Long-term efficacy and safety of canagliflozin in combination with insulin in Japanese patients with type 2 diabetes mellitus

Aim: The aim of this study was to assess the long-term efficacy and safety of canagliflozin as add-on therapy in Japanese patients with type 2 diabetes mellitus who had inadequate glycaemic control with insulin. Materials and methods: The study comprised a 16-week, double-blind period in which patients were randomized to either placebo (P; N = 70) or canagliflozin (100 mg, CAN; N = 76), followed by a 36-week open-label period in which all patients received canagliflozin. The efficacy endpoints included the change in HbA1c from baseline to end of treatment. The safety endpoints were adverse events, hypoglycaemic events, and laboratory test values. Results: The changes from baseline (mean ± standard deviation, last observation carried forward) in the P/CAN and CAN/CAN groups, respectively, were −1.09% ± 0.85% and −0.88% ± 0.86% for HbA1c, −1.40% ± 2.54% and −2.14% ± 2.75% for body weight, and 7.84% ± 14.37% and 8.91% ± 10.80% for HOMA2-%B (all, P < .001). Adverse events occurred in 85.1% of the P/CAN group and 92.0% of the CAN/CAN group. Hypoglycaemic events occurred in 43.3% and 54.7%, respectively. All hypoglycaemic events were mild in severity and insulin dose reduction decreased the incidence rate of hypoglycaemic events. Post-hoc ordinal logistic modelling/logistic modelling showed that lower serum C-peptide at Week 0 was a risk factor for hypoglycaemia in both the P and CAN groups in the double-blind period as well as in the canagliflozin all-treatment period. Conclusions: This study demonstrates the long-term efficacy and safety of canagliflozin combined with insulin in Japanese patients

Color record in self-monitoring of blood glucose improves glycemic control by better self-management.

[Background] Color affects emotions, feelings, and behaviors. We hypothesized that color used in self-monitoring of blood glucose (SMBG) is helpful for patients to recognize and act on their glucose levels to improve glycemic control. Here, two color-indication methods, color record (CR) and color display (CD), were independently compared for their effects on glycemic control in less frequently insulin-treated type 2 diabetes. [Subjects and Methods] One hundred twenty outpatients were randomly allocated to four groups with 2×2 factorial design: CR or non-CR and CD or non-CD. Blood glucose levels were recorded in red or blue pencil in the CR arm, and a red or blue indicator light on the SMBG meter was lit in the CD arm, under hyperglycemia or hypoglycemia, respectively. The primary end point was difference in glycated hemoglobin (HbA1c) reduction in 24 weeks. Secondary end points were self-management performance change and psychological state change. [Results] HbA1c levels at 24 weeks were significantly decreased in the CR arm by −0.28% but were increased by 0.03% in the non-CR arm (P=0.044). In addition, diet and exercise scores were significantly improved in the CR arm compared with the non-CR arm. The exercise score showed significant improvement in the CD arm compared with the non-CD arm but without a significant difference in HbA1c reduction. Changes in psychological states were not altered between the arms. [Conclusions] CR has a favorable effect on self-management performance without any influence on psychological stress, resulting in improved glycemic control in type 2 diabetes patients using less frequent insulin injection. Thus, active but not passive usage of color-indication methods by patients is important in successful SMBG

Carbohydrate intake is associated with time spent in the euglycemic range in patients with type 1 diabetes.

[Aims/Introduction]Greater glycemic variability and lack of predictability are important issues for patients with type 1 diabetes. Dietary factors are one of the contributors to this variability, but how closely diet is linked to glycemic fluctuation on a daily basis has not been investigated. We examined the association between carbohydrate intake and glycemic excursion in outpatients. [Materials and Methods]A total of 33 patients with type 1 diabetes were included in the analyses (age 44.5 ± 14.7 years, diabetes duration 15.1 ± 8.3 years, 64% female, 30% using insulin pump, glycated hemoglobin 8.1 ± 1.3%). Time spent in euglycemia (70–180 mg/dL), hyperglycemia (>180 mg/dL) and hypoglycemia (<70 mg/dL) of consecutive 48-h periods of continuous glucose monitoring data were collected together with simultaneous records of dietary intake, insulin dose and physical activity. Correlation analyses and multiple regression analyses were used to evaluate the contribution of carbohydrate intake to time spent in the target glycemic range. [Results]In multiple regression analyses, carbohydrate intake (β = 0.53, P = 0.001), basal insulin dose per kg per day (β = −0.31, P = 0.034) and diabetes duration (β = 0.30, P = 0.042) were independent predictors of time spent in euglycemia. Carbohydrate intake (β = −0.51, P = 0.001) and insulin pump use (β = −0.34, P = 0.024) were independent predictors of time spent in hyperglycemia. Insulin pump use (β = 0.52, P < 0.001) and bolus insulin dose per kg per day (β = 0.46, P = 0.001) were independent predictors of time spent in hypoglycemia. [Conclusions]Carbohydrate intake is associated with time spent in euglycemia in patients with type 1 diabetes

GLP-1 receptor agonist attenuates endoplasmic reticulum stress-mediated β-cell damage in Akita mice.

[Aims/Introduction]:  Endoplasmic reticulum (ER) stress is one of the contributing factors in the development of type 2 diabetes. To investigate the cytoprotective effect of glucagon-like peptide 1 receptor (GLP-1R) signaling in vivo, we examined the action of exendin-4 (Ex-4), a potent GLP-1R agonist, on β-cell apoptosis in Akita mice, an animal model of ER stress-mediated diabetes. [Materials and Methods]:  Ex-4, phosphate-buffered saline (PBS) or phlorizin were injected intraperitoneally twice a day from 3 to 5 weeks-of-age. We evaluated the changes in blood glucose levels, bodyweights, and pancreatic insulin-positive area and number of islets. The effect of Ex-4 on the numbers of C/EBP-homologous protein (CHOP)-, TdT-mediated dUTP-biotin nick-end labeling (TUNEL)- or proliferating cell nuclear antigen-positive β-cells were also evaluated. [Results]:  Ex-4 significantly reduced blood glucose levels and increased both the insulin-positive area and the number of islets compared with PBS-treated mice. In contrast, there was no significant difference in the insulin-positive area between PBS-treated mice and phlorizin-treated mice, in which blood glucose levels were controlled similarly to those in Ex-4-treated mice. Furthermore, treatment of Akita mice with Ex-4 resulted in a significant decrease in the number of CHOP-positive β-cells and TUNEL-positive β-cells, and in CHOP mRNA levels in β-cells, but there was no significant difference between the PBS-treated group and the phlorizin-treated group. Proliferating cell nuclear antigen staining showed no significant difference among the three groups in proliferation of β-cells. [Conclusions]:  These data suggest that Ex-4 treatment can attenuate ER stress-mediated β-cell damage, mainly through a reduction of apoptotic cell death that is independent of lowered blood glucose levels

Long-term Effect of Color Record Method in Self-monitoring of Blood Glucose on Metabolic Parameters in Type 2 Diabetes: A 2-year Follow-up of the Color IMPACT Study

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