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Aims Olfactory dysfunction is associated with the transition from normal cognition to dementia in persons without type 2 diabetes. This study aimed to investigate whether olfactory dysfunction could be an early marker of future dementia in older patients with type 2 diabetes. Methods This exploratory study included 151 older Japanese outpatients with type 2 diabetes who did not have a diagnosis of probable dementia at baseline. A multivariate logistic regression model was used to determine whether Open Essence (OE) test score at baseline is associated with the development of probable dementia. Results Over 3 years, approximately 9% of the study subjects developed probable dementia. Subjects with olfactory dysfunction at baseline developed probable dementia more frequently than those without. Multivariate logistic regression showed that lower OE test score, higher age, lower Mini-Mental State Examination (MMSE) score, higher total protein concentration, and more frequent use of a sulfonylurea are significantly associated with the development of probable dementia. Stepwise multivariate regression analysis demonstrated that change in OE test score over 3 years is significantly associated with change in MMSE score. Conclusions Our study suggested that olfactory dysfunction precedes the development of probable dementia in older patients with type 2 diabetes.

Background: While conventional cardiovascular risk factors and certain lifestyle habits are associated with arterial stiffness in patients with type 2 diabetes mellitus (T2DM), it is still unknown whether they are actually associated with arterial stiffness even after adjustment for conventional cardiovascular risk factors and lifestyle habits. The aim of this study was to identify variables that are associated with brachial-ankle pulse wave velocity (baPWV). Methods: The study participants comprised 724 Japanese T2DM outpatients free of history of cardiovascular diseases. Lifestyle habits were analyzed using self-reported questionnaires. The associations among conventional cardiovascular risk factors and lifestyle habits with baPWV were investigated by multivariable linear regression analysis. Results: The mean age of the study subjects was 57.8 ± 8.6 years, and 62.8% of those were males. The mean HbA1c was 7.0±1.0%, and the estimated duration of T2DM was 9.9 ± 7.2 years. Multiple linear regression analysis that included age and gender demonstrated that age and male sex were positively associated with baPWV. In a model adjusted for numerous conventional cardiovascular risk factors and lifestyle habits, age, duration of T2DM, systolic blood pressure, serum uric acid, urinary albumin excretion and poor sleep quality were positively associated with baPWV, while body mass index was negatively associated with baPWV. Conclusions: In Japanese T2DM, in addition to several conventional cardiovascular risk factors, poor sleep quality was associated with baPWV even after adjustment for numerous conventional cardiovascular risk factors and lifestyle habits. J Clin Med Res. 2017;9(4):297-302 doi: https://doi.org/10.14740/jocmr2870w

Background There is a high incidence of type 2 diabetes in Asian adults, even those with a normal body mass index (BMI) (23 kg/m2) at middle age is a risk factor for type 2 diabetes in Asians. In this historical cohort study, we investigated whether a slightly increased BMI at college age was also a risk factor for future diabetes in Japanese men. Methods Six hundred and sixty-one male alumni who graduated from a physical education school between 1971 and 1991 and who responded to follow-up investigation between 2007 and 2017 were included in this study. Participants were categorized into four categories: college BMI of

ObjectiveWhile certain lifestyle habits may be associated with arterial stiffness, there is limited literature investigating the relationship between lifestyle habits and longitudinal changes in arterial stiffness in patients with type 2 diabetes mellitus (T2DM). This is an exploratory study to determine whether lifestyle habits, in addition to conventional atherosclerotic risk factors, are associated with increased arterial stiffness.Research design and methodsThe study participants comprised 734 Japanese outpatients with T2DM and no history of apparent cardiovascular diseases. Lifestyle habits were analyzed using self-reported questionnaires, and brachial-ankle pulse wave velocity (baPWV) was measured at baseline, and at years 2 and 5. A multivariable linear mixed-effects model was used to determine the predictive value of lifestyle habits and possible atherosclerotic risk factors for longitudinal change in baPWV.ResultsOver 5 years of follow-up, baPWV values significantly increased. In a multivariable linear mixed-effects model that adjusted for age and gender, a low frequency of breakfast intake was significantly associated with persistently high baPWV, independently of other lifestyle habits. Furthermore, in a multivariable linear mixed-effects model that included both lifestyle habits and possible atherosclerotic risk factors, a low frequency of breakfast intake remained the only independent predictive factor for persistently high baPWV. Subjects who ate breakfast less frequently tended to have additional unhealthy lifestyle habits and atherosclerotic risk factors.ConclusionsOur analyses suggest that breakfast skipping is an independent lifestyle habit that is associated with persistently increased arterial stiffness in patients with T2DM.Trial registration numberUMIN000010932.

