The effects of ipragliflozin on the liver-to-spleen attenuation ratio as assessed by computed tomography and on alanine transaminase levels in Japanese patients with type 2 diabetes mellitus.

We assessed the effects of a 12-week ipragliflozin treatment on the liver-to-spleen attenuation ratio (L/S ratio) using computed tomography and on alanine transaminase (ALT) levels in Japanese patients with type 2 diabetes mellitus (T2DM). Sixty-two patients with T2DM [age, 56 ± 8 years; hemoglobin A1c (HbA1c) levels, 8.1 ± 0.9%; body mass index (BMI), 27.5 ± 3.3 kg/m2] were randomly assigned in a 2:1 ratio to receive ipragliflozin (50 mg/day; ipragliflozin group; n = 40) or continued treatment (control group; n = 22) for 12 weeks. The primary endpoints were changes in ALT levels; the secondary endpoints included changes in the L/S ratio and in the visceral fat area (VFA) and subcutaneous fat area (SFA) before and after 12 weeks of the treatment as assessed by computed tomography. ALT levels (-12.45 vs. +5.82 IU/l, P < 0.001), L/S ratio (+0.07 vs. -0.08, P < 0.001), SFA (-5.8 vs. +13.3 cm2, P < 0.05), and VFA (+1.4 vs. +20.4 cm2, P < 0.05) significantly changed from baseline in the ipragliflozin group compared with the values in the control group. Multiple regression analysis among all subjects revealed that the independent factor contributing to the %ΔALT and %ΔL/C ratio was treatment group alone (ipragliflozin group = 1; control group = 0; ß coefficient = -32.08, P < 0.001 and ß coefficient = 19.98, P < 0.05, respectively). Thus, ipragliflozin may lower ALT levels associated with increased L/S ratios, indicating its potential therapeutic efficacy in T2DM-associated hepatic steatosis.

Ipragliflozin lowers small, dense low-density lipoprotein cholesterol levels in Japanese patients with type 2 diabetes mellitus.

AIMS: This preliminary randomized, parallel-group comparative study evaluated the efficacy of ipragliflozin for reduction of small dense low-density lipoprotein cholesterol (sd LDL-C) levels in Japanese patients with type 2 diabetes mellitus (T2DM). METHODS: Sixty-two patients with T2DM (age, 56 ± 8 years; hemoglobin A1c levels, 8.1 ± 0.9%; BMI, 27.5 ± 3.3 kg/m2) were randomly assigned in a 2:1 ratio to receive ipragliflozin (50 mg/day) (treatment group; n = 40) or continued treatment (control group; n = 22) for 12 weeks. The primary endpoints were changes in sd LDL-C levels detected using the LipoPhor AS® system; the secondary endpoints included changes in the sd LDL-C/large buoyant LDL-C (lb LDL-C) ratio, a surrogate marker for LDL particle size, and percent changes in routine lipid parameters. RESULTS: The treatment group exhibited a statistically significant reduction from baseline for LDL-C levels (-0.37 mg/dL vs. 14.4 mg/dL, p = 0.038), sd LDL-C levels (-1.28 mg/dL vs. 2.81 mg/dL, p = 0.012), and sd LDL-C/lb LDL-C ratio (-3.20% vs. 4.58%, p = 0.040) compared with the control group. Multiple regression analysis among all subjects revealed change in TG levels (p = 0.011) and LDL-C levels (p = 0.024) as well as change in body weight (p = 0.006) as independent factors contributing to the reduction in sd LDL-C. CONCLUSIONS: Ipragliflozin may have a potential for lowering sd LDL-C levels associated with increasing LDL particle size in Japanese patients with T2DM.

Non-high-density cholesterol level as a predictor of maximum carotid intima-media thickness in Japanese subjects with type 2 diabetes: a comparison with low-density lipoprotein level.

AIM: To determine whether non-high-density lipoprotein cholesterol (non-HDL-C) level, in comparison with low-density lipoprotein cholesterol (LDL-C) level, is useful for predicting the values of various surrogate atherosclerosis markers in Japanese subjects with type 2 diabetes (T2DM). METHODS: Data were retrieved from medical records of 265 subjects with T2DM who underwent laboratory tests to evaluate for atherosclerosis by using the following parameters: brachial-ankle pulse wave velocity, mean and maximum carotid intima-media thickness (mean CIMT and max-CIMT), and ankle-brachial index, with simultaneous fasting blood sampling for routine lipid parameters. RESULTS: In a multiple stepwise regression analysis, non-HDL-C level, but not LDL-C level, positively correlated with max-CIMT (ß coefficient = 0.14, F = 6.84). Stepwise logistic regression analysis revealed that a 0.26 mmol/L (10 mg/dL) increase in non-HDL-C level, but not LDL-C level, was significantly associated with high risk of max-CIMT (≥1.1 mm; odds ratio, 1.096; 95 % confidence interval, 1.003-1.202; p = 0.046). However, in a receiver operating characteristic curve (ROC) analysis, the addition of non-HDL-C level to the three significant independent variables obtained from the stepwise analyses did not significantly increased the area under the ROC curve (from 0.7789 to 0.7864, p = 0.4343). CONCLUSIONS: Non-HDL-C levels may be non-inferior to LDL-C level for the prediction of high-risk max-CIMT in Japanese subjects with T2DM.

Chronic hyperglycemia may attenuate the serum-uric-acid-lowering effect of low-dose febuxostat in Japanese patients with type 2 diabetes mellitus.

