Rumi Fujikawa

Westernization of lifestyle markedly increases carotid intima-media wall thickness (IMT) in Japanese people.

To illustrate the impact of westernization of lifestyle on the development of pre-clinical atherosclerosis in Japanese people, we compared risk factors for atherosclerosis such as serum lipids, blood pressure, BMI, insulin resistance, and smoking habits between non-diabetic native Japanese and non-diabetic Japanese Americans. Two hundred and twenty two non-diabetic Japanese Americans living in Hawaii and 271 non-diabetic Japanese living in Hiroshima, Japan were studied. Carotid intima-media wall thickness (IMT) was measured in all subjects by one physician. For all measurements the same ultrasound instrumentation was used. Although no significant differences were seen in serum total cholesterol (TC), triglycerides, or LDL-cholesterol (LDL-C) levels between the two groups in the 1998 study, previous to 1998 these three parameters were significantly higher in Japanese Americans than native Japanese in our study which has spanned the past 20 years. IMT was significantly greater in Japanese Americans than native Japanese (1.20+/-0.03 mm vs. 0.98+/-0.03 mm, (mean+/-S.E.) respectively; P<0.0001). Moreover Japanese Americans reach an IMT of 1.1 mm at age 50, whereas the native Japanese reach this value at age 70. These observations indicate more rapid atherosclerosis progression in Japanese Americans. Based on our IMT measurements, the status and the estimated progression of atherosclerosis in Japanese Americans is increased. Since IMT is a validated endpoint for assessment of atherosclerotic disease risk, it can be concluded that Japanese Americans are at increased risk for cardiovascular disease.

Insulin resistance precedes the appearance of albuminuria in non-diabetic subjects: 6 years follow up study.

Microalbuminuria is a marker of increased risk of cardiovascular mortality in type 1 and type 2 diabetes, and in non-diabetic subjects. Little is known about the association between prospective changes of microalbuminuria and the risk factors of atherosclerosis, or gene polymorphism in non-diabetic subjects. We conducted a 6-year prospective study of risk factors for progression of albuminuria in non-diabetic subjects. The participants were 116 non-diabetic subjects who consecutively underwent medical examinations for Japanese-Americans living in Hawaii. In the baseline examination in 1992, normoalbuminuria was found in all subjects. After 6 years, 101 subjects remained normoalbuminuria (non-progressors), 15 subjects changing from normoalbuminuria to microalbuminuria or proteinuria and were defined as progressors. In progressors, compared with non-progressors, the fasting insulin level and HOMA-R were significantly higher at 3 years follow-up, and the systolic and diastolic pressure and Sigma insulin level were significantly higher at 6 years follow-up. Insulin resistance appeared earlier than the appearance of hypertension and albuminuria. In progressors, there was no significant correlation with angiotensin-converting enzyme (ACE) genotype or angiotensinogen (AGT) genotype compared with non-progressors. Therefore, the appearance of insulin resistance should be regarded as a remarkable mediator of albuminuria.

The impact of visceral adipose tissue and high-molecular weight adiponectin on cardio-ankle vascular index in asymptomatic Japanese subjects.

Few studies addressed the relation of visceral adiposity and high-molecular weight (HMW) adiponectin to arterial stiffness. We investigated the impact of visceral adipose tissue (VAT) and HMW adiponectin on cardio-ankle vascular index (CAVI) in asymptomatic Japanese subjects. We studied 487 consecutive subjects (271 men and 216 women) who underwent general health examination between October 2005 and May 2008. The abdominal, visceral, and subcutaneous adipose tissue areas were determined by low-dose x-ray computed tomography. Serum levels of total and HMW adiponectin were measured using the enzyme-linked immunosorbent assay system based on a monoclonal antibody to humans. Cardio-ankle vascular index was positively correlated with VAT area and negatively correlated with HMW adiponectin levels. We also found the positive association of the number of metabolic syndrome components with CAVI in both sexes. A stepwise multiple regression analysis revealed that age, VAT area, serum HMW adiponectin levels, and homeostasis model assessment of insulin resistance were independent determinants of CAVI. Receiver operating characteristic analyses demonstrated that the predictive value of the VAT area for the extent of CAVI (mild: <25th percentile vs severe: >75th percentile) exceeded that of total or HMW adiponectin levels in both sexes. In conclusion, increased CAVI is associated with both amounts of VAT measured by computed tomography and serum HMW adiponectin levels in asymptomatic Japanese subjects. Receiver operating characteristic analysis indicates that the VAT area is a lot better predictor of arterial stiffness than adiponectin levels.

