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Aims/Introduction: We investigated the effect of FreeStyle LibreTM on glycemic control in Japanese type 2 diabetes patients treated with basal–bolus insulin therapy. Materials and Methods: This prospective, 90‐day single‐arm study enrolled 94 adults with type 2 diabetes treated with insulin. A 14‐day masked baseline phase was followed by an 11‐week treatment phase during which participants used the device to monitor glucose levels. The primary end‐point was time spent in hypoglycemia (<70 mg/dL) for baseline versus study end (days 76–90). Secondary end‐points included other measures of glycemic control, along with patient satisfaction using the Japanese Diabetes Treatment and Satisfaction Questionnaire. Results: Time spent in hypoglycemia was low at baseline (0.51 ± 0.93 h/day) and did not significantly decrease at study end (0.47 ± 0.63 h/day, P = 0.6354). Time in range, time in hyperglycemia and estimated A1c all improved versus baseline (by +1.7 ± 3.0 h/day, −1.6 ±.4 h/day and −0.4 ± 0.8%, respectively, P < 0.0001 in each). Finger stick tests fell from 2.9 ± 1.3 to 1.9 ± 1.4/day, and mean scanning frequency during the intervention phase was 11.3/day. The mean treatment satisfaction score increased by 11.8 ± 5.3 (P < 0.0001). Two severe hypoglycemia‐related adverse events were reported; one of which was possibly related to the device. Three participants reported mild device‐related skin trauma, site discomfort or subcutaneous bleeding. Conclusions: Use of FreeStyle Libre by Japanese type 2 patients diabetes treated with basal–bolus insulin therapy showed a low baseline of hypoglycemia, and enabled improved glycemic control and treatment satisfaction. [ABSTRACT FROM AUTHOR]

This study focuses on Japanese type 2 diabetes outpatients with a rice intake higher than the recommended limit. We studied the use of smaller-than-conventional rice bowls in daily life and conducted a prospective study to assess its impacts on adherence to rice intake recommendations, weight, HbA1c value, and DDRQOL scores for 3 months. We selected 72 male participants whose current rice intake larger than guidelines, and whose rice bowls at home are larger than the recommended size. Study participants were randomly divided into two groups. The intervention group (IG) consisted of 36 participants who were asked to use a designated rice bowl smaller than that they normally use. A control group (CG) of 36 participants used their usual rice bowls. Both groups received dietary recommendations for rice intake from doctors at the start of the study. A questionnaire was administered at baseline and at the 1-month and 3-month marks. This interim report compared patients' adherence to rice intake recommendations, HbA1c value, and so on at the baseline and 1-month marks. With respect to the patients' adherence to rice intake recommendations at 1 month, 19 participants out of 36 (52.8%) in IG responded that they "mostly did," while only 10 subjects out of 36 (27.8%) in CG responded the same; more subjects in IG adhered to recommendations (p = 0.040). The mean weights of the subjects at the start of study was 74.2 kg in IG and 78.4 kg in CG. Mean HbA1c values were 6.74% in IG and 6.63% in CG. Neither indices showed any significance. The change in body weight over 1 month was -0.43 kg in IG and 0.27 kg in CG. The change in HbA1c values was -0.15% in IG and 0.09 % in CG. IG revealed a significant decrease in both factors (p = 0.004, p = 0.005 respectively). There was no significant difference in DDRQOL scores. The results suggest that smaller rice bowls increase patients' adherence to the recommended rice intake, leading to a decrease in body weight and HbA1c values. Disclosure: S. Sato: None. M. Shimpo: None. T. Tosaki: Research Support; Self; Abbott, Astellas Pharma Inc., AstraZeneca, Daiichi Sankyo, Kowa Company, Ltd., Lilly Diabetes, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd. H. Kamiya: Speaker's Bureau; Self; Astellas Pharma Inc., AstraZeneca K.K., Boehringer Ingelheim