Aim:We reevaluated waist circumference as a diagnostic criterion of metabolic syndrome (MetS) in Japanese. Methods: We enrolled 5,571 subjects (3,148 men and 2,423 women) who had health check-ups in our center. The criterion was reevaluated using the positive predictive value of a receiver-operating characteristics (ROC) curve at 10 different hypothesized lengths of waist circumference with or without a cluster of risk factors. We also drew ROC curves based on the atherosclerotic findings of clinical examinations. Results: Based on the ROC curves, the optimal waist circumference cut-off was 85 cm in men and 80 cm in women. Using this 80 cm cut-off point in women, misdiagnosis rates of MetS were lowered ( 19.1-56.6%) compared to the cut-off point currently in use. Integrating the influence of height, namely by using a waist-to-height 2 ratio, misdiagnosis rates in shorter populations were decreased in both men and women. Conclusion: These data suggested an optimal waist circumference cut-off to improve the diagnostic probability of MetS in Japanese women of 80 cm, as well as the utility of an easily detected anthropometric index such as a waist-to-height (cm 100/cm) or waist-to-height 2 (cm 10,000/cm 2 ) ratio, determined as 51 in men and 52 in women, or 30 in men and 33 in women, respectively. J Atheroscler Thromb, 2008; 15:94-99.Key words; Metabolic syndrome (MetS), Waist circumference, ROC curve, Height and 90 cm in women, accompanied by at least two of the following three risk factors: dyslipidemia, raised blood pressure, and raised fasting glucose. Although the cut-off point for waist circumference was defined by unique evidence corresponding to visceral fat area obtained by computed tomography (CT) scanning in Japanese subjects 9) , the optimal waist circumference cut-off has now become controversial. Because overt visceral fat obesity in Japanese is relatively low especially in women, waist circumference might lead to misdiagnosis, even when other risk factors are clustered. In fact, data obtained from 692 subjects in a community-based cohort study 10) and 329 subjects in a population-based study 11) in Japan indicate that a shorter waist circumference cut-off than those currently used would be optimal.

Aims/Introduction:  Human islet polypeptide S20G mutation (hIAPPS20G) is associated with earlier onset type 2 diabetes and increased amyloidogenicity and cytotoxicity in vitro vs wild‐type hIAPP (hIAPPWT), suggesting that amyloidogenesis may be pathogenic for type 2 diabetes. We compared the contributions of hIAPPS20G and hIAPPWT toward intra islet amyloid formation and development of type 2 diabetes in a unique physiologic knock‐in mouse model.Materials and Methods:  We replaced the mouse IAPP gene (M allele) with hIAPPWT (W allele) and hIAPPS20G (G allele) via homologous recombination and backbred transgenic mice against C57Bl/6 strain 5 generations to minimize genetic variation. Mice (3 month old) were maintained on control (CD) or high fat diet (HFD) for 15 months and studied at 3 month intervals by oral glucose tolerance testing (OGTT) and pancreas histology to assess glucose homeostastis, amyloidogeneisis, islet mass, β cell replication, and apoptosis.Results:  IAPP blood levels were indistinguishable in all mice. WW and GW mice maintained on both diets lacked intraislet amyloid at all ages. On both diets relative to MM controls WW and GW mice exhibit glucose intolerance (P < 0.008) with no differences in insulin secretion. However, GW mice secreted significantly more insulin (P < 0.03 that WW mice on both diets throughout the study. By 12 months on the high fat diet all mice increased their β cell mass about 3‐fold and were indistinguishable.Conclusions:  Physiologic expression of hIAPPWT and hIAPPS20G in C57Bl/6 mice produces mild glucose intolerance with inappropriately normal insulin secretion that is independent of intraislet amyloid formation. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00166.x, 2011)

The prevaleance of morbid obesity (body mass index of 35.0 or greater) is low in Japan (0.2-0.3%), and little systematic investigation of its cause in this population has been carried out. Leptin plays a central role in regulation of body weight; mice deficient in leptin develop marked obesity. We sought mutations in the leptin gene in 53 morbidly obese Japanese (maximum body mass index 35-60) including 46 with type 2 diabetes. Direct DNA sequencing was performed following polymerase chain reaction amplification. Apart from a silent mutation at codon 25 (CAA/CAG, glutamine) detected in eight subjects, no mutations were detected. We found a significantly higher prevalence of the variant leptin 25CAG allele among the 53 obese subjects (0.085) studied than in 132 nonobese control subjects (0.011, P<0.001). In Japanese populations mutations in the protein coding sequence of the leptin gene are unlikely to be a major cause of morbid obesity. However, the leptin 25CAG allele may be linked to morbid obesity in this population. Specifically, genetic variation located near the leptin gene may be involved in pathogenesis. The leptin polymorphism 25CAG appears to be a new genetic marker for obesity susceptibility, at least in Japanese.

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