Previous studies reported that the shape of glucose response curve during an oral glucose tolerance test (OGTT) could be a marker of insulin sensitivity in obese subjects. The biphasic response curve was defined by a second rise in glucose concentration of >4.5mg/dl after the decline in glucose during OGTT and subjects with biphasic response curve were insulin sensitive and had low risk of type 2 diabetes compared with subjects with monophasic response curve. While type 2 diabetes is often developed in non-obese Asians, it is still unclear whether the subjects with biphasic response curve are also insulin sensitive in non-obese healthy men. To clarify this, we studied 49 non-obese (BMI In conclusion, biphasic glucose response curve is a marker of elevated muscle insulin sensitivity with less visceral fat in non-obese Japanese healthy men. Disclosure H. Kaga: None. Y. Tamura: None. K. Takeno: None. S. Kakehi: None. Y. Someya: None. R. Suzuki: None. S. Kadowaki: None. D. Sugimoto: None. Y. Furukawa: None. T. Funayama: None. R. Kawamori: None. H. Watada: Advisory Panel; Self; AstraZeneca. Consultant; Self; Astellas Pharma US, Inc., AstraZeneca, Boehringer Ingelheim GmbH, Daiichi Sankyo Company, Limited, Sumitomo Dainippon Pharma Co., Ltd., Eli Lilly and Company, Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceuticals America, Inc., Kyowa Hakko Kirin Co., Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk A/S, Novartis AG, Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho Co., Ltd., Takeda Development Center Asia, Pte. Ltd.. Research Support; Self; Abbott, Astellas Pharma US, Inc., AstraZeneca, Bayer AG, Benefit One Health Care Co., Ltd., Boehringer Ingelheim GmbH, Bristol-Myers Squibb Company, Daiichi Sankyo Company, Limited, Sumitomo Dainippon Pharma Co., Ltd., Eli Lilly and Company, Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceuticals America, Inc., Kyowa Hakko Kirin Co., Ltd., Johnson & Johnson Diabetes Institute, LLC., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Nitto Boseki Co., Ltd., Novartis AG, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Pfizer Inc., Sanofi, Sanwa Kagaku Kenkyusho Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Development Center Asia, Pte. Ltd., Terumo Medical Corporation.

Increased plasma free fatty acid (FFA) level is reported to be an important cause of obesity-associated insulin resistance in muscle and liver. Increased plasma FFA level in obesity is induced by insufficient suppression of plasma FFA by insulin and this is defined as impaired insulin sensitivity in adipose tissue (Adipo-IS). However, significance of impaired Adipo-IS in non-obese healthy subjects is totally unknown. To clarify this, we studied 49 non-obese (BMI< 25kg/m2) apparently healthy Japanese men without any cardiometabolic risk factors (mean age; 40.2±5.3 y.o, mean BMI; 23.1±1.0 kg/m²). We performed a 2-step hyperinsulinemic euglycemic clamp test (10 and 20 mU/m2 per min, 3h for each) to measure insulin sensitivity in muscle and liver. In addition, plasma FFA levels were also measured at fasting and 2nd step during the glucose clamp. Ectopic fat levels in muscle and liver and visceral fat area (VFA) were measured by 1H-MRS and MRI, respectively. The plasma FFA level was decreased from 530.6±139.1μEq/l to 62.4±64.2μEq/l during hyperinsulinemic euglycemic clamp. Thus, the mean Adipo-IS, defined as %FFA suppression during glucose clamp, was 88.8±10.3%; however, there was a large individual variations in Adipo-IS. Interestingly, Adipo-IS was positively correlated to insulin sensitivity in muscle (r=0.60, p Disclosure D. Sugimoto: None. Y. Tamura: None. K. Takeno: None. H. Kaga: None. Y. Someya: None. R. Suzuki: None. S. Kadowaki: None. T. Funayama: None. Y. Furukawa: None. R. Kawamori: None. H. Watada: Advisory Panel; Self; AstraZeneca. Consultant; Self; Astellas Pharma US, Inc., AstraZeneca, Boehringer Ingelheim GmbH, Daiichi Sankyo Company, Limited, Sumitomo Dainippon Pharma Co., Ltd., Eli Lilly and Company, Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceuticals America, Inc., Kyowa Hakko Kirin Co., Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk A/S, Novartis AG, Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho Co., Ltd., Takeda Development Center Asia, Pte. Ltd.. Research Support; Self; Abbott, Astellas Pharma US, Inc., AstraZeneca, Bayer AG, Benefit One Health Care Co., Ltd., Boehringer Ingelheim GmbH, Bristol-Myers Squibb Company, Daiichi Sankyo Company, Limited, Sumitomo Dainippon Pharma Co., Ltd., Eli Lilly and Company, Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceuticals America, Inc., Kyowa Hakko Kirin Co., Ltd., Johnson & Johnson Diabetes Institute, LLC., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Nitto Boseki Co., Ltd., Novartis AG, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Pfizer Inc., Sanofi, Sanwa Kagaku Kenkyusho Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Development Center Asia, Pte. Ltd., Terumo Medical Corporation.

