Although multidisciplinary care (MDC) is necessary for controlling chronic kidney disease (CKD), its impact on compliance with management target values in the CKD guidelines remains unclear. This study was designed to clarify the relationship between compliance with management target values and renal prognosis in CKD outpatients who received MDC. There were 255 outpatients with pre-dialysis CKD who received MDC. Achievement rates of systolic, and diastolic blood pressure, hemoglobin, uric acid, low-density lipoprotein cholesterol, and hemoglobin A1c values determined according to CKD guidelines were compared before and 12 months after MDC. In addition, after dividing achievement rates of the target values at 12 months after MDC into four groups (A < 30% ≤ B < 60% ≤ C < 80% ≤ D), dialysis initiation and renal survival rates were compared. There was a significant increase in the overall achievement rate from 62.8 to 69.1% (p < 0.001). The higher the achievement rate after MDC, the lower the dialysis initiation rate (A 72.7%, B 35.3%, C 20.5%, D 8.2%, p < 0.001). There was also a significantly higher renal survival rate (p < 0.001). These findings suggest that MDC for CKD raised awareness of health literacy, and improved the achievement rate of target values. Furthermore, the higher the achievement rate, the later the initiation of dialysis, which led to improvement of renal survival. MDC can improve compliance with management target values for CKD, suggesting that it may improve renal prognosis.

Dedifferentiation has been implicated in β cell dysfunction and loss in rodent diabetes. However, the pathophysiological significance in humans remains unclear. To elucidate this, we analyzed surgically resected pancreatic tissues of 26 Japanese subjects with diabetes and 11 nondiabetic subjects, who had been overweight during adulthood but had no family history of diabetes. The diabetic subjects were subclassified into 3 disease stage categories, early, advanced, and intermediate. Despite no numerical changes in endocrine cells immunoreactive for chromogranin A (ChgA), diabetic islets showed profound β cell loss, with an increase in α cells without an increase in insulin and glucagon double-positive cells. The proportion of dedifferentiated cells that retain ChgA immunoreactivity without 4 major islet hormones was strikingly increased in diabetic islets and rose substantially during disease progression. The increased dedifferentiated cell ratio was inversely correlated with declining C-peptide index. Moreover, a subset of islet cells converted into exocrine-like cells during disease progression. These results indicate that islet remodeling with dedifferentiation is the underlying cause of β cell failure during the course of diabetes progression in humans.

OBJECTIVE:To elucidate the pathogenesis of postpancreatectomy diabetes mellitus (PPDM).RESEARCH DESIGN AND METHODS:Forty-eight patients without diabetes undergoing either pancreatoduodenectomy (PD) (n = 20) or distal pancreatectomy (DP) (n = 28) were included. A 75-g oral glucose tolerance test was performed every 6 months. Microbiome composition and short-chain fatty acids (SCFAs) in feces were examined before and 6 months after surgery. The association of histological characteristics of the resected pancreas with PPDM was examined.RESULTS:During follow-up (median 3.19 years), 2 of 20 PD patients and 16 of 28 DP patients developed PPDM. Proteobacteria relative abundance, plasma glucagon-like peptide 1 (GLP-1), and fecal butyrate levels increased only after PD. Postsurgical butyrate levels were correlated with postsurgical GLP-1 levels. With no significant difference in the volume of the resected pancreas between the surgical procedures, both β-cell and α-cell areas in the resected pancreas were significantly higher in DP patients than in PD patients. In DP patients, the progressors to diabetes showed preexisting insulin resistance compared with nonprogressors, and both increased α- and β-cell areas were predictors of PPDM. Furthermore, in DP patients, α-cell and β-cell areas were associated with ALDH1A3 expression in islets.CONCLUSIONS:We postulate that a greater removal of β-cells contributes to the development of PPDM after DP. Islet expansion along with preexisting insulin resistance is associated with high cellular plasticity, which may predict the development of PPDM after DP. In contrast, PD is associated with alterations of gut microbiome and increases in SCFA production and GLP-1 secretion, possibly protecting against PPDM development.

