown to improve diabetic control and reduce blood pressure in patients with type 2 diabetes mellitus. Its effects on micro- and macrovascular structure and function have not yet been reported.MethodsThis was a prospective, single-centre, placebo-controlled, double-blind, randomised crossover phase IIIb study conducted between March 2014 and February 2015. After a 4-week run-in/washout phase, patients (N = 59) received 6 weeks of either dapagliflozin 10 mg or placebo once daily. They then underwent a 1-week washout before crossing over to the other treatment. Changes in retinal capillary flow (RCF) and arteriole remodelling were evaluated using scanning laser Doppler flowmetry, while micro- and macrovascular parameters in the systemic circulation were assessed using pulse wave analysis.ResultsSix weeks of dapagliflozin treatment resulted in improvements in diabetes control, including blood glucose and insulin resistance, and reduced office and 24-h ambulatory blood pressure values. RCF decreased from 324 AU at baseline to 308 AU after treatment with dapagliflozin (p = 0.028), while there was little difference after the placebo (318 AU; p = 0.334). Furthermore, the arteriole remodelling that was seen after the placebo phase was not evident after the dapagliflozin phase. Central systolic and diastolic blood pressure values were significantly lower after 6 weeks of dapagliflozin, by 3.0 and 2.2 mmHg, respectively (p = 0.035 and 0.020, respectively vs. baseline).ConclusionsSix weeks of dapagliflozin treatment resulted in numerous beneficial effects. In addition to achieving superior diabetes control and blood pressure, parameters associated with the early stages of vascular remodelling were also improved. Trial registration http://www.clinicaltrials.gov (NCT02383238)

PurposeIn diabetes mellitus type 2, capillary rarefaction plays a pivotal role in the pathogenesis of end-organ damage. We investigated retinal capillary density in patients with early disease.MethodsThis cross-sectional study compares retinal capillary rarefaction determined by intercapillary distance (ICD) and capillary area (CapA), measured non-invasively and in vivo by scanning laser Doppler flowmetry, in 73 patients with type 2 diabetes, 55 healthy controls and 134 individuals with hypertension stage 1 or 2.ResultsIn diabetic patients, ICD was greater (23.2±5.5 vs 20.2±4.2, p = 0.013) and CapA smaller (1592±595 vs 1821±652, p = 0.019) than in healthy controls after adjustment for differences in cardiovascular risk factors between the groups. Compared to hypertensive patients, diabetic individuals showed no difference in ICD (23.1±5.8, p = 0.781) and CapA (1556±649, p = 0.768).ConclusionIn the early stage of diabetes type 2, patients showed capillary rarefaction compared to healthy individuals.

2Decreased capillary density influences vascular resistance and perfusion. The authors aimed to investigate the influence of the renin-angiotensin receptor blocker valsartan on retinal capillary rarefaction in hypertensive patients. Retinal vascular parameters were measured noninvasively and in vivo by scanning laser Doppler flowmetry before and after 4 weeks of treatment with valsartan in 95 patients with hypertension stage 1 or 2 and compared with 55 healthy individuals. Retinal capillary rarefaction was determined with the parameters intercapillary distance (ICD) and capillary area (CapA). In hypertensive patients, ICD decreased (23.4AE5.5 lm vs 21.5AE5.6 lm, P<.001) and CapA increased (1564AE621 vs 1776AE795, P=.001) after valsartan treatment compared with baseline. Compared with healthy normotensive controls (ICD 20.2AE4.2 lm, CapA 1821AE652), untreated hypertensive patients showed greater ICD (P<.001) and smaller CapA (P=.019), whereas treated hypertensive patients showed no difference in ICD (P=.126) and CapA (P=.728). Therapy with valsartan for 4 weeks diminished capillary rarefaction in hypertensive patients.

The protective cardiovascular (CV) effect of cocoa flavanol has been a target of many recent clinical prospective and retrospective investigations. Epidemiological data in different patient cohorts revealed an association between higher intake of flavanol-rich foods and decreased incidence of CV events, especially stroke and myocardial infarction. Cocoa flavanol has been shown to reduce systolic (2.8 mm Hg) and diastolic (2.2 mm Hg) office blood pressure (BP). Greater BP reduction has been found in hypertensive patients and people younger than 50 years. Cocoa flavanol intake exerts beneficial effects on pathophysiologic mechanisms of hypertension-related organ damage, such as improved endothelial function, anti-inflammatory potency, inhibition of platelet activation, and increased vasodilatory capacity. Recent clinical trials have focused on establishing a potential link between epidemiology and pathophysiology of flavanol and identified possible mechanisms for prevention of end-organ damage in patients at CV risk. This review summarizes the available data on the antihypertensive effects of cocoa flavanol beyond BP lowering effects, accentuates subgroup-specific protective actions of cocoa according to patients' different CV risk profile, and outlines potential cocoa flavanol-associated clinical implications.