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Aims/Introduction Type 1 diabetes is associated with poorer bone quality. Quantitative ultrasound provides an estimate of bone mineral density (BMD) and can also be used to evaluate bone quality, which is associated with an increased fracture risk in people with type 1 diabetes. The aim of this study was to evaluate the association between menopausal status and a bone turnover marker with heel BMD using quantitative ultrasound in women with type 1 diabetes and age‐ and body mass index‐matched controls. Materials and Methods A total of 124 individuals recruited in Kyoto and Osaka, Japan – 62 women with type 1 diabetes (mean age 47.2 ± 17.3 years) and 62 age‐, menopausal status‐, sex‐ and body mass index‐matched non‐diabetic control individuals (mean age 47.3 ± 16.3 years) – were enrolled in this study. Heel BMD in the calcaneus was evaluated using ultrasonography (AOS‐100NW, Hitachi‐Aloka Medical, Ltd., Tokyo, Japan). A bone turnover marker was also measured. Results The heel BMD Z‐score was significantly lower in premenopausal women with type 1 diabetes than in the premenopausal control group, but not in postmenopausal women with type 1 diabetes. Levels of tartrate‐resistant acid phosphatase‐5b, a bone resorption marker, were significantly higher in premenopausal women with type 1 diabetes than in the premenopausal control group, but not in postmenopausal women with type 1 diabetes. The whole parathyroid hormone level was significantly lower in both pre‐ and postmenopausal women with type 1 diabetes. Conclusions Lower heel BMD, higher tartrate‐resistant acid phosphatase‐5b level and lower parathyroid hormone were observed in premenopausal women with type 1 diabetes. Premenopausal women with type 1 diabetes require osteoporosis precautions for postmenopause.

Background Atrial fibrillation (AF) is the most common sustained arrhythmia, with growing evidence identifying obesity as an important risk factor for the development of AF. Although defective atrial myocyte excitability due to stress-induced remodeling of ion channels is commonly observed in the setting of AF, little is known about the mechanistic link between obesity and AF. Recent studies have identified increased cardiac late sodium current (INa,L) downstream of calmodulin-dependent kinase II (CaMKII) activation as an important driver of AF susceptibility. Methods Here, we investigated a possible role for CaMKII-dependent INa,L in obesity-induced AF using wild-type (WT) and whole-body knock-in mice that ablates phosphorylation of the Nav1.5 sodium channel and prevents augmentation of the late sodium current (S571A; SA mice). Results A high-fat diet (HFD) increased susceptibility to arrhythmias in WT mice, while SA mice were protected from this effect. Unexpectedly, SA mice had improved glucose homeostasis and decreased body weight compared to WT mice. However, SA mice also had reduced food consumption compared to WT mice. Controlling for food consumption through pair feeding of WT and SA mice abrogated differences in weight gain and AF inducibility, but not atrial fibrosis, premature atrial contractions or metabolic capacity. Conclusions These data demonstrate a novel role for CaMKII-dependent regulation of Nav1.5 in mediating susceptibility to arrhythmias and whole-body metabolism under conditions of diet-induced obesity.

Background: Continuous subcutaneous insulin infusion (CSII) is associated with improved glycemic control, a reduced incidence of hypoglycemia, and improved quality of life (QOL). To date, however, ...

Background: This study aimed to investigate the association between serum apolipoprotein A1 (ApoA1) levels, ischemic stroke subtypes and plaque properties. Methods: We enrolled 92 patients with ischemic stroke and 21 age-matched controls (CONT). The stroke patients were divided into three subtypes: cardioembolic (CE, n = 15), atherothrombotic infraction (ATBI, n = 52), and lacunar infarction (LI, n = 25). Carotid plaques were classified as low, intermediate, or high intensity, and either simple or mixed type. Serum lipids (total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG)), ApoA1, and ApoB were analyzed using commercially available kits. Results: There was no difference in TC, LDL-C, HDL-C, and ApoB levels among the four groups. Serum ApoA1 levels in the ATBI group were significantly lower compared with the CONT group. Among the ATBI group, the serum ApoA1 levels in the low-intensity plaque-type were significantly lower than those in the intermediate or hard-intensity plaque-type. Furthermore, serum ApoA1 levels in the mixed plaque-type were significantly lower than those in the simple type. Conclusions: These findings suggest that serum ApoA1 levels might be associated with the development of ATBI and plaque properties of the carotid artery. J Clin Med Res. 2020;12(9):598-603 doi: https://doi.org/10.14740/jocmr4284