This study was aimed to evaluate the effects of intensive exercise in addition to the administration of sodiumglucose cotransporter 2 inhibitor dapagliflozin (DAPA) on body composition, including fat-free mass, in type 2 diabetes. We randomly assigned 146 patients to 24 weeks of treatment with intensive exercise, including resistance training, plus 5 mg (up to 10 mg) of DAPA daily (IT group) or DAPA alone (CT group). The primary endpoint was the difference in the change in fat-free mass from baseline to 24 weeks between the groups. The skeletal muscle mass index (SMI); metabolic profile, including HbA1c; and regional fat mass were also determined. ANCOVA was used for the group comparison, with least squares mean (LSM) differences and 95% confidence interval (CI). There was no significant difference in the change in fatfree mass (LSM difference ?0.1 kg (95% CI: ?0.5 to 0.4) and SMI (LSM difference ?0.1 kg (95% CI: ?0.2 to 0.1) between the groups. In contrast, the reduction of trunk fat mass was significantly higher in the IT group than in the CT group ((LSM difference ?0.5 kg [95% CI ?0.9 to ?0.1]). Higher adherence to the resistance training tended to be associated with changes in HbA1c and high-sensitivity CRP levels. Our study suggests that intensive exercise do not prevent the reduction of fat-free mass after administration of SGLT2 inhibitors but can increase the reduction in abdominal fat, presumably leading to further improvements of hyperglycemia and chronic inflammation than DAPA alone in type 2 diabetes patients.

To elucidate the pathogenesis of post-pancreatectomy diabetes (PPDM), we carried out a prospective observational study in patients without diabetes undergoing partial pancreatectomy, investigating the effects of gut microbiota, incretins, and short-chain fatty acids (SCFAs) on postsurgical glucose metabolism. In addition, we analyzed histologically the resected pancreas to investigate whether increased cellular-plasticity and expansion of the islets could predict the development of PPDM. Forty-eight patients without diabetes, who underwent either pancreatoduodenectomy (PD) (n=20) or distal pancreatectomy (DP) (n=28), were included. To assess the post-surgical glucose metabolism, 75-g oral glucose tolerance test (OGTT) was performed every 6 months. Microbiome composition and SCFAs in feces were examined before and 6 months after the surgery. We also underwent immunostainings of insulin, glucagon, and ALDH1A3 (a progenitor cell marker) in the resected pancreatic samples obtained from patients following DP. During the follow-up (median 2.50 years), 2 out of 18 patients with PD and 16 out of 28 patients with DP developed PPDM. Microbiota shifted to a higher relative abundance of Proteobacteria after PD. After PD, fecal butyrate and plasma GLP-1 concentrations were significantly increased, which were not increased after DP. In all patients, postsurgical change in butyrate was strongly correlated with increased GLP-1 secretion. In DP patients, expansion of both α- and β-cell areas in the resected pancreas were significantly associated with the development of PPDM, and HR (95% CI) of ALDH1A3 positive cells (%) for PPDM was 1.127 (1.000-1.270). This study demonstrates that incidence of PPDM is much lower after PD than that after DP, which may be explained by marked changes in intestinal environment after PD. On the other hand, high cellular-plasticity and expansion of the islets in the resected pancreas can predict the development of PPDM after DP. Disclosure R. Bouchi: None. T. Fukuda: None. T. Takeuchi: None. K. Amo-Shiinoki: None. K. Tanabe: None. Y. Tanizawa: None. T. Yamada: Research Support; Self; Astellas Pharma Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Kissei Pharmaceutical Co., Ltd., Kowa Company, Ltd., Kyowa Hakko Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD, Novartis Pharma K.K., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. Y. Ogawa: Research Support; Self; Mitsubishi Tanabe Pharma Corporation. Speaker’s Bureau; Self; Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation. Funding Ministry of Education, Culture, Sports, Science and Technology of Japan (15K19507); Japan Foundation for Applied Enzymology; Takeda Science Foundation; AstraZeneca

