Visceral fat accumulation is associated with the development of metabolic disorders such as glucose intolerance, dyslipidemia, hypertension, and atherosclerotic cardiovascular diseases (1-8). However, the relationship between reduction of visceral fat and decrease in the number of metabolic risk factors has not been defined in the general population. Recently, we developed a new technique, the abdominal bioelectrical impedance analysis (BIA), to evaluate visceral fat area (VFA) (9). The aim of this study was to investigate whether reduction of visceral fat, estimated by the BIA, is associated with a decrease in the number of metabolic risk factors. RESEARCH DESIGN AND METHODS -The study group comprised 2,336 Japanese men (aged mean Ϯ SD 48.0 Ϯ 10.5 years, BMI 24.2 Ϯ 2.9 kg/m 2 ), who were employees of Amagasaki City Office, an urban area, and had undergone annual health check-ups in both 2004 and 2005. After the health check-up, the medical staff provided risk factor-oriented, rather than obesityoriented, health promotion programs to select individuals with visceral fat accumulation and multiple risk factors, with the aim of encouraging a scientific understanding of the spectrum of metabolic syndrome from visceral fat accumulation to atherosclerotic cardiovascular diseases. In this study, we used VFA estimated by the BIA, which was shown to correlate significantly with VFA determined by computed tomography (9). The measurement of VFA by BIA complied with the Guidelines of the Ethical Committees of Osaka University. Informed consent was obtained from all subjects.Overall obesity was defined as BMI of Ն25 kg/m 2 (10). We investigated the presence of three metabolic risk factors: elevated blood pressure (systolic blood pressure Ն130 mmHg and/or diastolic blood pressure Ն85 mmHg), dyslipidemia, and dysglycemia/impaired glucose tolerance. Dyslipidemia represented hypertriglyceridemia (fasting or postprandial triglyceride of Ն1.69 or 2.27 mmol/l [11,12], respectively, and/or low HDL cholesterol [HDL cholesterol Ͻ1.04 mmol/l]). Dysglycemia/impaired glucose tolerance represented hyperglycemia (fasting or postprandial serum glucose concentration of Ն6.1 or Ն7.77 mmol/l [13], respectively). Subjects who received specific treatment(s) for each of the metabolic risk factors were considered positive for that factor. Statistical analysisFischer's protected least significant difference test and Kruskal-Wallis were used to analyze the relationship between the number of metabolic risk factors and body fat distribution and between change in the number of metabolic risk factors and change in VFA, respectively. Significance level was set at P Ͻ 0.05.RESULTS -BMI and VFA varied considerably among individuals. We divided subjects into two groups according to BMI and into two groups according to VFA (Fig. 1A). Visceral fat accumulation was defined as VFA of Ն100 cm 2 (10,14). Among 1,497 nonobese subjects (BMI Ͻ25 kg/m 2 ), 401 (26.8%) had visceral fat accumulation. The mean number of metabolic risk factors in subjects with VFA Ն100 c...

Objective Visceral fat accumulation is an underlying component of the metabolic syndrome (MetS

Homeostasis model assessment of insulin resistance (HOMA-IR) is a simple and useful method for evaluating insulin sensitivity. But it is difficult to apply to type2 diabetes patients treated with insulin. We have devised a method for measuring HOMA-IR and investigated the validity of HOMA-IR for evaluating insulin sensitivity in patients with type 2 diabetes on insulin therapy. In the first arm of the study, 19 poorly controlled diabetic subjects were treated with insulin and underwent euglycemic clamp study. Then the relationship between insulin resistance index assessed by the clamp test (clamp-IR) and HOMA-IR was investigated in these subjects. Log transformed HOMA-IR correlated with log transformed M/I values derived from the standard euglycemic clamp (r=-0.753, p=0.002). In the second arm of the study, we investigated the relationship between HOMA-IR and various clinical parameters in 156 patients with poorly controlled diabetes after glycemic control. Log transformed HOMA-IR correlated negatively with age (r=-0.292, p=0.0002), HDL-C (r=-0.342, p<0.0001), log transformed serum adiponectin (r=-0.309, p=0.0006) and log transformed KITT (r=-0.264, p=0.0009), and positively with body mass index (r=0.499, p<0.0001), waist circumstance (r=0.461, p<0.0001), visceral fat area (r=0.401, p<0.0001), diastolic blood pressure (r=0.223, p=0.0054), log transformed triglyceride (r=0.497, p<0.0001), urinary CPR (r=0.216, p=0.0099), ΔCPR of glucagon stimulation test (r=0.496, p<0.0001) and log transformed insulinogenic index (r=0.325, p=0.0002). These results suggest that HOMA-IR is a useful test for the evaluation of insulin sensitivity even in patients with type 2 diabetes treated with insulin.

