Sitagliptin monotherapy has better effect on insulinogenic index than glimepiride monotherapy in Japanese patients with type 2 diabetes mellitus: a 52-week, multicenter, parallel-group randomized controlled trial.

BACKGROUND: The 52-week monotherapy with the dipeptidyl peptidase-4 inhibitor sitagliptin and the sulphonylurea glimepiride on early-phase insulin secretion in Japanese patients with type 2 diabetes mellitus (T2DM) is not known. METHODS: A randomized, parallel-group, open-label trial was conducted at 18 centers between February, 2011 and March, 2013. 171 outpatients with T2DM were recruited and randomly assigned to glimepiride or sitagliptin by minimization. Doses of glimepiride (0.25-1.0 mg/day) and sitagliptin (25-100 mg/day) were adjusted for hemoglobin A1c (HbA1c) > 6.9 %. Analyses were performed on full analysis set (FAS) of randomized subjects taking medications as allocated, and underwent 75 g oral glucose tolerance test (OGTTs) before and after treatment. The primary outcome was insulinogenic index to quantify early-phase insulin secretion after treatment, which was evaluated by analysis of covariance (ANCOVA). RESULTS: Of 171 enrolled subjects, 68 in the sitagliptin group and 65 in the glimepiride group were included in the FAS (mean age, 64 years; baseline (HbA1c), 7.4 %). The primary outcome revealed a significantly higher insulinogenic index in the sitagliptin group than that in the glimepiride group (p = 0.036). Sitagliptin also reduced plasma glucose levels at 60 and 120 min during OGTT compared with glimepiride, while achieving a similar improvement in HbA1c during treatment. Body weight did not change in either of the two groups, and one case of hypoglycemia was observed in the glimepiride group. CONCLUSIONS: Sitagliptin shows better effects on insulinogenic index after 52-week treatment compared with glimepiride in Japanese patients with T2DM. Trial registration University hospital Medical Information Network (UMIN) Clinical Trials Registry, No.00004791.

Enteral supplementation with glutamine, fiber, and oligosaccharide modulates incretin and glucagon-like peptide-2 secretion.

AIMS/INTRODUCTION: A dietary supplementation product enriched with glutamine, dietary fiber and oligosaccharide (GFO) is widely applied for enteral nutrition support in Japan. The aim of the present study was to evaluate the effects of GFO ingestion on secretion of incretins, gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), and glucagon-like peptide-2 (GLP-2). MATERIALS AND METHODS: We carried out a cross-over study involving 20 healthy Japanese volunteers. The participants received GFO or 17 g of glucose, the equivalent carbohydrate in GFO as the control. Plasma glucose, serum insulin, and plasma total GIP, total GLP-1 and total GLP-2 levels during GFO or glucose loading were determined. RESULTS: GFO loading produced significantly higher plasma GLP-1 levels at 30 min and 60 min, area under the curve-GLP-1 value, and area under the curve-GLP-2 value after administration compared with those by glucose loading. In contrast, plasma GIP levels at both 30 and 60 min, and area under the curve-GIP value after glucose loading were significantly higher than those after GFO loading. CONCLUSIONS: These results show that GFO ingestion stimulates GLP-1 and GLP-2 secretion, and reduces GIP secretion compared with glucose ingestion. Therefore, GFO could have an intestinotrophic effect as well as an ameliorating effect on metabolic disorders through modification of release of gut hormones.

A hospital-based cross-sectional study to develop an estimation formula for 2-h post-challenge plasma glucose for screening impaired glucose tolerance.

AIMS: To create and validate an estimation formula for 2-h post-challenge plasma glucose (2-hPG) as an alternative to oral glucose tolerance test (OGTT) for impaired glucose tolerance (IGT) screening. METHODS: 380 Japanese subjects (57.6% males, aged 58.5 (14.0); mean (SD) years) undergoing OGTT were included in this hospital-based cross-sectional study mainly at Kyoto University Hospital between 2000 and 2011. We determined the main predictive variables of 2-hPG from clinical variables and separated the subjects randomly into two groups: a derivation group to construct an estimation formula of 2-hPG on the basis of predictive variables and a validation group to evaluate the accuracy of the formula. RESULTS: Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) were highly correlated with 2-hPG measured by OGTT. Multiple linear regression analysis showed that estimated 2-hPG (e2-hPG) was calculated by the formula: e2-hPG = 1.66 × FPG (mmol/l) + 1.63 × HbA1c (%)-10.11 (R(2), coefficient of determination=60.2%). When the cut-off value was set to the diagnostic criteria of IGT, 7.8 mmol/l of e2-hPG, sensitivity, specificity, and negative predictive value (NPV) were 83.3%, 44.1%, and 74.3%, respectively. When the cut-off value was set lower (7.2 mmol/l), these values were 94.4%, 30.5%, and 85.7%, respectively. The area under the receiver operating characteristic (ROC) curve was 0.68. CONCLUSIONS: This high-sensitive estimation formula may be a useful alternative to OGTT for IGT screening. For the levels ≤ 7.2 mmol/l, this formula may also be useful in cross-sectional study to identify people whose glucose tolerance is normal.

An autopsy case of chronic progressive external ophthalmoplegia with renal insufficiency.

An autopsy of a 44-year-old Japanese woman with mitochondrial cytopathy confirmed the presence of chronic progressive external ophthalmoplegia (CPEO). Immunohistochemistry using antimitochondrial antibody was performed to observe the ultrastructure of the skeletal muscle and renal tissues. The patient was born of consanguineous parents, developed normally, and was of average intelligence. At 22 years of age, the patient noticed hearing loss, and subsequently, over time, developed a progressive generalized muscle weakness, which included limitation of eye movement and ptosis. At age 41, a muscle biopsy was performed using the modified Gomori trichrome method and demonstrated the presence of ragged red fibers. After the evaluation of her results in conjunction with her clinical course, she was diagnosed with CPEO. Renal insufficiency was discovered at age 30, and the patient died at the age of 44 of respiratory failure caused by respiratory muscle weakness and pneumonia. The autopsy revealed fiber size variation within the skeletal muscle, and an antimitochondrial antibody analysis demonstrated the accumulation of mitochondria between the bundles of myofibrils, as well as in subsarcolemmal locations. Ultrastructurally, abnormal mitochondria with disoriented cristae and paracrystalline inclusions were seen. Although no remarkable histological changes were noted in the kidneys, tubular epithelial cells exhibited accumulated abnormal mitochondria, similar to those seen in the skeletal muscle. Because mitochondrial diseases can affect other energy-dependent organs in addition to the skeletal muscle, immunohistochemical examinations employing an antimitochondrial antibody are useful for obtaining further ultrastructural observations that can assist in making a distinct diagnosis of this systemic disorder.