Hisato Tatsuoka

Possible link of pioglitazone with bladder cancer in Japanese patients with type 2 diabetes

We retrospectively examined the frequency of bladder cancer in Japanese patients with type 2 diabetes in relation to use of pioglitazone. Among a total of 663 patients identified to be taking pioglitazone, 9 had bladder cancer (1.36%). Overall the hazard ratio of 1.75 [95% CI: 0.89-3.45] for pioglitazone for bladder cancer was not significant. However the prevalence of bladder cancer was 2.10% in patients taking pioglitazone for less than 24 months which was significant increased (HR 2.73 [95% CI: 1.11-6.72]).

The Eradication of Helicobacter pylori does not Affect Glycemic Control in Japanese Subjects with Type 2 Diabetes

Since infection with Helicobacter pylori has been suggested to play a pathogenic role in diabetes mellitus, we investigated whether eradication therapy for H. pylori might affect glycemic control in Japanese subjects with type 2 diabetes. A total of 72 subjects (55 males, 17 females; aged 63.7 years) with type 2 diabetes who received eradication therapy for H. pylori were included. The change of their blood glycosylated hemoglobin (A1C) levels 3 months before (−3 m) the H. pylori eradication, as well as 3 months (3 m) and 6 months (6 m) after were evaluated. Their A1C levels did not show any significant change after therapy {6.9 [0.1]% (−3 m) to 7.0 [0.1]% (3 m); P = 0.3, 7.0 [0.1] (6 m); P = 0.3}. Our findings suggest that the eradication therapy for H. pylori does not, at least profoundly, affect glycemic control in Japanese subjects with type 2 diabetes.

Src regulates insulin secretion and glucose metabolism by influencing subcellular localization of glucokinase in pancreatic β‐cells

Src, a non‐receptor tyrosine kinase, regulates a wide range of cellular functions, and hyperactivity of Src is involved in impaired glucose metabolism in pancreatic β‐cells. However, the physiological role of Src in glucose metabolism in normal, unstressed β‐cells remains unclear. In the present study, we investigated the role of Src in insulin secretion and glucose metabolism.

Relationship between telmisartan dose and glycaemic control in Japanese patients with type 2 diabetes mellitus and hypertension: a retrospective study.

BACKGROUND AND OBJECTIVES Telmisartan has been reported to have beneficial effects on insulin resistance and lipid profiles by acting as a peroxisome proliferator-activated receptor-γ (PPARγ) agonist. In this study we investigated the relationship between telmisartan dose and glycaemic control in Japanese subjects with type 2 diabetes mellitus and hypertension. METHODS Patients (n = 263) who were prescribed telmisartan 20, 40 or 80 mg/day at our clinic were retrospectively identified from our clinical database. Only patients without changes in their treatments for diabetes and hypertension for 6 months after starting telmisartan were included in this study. Glycosylated haemoglobin A(1c) (HbA(1c)) levels were measured at 0, 3 and 6 months after starting telmisartan. RESULTS At 3 and 6 months after starting telmisartan, HbA(1c) levels were significantly decreased in patients treated with telmisartan 40 or 80 mg/day but not in patients treated with telmisartan 20 mg/day (mean ± standard error change at 6 months: -0.29 ± 0.10%, p < 0.001; -0.48 ± 0.15%, p < 0.001; and -0.03 ± 0.10%, p = 0.33; respectively). When patients were classified into two groups by telmisartan dose (20 vs ≥40 mg/day), there was no significant correlation between baseline HbA(1c) and change in HbA(1c) levels over time in the 20 mg/day group. However, in patients treated with ≥40 mg/day of telmisartan, baseline HbA(1c) was negatively correlated with the change in HbA(1c) at 6 months. Multiple regression analysis confirmed that baseline HbA(1c) and telmisartan dose were the predictive factors. CONCLUSION Our results suggest that telmisartan influences glycaemic control in a dose-dependent manner; doses ≥40 mg/day may be needed to improve glycaemic control. Our data also suggest that patients with higher baseline HbA(1c) may experience greater improvements in glycaemic control with telmisartan.