PURPOSE The physiological response induced by acute prolonged sitting is not fully understood. Therefore, we examined the effects of 8-h constant sitting on microcirculation and associated factors in the lower extremity among healthy males. We also evaluated the protective effects of lower-pressure thigh-length elastic compression garments on these parameters. METHODS Nine healthy males (age, 22.6 ± 1.4 years; body mass index, 22.4 ± 1.8 kg·m-2) completed the 8-h constant sitting experiment. Following baseline measurements, each subject was randomized to wear a lower-pressure elastic garment on the right or left leg from the inguinal region to the ankle joint, with the non-compressed contralateral leg as a control. Circumferences of the calf and malleolus, extracellular water contents, blood flow and shear rate of the dorsal metatarsal artery, and oxygen dynamics in the gastrocnemius muscles were measured in both extremities before, during, and after 8-h constant sitting. RESULTS Compared with baseline values, 8-h constant sitting caused enlargement of circumferences (calf, 2.4 ± 0.7%; malleolus, 2.7 ± 1.4%), retention of extracellular water in lower extremity muscles (10.1 ± 1.78%), deterioration of the blood flow (61.4 ± 16.2% of baseline) and shear rate of the dorsal metatarsal artery, and decrease in oxygenated hemoglobin and total hemoglobin levels in the gastrocnemius muscle (p < 0.05, respectively). When subjects wore the lower-pressure thigh-length compression garment, a significant reduction of these effects was observed (p < 0.05, for all). CONCLUSION Prolonged sitting for 8 h induced edema, as well as deterioration of the arterial blood flow, shear rate, and microcirculation in lower limb muscles. Conversely, application of the lower-pressure elastic garment successfully prevented the pathophysiologic deterioration associated with prolonged sitting.

Hepcidin-25 is suggested as a surrogate iron status marker in athletes who show exercise-induced anemia, however, the implications of hepcidin concentration in this population remain poorly understood. This study aimed to investigate the relationship between hepcidin and body fat levels in rugby football players. We included 40 male university rugby football players (RUG) and 40 non-athlete controls. All participants underwent an anthropometric analysis and blood testing that included both hepcidin-25 and ferritin levels. The hepcidin-25 level was slightly (11.6%, p = 0.50) higher, and the ferritin level was significantly (35.9%, p &lt, 0.05) lower, in the RUG group than in controls. The hepcidin-25 to-ferritin ratio was significantly higher (62.5%, p &lt, 0.05) in the RUG group. While significant U-shaped correlations were observed between the body fat and ferritin levels in both groups, the correlations between the hepcidin levels and fat mass index were significantly higher in the RUG group (RUG: r = 0.79, controls: r = 0.45). Notably, the RUG with the lower fat mass index group had a higher hepcidin-25 level, lower ferritin level, and then significantly higher hepcidin-25/ferritin ratio. The hepcidin-25/ferritin ratio may serve as a biomarker for iron status in RUG, especially RUG with lower fat mass.

Background Hemorrhagic infarction (HI) is among the most severe complications that can occur following the administration of intravenous recombinant tissue plasminogen activator (rt-PA). In the present study, we aimed to determine the optimal cut-off points of blood pressure (BP) for HI after rt-PA treatment, and to compare our findings with those for other prediction models. Methods We analyzed data from 109 consecutive patients with stroke treated at our hospital between 2009 and 2016. HI was confirmed via computed tomography or magnetic resonance imaging. Patients were classified into a symptomatic HI group, an asymptomatic HI group, and a non-HI group. BP was measured on admission and before rt-PA treatment. Glucose Race Age Sex Pressure Stroke Severity (GRASPS) and Totaled Health Risks in Vascular Events (THRIVE) scores were also calculated. Receiver operating characteristic (ROC) analysis was used to determine factors associated with symptomatic and asymptomatic HI. Results Among the 109 total patients, 25 patients developed symptomatic HI, while 22 patients developed asymptomatic HI. ROC analysis for predicting symptomatic and asymptomatic HI revealed that the area under the curve for pretreatment systolic BP (SBP) was .88 (95% confidence interval[CI]: .83-.94), while those for GRASPS and THRIVE scores were .75 (95% CI: .66-.85) and .69 (95% CI: .59-.79), respectively. We identified an optimal cut-off point of 160 mm Hg (sensitivity: 82.3%; specificity: 76.6%; diagnostic accuracy: 80.0%; positive predictive value: 76.6%; negative predictive value: 82.5%). Conclusions Pre-treatment SBP may be a simple predictor of symptomatic and asymptomatic HI in patients with stroke undergoing rt-PA treatment.