Sarcopenic obesity, defined as reduced skeletal muscle mass and power with increased adiposity, was reported to be associated with cardiovascular disease risks in previous cross-sectional studies. Whole body dual-energy X-ray absorptiometry (DXA) can simultaneously evaluate both fat and muscle mass, therefore, whole body DXA may be suitable for the diagnosis of sarcopenic obesity. However, little is known regarding whether sarcopenic obesity determined using whole body DXA could predict incident cardiovascular disease (CVD). The aim of this study was to investigate the impact of sarcopenic obesity on incident CVD in patients with type 2 diabetes.

Objective To examine whether the existence and severity of diabetic retinopathy (DR) could be associated with the prevalent sarcopenia and muscle quality in patients with type 2 diabetes. Research design and methods This is a cross-sectional study of 316 patients with type 2 diabetes (mean age 65 +/- 12 years; 38% female). Body compositions were measured by the dual-energy X-ray absorptiometry. Patients were divided into three groups: patients without DR (NDR), with non-proliferative DR (NPDR) and proliferative DR (PDR). Sarcopenia was diagnosed according to the criteria for Asians, using both skeletal muscle index (SMI) and grip strength (kg). Muscle quality was also determined by the grip strength divided by SMI. Logistic regression analyses were carried out to assess the cross-sectional association of the severity of DR with sarcopenia. In addition, linear regression analyses were performed to determine the associations between DR and muscle quality. Selection of covariates in the multivariate logistic and linear regression analyses was done by a stepwise procedure. Results Among the patients examined, NDR, NPDR and PDR were diagnosed in 261, 38 and 17 patients, respectively. The prevalence of sarcopenia significantly increased along with the progression of DR. Multivariate logistic regression analysis showed that PDR is significantly associated with sarcopenia (OR 7.78, 95% CI 1.52 to 39.81, p=0.014) and low muscle strength (OR 6.25, 95% CI 1.15 to 33.96, p=0.034). Multivariate linear regression analysis additionally showed that the existence of DR was significantly associated with the muscle quality (standardized beta -0.136, p=0.005 for NPDR, standardized beta -0.146, p=0.003 for PDR). Conclusions This study provides evidence that PDR is significantly associated with sarcopenia, and the existence of DR increases the risk for low muscle quality in patients with type 2 diabetes.

Background: To investigate the association of both latent autoimmune diabetes in adults (LADA) and type 2 diabetes (T2DM) with muscle mass and function (sarcopenia).Methods: Japanese patients with LADA (N = 20), T2DM (N = 208), and control subjects (N = 41) were included in this cross-sectional study. The definition of LADA was based on age of onset (>= 30), positive glutamic acid decarboxylase autoantibodies, and insulin requirement within the first 6 months after diagnosis. Sarcopenia was diagnosed by the criteria for Asians, using skeletal muscle index (male <7.0 and female <5A) and grip strength (male <26.0 kg and female <18.0 kg). The odds ratio (OR) with a 95% confidence interval (CI) was estimated using logistic regression.Results: The prevalence of sarcopenia was higher in LADA (35.0%) than in either T2DM (13.3%) or control subjects (9.8%). LADA was significantly associated with an increased risk for sarcopenia in a multivariate model in which age and body mass index were incorporated (OR: 9.57, 95% CI: 1.86-49.27). In contrast, T2DM tended to be associated with an increased risk for sarcopenia (OR: 2.99, 95% CI: 0.83-10.80).Conclusions: This study provides evidence that patients with LADA are at a high risk for sarcopenia compared to those with T2DM or to control subjects. (C) 2017 The Authors. Published by Elsevier Inc.

