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Aims Information on the clinical efficacy of SGLT2 inhibitors in the Japanese population is limited. The aim of this single-arm, single-center, open-label study was to confirm the body weight- and fat mass-lowering effects of canagliflozin (CANA) and the accompanying improvement in insulin resistance in Japanese patients with Type 2 diabetes mellitus (T2DM). Methods Thirty-eight patients were enrolled and administered 100 mg CANA once daily for 24 weeks. Blood and anthropometric parameters were examined before and after treatment. In a subset of patients, insulin sensitivity was assessed based on the glucose infusion rate (GIR) during a hyperinsulinemic euglycemic clamp test. Results CANA treatment significantly decreased hemoglobin A1c, fasting plasma glucose, and plasma liver enzyme levels, and increased plasma adiponectin levels. In addition, a significant reduction in body weight, visceral and subcutaneous fat area, fat and lean mass, and liver steatosis was also observed. The change in plasma adiponectin levels significantly correlated with the changes in both body fat mass and visceral fat area. GIR increased from 3.25 ± 1.53 to 4.11 ± 1.30 mg/kg/min (P Conclusions CANA improved insulin resistance and decreased visceral fat mass in Japanese patients with T2DM.

Aim This study aims to examine the humanistic and economic burden of cardiovascular disease (CVD)-related comorbidities and hypoglycaemia among respondents with type 2 diabetes (T2D) in Japan. Methods This study used the Japan National Health and Wellness Survey 2016 database. Respondents who self-reported a physician-diagnosed T2D were included. Respondents with or without the condition of interest (CVD-related comorbidities or hypoglycaemia) were compared via generalized linear models in terms of the outcome variables: (1) health-related quality of life (HRQoL), (2) work productivity and activity impairment, (3) healthcare resource utilization and (4) economic costs. Results A total of 1478 survey respondents reported a diagnosis of T2D (mean age 63.6 ± 10.6 years, mean HbA1c 6.91 ± 1.1%). Of whom, 804 subjects (54.4%) had at least one CVD related comorbidities, and 369 subjects (29.3%) reported experiences of hypoglycaemia episodes. Patients with CVD-related comorbidities or hypoglycaemia episodes had worse HRQoL, more work and activity impairment, increased health care visits, and higher costs. Conclusions CVD related comorbidities and hypoglycaemia remains a significant humanistic and economic burden in patients with T2D. The findings suggested that appropriate T2D management with proper medication choice are important to control CVD related comorbidities and hypoglycaemia among T2D patients to alleviate the burden.

This study aimed to clarify the differences in how sodium glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP1Ra) influence kidney function in Japanese patients with type 2 diabetes mellitus (T2DM).We retrospectively built two databases of patients with T2DM who visited the clinics of members of Kanagawa Physicians Association. We defined the renal composite outcome as either progression of albuminuria status and/or 15% deterioration in estimated glomerular filtration rate (eGFR) per year. We used propensity score matching to compare patient outcomes after SGLT2i and GLP1Ra treatments.The incidence of renal composite outcomes was significantly lower in SGLT2i-treated patients than in GLP1Ra-treated patients (n = 15[11%] and n = 27[20%], respectively, P = 0.001). Annual eGFR changes (mL/min/1.73 mRenal composite outcome incidence was lower in SGLT2i-treated patients than in GLP1Ra-treated patients.

Aims: This study investigated the hypoglycemia risk in people with type 2 diabetes (T2D) who initiated or switched to insulin glargine 300 U/mL (Gla-300) by stratifying them by age and renal function. Methods: We examined data from 4621 people with T2D (1227 insulin-naïve and 3394 insulin-experienced) of the X-STAR study, a prospective, observational, 12-month study conducted from December 2015 to August 2018 in Japan. Participants were stratified by age (

To determine the status of diabetes care by general practitioners and diabetes specialists in Japan, we conducted a nation-wide cross-sectional survey. We asked 8112 clinics and hospitals randomly, from throughout Japan, to participate in this study and 721 facilities agreed. A total of 15,652 patients aged from 15 to 97 with type 1 and type 2 diabetes were enrolled. Of these, 14,560 (93.0%) and 1092 (7.0%) patients were cared for by general practitioners and diabetes specialists, respectively. HbA1c levels were measured by a latex agglutination method, and age, height, body weight, type of diabetes and treatment modality were obtained from each patient. Mean HbA1c level for all patients treated by general practitioners was significantly lower than for those treated by the diabetes specialists (6.8±1.2% vs. 7.0±1.2%, p =0.0002). Mean HbA1c level for patients without insulin therapy was lower than for those treated with insulin, irrespective of caring physician. The proportion of patients treated with insulin therapy by diabetes specialists was higher (17.7%) than that by general practitioners (6.5%). This study showed that average HbA1c levels in Japanese patients treated by either general practitioners or specialists was acceptable, regardless of study limitations or bias.