K.K., Daiichi Sankyo, Eli Lilly Japan K.K., Fukuda Denshi, Kissei Pharmaceutical Co., Ltd., Kowa Company, Ltd., Kyowa Hakko Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K.K., Novartis Pharma K.K., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. M. Kondo: None. M. Kato: None. H. Shimoda: None. J. Nakamura: Research Support; Self; Astellas Pharma Inc., Boehlinger Ingelheim Japan Co., Ltd., Daiichi Sankyo, Eli Lilly Japan K.K., Japan Tobacco Inc., Kaken Pharmaceutical Co., Ltd., Kowa Company, Ltd., Kyowa Hakko Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K.K., Novartis Pharma K.K., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sanofi K.K., Sanwa Kagaku Kenkyusho, Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Abbott Japan Co., Ltd., ARKRAY, Astellas Pharma Inc., AstraZeneca K.K., Boehlinger Ingelheim Japan Co., Ltd.,, Daiichi Sankyo, Eli Lilly Japan K.K., Fukuda Denshi, Kissei Pharmaceutical Co., Ltd., Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K.K., Mylan, Novartis Pharma K.K., Novo Nordisk Pharma Ltd, Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. Funding: Japan Society for the Promotion of Science (JP19K20151) [ABSTRACT FROM AUTHOR]

Effects of SGLT2 inhibitors (SGLT2i) on renal functions were examined in patients with type 2 diabetes followed by our clinic. Subjects were 395 outpatients treated with SGLT2i (ipragliflozin 135; empagliflozin 101; canagliflozin 83; dapagliflozin 76; age 51.6 ± 11.3 years; duration of diabetes 7.21 ± 6.8 years; BMI 28.6 ± 4.5). Changes in eGFR at 1 year before and 2 years after the administration of SGLT2i versus at baseline were retrospectively analyzed in 2 groups divided by the baseline eGFR; eGFR<90 ml/min/1.73m2 group and eGFR≧90 group. The changes in urinary albumin excretion rate (UAER) and HbA1c levels were also examined. The average values of each four measures in a year were used as the levels for each period. In the eGFR<90 group (n = 179), the annual change in eGFR (ΔGFR) was -2.1 ± 5.5/year before administration of SGLT2i (p <0.001), -1.4 ± 7.5/year after 1 year (p = 0.020) and +0.2 ± 5.9/year between 1 and 2 years (p = 0.704). In the eGFR≧90 group (n = 164), ΔGFR was -1.2 ± 8.0/year before administration of SGLT2i (p = 0.180), -3.2 ± 11.6/year after 1 year (p = 0.001) and -1.2 ± 8.2/year between 1 and 2 years (p = 0.133). In the group with ΔGFR?-5/year before administration of SGLT2i (n = 56), ΔGFR was -9.1 ± 3.5/year before administration (p <0.001), -0.9 ± 8.9/year after 1 year (p = 0.473) and -2.4 ± 10.6/year between 1 and 2 years (p = 0.176). In the group with ΔGFR >-5/year before administration (n = 137), ΔGFR was +1.9 ± 5.3/year before administration (p <0.001), -4.1 ± 9.5/year after 1 year (p <0.001) and +0.6 ± 6.0/year between 1 and 2 years (p = 0.306). UAER changes in total subjects were +41.1 ± 267.5 mg/g creatinine/year before administration of SGLT2i (p = 0.039), -8.8 ± 220.1/year after 1 year (p = 0.474) and +8.0 ± 88.0/year between 1 and 2 years (p = 0.144). HbA1c levels were 7.27 ± 1.19% and 7.67 ± 1.31 at 1 year before and baseline, respectively, and decreased at 2 years (-0.49 ± 1.16%, p <0.001, n = 145). These observations suggest that SGLT2i may have protective effects on renal functions in the real-world clinical practice. Disclosure: T. Tosaki: Research Support; Self; Daiichi Sankyo Company, Limited, Sanofi K.K. Speaker's Bureau; Self; Astellas Pharma Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. S.T. Sato: None. M. Kondo: None. Y. Yamada: None. A. Inagaki: None. S. Tsunekawa: None. T. Himeno: None. Y. Kato: Speaker's Bureau; Self; Merck & Co., Inc. J. Nakamura: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Japan Tobacco Inc., Kissei Pharmaceutical Co., Ltd., Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Kowa Pharmaceu. Co. Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. H. Kamiya: Speaker's Bureau; Self; Astellas Pharma Inc., Eli Lilly Japan K.K., MSD K.K., Novartis Pharma K.K., Novo Nordisk Oharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K.K. [ABSTRACT FROM AUTHOR]