Goto, M, Chikako, M, Hirayama, T, Terada, S, Nirengi, S, Kurosawa, Y, Nagano, A, and Hamaoka, T. Partial range of motion exercise is effective for facilitating muscle hypertrophy and function through sustained intramuscular hypoxia in young trained men. J Strength Cond Res 33(5): 1286-1294, 2019-The acute response to and long-term effects of partial range of motion exercise (PRE) and full range of motion exercise (FRE) of elbow extensors were compared in young trained men. The PRE was expected to increase the intramuscular hypoxic environment, which was theorized to enhance muscular hypertrophy. Forty-four resistance-trained men were divided into 2 training groups, PRE (n = 22) or FRE (n = 22) group, and performed the PRE or FRE acute exercise protocol. The PRE (elbow range from 45° to 90°) and FRE (from 0° to 120°) acute protocols consisted of 3 sets of 8 repetitions, with an 8RM, and an equivalent workload. After the initial testing, the training program for each group, comprised 3 training sessions per week for 8 weeks, was started. The acute responses of area under the oxygenated hemoglobin (Oxy-Hb) curve, blood lactate concentration, and root mean square of electromyography were significantly higher both before and after PRE than FRE training. Long-term effects were produced by both PRE and FRE, with significant (p ≤ 0.05) increases in cross-sectional area (CSA) of triceps brachii and isometric strength. The CSA increased significantly greater after PRE (48.7 ± 14.5%) than after FRE (28.2 ± 10.9%). Furthermore, during the PRE program, a positive correlation was detected between the percent increase in CSA and area under the Oxy-Hb curves before and after 8-week exercise training (before 8-week exercise training: r = 0.59, after 8-week exercise training: r = 0.70, p < 0.01). These results suggest that intramuscular hypoxia might facilitate muscular hypertrophy with PRE being more effective than FRE.

Maslinic acid, derived from olive fruit, reduces pro-inflammation cytokines, which are involved in muscle fiber atrophy. Therefore, the maslinic acid ingestion may enhance the muscular response to resistance training through anti-inflammatory action. We therefore conducted a parallel, double-blind, randomized, placebo-controlled trial that examined whether a combination of maslinic acid supplementation and resistance training improve mobility functions in community-dwelling elderly persons. Over a 12-week period, 36 participants underwent moderate resistance training and are assigned to the maslinic acid supplementation (n = 17, 60 mg/day) or the placebo (n = 19) group. At baseline and at 12-weeks, we assessed body composition, grip strength, walking speed, leg strength, mobility functions, and knee pain scores. Following the 12-weeks, skeletal muscle mass, segmental muscle mass (right arm, left arm, and trunk) and knee pain score of the right leg were significantly improved in the maslinic acid group, while there was no change or parameters had worsened in the placebo group. Grip strength of the better side significantly increased only in the maslinic acid group. These results suggest that maslinic acid supplementation combined with moderate resistance training may increase upper muscle mass and grip strength, and reduce knee pain, could be effective for preventing mobility-related disability in elderly persons. Clinical trial registration number: UMIN000017207.

Background/objectives Disturbed circadian rhythm is associated with an increased risk of obesity and metabolic disorders. Brown adipose tissue (BAT) is a site of nonshivering thermogenesis (NST) and plays a role in regulating whole-body energy expenditure (EE), substrate metabolism, and body fatness. In this study, we examined diurnal variations of NST in healthy humans by focusing on their relation to BAT activity. Methods Forty-four healthy men underwent 18F-fluoro-2-deoxy-D-glucose positron emission tomography and were divided into Low-BAT and High-BAT groups. In STUDY 1, EE, diet-induced thermogenesis (DIT), and fat oxidation (FO) were measured using a whole-room indirect calorimeter at 27 °C. In STUDY 2, EE, FO, and skin temperature in the region close to BAT depots (Tscv) and in the control region (Tc) were measured at 27 °C and after 90 min cold exposure at 19 °C in the morning and in the evening. Results In STUDY 1, DIT and FO after breakfast was higher in the High-BAT group than in the Low-BAT group (P P P P = 0.056). Conclusion BAT-associated NST and FO were evident in the morning, but not in the evening, suggesting that the activity of human BAT is higher in the morning than in the evening, and thus may be involved in the association of an eating habit of breakfast skipping with obesity and related metabolic disorders.

Type 2 diabetes (T2D) substantially elevates the risk for heart failure, a major cause of death. In advanced T2D, energy metabolism in the heart is disrupted; glucose metabolism is decreased, fatty acids (FA) metabolism is enhanced to maintain ATP production, and cardiac function is impaired. This condition is termed diabetic cardiomyopathy (DCM). The exact cause of DCM is still unknown although altered metabolism is an important component. Although type 2 diabetes is characterized by insulin resistance, the traditional antidiabetic agents that improve insulin stimulation or sensitivity only partially improve DCM-induced cardiac dysfunction. Recently, sodium-glucose transporter-2 (SGLT2) inhibitors have been identified as potential pharmacological agents to treat DCM. This review highlights the molecular mechanisms underlying cardiac energy metabolism in DCM, and the potential effects of SGLT2 inhibitors.