Relationship between Telmisartan Dose and Glycaemic Control in Japanese Patients with Type 2 Diabetes Mellitus and Hypertension

AbstractBackground and Objectives: Telmisartan has been reported to have beneficial effects on insulin resistance and lipid profiles by acting as a peroxisome proliferator-activated receptor-γ (PPARγ) agonist. In this study we investigated the relationship between telmisartan dose and glycaemic control in Japanese subjects with type 2 diabetes mellitus and hypertension. Methods: Patients (n = 263) who were prescribed telmisartan 20, 40 or 80 mg/day at our clinic were retrospectively identified from our clinical database. Only patients without changes in their treatments for diabetes and hypertension for 6 months after starting telmisartan were included in this study. Glycosylated haemoglobin A1c (HbA1c) levels were measured at 0, 3 and 6 months after starting telmisartan. Results: At 3 and 6 months after starting telmisartan, HbA1c levels were significantly decreased in patients treated with telmisartan 40 or 80 mg/day but not in patients treated with telmisartan 20 mg/day (mean ± standard error change at 6 months: −0.29 ± 0.10%, p<0.001; −0.48 ± 0.15%, p<0.001; and −0.03 ± 0.10%, p = 0.33; respectively). When patients were classified into two groups by telmisartan dose (20 vs ≥40 mg/day), there was no significant correlation between baseline HbA1c and change in HbA1c levels over time in the 20 mg/day group. However, in patients treated with ≥40 mg/day of telmisartan, baseline HbA1c was negatively correlated with the change in HbA1c at 6 months. Multiple regression analysis confirmed that baseline HbA1c and telmisartan dose were the predictive factors. Conclusion: Our results suggest that telmisartan influences glycaemic control in a dose-dependent manner; doses ≥40 mg/day may be needed to improve glycaemic control. Our data also suggest that patients with higher baseline HbA1c may experience greater improvements in glycaemic control with telmisartan.

Reply to the comment of Wilbrink et al. on Retrospective analysis of liraglutide and basal insulin combination therapy in Japanese type 2 diabetes: The association between remaining β-cell function and the achievement of the HbA1c target 1 year after init

We have reported that the HbA1c‐lowering effects of liraglutide/basal insulin combination rely on remaining β‐cell function and that the cut‐off value of the C‐peptide immunoreactivity index (CPI), a β‐cell function‐related index frequently used in Japanese clinical settings, is 1.103 for the achievement of HbA1c <7.0% at 54 weeks after initiating the liraglutide/basal insulin combination. Wilbrink et al claimed that glucose‐lowering effects of glucagon‐like peptide‐1 receptor agonist liraglutide depend of duration of type 2 diabetes; while our resent study published in the Journal of Diabetes Investigation failed to detect such dependency. This discrepancy might be due to several reasons including co‐administration of basal insulin with liraglutide in our study; ethnic difference in T2D pathophysiology between the two study; and difference in sample size (The Usui study on liraglutide/basal insulin, n = 38; the Usui study on liraglutide monotherapy or SU combination, n=88; and the Wilbrink study, n = 69).

Relationship between deterioration of glycated hemoglobin‐lowering effects in dipeptidyl peptidase‐4 inhibitor monotherapy and dietary habits: Retrospective analysis of Japanese individuals with type 2 diabetes

The present study was designed to assess possible relationships between deterioration of the glycated hemoglobin (HbA1c)‐lowering effects in dipeptidyl peptidase‐4 inhibitor (DPP4i) monotherapy and macronutrient intake among individuals with type 2 diabetes. Type 2 diabetes patients who began and continued DPP4i monotherapy without any prescription change for 1 year were retrospectively stratified into two groups: (i) patients who maintained their HbA1c levels during the 0.5‐ to 1‐year period after DPP4i initiation (group A, ΔHbA1c [1–0.5 year] <0.4%, n = 53); and (ii) those whose HbA1c levels increased [group B, ΔHbA1c (1–0.5 year] ≥0.4%, n = 10). Group B had significantly higher ΔHbA1c (1–0.5 year), Δbodyweight (1–0.5 year) and fat intake, especially of saturated and monounsaturated fats; the carbohydrate and protein intake were similar between groups. Multiple regression analyses showed that fat intake, especially saturated fat intake, was significantly correlated with ΔHbA1c (1–0.5 year). Thus, dietary habits, especially saturated fat intake, might well contribute to deterioration of the HbA1c‐lowering effects in DPP4i monotherapy.

Retrospective analysis of liraglutide and basal insulin combination therapy in Japanese type 2 diabetes patients: The association between remaining β-cell function and the achievement of the glycated hemoglobin target 1 year after initiation

The glucose‐lowering effects of the glucagon‐like peptide‐1 receptor agonist, liraglutide, have been shown to rely on remaining β‐cell function. However, the possible associations of remaining β‐cell function with the glucose‐lowering effects of liraglutide in combination with basal insulin remain unknown and warrant investigation.