Japanese women have substantially lower BMI than women in other developed countries and the prevalence of underweight (BMI In conclusion, the present study suggested that main cause of hyperglycemia in underweight women with IGT was decreased Rd. In addition, decreased insulin secretion may partly contribute to the decreased Rd in those IGT subjects. Disclosure R. Suzuki: None. Y. Tamura: None. Y. Someya: None. H. Kaga: None. D. Sugimoto: None. S. Kadowaki: None. S. Kakehi: None. K. Takeno: None. T. Funayama: None. Y. Furukawa: None. J. Sato: Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca, Novo Nordisk Inc., Novartis Pharmaceuticals Corporation, Sanofi, Eli Lilly and Company, Kissei Pharmaceutical Co., Ltd., Sanwa Kagaku Kenkyusho Co., Ltd., Takeda Development Center Asia, Pte. Ltd., Daiichi Sankyo Company, Limited, Ono Pharmaceutical Co., Ltd.. R. Kawamori: None. H. Watada: Advisory Panel; Self; AstraZeneca. Consultant; Self; Astellas Pharma US, Inc., AstraZeneca, Boehringer Ingelheim GmbH, Daiichi Sankyo Company, Limited, Sumitomo Dainippon Pharma Co., Ltd., Eli Lilly and Company, Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceuticals America, Inc., Kyowa Hakko Kirin Co., Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk A/S, Novartis AG, Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho Co., Ltd., Takeda Development Center Asia, Pte. Ltd.. Research Support; Self; Abbott, Astellas Pharma US, Inc., AstraZeneca, Bayer AG, Benefit One Health Care Co., Ltd., Boehringer Ingelheim GmbH, Bristol-Myers Squibb Company, Daiichi Sankyo Company, Limited, Sumitomo Dainippon Pharma Co., Ltd., Eli Lilly and Company, Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceuticals America, Inc., Kyowa Hakko Kirin Co., Ltd., Johnson & Johnson Diabetes Institute, LLC., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Nitto Boseki Co., Ltd., Novartis AG, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Pfizer Inc., Sanofi, Sanwa Kagaku Kenkyusho Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Development Center Asia, Pte. Ltd., Terumo Medical Corporation.

