BackgroundRecent studies reported that sodium glucose cotransporter 2 (SGLT2) inhibitors can potentially reduce the risk of cardiovascular mortality in patients with type 2 diabetes mellitus (T2DM). However, there is little or no information on the therapeutic effects of SGLT2 inhibitors on the progression of atherosclerosis. This dapagliflozin effectiveness on vascular endothelial function and glycemic control (DEFENCE) study was designed to determine the effects of dapagliflozin, a SGLT2 inhibitor, on endothelial function in patients with early-stage T2DM.MethodsDEFENCE is a prospective, randomized, open-label, blinded-endpoint, parallel-group, comparative clinical trial. Between October 2015 and August 2016, 80 T2DM patients treated with 750 mg of metformin (hemoglobin A1c ≥6.0 and <8.0%, n = 80) were enrolled and randomized to receive either 1500 mg/day metformin (the metformin group, n = 40), or 750 mg/day metformin supplemented with 5 mg/day dapagliflozin (the dapagliflozin group, n = 40), for 16 weeks. The primary endpoint was a change in flow-mediated dilation (FMD) from baseline to the end of the 16-week treatment period. The secondary outcomes include changes in indexes of glycemic control, lipid metabolism, and oxidative stress, body composition, and safety evaluation.ResultsAlthough FMD tended to improve only in the dapagliflozin group, ΔFMD was comparable between the two groups. Analysis of patients with HbA1c >7.0% showed significant improvement of FMD in the dapagliflozin group than metformin group (P < 0.05). HbA1c, fasting plasma glucose, plasma glucagon, and body weight significantly decreased in both groups. Interestingly, urine 8-hydroxy-2′-deoxyguanosin, a biomarker of oxidative stress, was significantly lower in the dapagliflozin group than metformin group at 16 weeks (P < 0.001).ConclusionsDapagliflozin add-on therapy to metformin for 16 weeks improved endothelial function, as assessed by FMD, in patients with inadequately controlled early-stage T2DM. Improvement in oxidative stress may contribute to the improvement in FMD. Trial registration University Hospital Medical Information Network Clinical Trial Registry (UMIN000018754)Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-017-0564-0) contains supplementary material, which is available to authorized users.

No abstract

Aims/Introduction Hyperglycemia impairs energy substrate oxidation as a result of glucotoxicity. We examined whether the reduction of plasma glucose using a sodium–glucose cotransporter 2 inhibitor, in inpatient diabetes management, has any effect on: (i) treatment period and basal–bolus dosage of insulin that achieve euglycemia; (ii) fasting/postprandial energy expenditure (EE); and (iii) energy substrate oxidation. Materials and Methods This was a randomized, open‐label, 7‐day prospective study. Participants were type 2 diabetes patients with hyperglycemia, aged >20 years, with glycated hemoglobin >10%, daily mean preprandial blood glucose >11 mmol/L (200 mg/dL) and no previous antidiabetic medication. A total of 18 type 2 diabetes patients were randomized (1:1) to basal–bolus insulin titration algorithm (INS) alone or INS + dapagliflozin 5 mg/day (INS/DAPA). The main outcome measures were total daily insulin dose to achieve euglycemia, as well as EE and respiratory quotient during fasting and postprandial states, measured by indirect calorimetry. Results The rate of euglycemia was higher in the INS/DAPA compared with INS group (100 vs 55.6%, P = 0.04), whereas the total daily dose of insulin was 19% lower and was accompanied by a decreased basal–bolus ratio ( P = 0.02). Fasting and postprandial EE elevation were similar in both groups. The post‐treatment fasting respiratory quotient significantly increased in the INS/DAPA group (0.72 ± 0.05 vs 0.79 ± 0.08, P = 0.04), and the postprandial respiratory quotient elevation was abolished; the opposite trend was observed in the INS group ( P < 0.02). Conclusions INS/DAPA sustained fasting carbohydrate oxidation, postprandial lipid‐derived EE (failed to increase carbohydrate‐derived EE) and reduced basal insulin requirement might be related to further bodyweight loss. Clinical Trial Registry National University Hospital Medical Information Network UMIN000018997

Intermittent empagliflozin supplementation is a useful therapeutic option that empowers dietary self-management, improves glycaemic control and is accompanied by body weight loss and an increase in diabetes treatment-related QoL in patients with inadequately controlled type 2 diabetes.

It is well known the primary aldosteronism (PA) is most common endocrinological hypertension and accounted for 10% among all hypertension population, and it develops cardiovascular disease more frequently than blood pressure matched essential hypertension. Those patients with bilateral hyperaldosteronism, called idiopathic hyperaldosteronism (IHA), or unwilling for surgical treatment are treated by mineralcorticoid receptor antagonists (MRAs). Although it had been unclear how titrate MRAs to prevent atherosclerotic cardiovascular events, a managemental target for those patients was recently reported as plasma renin activity (PRA) ≥ 1.0 ng/ml/hr to prevent cardiovascular events (Hundemer GL, et. al. Lancet Diabetes Endocrinol. 2018 Jan;6(1):51-59). Thus, we investigated 77 cases of adrenal venous sampling performed patients with PA and followed up for 3 years in our hospital since 2007, including 24 males and 53 females, and their mean age was 56.3 ± 12.5 years old. All patients underwent AVS and showed bilateral hyperaldosteronism and treated with MRAs and followed up more than 3 years. We collected blood pressure, serum sodium and potassium concentration, estimated glomerular filtration ratio (eGFR), PRA, plasma aldosterone concentration (PAC), atherosclerotic parameter, such as mean intima media thickness (IMT), brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI). We evaluated the relationship of those patients’ PRA and aldosterone to renin ratio (ARR) with eGFR, IMT, baPWV, and ABI. The change of mean IMT after 3 year-follow up were 0.03 ± 0.11 mm vs. 0.06 ± 0.09 mm for well controlled (PRA ≥ 1.0 ng/ml/hr) and poorly controlled (PRA &lt; 1.0 ng/ml/hr), respectively, and no significant difference between them. In the other hand, the change of mean IMT after 3 year-follow up showed 0.03 ± 0.10 mm vs. 0.08 ± 0.10 mm for well controlled (PRA ≥ 1.0 ng/ml/hr and ARR &lt;20) and poorly controlled (PRA &lt; 1.0 ng/ml/hr or ARR ≥ 20), respectively, and the mean IMT increase was significantly lower in this group. The mean IMT increase showed significantly lower only with PRA ≥ 1.0 ng/ml/hr and ARR &lt;20 rather than PRA ≥ 1.0 ng/ml/hr alone. In our results, both PRA ≥ 1.0 ng/ml/hr and ARR&lt;20 are important to prevent or improve atherosclerosis, rather than only PRA ≥ 1.0 ng/ml/hr and should be titrated MRAs to achieve this target. In conclusion, our result revealed the titration of MRAs is important to prevent atherosclerotic cardiovascular event and not only PRA ≥ 1.0 ng/ml/hr, but both PRA and ARR &lt;20 should be achieved.