Adiponectin was identified as an adipocytokine in the human adipose tissue cDNA library. It has antiatherosclerotic and antidiabetic properties in experimental studies, and its blood levels are low in obesity, diabetes, cardiovascular diseases, and metabolic syndrome. Several studies have reported that weight reduction in massively obese subjects is associated with a rise in serum adiponectin (APN) concentration (1-3). However, the relationship between changes in APN and BMI, waist circumference (WC), and visceral fat accumulation (VFA) in general population has not been reported. The present study investigated 1-year change in APN (⌬APN) in relation to changes in BMI (⌬BMI), WC (⌬WC), and estimated visceral fat area (⌬eVFA) in middle-aged general population.The study subjects were 2,024 middle-aged Japanese (1,619 men [45.7 Ϯ 10.4 years] and 405 women [45.6 Ϯ 9.3 years], mean Ϯ SD) who were employees of Amagasaki city office and had undergone annual health checkup in both 2004 and 2005 and were not taking any medications for diabetes, hypertension, or dyslipidemia. The study was approved by the human ethics committee of Osaka University, and a signed informed consent was obtained from each participant. Height, weight, and WC were measured in standing position. BMI was calculated as weight in kilograms divided by the square of height in meters. WC at umbilical level was measured with a nonstretchable tape in late expiration while standing (in cm). VFA was estimated noninvasively by bioelectrical impedance analysis (BIA) (4). Briefly, the voltage recorded at the flank to the flow of current between the umbilicus and the back correlates significantly with VFA and is not influenced by subcutaneous fat. We reported previously that VFA estimated by BIA correlates significantly with that determined by computed tomography (4). APN was measured using latex particle-enhanced turbidimetric assay (5). ⌬APN correlated negatively with ⌬BMI, both in men (r ϭ Ϫ0.256, P Ͻ 0.0001) and women (r ϭ Ϫ0.223, P Ͻ 0.0001) and with ⌬WC in men only (r ϭ Ϫ0.191, P Ͻ 0.0001), but no correlation was found in women (P ϭ 0.097), and ⌬APN correlated negatively with ⌬eVFA in both men (r ϭ Ϫ0.189, P Ͻ 0.0001) and women (r ϭ Ϫ0.121, P ϭ 0.015).APN is likely influenced by genetic and environmental factors. It has been reported that APN is associated with single nucleotide polymorphisms in adiponectin gene. The present study demonstrated that changes in body fat, i.e., reduction in BMI, WC, and eVFA, correlated with a rise in APN in middle-aged general population, which to our knowledge is the first such report. We used BIA to evaluate VFA in the present study, and further research on both visceral and subcutaneous fat areas measured by computed tomography scan is needed to clarify the effects of visceral and subcutaneous adiposity on APN.

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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)

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Abstract. Visfatin is a novel adipocytokine that is expressed by the visceral fat cells. We investigated the role of genetic variation in the visfatin gene in the pathophysiology of type 2 diabetes and clinical variables in Japanese subjects. The 11 exons, and the promoter region of the visfatin gene were screened for single nucleotide polymorphisms (SNPs) by PCRdirect sequencing. We found SNPs in the promoter region (SNP -1535T>C), exon 2 (SNP + 131C>G, Thr44Arg), and exon 7 (SNP + 903G>A). The allele and genotype frequencies of these SNPs showed no significant differences between 200-448 diabetic and 200-333 control subjects. However, the -1535T/T genotype was associated with lower serum triglyceride levels (T/T vs. T/C + C/C (p = 0.015) and T/T vs. C/C (p = 0.043)) and higher HDL-cholesterol levels (T/T vs. C/C, p = 0.0496) in the nondiabetic subjects. Reporter gene assay of 3T3-L1 adipocytes revealed that the promoter activity of -1535T and -1535C was similar, suggesting that the observed association may reflect linkage disequilibrium between -1535T>C and causative variations of the visfatin gene. ADIPOCYTES secrete a variety of proteins known as adipocytokines, which have various important roles in metabolism [1,2]. Visfatin is a novel adipocytokine strongly expressed by the visceral fat cells of both humans and mice [3]. Visfatin is identical to pre-B cell colony-enhancing factor (PBEF) which has been identified as a growth factor for early stage B cells [4]. Visfatin has an insulin-like effect on cultured cells. It stimulates glucose uptake by adipocytes, myocytes and osteoblasts [3,5], and inhibits glucose release from liver cells [3]. In addition, administration of visfatin to mice has been shown to decrease the plasma glucose level [3], and mice that are heterozygous (+/-) for visfatin have higher plasma glucose levels than wild-type mice [3]. Furthermore, clinical studies have shown that plasma visfatin levels are about two-fold higher in type 2 diabetic patients than in nondiabetic controls [6,7]. These findings suggest a role of visfatin in glucose metabolism and in the pathogenesis of type 2 diabetes. It has been reported that variations of the genes for other adipocytokines (e.g. adiponectin) can influence the risk of type 2 diabetes [8][9][10][11][12][13], but the relation between visfatin gene polymorphism and type 2 diabetes remains unknown. The visfatin/PBEF gene consists of 11 exons and 10 introns spanning 34.7-kb and is located on chromosome 7q22.2 [14]. In the present study, we systematically investigated polymorphisms of the coding region and promoter region of this gene in Japanese subjects and then performed association studies in type 2 diabetic and non-diabetic subjects. We also examined the