BackgroundType 2 diabetes mellitus (T2DM) greatly increases the risks of cardiovascular disease and heart failure. In particular, left ventricular diastolic dysfunction that develops from the early stages of T2DM is an important factor in the onset and exacerbation of heart failure. The effect of sodium-glucose cotransporter 2 inhibitors on left ventricular diastolic function has not been elucidated. We have performed the first prospective study on the effects of canagliflozin on left ventricular diastolic function in T2DM.MethodsThis study was performed to evaluate the effects of additional treatment with canagliflozin for 3 months on left ventricular diastolic function in patients with T2DM. A total of 38 patients with T2DM were consecutively recruited for this study. Left ventricular diastolic function was assessed by echocardiography. The primary study outcome was a change in the septal E/e′ as a parameter of left ventricular diastolic function.ResultsA total of 37 patients (25 males and 12 females) were included in the analysis. Mean age of participants was 64.2 ± 8.1 years (mean ± SD), mean duration of diabetes was 13.5 ± 8.1 years, and mean HbA1c was 7.9 ± 0.7%. Of the participants, 86.5% had hypertension, 100% had dyslipidemia, and 32.4% had cardiovascular disease. Canagliflozin significantly improved left ventricular diastolic function (septal E/e′ ratio 13.7 ± 3.5–12.1 ± 2.8, p = 0.001). Furthermore, among the various parameters that changed through the administration of canagliflozin, only changes in hemoglobin significantly correlated with changes in the septal E/e′ ratio (p = 0.002). In multiple regression analysis, changes in hemoglobin were also revealed to be an independent predictive factor for changes in the septal E/e′ ratio.ConclusionsThis study showed for the first time that canagliflozin could improve left ventricular diastolic function within 3 months in patients with T2DM. The benefit was especially apparent in patients with substantially improved hemoglobin values.Trial registration UMIN Clinical Trials Registry UMIN000028141Electronic supplementary materialThe online version of this article (10.1186/s12933-018-0717-9) contains supplementary material, which is available to authorized users.

BackgroundIt is presently unclear whether glycemic variability (GV) is associated with baroreflex sensitivity (BRS), which is an early indicator of cardiovascular autonomic neuropathy. The present study is the first to examine the relationships between BRS and GV measured using continuous glucose monitoring (CGM).MethodsThis was a multicenter, prospective, open-label clinical trial. A total of 102 patients with type 2 diabetes were consecutively recruited for this study. GV was assessed by measuring the standard deviation (SD), glucose coefficient of variation (CV), and the mean amplitude of glycemic excursions (MAGE) during CGM. The BRS was analyzed from electrocardiogram and blood pressure recordings using the sequence method on the first day of hospitalization.ResultsA total of 94 patients (mean diabetes duration 9.7 ± 9.6 years, mean HbA1c 61.0 ± 16.8 mmol/mol [7.7 ± 1.5%]) were analyzed. In the univariate analysis, CGM-SD (r = − 0.375, p = 0.000), CGM-CV (r = − 0.386, p = 0.000), and MAGE (r = − 0.395, p = 0.000) were inversely related to BRS. In addition to GV, the level of BRS correlated with the coefficient of variation in the R–R intervals (CVR-R) (r = 0.520, p = 0.000), heart rate (HR) (r = − 0.310, p = 0.002), cardio-ankle vascular index (CAVI) (r = − 0.326, p = 0.001), age (r = − 0.519, p = 0.000), and estimated glomerular filtration rate (eGFR) (r = 0.276, p = 0.007). Multiple regression analysis showed that CGM-CV and MAGE were significantly related to a decrease in BRS. These findings remained after adjusting the BRS for age, sex, hypertension, dyslipidemia, HR, eGFR, CAVI, and CGM-mean glucose. Additionally, BRS was divided according to quartiles of the duration of diabetes (Q1–4). BRS decreased after a 2-year duration of diabetes independently of age and sex.ConclusionsGV was inversely related to BRS independently of blood glucose levels in type 2 diabetic patients. Measurement of BRS may have the potential to predict CV events in consideration of GV.Trial registration UMIN Clinical Trials Registry UMIN000025964, 28/02/2017Electronic supplementary materialThe online version of this article (10.1186/s12933-018-0683-2) contains supplementary material, which is available to authorized users.

