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author:("akita, kobei")
2.  Vascular complications and changes in body mass index in Japanese type 2 diabetic patients with abdominal obesity 
Background
Although many Asian type 2 diabetic patients have been considered to be not obese and have low capacity of insulin secretion, the proportion of obese patients with visceral fat accumulation has increased in recent years. We found previously considerable number of Japanese non-obese subjects (body mass index (BMI) < 25 kg/m2) with visceral fat accumulation and multiple cardiovascular risk factors. The aim of the study was to investigate the difference in clinical features of type 2 diabetic patients with and without visceral fat accumulation, focusing on vascular complications and changes in BMI.
Methods
We enrolled 88 Japanese hospitalized type 2 diabetic patients. Abdominal obesity represented waist circumference (WC) of ≥85 cm for males and ≥90 cm for females (corresponding to visceral fat area of 100 cm2). Subjects were divided into two groups; with or without abdominal obesity.
Results
Hypertension, dyslipidemia and cardiovascular diseases were significantly more in the patients with abdominal obesity. The prevalence of cardiovascular disease in the non-obese patients (BMI < 25 kg/m2) with abdominal obesity were similar in obese patients (BMI ≥25 kg/m2). The mean BMI of the patients with abdominal obesity was < 25 kg/m2 at 20 years of age, but reached maximum to more than 30 kg/m2 in the course. Furthermore, substantial portion of the type 2 diabetic patients (52% in males and 43% in females) were not obese at 20 year-old (BMI < 25 kg/m2), but developed abdominal obesity by the time of admission.
Conclusion
These results emphasize the need to control multiple risk factors and prevent atherosclerotic disease in patients with abdominal obesity. The significant weight gain after 20 years of age in patients with abdominal obesity stresses the importance of lifestyle modification in younger generation, to prevent potential development of type 2 diabetes and future atherosclerotic cardiovascular disease.
doi:10.1186/1475-2840-12-88
PMCID: PMC3698109  PMID: 23773268
Abdominal obesity; Type 2 diabetes; Waist circumference; Visceral fat accumulation; Body mass index; Cardiovascular disease
3.  A Pilot Investigation of Visceral Fat Adiposity and Gene Expression Profile in Peripheral Blood Cells 
PLoS ONE  2012;7(10):e47377.
Evidence suggests that visceral fat accumulation plays a central role in the development of metabolic syndrome. Excess visceral fat causes local chronic low-grade inflammation and dysregulation of adipocytokines, which contribute in the pathogenesis of the metabolic syndrome. These changes may affect the gene expression in peripheral blood cells. This study for the first time examined the association between visceral fat adiposity and gene expression profile in peripheral blood cells. The gene expression profile was analyzed in peripheral blood cells from 28 obese subjects by microarray analysis. Reverse transcription-polymerase chain reaction (RT-PCR) was performed using peripheral blood cells from 57 obese subjects. Obesity was defined as body mass index (BMI) greater than 25 kg/m2 according to the Japanese criteria, and the estimated visceral fat area (eVFA) was measured by abdominal bioelectrical impedance. Analysis of gene expression profile was carried out with Agilent whole human genome 4×44 K oligo-DNA microarray. The expression of several genes related to circadian rhythm, inflammation, and oxidative stress correlated significantly with visceral fat accumulation. Period homolog 1 (PER1) mRNA level in blood cells correlated negatively with visceral fat adiposity. Stepwise multiple regression analysis identified eVFA as a significant determinant of PER1 expression. In conclusion, visceral fat adiposity correlated with the expression of genes related to circadian rhythm and inflammation in peripheral blood cells.
doi:10.1371/journal.pone.0047377
PMCID: PMC3472996  PMID: 23091619
4.  Efficacy of liraglutide, a glucagon-like peptide-1 (GLP-1) analogue, on body weight, eating behavior, and glycemic control, in Japanese obese type 2 diabetes 
Background
We recently reported that short-term treatment with liraglutide (20.0 ± 6.4 days) reduced body weight and improved some scales of eating behavior in Japanese type 2 diabetes inpatients. However, it remained uncertain whether such liraglutide-induced improvement is maintained after discharge from the hospital. The aim of the present study was to determine the long-term effects of liraglutide on body weight, glycemic control, and eating behavior in Japanese obese type 2 diabetics.