β3-adrenergic receptor gene variant is associated with upper body obesity only in obese Japanese-American men but not in women

Abstract We investigated gender differences in the relationships between the Trp64Arg variant of the β 3 -adrenergic receptor (AR) gene in obesity and insulin resistance in nondiabetic subjects. In 476 nondiabetic Japanese-Americans (M/F=204/272), the Trp64Arg variant of the β 3 -AR gene was examined. The presence or absence of the Trp64Arg mutation was examined in DNA separated from leukocytes in peripheral blood using the PCR-RFLP method. The frequency of abnormal allele of the β 3 -AR gene was 0.18 for males and 0.17 for females, almost the same as the reported values in Japanese. There was no difference in the frequency of the β 3 -AR gene variant between obese and non obese subjects for each gender. However, among obese males (body mass index ≥24.2 kg/m 2 ), with the β 3 -AR gene mutation, the waist-to-hip ratio, fasting insulin, 2-h insulin, total insulin, and HOMA, an index of insulin resistance, were all significantly higher than obese males without the mutation . In females, the index of obesity, insulin resistance, or lipid metabolism did not differ significantly between the subjects with or without the β 3 -AR gene variant either in the obese and non-obese group. We suggest that the β 3 -AR gene variant is not important as an obesity-inducing factor in Japanese. However, in males, when obesity becomes obvious, the β 3 -AR gene variant is considered to influence the enhancement of insulin resistance, in association with visceral obesity.

Is there any association between subcutaneous adipose tissue area and plasma total and high molecular weight adiponectin levels

This study was conducted for the purpose of clarifying the correlations between the subcutaneous adipose tissue area and plasma total and high-molecular weight (HMW) adiponectin levels. The subjects of this study comprised 359 men and 142 women who underwent general health examinations from October 2005 to December 2006. The abdominal subcutaneous and visceral adipose tissue areas were measured using low-dose x-ray computed tomography. Total and HMW adiponectin levels were measured using the enzyme-linked immunosorbent assay system based on a monoclonal antibody to humans. There were negative correlations between the plasma total and HMW adiponectin levels and visceral and subcutaneous adipose tissue areas using simple correlation analysis. Multiple linear regression analysis clearly indicated that the subcutaneous adipose tissue area was independently correlated with the HMW adiponectin levels in men and closely related in women. Many studies reported that only the visceral adipose tissue area showed a significant correlation with metabolic syndrome. However, these results clearly indicate that it is also important to consider the subcutaneous adipose tissue area in metabolic syndrome.

Reduced prevalence of diabetes according to 1997 American Diabetes Association criteria

Aims/hypothesis. We examined the prevalence of diabetes and investigated the characteristics of subjects diagnosed by the American Diabetes Association and the World Health Organization criteria. Methods. A total of 1235 Japanese-Americans living in Hawaii and Los Angeles was studied. Of the subjects 114 were classified as previously diagnosed as having diabetes. A 75-g glucose tolerance test was given to the rest of the subjects. Results. When abnormal glucose tolerance was diagnosed by the American Diabetes Association criteria, it was possible to identify only 40 % of diabetic subjects who had not been previously diagnosed compared with the current World Health Organization criteria based on a glucose tolerance test. In addition, the subjects identified by the American Diabetes Association criteria had higher glucose concentrations and had less insulin secretory capacity and they were in need of intensive treatment for diabetes. On the other hand, the subjects not diagnosed by the American Diabetes Association criteria alone were those whose glucose tolerance would be more likely to improve with lifestyle modification. Conclusion/interpretation. It might be better to use the fasting plasma glucose criterion advocated by the American Diabetes Association in combination with a glucose tolerance test after taking a detailed medical history. To reduce the number of subjects requiring the glucose tolerance test, priority should be given to subjects with impaired fasting glucose (6.1 ≤ fasting plasma glucose < 7.0 mmol/l). [Diabetologia (1999) 42: 1168–1170]

