Yoshinobu Kondo

Effect of low-protein diet on kidney function in diabetic nephropathy: meta-analysis of randomised controlled trials.

Objective To evaluate the effect of low-protein diet on kidney function in patients with diabetic nephropathy. Design A systematic review and a meta-analysis of randomised controlled trials. Data sources MEDLINE, EMBASE, Cochrane Library, ClinicalTrials.gov, International Standard Randomised Controlled Trial Number (ISRCTN) Register and University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) from inception to 10 December 2012. Internet searches were also carried out with general search engines (Google and Google Scholar). Study selection Randomised controlled trials that compared low-protein diet versus control diet and assessed the effects on kidney function, proteinuria, glycaemic control or nutritional status. Primary and secondary outcome measures and data synthesis The primary outcome was a change in the glomerular filtration rate (GFR). The secondary outcomes were changes in proteinuria, post-treatment value of glycated haemoglobin A1C (HbA1c) and post-treatment value of serum albumin. The results were summarised as the mean difference for continuous outcomes and pooled by the random effects model. Subgroup analyses and sensitivity analyses were conducted regarding patient characteristics, intervention period, methodological quality and assessment of diet compliance. The assessment of diet compliance was performed based on the actual protein intake ratio (APIR) of the low-protein diet group to the control group. Results We identified 13 randomised controlled trials enrolling 779 patients. A low-protein diet was associated with a significant improvement in GFR (5.82 ml/min/1.73 m2, 95% CI 2.30 to 9.33, I2=92%; n=624). This effect was consistent across the subgroups of type of diabetes, stages of nephropathy and intervention period. However, GFR was improved only when diet compliance was fair (8.92, 95% CI 2.75 to 15.09, I2=92% for APIR <0.9 and 0.03, 95% CI −1.49 to 1.56, I2=90% for APIR ≥0.9). Proteinuria and serum albumin were not differed between the groups. HbA1c was slightly but significantly decreased in the low-protein diet group (−0.26%, 95% CI −0.35 to −0.18, I2=0%; n=536). Conclusions Low-protein diet was significantly associated with improvement of diabetic nephropathy. The adverse effects of low-protein diet were not apparent such as worsening of glycaemic control and malnutrition.

Defining criteria for the introduction of liraglutide using the glucagon stimulation test in patients with type 2 diabetes

To define a set of criteria using indices of β‐cell function, including results from the glucagon stimulation test, for liraglutide introduction in patients with type 2 diabetes.

Comparative study of sitagliptin with pioglitazone in Japanese type 2 diabetic patients: the COMPASS randomized controlled trial

To compare the efficacy and safety of these two agents and the impact on surrogate markers related to diabetic complications in Japanese type 2 diabetic patients.

The Effects of Bazedoxifene on Bone, Glucose, and Lipid Metabolism in Postmenopausal Women With Type 2 Diabetes: An Exploratory Pilot Study.

Background Selective estrogen receptor modulators (SERMs) decrease homocysteine and cross-linking of pentosidine and reduce low-density lipoprotein cholesterol (LDL-C), and they are expected to improve bone quality and atherosclerosis. Therefore, the potential effects of bazedoxifene on bone (bone resorption, bone formation, and bone quality), as well as on glucose and lipid metabolism markers, were examined in Japanese postmenopausal women with type 2 diabetes mellitus (T2DM). Methods Eligible patients received 20 mg of bazedoxifene tablets once daily and were followed up for 12 weeks. Bone resorption markers including tartrate-resistant acid phosphatase 5b (TRACP-5b), bone formation markers and bone quality markers such as homocysteine and serum pentosidine, total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and HbA1c were all measured. Results Twenty patients completed this study. All bone resorption markers decreased significantly 4 weeks after bazedoxifene treatment. In particular, TRACP-5b decreased significantly at 12 weeks (median percent change: -20.6%), and the minimum significant change (MSC) achievement rate of TRACP-5b was 65%. Bazedoxifene also decreased bone formation markers. However, bazedoxifene did not improve bone quality markers. LDL-C, HDL-C, and non-HDL-C were decreased, but TG was unchanged. Glucose metabolism was not changed after bazedoxifene treatment. In a subgroup analysis, the group of patients in whom the percent change in TRACP-5b exceeded the MSC had no change in pentosidine levels at 12 weeks. However, in the group of patients in whom the percent change in TRACP-5b did not exceed the MSC, pentosidine levels tended to increase. Conclusions Bazedoxifene may improve bone resorption markers and LDL-C without affecting glucose metabolism in Japanese postmenopausal women with T2DM.

Early liraglutide treatment improves β-cell function in patients with type 2 diabetes: a retrospective cohort study

Preclinical studies on liraglutide have suggested related improvements in β-cell function. Therefore, we investigated these effects in patients with type 2 diabetes (T2D) using the glucagon stimulation test (GST). We conducted a retrospective cohort study of 73 insulin-treated patients with T2D who had their treatment switched to liraglutide monotherapy. Their β-cell function was measured using a 1-mg intravenous GST at baseline and 24 weeks after treatment. The effect of liraglutide treatment on β-cell function was assessed by the change in the area under the curve (AUC) of serum C-peptide immunoreactivity during the GST (AUC-CPR). The AUC-CPR increased after 24 weeks of liraglutide treatment (9.80 ± 0.55 ng/mL⋅min to 11.50 ± 0.52 ng/mL⋅min, p = 0.001). In the univariate and adjusted multivariate regression analyses, a negative relationship between the change in the AUC-CPR and T2D duration was noted (β = -0.22, 95% confidence interval [CI] = -0.35 to -0.09, R(2) = 0.14, p = 0.001 and β = -0.20, 95% CI = -0.34 to -0.05, R2 = 0.23, p = 0.008, respectively). In the analysis using T2D duration tertiles, early liraglutide treatment (T2D duration ≤10 years) significantly improved the AUC-CPR (<4 years: +2.56 ± 0.73 ng/mL⋅min, p = 0.002; 4-10 years: +2.60 ± 0.56 ng/mL⋅min, p < 0.001), whereas late liraglutide treatment did not (>10 years: -0.33 ± 1.15 ng/mL⋅min, p = 0.78). We conclude that early liraglutide treatment potentially improves β-cell function and subsequently glycemic control in patients with T2D, preventing further diabetic complications.