Methods
Patients with obesity (body mass index (BMI) >25 kg/m2) and type 2 diabetes were hospitalized at Osaka University Hospital between November 2010 and December 2011. BMI and glycated hemoglobin (HbA1c) were examined on admission, at discharge and at 1, 3, and 6 months after discharge. For the liraglutide group (BMI; 31.3 ± 5.3 kg/m2, n = 29), patients were introduced to liraglutide after correction of hyperglycemic by insulin or oral glucose-lowering drugs and maintained on liraglutide after discharge. Eating behavior was assessed in patients treated with liraglutide using The Guideline For Obesity questionnaire issued by the Japan Society for the Study of Obesity, at admission, discharge, 3 and 6 months after discharge. For the insulin group (BMI; 29.1 ± 3.0 kg/m2, n = 28), each patient was treated with insulin during hospitalization and glycemic control maintained by insulin after discharge.
Results
Liraglutide induced significant and persistent weight loss from admission up to 6 months after discharge, while no change in body weight after discharge was noted in the insulin group. Liraglutide produced significant improvements in all major scores of eating behavior questionnaire items and such effect was maintained at 6 months after discharge. Weight loss correlated significantly with the decrease in scores for recognition of weight and constitution, sense of hunger, and eating style.
Conclusion
Liraglutide produced meaningful long-term weight loss and significantly improved eating behavior in obese Japanese patients with type 2 diabetes.
doi:10.1186/1475-2840-11-107
PMCID: PMC3459720  PMID: 22973968
Liraglutide; Glucagon-like peptide-1 (GLP-1); Obesity; Eating behavior; Diabetes; Incretin
5.  Short-term effects of liraglutide on visceral fat adiposity, appetite, and food preference: a pilot study of obese Japanese patients with type 2 diabetes 
Background
To examine the effects of liraglutide, a glucagon-like peptide-1 (GLP-1) analogue, on visceral fat adiposity, appetite, food preference, and biomarkers of cardiovascular system in Japanese patients with type 2 diabetes.
Methods
The study subjects were 20 inpatients with type 2 diabetes treated with liraglutide [age; 61.2 ± 14.0 years, duration of diabetes; 16.9 ± 6.6 years, glycated hemoglobin (HbA1c); 9.1 ± 1.2%, body mass index (BMI); 28.3 ± 5.2 kg/m2, mean ± SD]. After improvement in glycemic control by insulin or oral glucose-lowering agents, patients were switched to liraglutide. We assessed the estimated visceral fat area (eVFA) by abdominal bioelectrical impedance analysis, glycemic control by the 75-g oral glucose tolerance test (OGTT) and eating behavior by the Japan Society for the Study of Obesity questionnaire.
Results
Treatment with liraglutide (dose range: 0.3 to 0.9 mg/day) for 20.0 ± 6.4 days significantly reduced waist circumference, waist/hip ratio, eVFA. It also significantly improved the scores of eating behavior, food preference and the urge for fat intake and tended to reduce scores for sense of hunger. Liraglutide increased serum C-peptide immunoreactivity and disposition index.
Conclusions
Short-term treatment with liraglutide improved visceral fat adiposity, appetite, food preference and the urge for fat intake in obese Japanese patients with type 2 diabetes.
doi:10.1186/1475-2840-10-109
PMCID: PMC3260096  PMID: 22132774
liraglutide; glucagon-like peptide-1; obesity; eating behavior
6.  Cross-sectional and longitudinal study of association between circulating thiobarbituric acid-reacting substance levels and clinicobiochemical parameters in 1,178 middle-aged Japanese men - the Amagasaki Visceral Fat Study 
Background
Circulating thiobarbituric acid-reacting substance (TBARS) levels, a marker of systemic oxidative stress, are predictive of cardiovascular events. However, they has not been evaluated in Japanese, especially with regard to the factors that contribute to the changes in circulating TBARS levels. We investigated the cross-sectional and longitudinal relationships between circulating TBARS levels and various clinicobiochemical parameters in middle-aged men.
Methods
In this population-based study (The Amagasaki Visceral Fat Study), 1,178 Japanese male urban workers who had undergone health check-ups in 2006, 2007 and 2008 and were not on medications for metabolic disorders during the follow-up period, were enrolled. Serum TBARS levels were measured by the method of Yagi. The estimated visceral fat area (eVFA) by bioelectrical impedance was measured annually. After health check-ups, subjects received health education with lifestyle modification by medical personnel.