Effect of acarbose on glycemic control and lipid metabolism in patients with non—insulin-dependent diabetes mellitus

Abstract Acarbose was administered orally at a dosage of 300 mg/d for 4 months to 20 patients (8 men and 12 women) with non—insulin-dependent diabetes mellitus to assess its effects on glycermic control and lipid and lipoprotein metabolism and to determine whether its actions were influenced by the degree of glycemic control. No significant changes in body weight or fasting plasma glucose levels were reported, but levels of glycated hemoglobin A 1c (Hb A 1c ) decreased significantly from 9.1 ± 1.8% (mean ± SD) to 8.2 ± 1.6%. In addition, no significant changes in plasma insulin levels or in insulin resistance were reported. Triglyceride (TG) levels decreased significantly from 175.7 ± 140.2 mg/dL to 127.6 ± 94.1 mg/dL. During the 75-g oral glucose tolerance test, a significant decrease in ∑TG levels (sum of TG levels at baseline and at 30, 60, and 120 minutes after glucose load) from 654.3 ± 475.1 mg/dL to 498.0 ± 356.0 mg/dL was reported, and a significant decrease in ∑free fatty acids from 1.62 ± 0.48 mEq/L to 1.33 ± 0.47 mEq/L was noted. In addition, significant changes were noted in levels of apolipoprotein B (from 122.5 ± 43.0 mg/dL to 105.7 ± 31.4 mg/dL) and in remnant-like particles of TG (from 54.3 ± 67.3 mg/dL to 25.5 ± 27.8 mg/dL). The patients were classified into two groups for comparison: patients with good glycemic control (n = 10; Hb A 1c , 7.8 ± 1.0%) and patients with poor glycemic control (n = 10; Hb A 1c , 10.4 ± 1.4%). The improvement in the levels of Hb A 1c was greater in the latter group, but there was no clear improvement in insulin resistance in either group. Improvement in lipid metabolism was noted in both groups, but no significant differences between the two groups with respect to the degree of improvement were noted. These results showed that acarbose not only improved the levels of Hb A 1c but also improved TG-rich lipoprotein metabolism. Although the improvement in Hb A 1c levels was greater in the patients with poor glycemic control, the effect of acarbose on lipoprotein metabolism was unrelated to the degree of glycemic control.

Association between the postprandial glucose Levels and arterial stiffness measured according to the cardio-ankle vascular index in non-diabetic subjects.

OBJECTIVE Although a relationship between post-challenge hyperglycemia and arterial stiffness has been reported, the relationship between the postprandial glucose levels and cardio-ankle vascular index (CAVI) in non-diabetic subjects is not clear. This study thus evaluated the association between the postprandial glucose levels after a composite meal and the degree of arterial stiffness measured according to CAVI in non-diabetic subjects. METHODS The subjects included 1,291 individuals (655 men and 636 women; mean age, 48.6 years; range, 23-85 years) who underwent medical examinations, including blood tests and CAVI assessments, between October 2005 and April 2012. The 1-hour postprandial glucose levels were determined after a 600-kcal traditional Japanese meal. RESULTS The CAVI values were significantly higher in the subjects with higher 1-hour postprandial glucose levels (≥140 mg/dL in men; ≥158 mg/dL in women). A simple regression analysis indicated that the CAVI values were significantly correlated with the 1-hour postprandial glucose levels in men (r=0.286, p<0.0001) and women (r=0.228, p<0.0001). After adjusting for age, BMI, systolic blood pressure, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, 1-hour postprandial glucose, homeostatis model assessment of insulin resistance, estimated glemerular filtration rate, and high sensitive C-reactive protein, stepwise multiple regression analysis demonstrated that the 1-hour postprandial glucose level was an independent predictor associated with the CAVI in men (p=0.003) and older women 50 years of age or older (p=0.003). CONCLUSION This study demonstrated that the 1-hour postprandial glucose levels are associated with increased CAVI values in non-diabetic men and older women 50 years of age or older.