Akimichi Asano

Telmisartan Treatment Decreases Visceral Fat Accumulation and Improves Serum Levels of Adiponectin and Vascular Inflammation Markers in Japanese Hypertensive Patients

Hypertension contributes to the occurrence and progression of cardiovascular diseases. The angiotensin II type 1 receptor blocker telmisartan is reported to activate the peroxisome proliferator–activated receptor γ and improve insulin sensitivity. We investigated the effects of telmisartan treatment on visceral fat, serum adiponectin and vascular inflammation markers in Japanese hypertensive patients. This was an open-label, non-controlled study. Twenty-eight essential hypertensive patients (22 men and 6 women; age 60.6±1.9 years; body mass index [BMI] 25.5±0.6 kg/m2) participated. Fat area was assessed with computerized tomography. All the subjects were started on telmisartan 40 mg/day, which was increased to 80 mg/day to achieve the blood pressure target of less than 130/80 mmHg. We assessed the visceral and subcutaneous fat areas, serum adiponectin levels, and vascular inflammation markers at baseline and 24 weeks of telmisartan treatment. There were significant reductions in visceral fat area (from 103.1±7.9 to 93.3±8.4 cm2, p<0.01) and pulse wave velocity (from 1,706±52 to 1,587±51 cm/s, p<0.01) at 24 weeks. In contrast, significant increases in serum high-density lipoprotein cholesterol (from 5.06±0.15 to 5.32±0.13 mmol/L, p<0.05) and adiponectin levels (from 8.27±0.76 to 9.13±0.81 μg/mL, p<0.05) were observed. Also, there were reductions in the interleukin-6 level (from 2.26±0.27 to 1.60±0.14 pg/mL, p<0.01). We also conducted these investigations in male subjects alone and similar findings were obtained for all of these parameters. In conclusion, telmisartan treatment was associated with an improvement of vascular inflammation, reductions in visceral fat and increases in serum adiponectin.

The Relationship of Percent Body Fat by Bioelectrical Impedance Analysis with Blood Pressure, and Glucose and Lipid Parameters

The objective of this study was to clarify the clinical significance and usefulness of measuring percent body fat (PBF) when compared with body mass index (BMI) in the Japanese population. A total of 2,483 Japanese individuals (1,380 men and 1,103 women) who underwent a medical checkup from 1999-2002 were employed. PBF was determined using bioelectrical impedance analysis (BIA). Relationships of age, BMI and PBF with several metabolic parameters, including blood pressure, lipids and plasma glucose levels were assessed in both genders separately. In men, PBF was a stronger determinant of total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and triglycerides (TG) compared with age and BMI, whereas in women, age was the strongest determinant of TC and LDL-C. In both genders, BMI was the strongest determinant of serum HDL-C among age, PBF and BMI. Based on these data, we suggest that measuring PBF by BIA is superior to BMI for predicting TC, LDL-C and TG in Japanese men.

Association of LMNA 1908C/T polymorphism with cerebral vascular disease and diabetic nephropathy in Japanese men with type 2 diabetes

Objective  The LMNA 1908C/T polymorphism has been reported to be associated with dyslipidaemia, metabolic syndrome, adipose tissue metabolism and obesity phenotypes, suggesting that this polymorphism presents an increased risk of atherosclerosis and vascular diseases. However, there have been no previous reports on the relationship between the LMNA 1908C/T polymorphism and vascular diseases. The aim of this study therefore was to investigate the association between the LMNA 1908C/T polymorphism and the prevalence of vascular disease in Japanese patients with type 2 diabetes.

Effects of Fenofibrate Therapy on Plasma Ubiquinol-10 and Ubiquinone-10 Levels in Japanese Patients with Hyperlipidemia and Type 2 Diabetes Mellitus

Study Objective. To assess the effects of fenofibrate therapy on concentrations of plasma ubiquinol‐10 and ubiquinone‐10—the reduced and oxidized forms, respectively, of coenzyme Q10.