Results
The number of cardiovascular risk factors (hypertension, hyperglycemia, low HDL-C, hypertriglyceridemia, hyperuricemia, hyper-LDL-C and impaired renal function) augmented with the increases in log-eVFA (p < 0.0001) and log-TBARS (p < 0.0001). The combination of TBARS and eVFA had a multiplicative effect on risk factor accumulation (F value = 79.1, p = 0.0065). Stepwise multiple regression analysis identified log-eVFA, as well as age, log-body mass index (BMI), LDL-C, log-adiponectin, γ-glutamyl transpeptidase (γ-GTP) and uric acid as significant determinants of log-TBARS. Stepwise multiple regression analysis identified one-year changes in eVFA as well as BMI, γ-GTP and estimated glomerular filtration rate (eGFR) as significant determinants of one-year change in TBARS, and biennial changes in eVFA as well as BMI and γ-GTP, eGFR as significant determinants of biennial change in TBARS.
Conclusions
The present study showed a significant cross-sectional and longitudinal correlation between TBARS and eVFA, as well as BMI and γ- GTP, eGFR. Visceral fat reduction may independently associate with the improvement in systemic ROS in middle-aged Japanese men.
Trial Registration
The Amagasaki Visceral Fat Study UMIN000002391.
doi:10.1186/1743-7075-8-82
PMCID: PMC3286396  PMID: 22108213
visceral fat accumulation; systemic reactive oxidative stress; visceral fat reduction
7.  Insulin tolerance test predicts the effectiveness of insulin sensitizers in japanese type 2 diabetic patients 
Diabetes Therapy  2011;1(2):121-130.
Introduction
The purpose of this study was to assess the efficacy of the insulin tolerance test (ITT) in predicting the effectiveness of insulin sensitizers in type 2 diabetic patients.
Methods
We retrospectively reviewed 360 consecutive patients with type 2 diabetes admitted to Osaka University Hospital, Japan. In 163 of these hospitalized patients, insulin resistance was evaluated by the ITT after their blood glucose level was ameliorated. We then analyzed the association between their clinical characteristics and their glycemic control 6 months after discharge.
Results
The rate constant for plasma glucose disappearance, KITT, was negatively correlated with body mass index (BMI), waist circumference (WC), and visceral fat area (VFA). The median value of KITT was 1.56 (%/min). In the KITT > 1.56 group (n=81), hemoglobin A1c (HbA1c) significantly increased in both patients treated with insulin sensitizers (n=10) and patients not treated with insulin sensitizers (n=71). In the KITT ≤1.56 group (n=82), HbA1c significantly increased in patients not treated with insulin sensitizers (n=60); however, it was maintained well in the patients treated with insulin sensitizers (n=22). When the patients were divided and analyzed according to the median values of BMI, WC, or VFA, the glycemic control change was not different between the two groups with insulin sensitizers for each parameter.
Conclusion
Insulin sensitizers were effective in type 2 diabetic patients with high insulin resistance estimated by the ITT. The ITT could be useful to predict the effectiveness of insulin sensitizers.
doi:10.1007/s13300-010-0011-7
PMCID: PMC3138481  PMID: 22127749
insulin resistance; insulin sensitizer; insulin tolerance test; type 2 diabetes
8.  Insulin tolerance test predicts the effectiveness of insulin sensitizers in japanese type 2 diabetic patients 
Diabetes Therapy  2011;1(2):121-130.
Introduction
The purpose of this study was to assess the efficacy of the insulin tolerance test (ITT) in predicting the effectiveness of insulin sensitizers in type 2 diabetic patients.
Methods
We retrospectively reviewed 360 consecutive patients with type 2 diabetes admitted to Osaka University Hospital, Japan. In 163 of these hospitalized patients, insulin resistance was evaluated by the ITT after their blood glucose level was ameliorated. We then analyzed the association between their clinical characteristics and their glycemic control 6 months after discharge.
Results
The rate constant for plasma glucose disappearance, KITT, was negatively correlated with body mass index (BMI), waist circumference (WC), and visceral fat area (VFA). The median value of KITT was 1.56 (%/min). In the KITT > 1.56 group (n=81), hemoglobin A1c (HbA1c) significantly increased in both patients treated with insulin sensitizers (n=10) and patients not treated with insulin sensitizers (n=71). In the KITT ≤1.56 group (n=82), HbA1c significantly increased in patients not treated with insulin sensitizers (n=60); however, it was maintained well in the patients treated with insulin sensitizers (n=22). When the patients were divided and analyzed according to the median values of BMI, WC, or VFA, the glycemic control change was not different between the two groups with insulin sensitizers for each parameter.
Conclusion
Insulin sensitizers were effective in type 2 diabetic patients with high insulin resistance estimated by the ITT. The ITT could be useful to predict the effectiveness of insulin sensitizers.
doi:10.1007/s13300-010-0011-7
PMCID: PMC3138481  PMID: 22127749
insulin resistance; insulin sensitizer; insulin tolerance test; type 2 diabetes

Results 1-8 (8)