Background: Information about factors related to better adherence to continuous glucose monitoring (CGM) sensor adherence is quite limited. Materials and Methods: Forty-six participants with type 1 diabetes using continuous subcutaneous insulin infusion (CSII) without CGM were recruited. The participants’ characteristics and diabetes-related quality of life (QOL) were evaluated at baseline and one year after starting to use CGM. Participants wearing the sensor for ≥60% of the time were considered as adherent. Results: The mean age of the 46 participants was 44.1 ± 15.0 years old and the mean glycohemoglobin (HbA1c) was 7.7 ± 1.0%; 60.9% of the participants were classified as adherent. The duration of using CSII was longer in the adherent group, and the degree of diabetic retinopathy was significantly different. There were no significant differences in age, frequency of self-monitoring of blood glucose, or Hypoglycemia Fear Survey (HFS-B for behavior, HFS-W for worry) score at baseline between the adherent and nonadherent groups. The Problem Areas in Diabetes (PAID) score at baseline was significantly higher and the total CSII-QOL score at baseline was significantly lower in the adherent group. The usage of dual-wave bolus was significantly increased in the adherent group (34.6%-61.5%, P = .016), but not in the nonadherent group (33.3%-33.3%, P > .999). The HbA1c level showed a significant improvement in the adherent group (7.8%-7.3%, P Conclusions: Higher adherence to CGM sensors may be associated with a heavier emotional burden of diabetes and a worse QOL in relation to CSII at baseline.

Objectives Frequent self-weighing is associated with weight loss and maintenance, but the relationship between frequent self-weighing and the incidence of type 2 diabetes (T2D) remains unclear. The study aim was to examine the association between self-weighing frequency and the incidence of T2D in people with impaired fasting glucose (IFG). Results We tested the hypothesis that self-weighing frequency and the incidence of T2D are associated in 2607 people with IFG (1240 in the intervention arm; 1367 in the self-directed control arm). Both arms received a weighing scale with storage function. Healthcare providers offered a one-year goal-focused lifestyle intervention via phone. Participants were divided into 4 categories based on self-weighing frequency (No data sent [reference group], low: Trial registration This trial has been registered with the University Hospital Medical Information Network (UMIN000000662).

Being born with large birthweight is considered as a risk of non-communicable diseases later in life. However, it is not fully understood what kind of maternal dietary intake during pregnancy affect large birthweight. Therefore, we examined the association of dietary intakes and its changes during pregnancy with large-for-gestational-age (LGA) births in Japanese pregnant women. In the prospective study, 245 pregnant women who visited Kyoto Medical Center were enrolled. Nutrition survey using brief-type self-administered diet history questionnaire (BDHQ) at all trimester was completed in 171 pregnant women. Based on birthweight and gestational age, participants were divided into three groups, such as small-for-gestational-age (

Background Atrial fibrillation (AF) is the most common sustained arrhythmia, with growing evidence identifying obesity as an important risk factor for the development of AF. Although defective atrial myocyte excitability due to stress-induced remodeling of ion channels is commonly observed in the setting of AF, little is known about the mechanistic link between obesity and AF. Recent studies have identified increased cardiac late sodium current (INa,L) downstream of calmodulin-dependent kinase II (CaMKII) activation as an important driver of AF susceptibility. Methods Here, we investigated a possible role for CaMKII-dependent INa,L in obesity-induced AF using wild-type (WT) and whole-body knock-in mice that ablates phosphorylation of the Nav1.5 sodium channel and prevents augmentation of the late sodium current (S571A; SA mice). Results A high-fat diet (HFD) increased susceptibility to arrhythmias in WT mice, while SA mice were protected from this effect. Unexpectedly, SA mice had improved glucose homeostasis and decreased body weight compared to WT mice. However, SA mice also had reduced food consumption compared to WT mice. Controlling for food consumption through pair feeding of WT and SA mice abrogated differences in weight gain and AF inducibility, but not atrial fibrosis, premature atrial contractions or metabolic capacity. Conclusions These data demonstrate a novel role for CaMKII-dependent regulation of Nav1.5 in mediating susceptibility to arrhythmias and whole-body metabolism under conditions of diet-induced obesity.