Metabolic diseases easily develop in non-obese Asians. We recently found that insulin resistance (IR) in muscle is closely associated with metabolic abnormalities in non-obese Japanese men and muscle IR is correlated well with both visceral fat accumulation (VFA) and fatty liver (FL). However, VFA and FL are correlated well with each other, thus it is unclear which is a better marker of muscle IR.To clarify this, we studied 87 nondiabetic non-obese middle-aged Japanese men. Using a two-step hyperinsulinemic euglycemic clamp, we evaluated insulin sensitivity (IS) in muscle and liver. Intrahepatic lipid (IHL) and visceral fat area are measured by 1H-MRS and MRI, respectively. According to the generally accepted definition, subject was divided into 4 groups by the presence or absence of VFA (visceral fat area 100cm2) and FL (IHL 5%); control (non-VFA non-FL; n=54), VFA alone (n=18), FL alone (n=7), VFA+FL (n=8). Hepatic-IS was similar among the groups. On the other hand, muscle-IS was significantly lower in groups of FL alone and VFA+FL than the control group. Interestingly, muscle-IS of VFA alone group was comparable to the control group, and it was significantly higher than FL alone group (Figure). These differences were still significant after adjustment for confounders. These data suggested that FL is a better marker than VFA in nondiabetic non-obese men in terms of sensitivity to detect muscle IR. Disclosure S. Kadowaki: None. Y. Tamura: None. Y. Someya: None. K. Takeno: None. T. Funayama: None. Y. Furukawa: None. S. Kakehi: None. H. Kaga: None. R. Suzuki: None. D. Sugimoto: None. R. Kawamori: None. H. Watada: Advisory Panel; Self; AstraZeneca. Consultant; Self; Astellas Pharma US, Inc., AstraZeneca, Boehringer Ingelheim GmbH, Daiichi Sankyo Company, Limited, Sumitomo Dainippon Pharma Co., Ltd., Eli Lilly and Company, Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceuticals America, Inc., Kyowa Hakko Kirin Co., Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk A/S, Novartis AG, Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho Co., Ltd., Takeda Development Center Asia, Pte. Ltd.. Research Support; Self; Abbott, Astellas Pharma US, Inc., AstraZeneca, Bayer AG, Benefit One Health Care Co., Ltd., Boehringer Ingelheim GmbH, Bristol-Myers Squibb Company, Daiichi Sankyo Company, Limited, Sumitomo Dainippon Pharma Co., Ltd., Eli Lilly and Company, Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceuticals America, Inc., Kyowa Hakko Kirin Co., Ltd., Johnson & Johnson Diabetes Institute, LLC., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Nitto Boseki Co., Ltd., Novartis AG, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Pfizer Inc., Sanofi, Sanwa Kagaku Kenkyusho Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Development Center Asia, Pte. Ltd., Terumo Medical Corporation.

Sustainable agriculture is spreading in Japan in response to growing concerns about the environmental burden of the agriculture sector, but less than 1% of the total crop area for each vegetable in Japan is grown sustainably. Environmentally friendly agricultural products are produced by using organic and low-input farming techniques; low-input farming aims to reduce chemical inputs, such as fertilizers, pesticides, and herbicides, by half. Here, we used komatsuna (Japanese mustard spinach, Brassica rapa var. perviridis) as a model vegetable to study the environmental impact of low-input farming and ways to promote the purchase of organically and low-input farmed vegetables. We first assessed greenhouse gas emissions resulting from organic, low-input, and conventional farming of komatsuna. We also evaluated the effectiveness of providing consumers with detailed farm management and seasonality information to market organically and low-input farmed vegetables. We estimated marginal willingness-to-pay (MWTP) using choice-based conjoint analysis, based on attributes of price, fertilizer use, pesticide use, and region of origin. For seasonality, the questionnaire incorporating these attributes was conducted twice: once assuming purchasing in season, the other out of season. The greenhouse gas emissions of organic farming per area (196.7 kg CO2-eq/10 a/year) and per yield (72.3 kg CO2-eq/t/year) were less than those of low-input (322.6 kg CO2-eq/10 a/year, 120.7 kg CO2-eq/t/year) and conventional (594.0 kg CO2-eq/10 a/year, 220.7 kg CO2-eq/t/year) farming. MWTPs were highest for pesticide-free komatsuna (76.9 yen out of season, 66.2 yen in season), followed by full organic fertilizer (66.0 yen out of season, 63.4 yen in season), half organic fertilizer (35.8 yen out of season, 19.8 yen in season), and half pesticide (29.2 yen out of season, 21.0 yen in season). Consumers showed greater preference for organically and low-input farmed komatsuna out of season than in season. Consumers were more interested in pesticide information than in fertilizer and region of origin information. Our findings suggest that providing detailed cultivation and seasonality information would be a beneficial consumer communication tool to increase the market for sustainable agricultural products.

Aims/Introduction Dipeptidyl peptidase-4 inhibitors and glinides are effective in reducing postprandial hyperglycemia. However, little information is available on the comparative effects of the two drugs on the levels of postprandial glucose. The aim of the present study was to compare the effects of sitagliptin and nateglinide on meal tolerance tests in drug-naive patients with type 2 diabetes mellitus. Materials and Methods The study participants were 19 patients with type 2 diabetes mellitus, which was inadequately controlled by diet and exercise. An open-label, prospective, cross-over trial was carried out to compare the effects of single-dose sitagliptin and nateglinide on the postprandial glucose level and its related hormones during meal tests. Results The change in area under the curve (AUC) of glucose from 0 to 180 min (AUC0–180 min) during the meal test by nateglinide was similar to that by sitagliptin. As expected, the change in active glucagon like peptide-1 was significantly higher after a single-dose of sitagliptin than nateglinide. Then, insulin secretion relative to glucose elevation (ISG) (ΔISG0–180 min: ΔAUC0–180 min insulin/AUC0–180 min glucose) was significantly enhanced by nateglinide compared with sitagliptin. Conversely, glucagon level (ΔAUC0–180 min glucagon) was increased by administration of nateglinide, whereas the glucagon level was reduced by administration of sitagliptin. Conclusions The effects of sitagliptin on postprandial glucose levels were similar to those of nateglinide in drug-naive type 2 diabetes patients. However, the induced changes in insulin, active glucagon-like peptide-1 and glucagon during meal loading suggest that reduction of postprandial hyperglycemia was achieved by the unique effect of each drug.