Precise monthly achievement rates for reaching guideline targets for HbA 1c , blood pressure (BP), and lipid levels remain unknown. We evaluated achievement rates on a monthly basis in persons with type 2 diabetes mellitus (T2DM) and explored related factors. RESEARCH DESIGN AND METHODS This retrospective study initially analyzed data on 104,601 persons with T2DM throughout Japan. Patients whose HbA 1c , BP, and LDL cholesterol were measured ‡12 times during a 24-month period were included. We evaluated monthly achievement rates. Achieved targets were defined as HbA 1c <7%, BP <130/ 80 mmHg, and LDL cholesterol <100 mg/dL. Achievement of all targets was expressed as the "all ABC achievement." RESULTS A total of 4,678 patients were analyzed. The achievement rates of all ABC, HbA 1c , BP, and LDL cholesterol were lowest in winter, with those for systolic BP (SBP) being particularly low (all ABC, summer 15.6%, winter 9.6%; HbA 1c , 53.1%, 48.9%; SBP, 56.6%, 40.9%; LDL cholesterol, 50.8%, 47.2%). In winter, age ‡65 years (odds ratio 0.47 [95% CI 0.34-0.63]) was independently related to decreased achievement rates for SBP, BMI ‡25 kg/m 2 (BMI 25-30 kg/m 2 , 0.45 [0.29-0.70]; BMI ‡30 kg/m 2 , 0.35 [0.22-0.57]), and diabetes duration ‡10 years (0.53 [0.37-0.76]) were independently related to lower achievement rates for HbA 1c. Insulin use and sulfonylurea use were independently associated with the decreased all ABC achievement rates in both summer and winter. CONCLUSIONS The all ABC achievement rate for guideline targets changed on a monthly basis. Seasonal variations in the all ABC achievement rate should be considered when managing T2DM in ordinary clinical practices.

Type 2 diabetes mellitus (T2DM) substantially increases the risk of cardiovascular events, including heart failure (HF), due to complications such as hypertension, obesity and dyslipidemia based on metabolic syndrome, which plays the central pathological role in HF. A reason is that T2DM causes left ventricular (LV) diastolic dysfunction beginning in the early phase of the disease, which in turn increases the risk of development of HF independently of the control of blood glucose levels, blood pressure or the presence of coronary artery diseases. Intracellular metabolic disorders and increased oxidative stress due to hyperglycemia, increased insulin resistance and chronic inflammation are pathogenic mechanisms involved in the LV diastolic dysfunction caused by T2DM. These mechanisms lead to structural changes in the heart such as LV hypertrophy and interstitial fibrosis, resulting in HF. The prevalence of HF with preserved ejection fraction (HFpEF), the major pathology of LV diastolic dysfunction, has been increasing recently, and a high incidence of HFpEF in patients with T2DM was reported. An effective therapy has not been established for HFpEF because multiple comorbidities such as advanced age, hypertension, obesity, dyslipidemia, chronic kidney disease and atrial fibrillation as well as diabetes are involved in its pathology. In the present review, we review the involvement of associated conditions such as hypertension, obesity and advanced age from the aspect of the T2DM and LV diastolic dysfunction and discuss the possibility of the development of a new therapeutic strategy for LV diastolic dysfunction and HFpEF.