Objectives Using annual health check‐up data, the aim of this study was to identify target populations for lifestyle interventions to effectively prevent diabetes in a real‐world setting. Methods The Japan Diabetes Outcome Intervention Trial‐1, a prospective, cluster‐randomized controlled trial, was launched to test if year‐long telephone‐delivered lifestyle support by health professionals can prevent the development of type 2 diabetes (T2D) in people with impaired fasting glucose (IFG) identified at health check‐ups. A total of 2607 participants aged 20‐65 years with IFG were randomized to an intervention arm (n = 1240) or a control arm (n = 1367). We performed subgroup analysis to examine the effects of the intervention on the incidence of T2D in participants with body mass index (BMI) ≥25, metabolic syndrome (MetS), and non‐alcoholic or alcoholic elevated liver enzymes at the baseline. Cox regression analysis adjusted for sex was used to calculate the hazard ratios (HRs). Results In addition to IFG, the presence of BMI ≥25, MetS, and elevated liver enzymes increased the incidence of diabetes by two‐ or three‐fold. During a median follow‐up period of 4.9 years, only the non‐alcoholic elevated liver enzyme group showed a low incidence rate owing to lifestyle interventions (adjusted HR: 0.42, 95% confidence interval: 0.18‐0.98). Conclusion The results suggest that people who have IFG and non‐alcoholic elevated liver enzymes are a good target population for lifestyle interventions to effectively reduce the incidence of diabetes in a real‐world setting.

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder among reproductive-aged women. While PCOS is associated with an increased risk of obesity and insulin resistance, little is known regarding the prevalence of and risk factors for nonalcoholic fatty liver disease (NAFLD) among Japanese women with PCOS. We estimated the prevalence of and risk factors for elevated liver enzymes, as the index of NAFLD, in Japanese women with PCOS. Methods: We retrospectively reviewed 102 reproductive-aged women who visited the Department of Gynecology, Kyoto Medical Center in Japan from January 2000 to September 2016. Inclusion criterion was confirmed diagnosis of PCOS using International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10) codes. Exclusion criteria were women with a history of liver diseases, missing body mass index (BMI) and serum alanine aminotransferase (ALT) data, and pregnancy. Data regarding age; BMI; and levels of blood glucose, serum lipid, liver enzymes, and sex hormones were obtained from medical records. Elevated liver enzymes was defined as ALT > 19 IU/L. Optimal cutoffs for risk factors for elevated liver enzymes were calculated to determine predictors of elevated liver enzymes using area under the curve (AUC) by receiver-operating characteristics (ROC). Results: The prevalence of elevated liver enzymes was 33.3%. BMI was significantly higher in PCOS patients than in those without elevated liver enzymes (25.3 vs. 20.7 kg/m 2 , P < 0.05). ROC analyses were performed using BMI and blood glucose and testosterone levels because BMI and blood glucose showed differences between the groups and testosterone is related to fatty liver. AUC of the model including BMI and blood glucose and testosterone levels was 0.861 (sensitivity, 66.7%; specificity, 100%). Conclusions: These findings suggest that elevated liver enzymes are common in women with PCOS. An algorism using BMI and blood glucose and testosterone levels might be useful to determine elevated liver enzymes in women with PCOS. Our finding may be useful for the study of NAFLD among Japanese women with PCOS since several previous studies have indicated elevated liver enzymes to be related to the potential presence of NAFLD. Further examination, including abdominal ultrasonography and/or liver biopsy data, is required to confirm these results. J Clin Med Res. 2018;10(12):904-910 doi: https://doi.org/10.14740/jocmr3639

Aims / Introduction We investigated the safety of the batteries and power units used in insulin pumps in Japan. Materials and Methods A self-administered questionnaire was sent to the 201 members of the Association for Innovative Diabetes Treatment in Japan (ASINDTJ). Results Fifty-six members responded, and among the 1,499 active devices, 66 had episodes of trouble related to the batteries and power units. The ratio of reported troubles to the number of insulin pumps was significantly higher in insulin pumps with CGM sensor compared to insulin pumps without CGM sensor (Odds ratio 2.82, P < 0.05). The cause and the consequences varied. The brands of the batteries varied; alkaline batteries purchased at drug stores and other shops accounted for 19.7%. Termination of battery life within 72 hours of usage was reported most frequently (50.0%), suspension of the insulin pump (21.2%) and leakage of the battery fluid (4.5%) followed. Fifty-three point two percent of the reported insulin pumps needed to be replaced, and 37.1% of them recovered after replacement of the battery. Conclusions As trouble related to the batteries and power units of insulin pumps was frequent, practical guidance should be provided to respective patients regarding the usage of reliable batteries, and to be well prepared for unexpected insulin pump failure. This article is protected by copyright. All rights reserved.

