Associations of Plasma Concentration Profiles of Dapagliflozin, a Selective Inhibitor of Sodium-Glucose Co-Transporter Type 2, with Its Effects in Japanese Patients with Type 2 Diabetes Mellitus.

This study was conducted to evaluate the long-term plasma concentration profiles of dapagliflozin and its effects on the glycated hemoglobin (HbA1c) level, body weight, and estimated glomerular filtration rate (eGFR) in 72 Japanese outpatients with type 2 diabetes mellitus (T2DM) receiving metformin and a dipeptidyl peptidase-4 inhibitor. At baseline, HbA1c level, body weight, and eGFR were 6.9 ± 0.

Mealtime dosing of a rapid-acting insulin analog reduces glucose variability and suppresses daytime cardiac sympathetic activity: a randomized controlled study in hospitalized patients with type 2 diabetes.

Objective: Glucose variability induces endothelial dysfunction and cardiac autonomic nerve abnormality. Here we compared the effects of mealtime insulin aspart and bedtime insulin detemir on glucose variability, endothelial function, and cardiac autonomic nerve activity among Japanese patients with type 2 diabetes.

Research Design And Methods: Forty hospitalized patients received either mealtime insulin aspart or bedtime insulin detemir treatment for 2 weeks.

Effects of metformin and alogliptin on body composition in people with type 2 diabetes.

Aims/introduction: The aim of the present study was to investigate the effects of metformin and a dipeptidyl peptidase-4 inhibitor, alogliptin, on body composition in a 12-week randomized add-on trial in Japanese participants with type 2 diabetes.

Materials And Methods: A total of 84 participants with poorly controlled type 2 diabetes undergoing antidiabetic therapy were randomly assigned to receive alogliptin (25 mg, once daily) or metformin (1,000 mg, twice daily) for 12 weeks. The primary efficacy end-point was body composition.

Ursodeoxycholic acid potentiates dipeptidyl peptidase-4 inhibitor sitagliptin by enhancing glucagon-like peptide-1 secretion in patients with type 2 diabetes and chronic liver disease: a pilot randomized controlled and add-on study.

Objective: We evaluated the effects of ursodeoxycholic acid (UDCA) on glucagon-like peptide-1 (GLP-1) secretion and glucose tolerance in patients with type 2 diabetes with chronic liver disease.

Research Design And Methods: Japanese patients with type 2 diabetes (glycated hemoglobin (HbA1c) levels ≥7.0%) and chronic liver disease were included in this study.

Pleiotropic effects of sitagliptin versus voglibose in patients with type 2 diabetes inadequately controlled via diet and/or a single oral antihyperglycemic agent: a multicenter, randomized trial.

Purpose: A step-up strategy for diet therapy and/or single oral antihyperglycemic agent (OHA) regimens has not yet been established. The aim of this study was to evaluate hemoglobin A1c (HbA1c) as a primary end point, and the pleiotropic effects on metabolic and cardiovascular parameters as secondary end points, of sitagliptin versus voglibose in patients with type 2 diabetes with inadequate glycemic control while on diet therapy and/or treatment with a single OHA.

Methods: In this multicenter, randomized, open-label, parallel-group trial, a total of 260 patients with inadequately controlled type 2 diabetes (HbA1c levels >6.

Sitagliptin versus mitiglinide switched from mealtime dosing of a rapid-acting insulin analog in patients with type 2 diabetes: a randomized, parallel-group study.

Purpose: We determined the feasibility of substituting sitagliptin or mitiglinide for bolus insulin injection therapy in patients with type 2 diabetes.

Methods: 60 patients with type 2 diabetes were enrolled and randomized to switch from mealtime dosing of a rapid-acting insulin analog to either sitagliptin or mitiglinide for 16 weeks.

Results: Body weight, body mass index, and waist circumference decreased significantly in both groups at the end of the study.

Renoprotective effects of atorvastatin compared with pravastatin on progression of early diabetic nephropathy.

Introduction: Several studies have shown that statins suppress the progression of diabetic nephropathy. However, few reports have directly compared the renoprotective effects between potent and conventional statins.

Materials And Methods: Patients with diabetic nephropathy, selected as those with a serum creatinine level of 0.

Vildagliptin vs liraglutide as a second-line therapy switched from sitagliptin-based regimens in patients with type 2 diabetes: A randomized, parallel-group study.

Introduction: A step-up strategy for dipeptidyl peptidase (DPP)-4 inhibitor-based regimens has not yet been established. In addition, similarities and differences between DPP-4 inhibitors and glucagon-like peptide (GLP)-1 receptor agonists remain to be elucidated in humans. We investigated the pleiotropic effects of vildagliptin vs liraglutide in patients with type 2 diabetes on sitagliptin-based regimens in an open-label, randomized, clinical trial.

Liver steatosis is associated with insulin resistance in skeletal muscle rather than in the liver in Japanese patients with non-alcoholic fatty liver disease.