BackgroundThe relationship between long-term glycemic variability (GV) represented by visit-to-visit HbA1c variability and baroreflex sensitivity (BRS) in type 2 diabetes mellitus (T2DM) has not been clarified by previous literature. The present study is the first to examine the relationships between visit-to-visit HbA1c variability and BRS.MethodsThis retrospective study initially analyzed data on 94 patients with T2DM. Visit-to-visit HbA1c variability was evaluated using the intrapersonal coefficient of variation (CV), standard deviation (SD), and adjusted SD of 8 or more serial measurements of HbA1c during a 2-year period. The BRS was analyzed using the sequence method. Short-term GV was assessed by measuring the glucose CV during 24-h continuous glucose monitoring (CGM). The primary objective was to determine if there was a relationship between visit-to-visit HbA1c variability (HbA1c CV) and BRS. Secondary objectives were to examine the relationship between other variables and BRS and the respective and combined effects of long-term GV (HbA1c CV) and short-term GV (CGM CV) on BRS.ResultsA total of 57 patients (mean age 67.2 ± 7.7 years, mean HbA1c 7.3 ± 1.0%) who met this study’s inclusion criteria were finally analyzed. In the univariate analysis, HbA1c CV (r = − 0.354, p = 0.007), HbA1c SD (r = − 0.384, p = 0.003), and adjusted HbA1c SD (r = − 0.391, p = 0.003) were significantly related to low levels of BRS. Multiple regression analysis showed that HbA1c CV, HbA1c SD, and adjusted HbA1c SD were inversely related to BRS. Furthermore, although the increase in either long-term GV (HbA1c CV) or short-term GV (CGM CV) as determined by 24-h CGM was inversely correlated with BRS, additional reductions in BRS were not shown in participants with both HbA1c CV and CGM CV values above the median.ConclusionsVisit-to-visit HbA1c variability was inversely related to BRS independently of the mean HbA1c in patients with T2DM. Therefore, visit-to-visit HbA1c variability might be a marker of reduced BRS in T2DM.

The evaluation of baroreflex sensitivity (BRS), which maintains systemic circulatory homeostasis, is an established tool to assess cardiovascular autonomic neuropathy in type 2 diabetes mellitus (T2DM). As BRS plays an important function in blood pressure regulation, reduced BRS leads to an increase in blood pressure variability, which further leads to reduced BRS. This sequence of events becomes a vicious cycle. The major risk factors for reduced BRS are T2DM and essential hypertension, but many other risk factors have been reported to influence BRS. In recent years, reports have indicated that glycemic variability (GV), such as short-and longterm GV that are considered important risk factors for macrovascular and microvascular complications, is involved in reductions in BRS independently of blood glucose levels. In this review, we discuss reduced BRS in T2DM, its features, and the potential for its reversal.(Int Heart J 2019; 60: 241-246)

Compared with glargine U100 treatment, glargine U300 treatment improved the MODD as assessed by CGM in type 2 diabetes patients. These findings suggest that the durability of basal insulin may be associated with day-to-day glycemic variability in type 2 diabetes patients.

Sodium–glucose cotransporter 2 (SGLT2) inhibitors are oral antidiabetic drugs that promote urinary glucose excretion. Conversely, they cause behavioural changes, such as hyperphagia, that result in a positive energy balance. The relationship between energy homeostasis and SGLT2 inhibitors-induced behavioural changes remains unclear. Here we show that ipragliflozin, a SGLT2 inhibitor, time-dependently affects behaviour and enhances energy expenditure in normal and type 2 diabetic Goto–Kakizaki (GK) rats, using continuous glucose telemetry. Alongside increased urinary glucose excretion, ipragliflozin increased total food and water intakes in normal and GK rats. In normal rats, ipragliflozin treatment acutely disturbed the circadian rhythms of food and water intakes, activity, and body temperature. Subsequently, these rhythms gradually returned towards a normal state. However, activity and body temperature remained suppressed. In GK rats, ipragliflozin did not affect circadian rhythms. Blood glucose values assessed by glucose telemetry were significantly reduced in both ipragliflozin-treated groups. Despite these behavioural and glycaemic changes, ipragliflozin significantly increased oxygen consumption during dark and light periods in both groups. Ipragliflozin reduced body weight in normal rats only. Thus, ipragliflozin decreases blood glucose beyond compensatory hyperphagia in normal and GK rats, resulting in enhanced basal energy expenditure, despite acutely altering circadian rhythms in normoglycaemic individuals.