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author:("ozawa, junii")
1.  Usefulness of the insulin tolerance test in patients with type 2 diabetes receiving insulin therapy 
Abstract
Aims/Introduction
To establish the validity of the plasma glucose disappearance rate (KITT), derived from an insulin‐tolerance test (ITT), for evaluating the insulin sensitivity of patients with type 2 diabetes after insulin therapy.
Materials and Methods
In the first arm of the study, 19 patients with poorly controlled diabetes were treated with insulin and underwent an ITT and a euglycemic clamp test (clamp‐IR). The relationship between the insulin resistance index, as assessed by both the clamp‐IR and KITT tests, was examined. In the second arm of the study, the relationships between KITT values and various clinical parameters were investigated in 135 patients with poorly controlled diabetes, after achieving glycemic control with insulin.
Results
In study 1, a close correlation between KITT and the average glucose infusion rate during the last 30 min of the standard clamp‐IR test (M‐value) was noted (P < 0.001). In study 2, body mass index (P = 0.0011), waist circumference (P = 0.0004), visceral fat area (P = 0.0011) and the log‐transformed homeostasis model assessment of insulin resistance value (P = 0.0003) were negatively correlated with the log‐transformed KITT. High‐density lipoprotein cholesterol (P = 0.0183), low‐density lipoprotein cholesterol (P = 0.0121) and adiponectin (P = 0.0384) levels were positively correlated with the log‐transformed KITT.
Conclusions
The ITT is a valid and useful test for evaluating the insulin sensitivity of patients with diabetes, even after treatment with insulin.
doi:10.1111/jdi.12143
PMCID: PMC4020335  PMID: 24843779
Insulin resistance; Insulin therapy; Insulin tolerance test
4.  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
5.  Dipeptidyl peptidase‐4 inhibitors are effective in Japanese type 2 diabetic patients with sustained endogenous insulin‐secreting capacity, a higher body mass index and insulin resistance 
Abstract
Aims/Introduction
Recently, dipeptidyl peptidase‐4 (DPP‐4) inhibitors have become available in Japan. It has not yet been clarified what clinical parameters could discriminate DPP‐4 inhibitor‐effective patients from DPP‐4 inhibitor‐ineffective patients.
Materials and Methods
We reviewed 33 consecutive patients with type 2 diabetes admitted to Osaka University Hospital for glycemic control. All of the patients were treated with medical nutrition therapy plus insulin therapy to improve fasting plasma glucose (FPG) and postprandial glucose below 150 and 200 mg/dL, respectively. After insulin secretion and insulin resistance were evaluated, insulin was replaced by DPP‐4 inhibitors. The efficacy of DPP‐4 inhibitors was determined according to whether glycemic control was maintained at the target levels.
Results
Dipeptidyl peptidase‐4 inhibitors were effective in 16 of 33 patients. DPP‐4 inhibitor‐effective patients were younger than DPP‐4 inhibitor‐ineffective patients. Body mass index (BMI) was significantly higher in DPP‐4 inhibitor‐effective patients. Endogeneous insulin‐secreting capacity, including insulinogenic index (II), fasting plasma C‐peptide (F‐CPR) and C‐peptide index (CPI), was more sustained in DPP‐4 inhibitor‐effective patients than DPP‐4 inhibitor‐ineffective patients. Insulin resistance evaluated by homeostasis model assessment of insulin resistance (HOMA‐IR) was significantly higher in DPP‐4 inhibitor‐effective patients than DPP‐4 inhibitor‐ineffective patients. In receiver operating characteristic analyses, the cut‐off values for predicting the efficacy of DPP‐4 inhibitors were 0.07 for II, 1.5 ng/mL for F‐CPR, 1.0 for CPI, 23.0 kg/m2 for BMI, 1.3 for HOMA‐IR and 67.5 years for age.
Conclusions
Dipeptidyl peptidase‐4 inhibitors were effective in Japanese type 2 diabetic patients with sustained endogenous insulin‐secreting capacity, a higher BMI and insulin resistance.
doi:10.1111/jdi.12016
PMCID: PMC4019274  PMID: 24843651
Dipeptidyl peptidase‐4 inhibitor; Insulin secretion; Type 2 diabetes
6.  A Case of Hypogonadotropic Hypogonadism Caused by Opioid Treatment for Nonmalignant Chronic Pain 
Case Reports in Medicine  2012;2012:740603.
We report a case of 42-year-old male patient with hypogonadotropic hypogonadism. He suffered from general fatigue and erectile dysfunction after the treatment with transdermal fentanyl for chronic pain by traffic injury. Endocrine examinations and hormone stimulating tests showed that he had hypogonadotropic hypogonadism. Brain magnetic resonance imaging (MRI) showed no abnormal findings, and he had no past history of accounting for acquired hypogonadotropic hypogonadism. Therefore, his hypogonadism was diagnosed to be caused by opioid treatment. Although opioid-induced endocrine dysfunctions are not widely recognized, this case suggests that we should consider the possibility of endocrine dysfunctions in patients with opioid treatment.
doi:10.1155/2012/740603
PMCID: PMC3541691  PMID: 23326276
7.  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
8.  Liraglutide is effective in type 2 diabetic patients with sustained endogenous insulin‐secreting capacity 
Abstract
Aims/Introduction:  Recently, glucagon‐like peptide‐1 (GLP‐1) receptor agonists of liraglutide have become available in Japan. It has not yet been clarified what clinical parameters could discriminate liraglutide‐effective patients from liraglutide‐ineffective patients.
Materials and Methods:  We reviewed 23 consecutive patients with type 2 diabetes admitted to Osaka University Hospital for glycemic control. All of the patients were treated with diet plus insulin (or plus oral antidiabetic drugs) to improve fasting plasma glucose (FPG) and postprandial glucose below 150 and 200 mg/dL, respectively. After insulin secretion and insulin resistance were evaluated, insulin was replaced by liraglutide. The efficacy of liraglutide was determined according to whether glycemic control was maintained at the target levels.
Results:  Liraglutide was effective in 13 of 23 patients. There were significant differences in the parameters of insulin secretion, including fasting C‐peptide (F‐CPR), C‐peptide index (CPI), insulinogenic index (I.I.) and urine C‐peptide (U‐CPR), between liraglutide‐effective and ‐ineffective patients. The duration of diabetes was significantly shorter in liraglutide‐effective patients than in liraglutide‐ineffective patients. In receiver operating characteristic analyses, the cut‐off value for predicting the efficacy of liraglutide was 0.14 for I.I., 1.1 for CPI, 1.5 ng/mL for F‐CPR, 33.3 μg/day for U‐CPR and 19.5 years for duration of type 2 diabetes.
Conclusions:  Insulin secretion evaluated by F‐CPR, CPI, I.I., U‐CPR and the duration of type 2 diabetes were useful parameters for predicting the efficacy of liraglutide in patients with type 2 diabetes. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00168.x, 2011)
doi:10.1111/j.2040-1124.2011.00168.x
PMCID: PMC4014952  PMID: 24843579
Glucagon‐like peptide‐1; Incretin; Type 2 diabetes
9.  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
10.  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
11.  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 1-11 (11)