Impact of Serum Retinol-Binding Protein 4 Levels on Regulation of Remnant-Like Particles Triglyceride in Type 2 Diabetes Mellitus

Background. Although retinol-binding protein 4 (RBP4) associates with insulin resistance and remnant-like particles triglyceride (RLP-TG) elevated in the insulin resistant state, few data exist regarding the relationship between RBP4 and RLP-TG. Subjects and Methods. The study included 92 Japanese type 2 diabetic mellitus (T2DM) male patients (age 60.5 ± 13.6 years, body mass index (BMI) 24.7 ± 4.1 kg/m2, waist circumference (WC) 88.4 ± 10.7 cm, and HbA1c (NGSP) 7.2 ± 1.9%). Patients on medications affecting insulin sensitivity, including fibrates, biguanides, and thiazolidinedione, were excluded. Visceral fat area (VFA) and subcutaneous fat area (SFA) were measured by computed tomography. Results. RBP4 levels showed a significant positive correlation with RLP-TG (r = 0.2544 and P = 0.0056), TG (r = 0.1852 and P = 0.041), RLP-TG/TG (r = 0.23765 and P = 0.0241), and age (r = −0.2082 and P = 0.0219), although there was no significant correlation with VFA, SFA, adiponectin levels, or homeostasis model of assessment insulin resistance (HOMA-R). Multiple regression analysis revealed that RBP4 was an independent determinant of RLP-TG (P = 0.0193) but was not a determinant of TG. Conclusions. RBP4 correlates positively with serum RLP-TG independent of fat accumulation in T2DM. RBP4 may regulate remnant metabolism independent of glycemic control in T2DM.

Association between CTLA-4 +49 A/G polymorphism and type 1B diabetes in Japanese population.

Abstract+49 A/G polymorphism of CTLA-4 gene has been suggested to be associated with type 1 diabetes in some populations. However, a functional significance of the +49 A/G polymorphism is unknown, because it is believed the polymorphism does not affect the function of the CTLA-4 molecule. In this study, we examined the +49 A/G polymorphism of the CTLA-4 gene in 30 Japanese type 1 diabetic patients (14 type 1B and 16 type 1A) and 40 non-diabetic subjects in a case-control study, and stratified patients according to genotype of the polymorphism. The distribution of genotype frequencies differed between type 1 diabetic patients and controls (p<0.01). When the subjects were subdivided into type 1A and type 1B subgroups, a significant difference in G allele frequency was found only between type 1B patients and controls, whereas G allele frequency tended to be higher in type 1A diabetic patients than controls. Type 1B patients displayed more severe metabolic decompensation (higher plasma glucose concentration, lower urinary C-peptide levels, higher insulin requirement, and higher serum amylase levels), and were found to be more prone to diabetic ketoacidosis than type 1A patients. After stratification by genotype, differences in urinary C-peptide and serum amylase levels between type 1A and type 1B patients were found to be due to differences in the GG genotype subgroup, whereas in the AG subgroup those differences disappeared. In conclusion, the +49 A/G polymorphism of CTLA-4 gene was associated with the occurrence of type 1B diabetes in a Japanese population, and type 1B diabetics with a GG genotype were associated with more severe cell dysfunction than their type 1A counterparts.

Two novel mutations of PTEN gene in Japanese patients with Cowden syndrome

Cowden syndrome (CS), also known as multiple hamartoma syndrome, is an autosomal dominant cancer syndrome associated with high risk of breast and thyroid cancer. In three unrelated Japanese CS patients, three PTEN germline mutations were identified, including two novel ones: 589A → T, resulting in Lys197Stop, and 219‐222delAAGA. We also detected a previously reported mutation: 697C → T, resulting in Arg233Stop. Reports from Western countries have indicated that approximately two‐thirds of mutations are found in exons 5, 7, and 8, which is almost the same frequency as found in Japanese CS. No genotype–phenotype correlations have been found in CS patients from 21 Japanese families.