Objective: This study was to investigate whether switching sulfonylurea to mitiglinide/voglibose could improve glycemic variability and endothelial dysfunction in patients with type 2 diabetes. Methods:This was a single arm study of 6 Japanese patients with type 2 diabetes (n =6, 5 male, 72 ± 7 year-old).Patients with 0.25-1.0mg of glimepiride (0.8 ± 0.3 mg) with HbA1c between 6.5-7.5% were enrolled and were switched from glimepiride to mitiglinide/voglibose (fixed-dose combination of mitiglinide 10 mg and voglibose 0.2 mg three times a day) for 3 months.Results: Mean amplitude of glycemic excursion (MAGE) was significantly decreased from 3.4 ± 1.3 to 1.6 ± 0.6 mmol/l (P = 0.014).Both fasting and postprandial FMD also significantly improved (5.3 ± 1.6 vs. 7.1 ± 1.7, P = 0.043 and 3.5 ± 1.5 vs. 5.2 ± 1.1, P = 0.043).The declines of insulin and C-peptide levels at 120 min were significantly correlated with the increase in postprandial FMD (r = -0.97,P = 0.013, and r = -1.00,P = 0.004).Conclusions: Glycemic variability and endothelial dysfunction at fasting and postprandial states were improved by mitiglinide/voglibose and it may be through the attenuation of hyperinsulinemia.We focused on the potential of the combination treatment to ameliorate endothelial dysfunction due to reducing the postprandial hyperglycemia [9,10], because previous studies showed that each monotherapy of glinide and α-glucosidase inhibitor ameliorated endothelial dysfunction [11,12].In this context, we conducted this pilot study to investigate whether switching from SU to mitiglinide/ voglibose could reduce the fluctuation of blood glucose, eventually decreasing in the hypoglycemic episodes and amelioration of endothelial dysfunction in patients with type 2 diabetes. Subjects and methodsPatients with less than 1.0 mg of glimepiride (0.8 ± 0.3 mg) with HbA1c between 6.5-7.5% (n =6, 5 male, 72 ± 7 year-old) were enrolled.Two patients were treated with metformin and 1 patient with vildagliptin at the base line.The patients were switched from glimepiride to mitiglinide/voglibose (fixed-dose combination of mitiglinide 10 mg

Introduction Epicardial fat (EF) was reported to be independently associated with cardiovascular disease regardless of obesity. We have previously reported that a sodium-glucose co-transporter-2 (SGLT2) inhibitor, luseogliflozin, reduces the EF volume (EFV) in parallel with the reduction of body weight in obese patients (BMI ≥25 kg/m 2 ) with type 2 diabetes. However, it is unknown whether SGLT2 inhibitors could reduce EFV in non-obese patients (BMI <25 kg/m 2 ) with type 2 diabetes. Therefore, we evaluated the effect of SGLT2 inhibitors on the EFV in non-obese type 2 diabetic patients with visceral obesity in this pilot study. Methods Nine of type 2 diabetic patients (mean age 66 ± 8 years; 33% female) with HbA 1c 6.5–9.0%, body mass index (BMI, kg/m 2 ) <25.0, and visceral fat area (VFA, cm 2 ) ≥100 were enrolled. Participants were administered ipragliflozin 50 mg daily. EFV [median (interquartile range), cm 3 ] was measured by magnetic resonance imaging. Primary endpoint was the change in EFV at 12 weeks. VFA and liver attenuation index (LAI), skeletal muscle index (SMI), and body fat (%) were also assessed at baseline and at 12 weeks. Results The EFV was significantly reduced from 102 (79–126) cm 3 to 89 (66–109) cm 3 by ipraglifrozin ( p = 0.008). The body weight, BMI, HbA 1c , fasting plasma glucose, insulin, homeostasis model assessment-insulin resistance, triglycerides, leptin, body fat, android, gynoid, and VFA were significantly reduced and high-density lipoprotein cholesterol was significantly increased by ipraglifrozin at 12 weeks, whereas SFA and LAI were unchanged. The change in EFV was significantly correlated with the change in BMI. Conclusions A12-week intervention of ipragliflozin reduced the EFV in non-obese type 2 diabetic patients with visceral adiposity. Clinical Trial Registration UMIN Clinical Trial Registry: UMIN000019071. Funding Astellas Pharma Inc. and the Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