AIMS: This study investigated the independent predictors of the serum uric acid (sUA)-lowering effect of low-dose febuxostat, a novel xanthine oxidase inhibitor, in Japanese patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: Data of 130 T2DM patients who had been taking febuxostat 10 mg once daily for elevated sUA (≥7 mg/dl) for at least 12 weeks were retrieved from medical records. Spearman's rank correlation coefficients were calculated to determine the correlations between sets of two independent continuous variables. Multiple stepwise linear regression analysis was used to determine independent predictors of the percent change of sUA levels after 12 weeks of febuxostat treatment (%ΔsUA). RESULTS: Among all patients, %ΔsUA was significantly correlated with age (ρ = 0.192, P = 0.030) and mean glycated hemoglobin (HbA1c) level (ρ = -0.186, P = 0.036). Multiple stepwise linear regression analysis of all patients revealed that major independent factors contributing to %ΔsUA were mean HbA1c (ß = -3.14, P = 0.022) and mean glycated albumin (ß = -0.743, P = 0.013) levels. CONCLUSIONS: High HbA1c and glycated albumin levels significantly attenuated the sUA-lowering effect of low-dose febuxostat in Japanese patients with T2DM. Further detailed analysis using a larger population is warranted to confirm these findings.

Switching from atorvastatin to rosuvastatin lowers small, dense low-density lipoprotein cholesterol levels in Japanese hypercholesterolemic patients with type 2 diabetes mellitus.

AIMS: This open-label, randomized, parallel-group comparative study compared the efficacy of rosuvastatin (5mg/day) and atorvastatin (10mg/day) for reduction of small dense low-density lipoprotein cholesterol (sd LDL-C) levels in Japanese patients with type 2 diabetes mellitus (T2DM). METHODS: Patients with T2DM and hypercholesterolemia with detectable sd LDL-C after receiving 10mg/day atorvastatin for ≥ 24 weeks were randomly assigned to receive rosuvastatin (5mg/day; switched treatment) or atorvastatin (10mg/day; continued treatment) for 12 weeks. The primary endpoints were changes in sd LDL-C levels and sd LDL-C/total LDL-C ratio evaluated using the LipoPhor AS(®) system. RESULTS: There were no significant percent changes from baseline for LDL-C levels between the switched (n=55) and the continued treatment group (n=56). However, the former group exhibited a statistically significant reduction from baseline of sd LDL-C levels, sd LDL-C/total LDL-C ratio compared with the latter group (-3.8 mg/dL vs. -1.4 mg/dL, p=0.014; -2.3% vs. -0.6%, p=0.004, respectively). Multiple regression analysis among all subjects revealed that independent factors contributing to the reduction in sd LDL-C levels were a change in LDL-C (p=0.003) and triglyceride (TG) levels (p=0.006), treatment group (the switched group=1, the continued group=0; standard coefficient=-1.2, p=0.034) and baseline glycated hemoglobin A1c (HbA1c) (p=0.045), respectively. CONCLUSION: Switching from 10mg atorvastatin to 5mg rosuvastatin may be a useful therapeutic option to reduce sd LDL-C levels in Japanese hypercholesterolemic patients with T2DM.

Obesity may attenuate the HbA1c-lowering effect of sitagliptin in Japanese type 2 diabetic patients.

UNLABELLED: Aims/Introduction: The aim of the present study was to assess the independent predictors of the HbA1c-lowering effect of sitagliptin in Japanese type 2 diabetic patients. MATERIALS AND METHODS: Data were retrieved from the medical records of 151 type 2 diabetic patients who had been taking sitagliptin 25 or 50 mg once daily for inadequate glycemic control for at least 12 weeks, with or without other oral hypoglycemic agents. Spearman's rank correlation coefficients were calculated to investigate correlations between two independent continuous variables. Multiple stepwise regression analysis was used to identify independent predictors of reductions in HbA1c levels after 12 weeks of sitagliptin treatment (ΔHbA1c). RESULTS: In all patients combined, Spearman's rank correlation coefficients showed that ΔHbA1c was significantly correlated with baseline HbA1c alone (r = 0.371, P < 0.0001). However, multiple linear regression analysis among all patients using baseline variables revealed that the independent factors contributing to ΔHbA1c, in order of importance, were method of prescribing (P < 0.0001), baseline HbA1c (P < 0.0001), body mass index (BMI; P = 0.004), and duration of diabetes (P = 0.024). CONCLUSIONS: Our analysis may provide novel evidence that increased BMI contributes, in part, to attenuation of the HbA1c-lowering effect of sitagliptin in Japanese type 2 diabetic patients. Analysis of a larger population over a longer period of time is warranted to confirm these findings. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00156.x, 2011).

Improvement of cardiac function after treatment with octreotide followed by trans-sphenoidal surgery in an acromegalic patient who presented with congestive heart failure.

Cardiovascular disease is a major cause of mortality and morbidity in patients with acromegaly. We describe the case of a 43-year-old man with acromegaly who presented with severe congestive heart failure. Treatment with the somatostatin analog octreotide improved cardiac function with an increase in left ventricular ejection fraction (LVEF) from 11% to 27%. LVEF further increased to 43% after trans-sphenoidal surgery. Recovery was uneventful. We emphasize the need for early diagnosis and effective treatment of acromegaly to prevent cardiovascular complications. Octreotide therapy or trans-sphenoidal surgery, if possible, should be considered to control cardiac function even in acromegalic patients with severe congestive heart failure.