Background Hypertension is developed easily in Asian adults with normal body mass index (BMI) (~23 kg/m2), compared with other ethnicities with similar BMI. This study tested the hypothesis that slightly increased BMI at young age is a risk factor for future hypertension in Japanese men by historical cohort study. Methods The study participants were 636 male alumni of the physical education school. They had available data on their physical examination at college age and follow-up investigation between 2007 and 2011. The participants were categorized into six categories: BMI at college age of

This study investigated the safety and efficacy of metformin up-titration in Japanese patients with type 2 diabetes mellitus treated with vildagliptin (100 mg/day) and low-dose metformin (500 or 750 mg/day).Fifty patients were randomly allocated to the control group (maintaining the initial low-dose of metformin) and the dose increase group (up-titrating of metformin to 1,500-2,250 mg/day) for 24 weeks. The primary outcome was change in HbA1c from baseline to 24 weeks.Among the 25 patients allocated to the dose increase group, four patients were not able to complete the study protocol because of gastrointestinal symptoms. HbA1c in the dose increase group was significantly but modestly lower than in the control group (change in HbA1c: 0.22 ± 0.57 vs. -0.15 ± 0.58%, group comparison, P 0.05). The dose increase group did not gain weight during the study period, and no hypoglycemic events were reported in both groups. The rate of gastrointestinal symptoms in the dose increase group was profoundly higher than in the control group (32 vs. 0%, P 0.01).In Japanese patients with type 2 diabetes treated with vildagliptin and low-dose metformin, metformin up-titration significantly but modestly improved glycemic control without hypoglycemia and weight gain.

Aims Recent clinical studies identified the relation between olfactory dysfunction and cognitive impairment in the elderly without type 2 diabetes mellitus. The aim of the present study was to define the relation between olfactory function and cognition in elderly patients with type 2 diabetes mellitus. Methods The study participants comprised 250 elderly (age, 68–77, median 72) Japanese outpatient with type 2 diabetes mellitus free of clinically-evident cognitive impairment. Olfactory and cognitive functions were evaluated by the Open Essence (OE) test and Mini-mental State Examination (MMSE), respectively. Results Based on the MMSE score, 62.0%, 24.4%, and 13.6% of the participants were considered to have no impairment, possible cognitive impairment and probable dementia, respectively. The OE test score of the probable dementia group was significantly lower than other groups. Furthermore, age and serum uric acid were significantly higher in the probable dementia group than other groups. Simple correlation analysis showed positive correlation between the MMSE score and diastolic blood pressure, education, OE test score, total cholesterol, LDL cholesterol, folic acid, and negative correlation with age, HbA 1c , aspartate aminotransferase, serum adiponectin and urinary albumin excretion. Multivariate regression analysis showed that OE test score correlated significantly and independently with MMSE score (standardized coefficients β = 0.542, R 2 = 0.478, P Conclusions The results suggested the association of olfactory dysfunction with cognitive impairment in elderly patients with type 2 diabetes mellitus.

Aims/Introduction To investigate the efficacy and safety of vildagliptin, a potent dipeptidyl peptidase-4 inhibitor, as add-on to nateglinide, compared with switching to vildagliptin in Japanese type 2 diabetes patients poorly controlled with nateglinide. Materials and Methods A total of 40 patients inadequately controlled with nateglinide were randomized to the switching group (n = 20, switching from nateglinide to vildagliptin) or combination group (n = 20, nateglinide plus vildagliptin). A meal tolerance test was carried out at weeks 0 and 24. Results The mean changes in glycated hemoglobin from baseline to week 24 were −1.2 ± 0.3% and −0.3 ± 0.5% in patients of the combination and switching groups, respectively, and the difference between the groups was statistically significant (P

Objective Quality of life (QOL) is recognized as an important medical outcome. The aim of this study was to test the validity and reliability of the Japanese version of the Diabetes Quality-Of-Life (J-DQOL) questionnaire originally developed by the Diabetes Control and Complications Trial.