Aims/Introduction The distributer of the anti-glutamic acid decarboxylase antibody assay kit using radioimmunoassay (RIA) recently announced its discontinuation, and proposed an alternative kit using enzyme-linked immunosorbent assay (ELISA). The aim of the present study was to investigate the diagnostic values of the anti-glutamic acid decarboxylase antibody by RIA and ELISA among type 1 diabetes mellitus patients and control participants. Materials and Methods A total of 79 type 1 diabetes mellitus patients and 79 age-matched controls were enrolled and assessed using RIA and ELISA. Sensitivity, specificity, positive predictive values and negative predictive values were calculated for cut-off values (RIA = 1.5 U/mL and ELISA = 5.0 U/mL, respectively). Kappa coefficients were used to test for agreements between the RIA and ELISA methods regarding the diagnosis of type 1 diabetes mellitus. Results The sensitivity, specificity, positive predictive values, and negative predictive values for diagnosing type 1 diabetes mellitus were 57.0, 97.5, 95.7, and 69.4% by RIA, and 60.8, 100.0, 100.0 and 71.8% by ELISA, respectively. The diagnosis of type 1 diabetes mellitus using the RIA and ELISA methods showed substantial agreement with the kappa values of 0.74 for all participants, and of 0.64 for the acute type; however, there was moderate agreement with the kappa value of 0.56 for the slowly progressive type. Conclusions The present study suggests that both anti-glutamic acid decarboxylase antibody by RIA and ELISA was useful for diagnosing type 1 diabetes mellitus. However, in the slowly progressive type, the degree of agreement of these two kits was poorer compared with those in all participants or in the acute type.

Background: Limited evidence is available about the relationship of lifestyle factors with glycated hemoglobin (HbA1c) in subjects with impaired glucose tolerance. The aim of study was to identify such determinant factors of HbA1c in subjects with impaired glucose tolerance. Methods: This cross-sectional study included 121 men and 124 women with impaired glucose tolerance, who were diagnosed based on a 75-g oral glucose tolerance test. Demographic and biochemical parameters, including the body mass index (BMI), fasting plasma glucose (FPG), 2-h post-load glucose (2-h PG), and HbA1c, were measured. The pancreatic β-cell function and insulin resistance were assessed using homeostasis model assessment (HOMA-β). Dietary intake was assessed by a food frequency questionnaire. Results: The levels of FPG, 2-h PG, and carbohydrate intake were correlated with the HbA1c level in men, while the FPG and 2-h PG levels were correlated with the HbA1c level in women. In multiple regression analyses, BMI, FPG, 2-h PG, and white rice intake were associated with HbA1c levels in men, while BMI, FPG, HOMA-β, and bread intake were associated with HbA1c levels in women. Conclusions: The present findings suggest that a substantial portion of HbA1c may be composed of not only glycemic but also several lifestyle factors in men with impaired glucose tolerance. These factors can be taken into consideration as modifiable determinants in assessing the HbA1c level for the diagnosis and therapeutic monitoring of the disease course. J Clin Med Res. 2017;9(4):360-365 doi: https://doi.org/10.14740/jocmr2928w

Influence of different load exercise to muscle activity during subsequent exercise with 75% of one repetition maximum (RM) load among trained and untrained individuals was verified. Resistance-trained men who were involved in resistance training (n = 16) and healthy young men who did not exercise regularly (n = 16) were recruited for this study. Each subject performed bench pressing with a narrow grip exercise using two different training set methods, the drop-set (DS) (3 sets × 2-10 repetitions with 95-75% of 1RM) and the reverse drop-set (RDS) (3 sets × 3-10 repetitions with 55-75% of 1RM). The mean concentric contraction power, root mean square (RMS) of electromyography (EMG), area under the oxygenated hemoglobin (Oxy-Hb) curve, and time constant for muscle oxygen consumption (TcVO2mus) values of the triceps brachii were measured during and after the DS and RDS. The trained group demonstrated significantly higher mean muscle power (242.9 ± 39.6 W vs. 215.8 ± 31.7 W), RMS of EMG (86.4 ± 10.4 % vs. 68.3 ± 9.6 %), and area under the Oxy-Hb curve (38.6 ± 7.4 %• sec vs. 29.3 ± 5.8 %• sec) values during the DS than during the RDS (p < 0.05). However, in the untrained group none of the parameters differed significantly for both the DS and RDS. Furthermore, a negative correlation was detected between the area under the Oxy-Hb curve and muscle thickness (r = -0.51, p < 0.01). Long-term effects of DS on muscle strengthening and hypertrophy will be explored in further research.

Background Given the major role of glucose-dependent insulinotropic polypeptide (GIP) in the regulation of adiposity, this study examined the effects induced by a diet based on the Japanese tradition (SMART WASHOKU) on the visceral fat area (VFA) and GIP secretions. Methods Overweight/obese men (n = 21; mean age, 41.0 ± 9.0 years; mean BMI, 25.2 ± 2.0 kg/m2) without diabetes were placed on either a SMART WASHOKU or control meal for 2 weeks, in a randomized, cross-over setup with a four-week washout period. Results For the meal tolerance test, blood samples were collected at 0, 30, 60, 120, 180, and 240 min post-meal, followed by measuring blood glucose, insulin, GIP, and glucagon-like peptide-1 (GLP-1) levels. Relative to a control meal, SMART WASHOKU meal yielded significantly lower plasma postprandial GIP concentrations (AUC: 700.0 ± 208.0 vs. 1117.0 ± 351.4 pmol/L・4 h, P