Aims: Efficacy of a GLP-1 receptor agonist, dulaglutide, on renal functions in type 2 diabetic patients under the real-world clinical practice in Japan was retrospectively examined. Subjects: 154 patients with type 2 diabetes treated with dulaglutide (0.75 mg once weekly) in our clinic (mean administration period 540.7 ± 332 days; mean age 58.1 years; mean duration of diabetes 10.5 years). Methods: Dulaglutide was added to the conventional antidiabetes drugs. The dose of sulfonylurea was reduced by 50-67% and all the DPP-4 inhibitors were discontinued. The annual changes in eGFR between 1 year before and 2 years after the administration of dulaglutide were retrospectively analyzed in 2 groups divided by the baseline eGFR; eGFR<90 ml/min/1.73m2 group and eGFR≧90 group. Changes in HbA1c levels and body weight were also evaluated. Results: eGFR in the eGFR<90 group (n = 90) rapidly declined (-5.4 ± 7.8/year) before the administration of dulaglutide (p <0.001). However, the decline was moderate after the administration of dulaglutide (-1.2 ± 7.1/year after 1 year, p = 0.134; -1.1 ± 5.8/year between 1 and 2 years, p = 0.179). In contrast, eGFR in the eGFR≧90 group (n = 57) was not declined before the administration of dulaglutide (+ 1.4 ± 6.6/year, p = 0.318), and significantly decreased after the administration of dulaglutide (-2.9 ± 10.0/year after 1 year, p = 0.036; -2.5 ± 6.8/year between 1 and 2 years, p = 0.048). HbA1c levels were 8.70 ± 1.76% at baseline, -1.32 ± 1.69% at 1 year (p <0.001, n = 86), -1.19 ± 1.56% at 2 years (p <0.001, n = 39). Body weight were 71.3 ± 15.2 kg at baseline, -1.86 ± 3.38 kg at 1 year (p <0.001, n = 86), -2.04±3.33 kg at 2 years (p=0.001, n=39). Conclusions: These observations suggest that dulaglutide may ameliorate renal hyperfiltration and protect renal functions. Disclosure: S.T. Sato: None. T. Tosaki: Research Support; Self; Daiichi Sankyo Company, Limited, Sanofi K.K. Speaker's Bureau; Self; Astellas Pharma Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. M. Kondo: None. Y. Yamada: None. A. Inagaki: None. S. Tsunekawa: None. T. Himeno: None. Y. Kato: Speaker's Bureau; Self; Merck & Co., Inc. J. Nakamura: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Japan Tobacco Inc., Kissei Pharmaceutical Co., Ltd., Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Kowa Pharmaceu. Co. Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. H. Kamiya: Speaker's Bureau; Self; Astellas Pharma Inc., Eli Lilly Japan K.K., MSD K.K., Novartis Pharma K.K., Novo Nordisk Oharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K.K. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem cells (MSCs) have been reported to differentiate multilineage cell types and to secrete various cytokines that induce angiogenesis. Therefore, transplantation of MSCs is a promising strategy for the treatment of ischemic diseases such as myocardial infarction and arteriosclerosis obliterans. On the other hand, decreased nerve blood flow has been recognized as one of the pathophysiological characteristic features of diabetic polyneuropathy (DPN). This study was conducted to investigate the effects of MSC transplantation on DPN. Material and method: MSCs were isolated from bone marrow of Spraugue-Dawley (SD) rats, cultured and collected. Diabetes was induced by intraperitoneal injection of STZ to 6-week-old male SD rats. After 8 weeks, MSCs (1 * 10⌃6 cells/limb) with saline and saline alone (S) were injected into the right and left hindlimb muscles of control (C) and diabetic (D) rats, respectively. Four weeks later, nerve conduction velocity (NCV), nerve blood flow of sciatic nerves (SNBF), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) mRNA expressions in thigh muscles, capillary densities in sciatic nerves and gastrocnemius, and sural nerve morphometry were evaluated. Result: Decreased SNBF (C+S: 22.8±3.0 ml/min/100g, D+S: 9.2±5.3) and NCV (C+S: 53.1±2.1 m/s, D+S: 37.6±3.4) in diabetic rots were significantly ameliorated by MSC transplantation (SNBF: 18.2±5.3, NCV: 