Aims/Introduction ‘Morningness’ and ‘eveningness’ represent the sleep–wake patterns of the circadian rhythm might also affect glycemic control in patients with type 2 diabetes. The aim of this study was to examine the relationship between the morningness–eveningness trait and metabolic parameters. Materials and Methods The study participants comprised 101 Japanese male workers with type 2 diabetes treated in an outpatient clinic. Blood samples were obtained, and a morningness–eveningness questionnaire (MEQ), where a high score represents morningness; and the Pittsburg Sleep Quality Index (PSQI), where the higher the score the worse the sleep quality, were carried out. Results MEQ correlated positively with age, and high-density lipoprotein cholesterol (HDL-C), and negatively with glycated hemoglobin (HbA1c) and PSQI. Multivariate regression analysis showed that MEQ was significantly associated with HbA1c and HDL-C. In addition, we classified the study patients into three groups: ‘morning type’, ‘neither type’ and ‘evening type’ according to the sum of the MEQ score, and analyzed the difference between morning type (n = 32) and evening type (n = 11). We found that HbA1c, low-density lipoprotein cholesterol and PSQI of the morning type group were significantly lower than those of the evening type group. Conclusions The present study suggests that ‘eveningness’ type male Japanese workers with type 2 diabetes suffer inadequate glycemic control.

The molecular clock of neutral mutations, which represents linear mutation fixation over generations, is theoretically explained by genetic drift in fitness-steady evolution or hitchhiking in adaptive evolution. The present study is the first experimental demonstration for the molecular clock of neutral mutations in a fitness-increasing evolutionary process. The dynamics of genome mutation fixation in the thermal adaptive evolution of Escherichia coli were evaluated in a prolonged evolution experiment in duplicated lineages. The cells from the continuously fitness-increasing evolutionary process were subjected to genome sequencing and analyzed at both the population and single-colony levels. Although the dynamics of genome mutation fixation were complicated by the combination of the stochastic appearance of adaptive mutations and clonal interference, the mutation fixation in the population was simply linear over generations. Each genome in the population accumulated 1.6 synonymous and 3.1 non-synonymous neutral mutations, on average, by the spontaneous mutation accumulation rate, while only a single genome in the population occasionally acquired an adaptive mutation. The neutral mutations that preexisted on the single genome hitchhiked on the domination of the adaptive mutation. The successive fixation processes of the 128 mutations demonstrated that hitchhiking and not genetic drift were responsible for the coincidence of the spontaneous mutation accumulation rate in the genome with the fixation rate of neutral mutations in the population. The molecular clock of neutral mutations to the fitness-increasing evolution suggests that the numerous neutral mutations observed in molecular phylogenetic trees may not always have been fixed in fitness-steady evolution but in adaptive evolution., Author Summary Mutations that have little influence on biological function are referred to as neutral mutations and frequently appear in molecular phylogenetic analyses. The fixation of neutral mutations in populations has been attributed to genetic drift in fitness-steady evolutionary processes or hitchhiking in adaptive evolution. We examined the fitness-increasing evolution of Escherichia coli for thermal adaptation to observe the fixation dynamics of genome-wide mutations. In the adaptive evolution, all genomes in the population equally accumulated neutral mutations by replication errors. The infrequent occurrence of an adaptive mutation on one of the genomes by chance resulted in the fixation of the neutral mutations that had pre-accumulated in the same genome by hitchhiking. Via successive hitchhiking events, the neutral mutations were fixed in the population linearly over generations at the same rate as the spontaneous mutation accumulation rate in the genome. The molecular clock of neutral mutations thus functions even in adaptive evolution. The evolutionary period characterized by the accumulation of numerous neutral mutations observed in molecular phylogenetic trees may not be specific to neutral evolution but may occur in adaptive evolution as well.

