Noriko Takebe

Psychosocial factors are independent risk factors for the development of Type 2 diabetes in Japanese workers with impaired fasting glucose and/or impaired glucose tolerance

Aims  We prospectively studied Japanese workers with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) and analysed possible risk factors for diabetes, including psychosocial factors such as stress.

Association of Advanced Glycation End Products with coronary Artery Calcification in Japanese Subjects with Type 2 Diabetes as Assessed by Skin Autofluorescence

Aim: Advanced glycation end products (AGE) are considered to be among the critical pathogenic factors involved in the progression of diabetic complications. Skin autofluorescence (AF), a noninvasive measurement of AGE accumulation, has been recognized as a useful and convenient marker for diabetic vascular diseases in Caucasians. This study aimed to evaluate the association of tissue AGE, assessed using skin AF, with coronary artery calcification in Japanese subjects with type 2 diabetes. Methods: In total, 122 Japanese subjects with type 2 diabetes enrolled in this cross-sectional study underwent multi-slice computed tomography for total coronary artery calcium scores (CACS) estimation and examination with a skin AF reader. Results: Skin AF positively correlated with age, sex, diabetes duration, pulse wave velocity, systolic blood pressure, serum creatinine, and CACS. In addition, skin AF results negatively correlated with BMI, eGFR, and serum C-peptide concentration. According to multivariate analysis, age and systolic blood pressure showed strong positive correlation and eGFR showed negative correlation with skin AF values. Multiple linear regression analyses revealed a significant positive correlation between skin AF values and logCACS, independent of age, sex, diabetes duration, HbA1c, BMI, IMT, and blood pressure. However, skin AF showed no association with serum levels of AGE, such as Nε-(carboxymethyl) lysine and 3-deoxyglucosone. Conclusion: Skin AF results positively correlated with CACS in Japanese subjects with type 2 diabetes. This result indicates that AGE plays a role in the pathogenesis of diabetic macrovascular disease. Measurement of skin AF values may be useful for assessing the severity of diabetic complications in Japanese subjects.

Analysis of cell cycle-related proteins in gastric intramucosal differentiated-type cancers based on mucin phenotypes: a novel hypothesis of early gastric carcinogenesis based on mucin phenotype

BackgroundAbnormalities of cell cycle regulators are common features in human cancers, and several of these factors are associated with the early development of gastric cancers. However, recent studies have shown that gastric cancer tumorigenesis was characterized by mucin expression. Thus, expression patterns of cell cycle-related proteins were investigated in the early phase of differentiated-type gastric cancers to ascertain any mechanistic relationships with mucin phenotypes.MethodsImmunostaining for Cyclins D1, A, E, and p21, p27, p53 and β-catenin was used to examine impairments of the cell cycle in 190 gastric intramucosal differentiated-type cancers. Mucin phenotypes were determined by the expressions of MUC5AC, MUC6, MUC2 and CD10. A Ki-67 positive rate (PR) was also examined.ResultsOverexpressions of p53, cyclin D1 and cyclin A were significantly more frequent in a gastric phenotype than an intestinal phenotype. Cyclin A was overexpressed in a mixed phenotype compared with an intestinal phenotype, while p27 overexpression was more frequent in an intestinal phenotype than in a mixed phenotype. Reduction of p21 was a common feature of the gastric intramucosal differentiated-type cancers examined.ConclusionsOur results suggest that the levels of some cell cycle regulators appear to be associated with mucin phenotypes of early gastric differentiated-type cancers.

Positive association of free triiodothyronine with pancreatic β-cell function in people with prediabetes

To analyse the effects of thyroid hormones on β‐cell function and glucose metabolism in people with prediabetes who are euthyroid.

Association of the TNF-α-C-857T Polymorphism With Resistance to the Cholesterol-Lowering Effect of HMG-CoA Reductase Inhibitors in Type 2 Diabetic Subjects