A 52-year-old woman was treated with sensor augmented pump therapy after undergoing total pancreatectomy for a nonfunctional pancreatic neuroendocrine tumor (NET). The secretion of both endogenous insulin and pancreatic glucagon were completely depleted. Octreotide long acting repeatable (Oct-LAR) was administered for the treatment of liver metastasis of NET. Both the fasting and postprandial glucagon levels decreased immediately after the administration of Oct-LAR. In a continuous glucose monitoring analysis, episodes of nocturnal hypoglycemia was found to increase and an improvement of postprandial hyperglycemia was observed. This case suggests that octreotide may reduce the glucose level in both the fasting and postprandial states, in part by the suppression of extrapancreatic glucagon.

To investigate whether the ratio of visceral fat area (VFA) to subcutaneous fat area (SFA; V/S ratio) could be predictive of cardiovascular disease (CVD) as compared with VFA or SFA in patients with diabetes.

Sarcopenia is defined as an age-related loss of skeletal muscle mass and strength, and is a major cause of disability and mobility limitations. Recent studies have demonstrated that type 2 diabetes and insulin signaling deficiencies contribute to the progression of sarcopenia, suggesting that a sufficient supply of insulin to the skeletal muscles may be important for the maintenance of muscle function; however, little has been reported regarding whether insulin treatment can protect against sarcopenia. We conducted a retrospective observational study to examine the impact of insulin treatment on the muscle mass of patients with type 2 diabetes. A total of 312 patients (mean age: 64 ± 11 years; 40.8% female; 27.6% treated with insulin) were studied in this retrospective observational study. Skeletal muscle index (SMI) and grip strength (kg) were used to assess sarcopenia. The prevalence of sarcopenia was 18.0%. Insulin treatment was shown to be protective against the annual decline of SMI (standardized β 0.195; p = 0.025) even after adjusting for covariates, including age, gender, duration of diabetes, and body mass index. In a cohort matched by propensity scores, insulin treatment significantly increased the 1-year change in SMI (mean ± SE) compared with non-insulin-treated group (2.40 ± 0.98% vs. −0.43 ± 0.98%; p = 0.050). Our data suggest that insulin treatment could attenuate the progression of sarcopenia in patients with type 2 diabetes.

Activation of dipeptidyl peptidase 4 has been reported to be associated with impairment of insulin signalling in skeletal muscle, presumably leading to loss of muscle function. This study was aimed to investigate whether the use of dipeptidyl peptidase 4 inhibitors (DPP4i) could attenuate the progressive loss of muscle mass in patients with type 2 diabetes.

Sarcopenia, defined as age‐related loss of skeletal muscle mass and function, increases the risk of albuminuria. However, it has still unknown whether sarcopenia could increase the risk for the progression of albuminuria. A total 238 patients with type 2 diabetes (mean age 64 ± 12 years; 39.2% women) were studied in the present retrospective observational study. The prevalence of sarcopenia was 17.6%. During the median follow‐up period of 2.6 years, albuminuria was measured 5.8 ± 1.8 times, and progression of albuminuria was observed in 14.9% of patients with normoalbuminuria, as was 11.5% in those with microalbuminuria. Sarcopenia was significantly associated with both progression (hazard ratio 2.61, 95% confidence interval 1.08–6.31, P = 0.034) and regression (hazard ratio 0.23, 95% confidence interval 0.05–0.98, P = 0.048) of albuminuria by multivariate Cox regression analysis. The present data suggest that sarcopenia is an important determinant of both progression and regression of albuminuria in patients with type 2 diabetes.