Background While poor sleep quality can worsen cardiovascular risk factors such as glucose and lipid profiles in patients with type 2 diabetes mellitus (T2DM), the relationship between sleep quality and atherosclerosis remains largely unknown. The aim of this study was to examine this relationship. Methods The study participants comprised 724 Japanese T2DM outpatients free of history of cardiovascular diseases. The relationships between sleep quality (assessed by the Pittsburgh Sleep Quality Index (PSQI)) and various clinical and laboratory parameters were investigated. Results The mean PSQI was 5.1 ± 3.0 (±SD). Patients were divided into three groups based on the total PSQI score; subjects with good sleep quality (n = 462), average sleep quality (n = 185), and poor sleep quality (n = 77). In the age/gender-adjusted model, patients with poor sleep quality tended to be obese, evening type and depressed. However, other lifestyles showed no significant trends. Alanine aminotransferase, fasting blood glucose, HbA1c, systolic blood pressure, urinary albumin excretion, and brachial-ankle pulse wave velocity (baPWV) tended to be higher in patients with poor sleep quality. High baPWV was the only parameter that correlated with poor sleep in a model adjusted for several other lifestyle factors. Conclusions Our study indicates that poor sleep quality in T2DM patients correlates with increased arterial wall stiffness, a marker of atherosclerosis and a risk factor for cardiovascular diseases.

Introduction While individuals tend to show accumulation of certain lifestyle patterns, the effect of such patterns in real daily life on cardio-renal—metabolic parameters remains largely unknown. This study aimed to assess clustering of lifestyle patterns and investigate the relationships between such patterns and cardio-renal-metabolic parameters. Participants and methods The study participants were 726 Japanese type 2 diabetes mellitus (T2DM) outpatients free of history of cardiovascular diseases. The relationship between lifestyle patterns and cardio-renal-metabolic parameters was investigated by linear and logistic regression analyses. Results Factor analysis identified three lifestyle patterns. Subjects characterized by evening type, poor sleep quality and depressive status (type 1 pattern) had high levels of HbA1c, alanine aminotransferase and albuminuria. Subjects characterized by high consumption of food, alcohol and cigarettes (type 2 pattern) had high levels of γ-glutamyl transpeptidase, triglycerides, HDL-cholesterol, blood pressure, and brachial-ankle pulse wave velocity. Subjects characterized by high physical activity (type 3 pattern) had low uric acid and mild elevation of alanine aminotransferase and aspartate aminotransferase. In multivariate regression analysis adjusted by age, gender and BMI, type 1 pattern was associated with higher HbA1c levels, systolic BP and brachial-ankle pulse wave velocity. Type 2 pattern was associated with higher HDL-cholesterol levels, triglycerides, aspartate aminotransferase, ɤ- glutamyl transpeptidase levels, and diastolic BP. Conclusions The study identified three lifestyle patterns that were associated with distinct cardio-metabolic-renal parameters in T2DM patients. Trial registration UMIN000010932

"Morningness" and "Eveningness" represent lifestyle patterns including sleep-wake patterns. Although previous studies described a relationship between the morningness-eveningness trait and glycemic control in patients with type 2 diabetes mellitus (T2DM), the mechanism underlying this association remains unknown. The study participants comprised 725 Japanese T2DM outpatients free of history of cardiovascular diseases. Various lifestyles were analyzed using self-reported questionnaires, including morningness-eveningness questionnaire (MEQ). The relationships between morningness-eveningness trait and various biochemical parameters were investigated by linear regression analysis and logistic regression analysis. We classified the study patients into three groups, morning type (n=117), neither type (n=424) and evening type (n=184). Subjects of the evening type had high levels of alanine aminotransferase, triglyceride, fasting blood glucose and HbA1c and low high-density lipoprotein-cholesterol level in a model adjusted for age and gender. Furthermore, multivariate analysis showed that the evening type was associated with high HbA1c and estimated glomerular filtration rate even after adjustment for other lifestyle factors known to affect metabolic control. The results suggest that T2DM patients with eveningness trait are under inadequate metabolic control independent of other lifestyle factors. Thus, the evening trait of T2DM patients represents an important target for intervention to ensure appropriate metabolic function.