Objective: Given the major role of glucose-dependent insulinotropic polypeptide (GIP) in the regulation of adiposity, this study examined the effects induced by a diet based on the Japanese tradition (SMART WASHOKU) on the visceral fat area (VFA) and GIP secretions. Research Design and Methods: Overweight/obese men (n=21; mean age: 41 ± 9 y; mean BMI: 25.2 ± 2.0 kg/m2) without diabetes were placed on either a SMART WASHOKU (protein/fat=1.0, fiber/carb ratio≥0.063, and omega-3 PUFA/fat ratio ≥0.054) or isocaloric control meal for two weeks, in a randomized, double-blind, cross-over setup with a four-week washout period. For the meal tolerance test, blood samples were collected at 0, 30, 60, 120, 180, and 240 minutes post-meal, followed by measuring blood glucose, insulin, GIP, and glucagon-like peptide-1 (GLP-1) levels. Results: Relative to a control meal, SMART WASHOKU meal yielded significantly lower plasma postprandial GIP concentrations (AUC: 700.0 ± 208.0 vs. 1117.0 ± 351.4, P < 0.05); however, between meals, there was no significant difference in the levels of GLP-1, PYY, and ghrelin. Relative to control meal, a SMART WASHOKU intervention produced a modest but significant reduction of VFA in our participants (-3.4 ± 12.3 vs. -13.0 ± 9.3 cm2, P < 0.05). Compared with the control meal, SMART WASHOKU meal did not modify the concentrations of AST, ALT, GGT, and hs-CRP; however, we did observe a significantly reduced in the levels of LDL-cholesterol, triglyceride, and HbA1c. Conclusions: Based on our findings, we conclude that in overweight/obese men, a SMART WASHOKU meal would be helpful in decreasing VFA and improving metabolic parameters, possibly via suppressing GIP secretion. Disclosure N. Sakane: Board Member; Spouse/Partner; Kao Corporation. H. Takase: Employee; Self; Kao Corporation. J. Suzuki: Employee; Self; Kao Corporation. C. Suzukamo: Employee; Self; Kao Corporation. S. Nirengi: None. A. Suganuma: None. N. Osaki: Employee; Self; Kao Corporation. Funding Kao Corporation; Japan Society for the Promotion of Science (18K01988); Strategic Innovation Project of Japan (14533567); Bio-oriented Technology Research Advancement Institution, NARO

Background: Evidence of the long-term benefits of telephone-delivered lifestyle interventions is limited. This study investigated the ability of telephone-delivered lifestyle intervention ...

Brown adipose tissue (BAT) is responsible for non-shivering thermogenesis and is an attractive therapeutic target for combating obesity and related diseases. Human BAT activity has been evaluated by 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18FDG-PET/CT) under acute cold exposure, but the method has some serious limitations, including radiation exposure. Infrared thermography (IRT) may be a simple and less-invasive alternative to evaluate BAT activity. In the present study, to establish an optimal condition for IRT, using a thermal imaging camera, skin temperature was measured in the supraclavicular region close to BAT depots (Tscv) and the control chest region (Tc) in 24 young healthy volunteers. Their BAT activity was assessed as the maximal standardized uptake value (SUVmax) by 18FDG-PET/CT. Under a warm condition at 24-27°C, no significant correlation was found between the IRT parameters (Tscv, Tc,, and the difference between Tscv and Tc,, Δtemp) and SUVmax, but 30-120 min after cold exposure at 19°C, Tscv and Δtemp were significantly correlated with SUVmax (r = 0.40-0.48 and r = 0.68-0.76). Δtemp after cold exposure was not affected by mean body temperature, body fatness, and skin blood flow. A lower correlation (r = 0.43) of Δtemp with SUVmax was also obtained when the participant's hands were immersed in water at 18°C for 5 min. Receiver operating characteristic analysis revealed that Δtemp after 30-60 min cold exposure can be used as an index for BAT evaluation with 74% sensitivity, 92% specificity, and 79% diagnostic accuracy. Thus, IRT may be useful as a simple and less-invasive method for evaluating BAT, particularly for large-scale screening and longitudinal repeat studies.