OBJECTIVE An association of the C-857T polymorphism of the tumor necrosis factor-α (TNF-α) gene promoter region with LDL cholesterol levels has been reported. This study was designed to evaluate the relationship between the TNF-α-C-857T polymorphism and LDL cholesterol levels according to statin treatment in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS DNA was obtained from 322 Japanese subjects (160 male and 162 female) with type 2 diabetes, and TNF-α-C-857T polymorphisms were determined by direct sequencing. Serum LDL cholesterol was measured by a direct method. RESULTS Although serum LDL cholesterol levels were significantly higher in the T carriers (C/T + T/T) than in the non–T carriers (C/C) (3.14 ± 0.86 vs. 2.89 ± 0.75 mmol/l, P < 0.05), there was no difference in LDL cholesterol levels between the non–T carriers and the T carriers in statin-untreated subjects (2.87 ± 0.73 vs. 2.89 ± 0.76 mmol/l, NS), whereas in statin-treated subjects, LDL cholesterol levels were significantly higher in the T carriers than in the non–T carriers (3.43 ± 0.89 vs. 2.90 ± 0.78 mmol/l, P = 0.0007). There were no differences in HDL cholesterol and triglyceride levels between the non–T carriers and the T carriers in both statin-treated and -untreated subjects. The percent decrease in LDL cholesterol levels after administration of statins was significantly smaller in the T carriers compared with the non–T carriers (27.6 vs. 36.4%, P = 0.031). CONCLUSIONS The mutant allele of the C-857T promoter polymorphism of the TNF-α gene may predispose to resistance to the LDL cholesterol–lowering effect of statins and could be one of the markers used to predict the efficacy of statins.

Association of epicardial adipose tissue with serum level of cystatin C in type 2 diabetes

Objective Accumulation of epicardial adipose tissue (EAT) is considered to be a cardiovascular risk factor independent from visceral adiposity, obesity, hypertension and diabetes. We explored the parameters related to EAT accumulation, aiming to clarify the novel pathophysiological roles of EAT in subjects with type 2 diabetes (T2DM). Methods We examined the laboratory values, including cystatinC, and surrogate markers used for evaluating atherosclerosis. EAT was measured as the sum of the adipose tissue area, obtained by plain computed tomography scans in 208 subjects with T2DM but no history of coronary artery disease. Results EAT correlated positively with age, body mass index (BMI), visceral fat area, leptin, cystatin C and C-peptide, while correlating negatively with adiponectin, estimated glomerular filteration rate (eGFR) and the liver-to-spleen ratio. Multiple linear regression analysis revealed serum cystatin C (β = 0.175), leptin (β = 0.536), BMI (β = 0.393) and age (β = 0.269) to be the only parameters showing independent statistically significant associations with EAT. When cystatin C was replaced with eGFR, eGFR showed no significant correlation with EAT. In reverse analysis, serum cystatin C was significantly associated with EAT after adjustment in multivariate analysis. Discussion EAT accumulation and elevated cystatin C have been independently regarded as risk factors influencing atherosclerosis. The strong association between EAT and cystatin C demonstrated herein indicates that EAT accumulation may play an important role in Cystatin C secretion, possibly contributing to cardiometabolic risk in T2DM patients.

Response to the dipeptidyl peptidase‐4 inhibitors in Japanese patients with type 2 diabetes might be associated with a diplotype of two single nucleotide polymorphisms on the interleukin‐6 promoter region under a certain level of physical activity

Muscle‐derived interleukin‐6 (IL‐6) has been reported to promote glucagon‐like peptide‐1 (GLP‐1) secretion, and we explored the association of single nucleotide polymorphisms (SNPs) in the human IL‐6 promoter region with the responsiveness to dipeptidyl peptidase‐4 inhibitors (DPP‐4Is), drugs that increase circulating GLP‐1.

Non-Islet Cell Tumor Hypoglycemia Is Caused by Big IGF-II in a Patient with a Carcinosarcoma of the Uterus

We report a 72-year-old Japanese woman with severe hypoglycemia. The laboratory data, which revealed the suppression of serum insulin, suggested the existence of non-islet cell tumor hypoglycemia (NICTH). Abdominal computed tomography demonstrated the presence of a huge uterine tumor. The patient was treated with a continuous infusion of glucose, but died of sepsis on day 46. An autopsy revealed the pathological diagnosis to be a carcinosarcoma of the uterus. Interestingly, an immunohistochemical study discovered the expression of insulin-like growth factor (IGF)-II in both the carcinoma and sarcoma cells. In addition, an immunoblot analysis of blood samples revealed the presence of circulating big IGF-II. Therefore, this is a novel case of NICTH that was caused by a uterine carcinosarcoma.

Involvement of oxidative stress in atherosclerosis development in subjects with sarcopenic obesity

Co‐existing decreased muscle mass and increased visceral fat, an age‐associated change called sarcopenic obesity, results in fragility and cardiovascular disease. To assess the pathogenesis of sarcopenic obesity, we assessed the associations of clinical parameters with psoas muscle mass in elderly male subjects with obesity and type 2 diabetes.