Background In Japan, although the incidence of overweight (BMI ≥ 25) is still low compared with that in Europe and the United States, the prevalence of type 2 diabetes has increased over the last 15 years,. In both Japanese and Caucasian populations it has been reported that a high level of cardiorespiratory fitness protects against the development of type 2 diabetes. However, there are no reports focused specifically on athletes that investigate whether high cardiorespiratory fitness at a young age can prevent disease later in life. We examined the relationship between cardiorespiratory fitness at a young age and the development of type 2 diabetes in Japanese athletes using a cohort study. Methods The cardiorespiratory fitness of male alumni of the physical education department of Juntendo University, as measured by stored data of a 1,500-m endurance run in college (1971–1991) was compared with their incidence of type 2 diabetes as determined by follow-up questionnaires (2007–2009). This study used Cox’s proportional hazards models and adjusted for age, year of graduation, BMI, smoking, and sports club participation at college age. Results We collected data on cardiorespiratory fitness at college age and medical history survey data during 2007–2009 from 570 male alumni. The median follow-up period was 26 years (IQR: 23–29 years), and 22 men had developed type 2 diabetes. An inverse relationship was observed between incidence of type 2 diabetes and level of cardiorespiratory fitness at time of college after adjustment for age, year of graduation, BMI, smoking, and sports participation. The adjusted hazards ratio and 95% CI by category (low, medium, and high) were 1.00 (reference), 0.40 (0.14–1.13) and 0.26 (0.07–1.00) (p = 0.03 for trend). Conclusions A high level of cardiorespiratory fitness at a young age can help prevent type 2 diabetes later in life.

Three hydroxy-1,8-cineole glucopyranosides, (1R, 2R, 4S)- and (1S, 2S, 4R)-trans-2-hydroxy-1,8-cineole beta-D-glucopyranosides, and (1R, 3S, 4S)-trans-3-hydroxy-1,8-cineole beta-D-glucopyranoside, which are possible precursors of acetoxy-1,8-cineoles as unique aroma components, were isolated from the rhizomes of greater galangal (Alpinia galanga W.). Their structures were analyzed by FAB-MS and NMR spectrometry, and the absolute configulation of each aglycone was determined by using a GC-MS analysis with a capillary column coated with a chiral stationary phase. The composition of the diastereomers of (1R, 2R, 4S)- and (1S, 2S, 4R)-trans-2-hydroxy-1,8-cineole beta-D-glucopyranosides in the rhizomes was determined as 3:7 by a GC-MS analysis after preparing the trifluoroacetate derivatives of the glucosides.

(S)-(+)-O-methylmandelate esters of trans- and cis-1,3, 3-trimethyl-2-oxabicyclo[2.2.2]octan-5- and 6-ols (2- and 3-hydroxy-1,8-cineoles) were prepared, and eight diastereomers were separated. The absolute configuration of the asymmetric carbons of the cineole moiety of each diastereomer was determined by (1)H NMR data according to the Mosher theory. Each mandelate was reduced with LiAlH(4) to obtain optically pure hydroxy-1,8-cineoles, this being followed by acetylation to afford optically pure acetoxy-1, 8-cineoles. These acetates were subjected to chiral GC, using a cyclodextrin column, and the enantiomeric purity of trans- and cis-1, 3,3-trimethyl-2-oxabicyclo[2.2.2]octan-5- and 6-yl acetates in the aroma concentrate from the rhizomes of Alpinia galanga was determined as 93.9 (5S), 19.4 (5R), 63.5 (6R), and 100 (6R) % ee, respectively. The aroma character of each enantiomer was also evaluated by GC-sniffing.

The rhizomes of greater galangal (Alpinia galanga Willd. L.) are widely used as a spice throughout south-east Asian countries. A flavor concentrate was prepared by steam distillation under reduced pressure, and the odor character and some potent odorants of the oxygenated compound fraction that presented the characteristic odor of galanga were investigated by GCMS and aroma extract dilution analysis. Monoterpenoids of linalool and geranyl acetate, 1,8- cineole and acetoxy-I,8-cineoles, and some C6-C3 compounds of the derivatives of eugenol and chavicol were determined as important odor components. In addition, the optical purity and odor difference between the enantiomers were determined by GC and GC eluate sniffing, using a cyclodextrin column. I’ -Acetoxychavicol acetate was present in the optically active 5- configuration in the essential oil of the rhizomes. Only the (S)-enantiomer possessed the characteristic cool, woody and ginger-like odor, in contrast of no odor of the (R)-enantiomer which played an important role in the odor of the fresh rhizomes, because this compound was degraded during cooking. Among the eight isomers of acetoxy-l ,8-cineoles, (1R, 4S, 6R)- 1,3,3-trimethyl-2-oxabicyclo[2,2,2]oct-6-yl acetate (trans-2-acetoxy-l,8-cineole) which presented a woody and galanga-like odor was the most important odor constituent in the rhizomes of greater galangal.