Increased visceral adiposity is strongly associated with non-alcoholic fatty liver disease (NAFLD). However, little attention has been paid to the association between the change in subcutaneous adipose mass and the progression of non-alcoholic fatty liver disease (NAFLD). We aimed to investigate whether increased subcutaneous adipose tissue (gynoid fat mass) could be protective against the progression of NAFLD in Japanese patients with type 2 diabetes.

Aims/Introduction: To investigate the impact of increased visceral adiposity with normal weight (OB[-]VA[+]) on the prevalence of non-alcoholic fatty liver disease in patients with type 2 diabetes.Materials and Methods: This was a cross-sectional study of 140 Japanese patients with type 2 diabetes (mean age 65 +/- 11 year; 44.6% women). Visceral fat area (VFA; cm(2)) and liver attenuation index (LAI) were assessed by abdominal computed tomography. The patients were divided into four groups by VFA and body mass index (BMI; kg/m(2)) as follows: BMI <25 kg/m(2) and VFA <100 cm(2) (OB[-]VA[-]), BMI >= 25 kg/m(2) and VFA <100 cm(2) (OB[+]VA[-]), BMI <25 kg/m(2) and VFA >= 100 cm(2) (OB[-] VA[+]), and BMI >= 25 kg/m(2) and VFA >= 100 cm(2) (OB[+]VA[+]). Multivariate linear regression and logistic regression analysis were carried out to determine the impact of OB(-)VA(+) on LAI.Results: In the present study, 25.0% were OB(-)VA(+) patients, where the LAI levels were lower (1.09 +/- 0.22) than those in OB(-)VA(-) patients (1.23 +/- 0.15), and were equivalent to those in OB(+)VA(+) patients (1.03 +/- 0.26). In multivariate linear regression analysis, OB(-)VA(+) was independently associated with LAI (standardized beta-0.212, P = 0.014). In multivariate logistic regression analysis, OB(-)VA(+) was a significant predictor of LAI <0.9 (odds ratio 5.88, 95% confidence interval 1.03-33.52, P = 0.046).Conclusions: The present study provides evidence that increased visceral adiposity with normal weight is a strong predictor for the prevalence of non-alcoholic fatty liver disease in Japanese patients with type 2 diabetes.

OBJECTIVE:Among indirect measures of visceral adiposity, A Body Shape Index (ABSI), which is defined as waist circumference (WC)/(body mass index (BMI)(2/3)×height(1/2)), is unique in that ABSI is positively correlated with visceral adiposity and is supposed to be independent of BMI. ABSI has been also shown to be linearly and positively associated with visceral fat mass and all-cause and cardiovascular disease (CVD) in the general population. It is, however, uncertain whether ABSI could be associated with arterial stiffness in patients with diabetes. METHODS:This is a cross-sectional study of 607 patients with type 2 diabetes (mean age 64±12 years; 40.0% female). Visceral fat area (VFA, cm(2)) and subcutaneous fat area (SFA, cm(2)) were assessed with a dual-impedance analyzer. In order to estimate the risk for CVD, brachial-ankle pulse wave velocity (baPWV, cm) was used for the assessment of arterial stiffness. RESULTS:ABSI was significantly and positively correlated with VFA (r=0.138, p=0.001) and negatively associated with BMI (r=-0.085, p=0.037). The correlation of z-score for ABSI with VFA remained significant (r=0.170, p<0.001) but not with BMI (r=0.009, p=0.820). ABSI (standardized β 0.095, p=0.043) but not WC (standardized β -0.060, p=0.200) was significantly and positively correlated with baPWV in the multivariate model including BMI as a covariate. CONCLUSIONS:ABSI appears to reflect visceral adiposity independently of BMI and to be a substantial marker of arterial stiffening in patients with type 2 diabetes.

We aimed to investigate whether visceral adiposity could modify the impact of blood pressure on arterial stiffness and albuminuria in patients with type 2 diabetes.