46.8±5.5). VEGF and bFGF mRNA expressions in diabetic rats significantly increased by 1.79-fold and 1.62-fold in MSCs-injected thigh muscles, respectively, compared with those in saline alone-injected thigh muscles. Capillary densities in sciatic nerve (SN) and gastrocnemius (GC) were decreased in diabetic rats (SN: 25.7±8.8/nerve fiber, GC: 0.38±0.04/muscle fiber) compared with control rats (SN: 37.3-±3.5, GC: 0.53±0.05). MSC transplantation improved these deficits (SN: 36.0±10.2, GA: 0.55±0.08). Sural nerve morphometry showed decreased axonal circularity in diabetic rats (C+S: 0.794±0.010, D+S: 0.771±0.011), which was normalized by MSC transplantation (0.794±0.021). Conclusion: These results indicate that MSC transplantation would ameliorate impaired microcirculation in diabetic nerves and have therapeutic values for DPN. [ABSTRACT FROM AUTHOR]

It has been reported that transplantation of endothelial progenitor cells (EPCs) has therapeutic values for ischemic diseases through neovascularization. EPCs in vivo play an important role in re-endothelization against endothelial damages. In diabetic patients, however, functional deficits in EPCs have been observed, which would contribute to the development of diabetic macroangiopathy. On the other hand, anti-arteriosclerotic effects of adiponectin have been demonstrated through its direct actions to vascular cells. However, interactions between EPCs and adiponectin have not been evaluated. In the present study, therefore, effects of adiponectin on cellular functions of EPCs were investigated. EPCs ware isolated from human peripheral blood using a Histopaque-density centrifugation method, plated on fibronectin-coated dishes and cultured in a M199 medium with 20% FBS and bovine brain extract for 7days. An adiponectin receptor (AdipoR1) was identified by western blot analyses. After an another 24h-culture under the serum free condition, adiponectin was added and the phosphorylation of Akt and endothelial nitric oxide synthase (eNOS) were measured by western blot analyses by using phosphospecific antibodies of Akt and eNOS. For analyses of migration activities of EPCs, cells were seeded on upper chambers of Boyden chambers, and FBS, adiponectin or VEGF was added into lower chambers. After 12 hs, the number of cells that passed transwells was counted. In addition, effects of adiponectin on migration activities were examined in the presence of several inhibitors. AdipoR1 was identified as the single band in EPCs. The phosphorylation of Akt and eNOS was significantly increased by adiponectin in a time dependent manner, and the maximal phosphorylation of Akt and eNOS were observed 10 and 30 min, respectively. Migration activities of EPCs were increased by adiponectin in a dose dependent manner as well as VEGF. Adiponectin-induced enhancement of migration activities were completely inhibited by a PI3-kinase inhibitor, LY294002, but partially by an eNOS inhibitor, L-NAME (92% suppression by LY294002 and 45% suppression by L-NAME). These observations suggest that adiponectin promotes migration activities of EPCs mainly through PI3-kinase/Akt and partially through eNOS. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the effectiveness at 1 and 3 months of using a smaller rice bowl for diet therapy among Japanese men with type 2 diabetes., Methods: A parallel-group randomized controlled trial was conducted at a medical clinic in Japan. The participants were men with type 2 diabetes mellitus, aged 20-80 years, with glycosylated hemoglobin <8.5%, and who ate rice one or more times per day at home. The intervention group (36 men) received a small rice bowl from which to eat the usual diet therapy, and the control group (38 men) received only the usual diet therapy., Results: The changes in weight and body mass index among the intervention group at 1 month were significantly higher than those in the control group. There were no significant differences between the two groups at 3 months., Conclusion: The effects of using a small rice bowl were minor and short-term.