The Effects of Ramelteon on Glucose Metabolism and Sleep Quality in Type 2 Diabetic Patients With Insomnia: A Pilot Prospective Randomized Controlled Trial

Background Insomnia is associated with the onset and development of diabetes. Melatonin affects sleep quality and glucose metabolism in diabetic patients with insomnia. We administered ramelteon, an agonist of melatonin, to type 2 diabetic patients and investigated its effects on glucose metabolism and insomnia. Methods This multicenter, prospective, randomized, and observational pilot study was performed between April 2014 and April 2015 at three institutes in Japan. Patients were prescribed ramelteon 8 mg/day for 3 months (first period). And patients were divided at random into the continuation group that continued taking ramelteon and the discontinuation group that discontinued taking ramelteon for 3 additional months (second period). The primary endpoint was change in glycated hemoglobin (HbA1c) level. Secondary endpoints were changes in global Pittsburgh sleep questionnaire index (PSQI) score and other glucose metabolism makers. Results We enrolled 42 patients, and 32 patients completed the first period. Their mean HbA1c was 6.7%, and global PSQI score was 8.1 on average. HbA1c level did not change but global PSQI score improved from 8.1 to 7.2 by ramelteon (P = 0.030). Thirty-one patients completed the second period. HbA1c level did not change in the continuation group, but it increased from 6.7% to 6.9% (P = 0.003) in the discontinuation group. Global PSQI score did not change in each group. There was no rebound insomnia. Conclusion Treatment with ramelteon did not change the HbA1c level but improved sleep quality in type 2 diabetic patients with insomnia. Discontinuation of ramelteon slightly increased the HbA1c level and did not worsen sleep quality.

A randomized controlled trial of liraglutide versus insulin detemir plus sitagliptin: Effective switch from intensive insulin therapy to the once‐daily injection in patients with well‐controlled type 2 diabetes

This study aimed to compare the efficacy and safety of liraglutide versus insulin detemir plus sitagliptin in Japanese patients with type 2 diabetes treated with a basal‐bolus insulin regimen. In this multicenter, open‐label trial, 90 patients whose diabetes had been controlled well or moderately (glycated hemoglobin [HbA1c] ≤ 7.3%) with basal‐bolus insulin regimen were randomly assigned to a liraglutide group or a detemir group and were followed up for 24 weeks. The primary end point was HbA1c change from baseline to 24 weeks. Of the 90 enrolled patients, 82 completed this trial. At 24 weeks, the mean changes in HbA1c from baseline were 0.1% ± 0.9% versus 0.3% ± 0.8% in the liraglutide versus detemir groups, respectively (P = .46). The “overall” satisfaction score for the Diabetes Treatment Satisfaction Questionnaire changed from 25.2 ± 7.4 to 29.9 ± 5.3 (P < .001) and from 26.4 ± 6.1 to 28.3 ± 6.4 (P = .12) in the liraglutide and detemir groups, respectively. Although the mean change difference in HbA1c between both groups was not significant, switching from a basal‐bolus insulin regimen to liraglutide once daily improved patient satisfaction levels without loss of glycemic control.

Comparison of Azelnidipine and Trichlormethiazide in Japanese Type 2 Diabetic Patients with Hypertension: The COAT Randomized Controlled Trial

Objective This study compared the efficacy and safety of azelnidipine with that of trichlormethiazide in Japanese type 2 diabetic patients with hypertension. Methods In a multicenter, open-label trial, 240 patients with adequately controlled diabetes (HbA1c ≤ 7.0%) under lifestyle modification and/or administration of hypoglycemic agents and inadequately controlled hypertension (systolic blood pressure [sBP] ≥ 130 mmHg or diastolic blood pressure [dBP] ≥ 80 mmHg) who were being treated with olmesartan were enrolled. Participants were randomly assigned to an azelnidipine group or a trichlormethiazide group and were followed up for 48 weeks. Main outcome measure was the difference in the change in HbA1c levels from the baseline values at 48 weeks between these two groups. Results Of the 240 subjects that were enrolled, 209 subjects (azelnidipine group: 103 patients, trichlormethiazide group: 106 patients) completed this trial. At 48 weeks, the following changes were observed in the azelnidipine and trichlormethiazide groups, respectively: HbA1c levels, 0.19 ± 0.52% and 0.19 ± 0.54%; sBP/dBP, -10.7 ± 9.6/-6.6 ± 6.6 mmHg and -7.1 ± 7.7/-3.3 ± 6.1 mmHg (P < 0.001 for both sBP and dBP). In both groups, dizziness (12 patients [11.7%] and 16 patients [15.1%]) and edema (16 patients [15.5%] and 7 patients [6.6%], P = 0.047) were observed during the 48-week follow-up period. Conclusions Azelnidipine was more effective for controlling blood pressure than trichlormethiazide in Japanese type 2 diabetes patients, whereas trichlormethiazide was more effective for reducing albuminuria than azelnidipine. Both of these agents, however, similarly exacerbated glycemic control in type 2 diabetic patients with hypertension. Trial Registration UMIN 000006081.