We found a slight elevation of serum creatinine in the subjects treated with sitagliptin for 2 years and a correlation between creatinine elevation and HbA1c reduction. These results suggest that creatinine elevation is associated with activation of incretin, most possibly with up-regulation of diuretic activity of GLP-1.

We investigated a possible association between serum plasminogen activator inhibitor-1 (PAI-1) levels and renal dysfunction in 124 type 2 diabetes patients. Multiple linear regression analyses indicated that the PAI-1 levels were significantly inversely correlated with estimated glomerular filtration rate (eGFR) independent of albuminuria, BMI, LDL-C, and triglyceride.

We evaluated the efficacy and safety of sitagliptin after 3 months' treatment in Japanese type 2 diabetic patients and examined changes in clinical factors. Baseline HbA1c, PPG, BMI, and duration of diabetes may be predictors of HbA1c reduction when using sitagliptin in Japanese type 2 diabetic patients.

The aim of this study was to evaluate the relationship between the diagnosis of metabolic syndrome (MetS) or its components and the prevalence of microvascular and macrovascular complications in 130 Japanese type 2 diabetic patients. Out of the 130 patients, 58.5% satisfied the criteria of the MetS as defined by the IDF guideline. The results of logistic regression analysis with adjustment for three variables (age, gender and duration of diabetes) revealed that the presence of MetS as defined by the IDF guideline was not independently related to the presence of proliferative retinopathy, proteinuria, neuropathy, or macrovascular disease in the diabetic patients. The waist circumference per se was not associated with diabetic neuropathy, retinopathy, nephropathy, or macrovascular diseases. These results suggest that neither the presence of MetS, as defined by the IDF guideline, nor the waist circumference was associated with the presence of either microvascular or macrovascular complications in Japanese type 2 diabetic patients.

Miglitol, a pseudomonosaccharide alpha-glucosidase inhibitor (alphaGI), was more effective at reducing blood glucose levels at 30 and 60 min after a meal than voglibose. Speculating that miglitol administered even after the start of a meal may be effective, we evaluated the timing of administration of miglitol on the plasma glucose and serum insulin levels in 13 type 2 diabetic patients. Miglitol was administered in four different intake manners in each patient (control: no miglitol; intake 1: just before breakfast; intake 2: 15 min after the beginning of breakfast; intake 3: 30 min after the beginning of breakfast). The area under the curve (AUC) of plasma glucose was significantly decreased under all the intake conditions, as compared with the AUC in the control. The AUC of serum insulin tended to be lower in all the three groups than in the control, although the differences were not statistically significant. Thus, miglitol administered anytime within 30 min after the start of a meal is effective for glycemic control. These results suggest that if patients miss taking miglitol at the beginning of a meal, they can still take the drug until 30 min after starting their meal.

Phosphodiesterase (PDE) 3B, a major isoform of PDE in adipocytes, mediates the antilipolytic action of insulin. PDE3B gene expression is generally reduced in adipocytes of either monogenic or polygenic rodent models of obese, insulin-resistance. An increased fat cell size, a common feature of obesity, could account for this reduction. Insulin receptor substrate-1 (IRS-1) (−/−) mice are lean with a reduced fat cell size and have insulin resistance due to a primary defect of insulin signaling. To determine whether the regulation of PDE3B gene expression is correlated with fat cell size, we examined this gene expression in adipose tissues of IRS-1 (−/−) mice. In IRS-1 (−/−) mice, PDE3B mRNA and protein levels were increased 1.24- and 1.35-fold those in C57BL/6J control mice, respectively. Independently, the fold induction of PDE activity by insulin (insulin-induced/basal) was 1.7-fold in control mice, but was reduced to 1.35-fold in IRS-1 (−/−) mice. Thus, PDE3B gene expression may be inversely correlated with a fat cell size, whereas insulin-induced PDE3B activation is mediated through IRS-1.

We investigated the association between the serum level of gamma-glutamyltransferase (GGT) and parameters of adiposity and lipid profile, including the serum triglyceride (TG), HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) levels in Japanese patients with type 2 diabetes mellitus and non-diabetic subjects. A total of 257 Japanese subjects (169 patients with type 2 diabetes and 88 non-diabetic subjects) were enrolled in the study. To assess the hepatic fat content, the ratio of the CT attenuation value of the liver to that of the spleen (L/S ratio) was calculated. Serum GGT was significantly correlated with the waist circumference, BMI, visceral fat area (VFA), L/S ratio and TG, but not with the subcutaneous fat area (SFA). The serum GGT was still correlated with the VFA and TG, but not with the SFA, after adjustment for the four variables of age, gender, serum HbA1c and the L/S ratio. Our finding that the serum GGT is specifically associated with the VFA, but not with the SFA, suggests that the serum GGT may be useful as a convenient indicator of VFA in the clinical treatment of obesity.