Objective We investigated the efficacy, safety, and patient satisfaction of once-weekly DPP-4 inhibitors (DPP-4Is). Methods Either of two once-weekly DPP-4Is, trelagliptin or omarigliptin, was administered alone or in combination with other antidiabetic drugs in 80 outpatients with type 2 diabetes mellitus for 3 months. The HbA1c, glycoalbumin (GA), body weight, and the Diabetes Treatment Satisfaction Questionnaire (DTSQ) scores were evaluated. Results Patients switching from other daily DPP-4Is (n=29) showed no significant changes in the HbA1c or GA levels. However, the HbA1c and GA levels of patients who had been naïve to DPP-4Is (n=37) significantly improved from 9.31±2.53% to 7.02±1.20% (p<0.001) and 26.7±11.8% to 17.3±5.7% (p<0.001), respectively. Several non-serious adverse events were reported, including nausea (n=1), abdominal distension (n=1), and constipation (n=1). In the DTSQs, the total score for six questions on the primary factors representing patient treatment satisfaction was not markedly changed in patients switching from daily to weekly DPP-4Is but was significantly improved from 21.0 to 28.0 (p<0.001) in patients naïve to DPP-4Is. Conclusion These findings suggest that the use of a once-weekly DPP-4I is effective and well-tolerated in diabetes treatment and improves treatment satisfaction.

Objective and Methods An SGLT2 inhibitor (ipragliflozin, dapagliflozin, luseogliflozin, tofogliflozin, or canagliflozin) was administered to 132 outpatients with type 2 diabetes mellitus with or without other antidiabetic drugs for 6 months to evaluate its efficacy, the incidence of adverse events, and its influence on the renal function. Results The patient's mean glycated hemoglobin level significantly improved from 7.52±1.16% to 6.95±0.98% (p<0.001). The body weight of the patients was significantly reduced from 78.0±15.3 kg to 75.6±15.1 kg (p<0.001). The estimated visceral fat area was also significantly reduced from 108.4±44.6 cm 2 to 94.5±45.3 cm 2 (p<0.001). The waist circumference, blood pressure, serum alanine aminotransferase, γ-glutamyl transpeptidase, and uric acid levels also showed a significant decrease. The urinary albumin/creatinine ratio (U-ACR) was significantly reduced in the patients whose U-ACR levels were 30-300 mg/gCr at the baseline. The mean eGFR significantly decreased in the patients with a pre-treatment eGFR value of ≥90 mL/min/1.73 m 2 but remained unchanged in the patients with a pre-treatment value of <90 mL/min/1.73 m 2 . A total of 13 adverse events were noted, including systemic eruption (n=1), cystitis (n=2), pudendal pruritus (n=2), nausea (n=1), malaise (n=1), a strong hunger sensation and increased food ingestion (n=1), and non-serious hypoglycemia (n=5). Conclusion SGLT2 inhibitors seemed to be useful in the treatment of obese type 2 diabetes mellitus patients. Furthermore, these data suggest that SGLT2 inhibitors may protect the renal function.

Introduction: Dental pulp stem cells (DPSCs) are mesenchymal stem cells located in dental pulp and are thought to be a potential source for cell therapy since DPSCs can be easily obtained from teeth extracted for orthodontic reasons. Obtained DPSCs can be cryopreserved until necessary and thawed and expanded when needed. The aim of this study is to evaluate the therapeutic potential of DPSC transplantation for diabetic polyneuropathy., Methods: DPSCs isolated from the dental pulp of extracted incisors of Sprague-Dawley rats were partly frozen in a -80 °C freezer for 6 months. Cultured DPSCs were transplanted into the unilateral hindlimb skeletal muscles 8 weeks after streptozotocine injection and the effects of DPSC transplantation were evaluated 4 weeks after the transplantation., Results: Transplantation of DPSCs significantly improved the impaired sciatic nerve blood flow, sciatic motor/sensory nerve conduction velocity, capillary number to muscle fiber ratio and intra-epidermal nerve fiber density in the transplanted side of diabetic rats. Cryopreservation of DPSCs did not impair their proliferative or differential ability. The transplantation of cryopreserved DPSCs ameliorated sciatic nerve blood flow and sciatic nerve conduction velocity as well as freshly isolated DPSCs., Conclusions: We demonstrated the effectiveness of DPSC transplantation for diabetic polyneuropathy even when using cryopreserved DPSCs, suggesting that the transplantation of DPSCs could be a promising tool for the treatment of diabetic neuropathy.