Aims/introduction: To examine the association between liver histological features and organ-specific insulin resistance indices calculated from 75-g oral glucose tolerance test data in patients with non-alcoholic fatty liver disease.

Materials And Methods: Liver biopsy specimens were obtained from 72 patients with non-alcoholic fatty liver disease, and were scored for steatosis, grade and stage. Hepatic and skeletal muscle insulin resistance indices (hepatic insulin resistance index and Matsuda index, respectively) were calculated from 75-g oral glucose tolerance test data, and metabolic clearance rate was measured using the euglycemic hyperinsulinemic clamp method.

Ectopic fat accumulation and distant organ-specific insulin resistance in Japanese people with nonalcoholic fatty liver disease.

Objective: The aim of this study was to examine the association between ectopic fat and organ-specific insulin resistance (IR) in insulin-target organs in patients with nonalcoholic fatty liver disease (NAFLD).

Methods: Organ-specific IR in the liver (hepatic glucose production (HGP) × fasting plasma insulin (FPI) and suppression of HGP by insulin [%HGP]), skeletal muscle (insulin-stimulated glucose disposal [Rd]), and adipose tissue (suppression of FFA by insulin [%FFA]) was measured in 69 patients with NAFLD using a euglycemic hyperinsulinemic clamp with tracer infusion ([6,6-2H2]glucose). Liver fat, intramyocellular lipid (IMCL), and body composition were measured by liver biopsy, proton magnetic resonance spectroscopy, and bioelectrical impedance analysis, respectively.

The effects of ezetimibe on non-alcoholic fatty liver disease and glucose metabolism: a randomised controlled trial.

Aims/hypothesis: The cholesterol absorption inhibitor ezetimibe has been shown to ameliorate non-alcoholic fatty liver disease (NAFLD) pathology in a single-armed clinical study and in experimental animal models. In this study, we investigated the efficacy of ezetimibe on NAFLD pathology in an open-label randomised controlled clinical trial.

Methods: We had planned to enrol 80 patients in the trial, as we had estimated that, with this sample size, the study would have 90% power.

Proteasome dysfunction mediates obesity-induced endoplasmic reticulum stress and insulin resistance in the liver.

Chronic endoplasmic reticulum (ER) stress is a major contributor to obesity-induced insulin resistance in the liver. However, the molecular link between obesity and ER stress remains to be identified. Proteasomes are important multicatalytic enzyme complexes that degrade misfolded and oxidized proteins.

Metformin prevents and reverses inflammation in a non-diabetic mouse model of nonalcoholic steatohepatitis.

Background: Optimal treatment for nonalcoholic steatohepatitis (NASH) has not yet been established, particularly for individuals without diabetes. We examined the effects of metformin, commonly used to treat patients with type 2 diabetes, on liver pathology in a non-diabetic NASH mouse model.

Methodology/principal Findings: Eight-week-old C57BL/6 mice were fed a methionine- and choline-deficient plus high fat (MCD+HF) diet with or without 0.

Duodenal adenocarcinoma with neuroendocrine features in a patient with acromegaly and thyroid papillary adenocarcinoma: a unique combination of endocrine neoplasia.

A 67-year-old woman with familial clustering of thyroid papillary adenocarcinoma was diagnosed with acromegaly due to pituitary macroadenoma. She had multiple skin vegetations, but had no parathyroid and pancreas diseases. Before transsphenoidal surgery, she was further diagnosed as having a duodenal tumor and multiple hypervascular liver nodules.

Pharmacokinetics and pharmacodynamics of insulin aspart in patients with type 2 diabetes: assessment using a meal tolerance test under clinical conditions.

1. Few studies have evaluated the pharmacokinetics of rapid-acting insulin analogues in patients with Type 2 diabetes, especially under clinical conditions. The aim of the present study was to assess both the pharmacokinetics and pharmacodynamics of insulin aspart in Type 2 diabetic patients who were being treated with the analogue alone.

Carcinosarcoma of the liver.

Herein we present a 73-year-old man with primary carcinosarcoma of the liver, a rare malignant tumor of the liver. The case was followed up due to HBV-related liver cirrhosis. Regular check-up by ultrasound demonstrated a hyperechoic tumor in the left lobe of the liver, and he was referred and admitted to our hospital.

Possible role of alpha-cell insulin resistance in exaggerated glucagon responses to arginine in type 2 diabetes.

Objective: Inappropriate excessive secretion of glucagon, which contributes to postprandial hyperglycemia, is a novel target for the treatment of diabetes. In this study, we sought to determine the factors associated with exaggerated glucagon secretion in response to an arginine challenge in patients with type 1 and type 2 diabetes.

Research Design And Methods: Changes in circulating C-peptide immunoreactivity (CPR) and immunoreactive glucagon (IRG) after an arginine challenge were investigated in 35 patients with type 1 diabetes, 130 patients with type 2 diabetes, and 35 nondiabetic control subjects.