To determine the relationship between the R577X polymorphism of the α-actinin-3 (ACTN3), which may play a role in the individual differences observed in the effects of exercise on health benefits and antiatherogenic markers (i.e., high-density lipoprotein cholesterol [HDL-C] and adiponectin) in athletes.Seventy-six male rugby players (mean age 19.8 years) were enrolled in this study. Genomic DNA was extracted from peripheral blood samples, and restriction fragment length polymorphism-polymerase chain reactions were conducted to assess ACTN3 genotypes. Body mass index (BMI), waist circumference, serum lipids including HDL-C, and adiponectin levels were measured. Current smoking and alcohol intake habits were evaluated with a questionnaire. All of the parameters were compared between 2 groups displaying frequently observed genotypes: one group consisting of patients having either the R/R or R/X genotype and a second group with the X/X genotype.The frequency of the X allele was 0.55 and the distribution of the genotypes was 35.5% (n = 27) for X/X, 39.5% (n = 30) for R/X, and 25.0% (n = 19) for R/R. Serum HDL-C and adiponectin levels were significantly higher in X/X genotype compared to the R/R or R/X genotype (HDL-C 1.6 ± 0.3 [SD] vs. 1.4 ± 0.2 mmol/L; P.01, adiponectin 8.8 ± 2.6 vs. 6.9 ± 2.3 μg/mL; P.01), even after adjustments for confounders (P.01).There may be a relationship between the ACTN3 genotype and HDL-C and adiponectin levels in rugby players. This may be useful information when determining the individual responses of antiatherogenic markers to exercise.ACTN3 = α-actinin-3 BMI = body mass index CVD = cardiovascular disease HDL-C = high-density lipoprotein cholesterol LDL-C = low-density lipoprotein cholesterol R = arginine (R) at amino acid position 577 of the ACTN3 protein TC = total cholesterol TG = triglyceride X = truncation at amino acid position 577 of the ACTN3 protein.

OBJECTIVES: Inverse associations are observed between vegetable intake and diabetes, cardiovascular disease, cancer, and all-cause mortality. The decisional balance tool is a promotional tool targeting the perceived pros and cons of behavior adoption. The aim of this study was to develop and validate a decisional balance tool to assess the perceived benefits and barriers of vegetable intake in adults. METHODS: A total of 379 adults aged 20–70 years (mean age, 30.5 ± 12.6 years; male, 21.4%) were enrolled in this study. Demographic parameters (age, body mass index, marital status, employment status, house income, and family members), vegetable intake, stage of changes (precontemplation, contemplation, preparation, action/maintenance), the importance of change, and confidence (self-efficacy) were measured using a web-based survey. After constructing an initial item pool based on expert consultations and existing scales, Phase 1 of the study was launched, involving an exploratory factor analysis of 15 perceived benefits and 15 perceived barriers. The participants responded on a 5-point Likert scale. An exploratory factor analysis was conducted, and internal validity, external validity, and reliability were tested. Decisional balance was estimated by subtracting the barriers from the perceived benefits. RESULTS: The final 24 items had a two-domain structure in perceived benefits (“pleasure” and “healthy”) and a three-domain structure in perceived barriers (“not attractive,” “low priority,” and “hard to get”) with high internal consistency (Cronbach's alpha = 0.82, 0.79, 0.82, 0.76, and 0.76, respectively). The test–retest reliability study showed substantial values of the intraclass correlation coefficient (0.77). The perceived benefits score was positively correlated with vegetable servings, although the perceived barrier score was negatively correlated with vegetable servings (Spearman's correlation = 0.324 and −0.435, respectively). Significant and meaningful differences were observed between the stages of change in the pros and cons of vegetable intake (p for trend = 0.016). CONCLUSIONS: These findings suggest that this questionnaire is a valid, reliable tool for assessing the pros and cons of vegetable intake in adults. FUNDING SOURCES: JSPS KAKENHI.

Background High-density lipoprotein (HDL) containing apolipoprotein A-I is associated with the pathogenesis of Alzheimer's disease (AD). HDL particle size is modified in the presence of pathological conditions, while the significance of the HDL particle size remains controversial. Objective The aim of this study was to investigate the HDL lipoprotein subclasses in mild cognitive impairment (MCI) and AD. Methods This cross-sectional study included 20 AD patients, 17 MCI patients, and 17 age-matched controls without cognitive impairment, selected from the database of the Study of Outcome and aPolipoproteins in Dementia (STOP-Dementia) registry. The diagnoses of AD and MCI were performed by expert neurologists according to the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition criteria. Serum HDL subclasses were measured by electrophoretic separation of lipoproteins using the Lipoprint System. The neutrophil-lymphocyte ratio (NLR), a marker of inflammation, was calculated by dividing the neutrophil count by the lymphocyte count. Results Small-sized HDL particle levels in the MCI group were significantly higher than in the control group, although there was no difference in serum HDL-cholesterol levels between MCI and control groups. NLR in the MCI group was higher than in the control group, but this difference was non-significant (p = 0.09). There was no difference in HDL subclasses or NLR between the AD and control groups. Conclusion These findings suggest that HDL subclasses might be associated with the development of MCI.

Objectives: Limited understanding of the causes of variability in individual response to similar lifestyle changes makes it challenging to design individualized diet plans for diabetes prevention. We previously reported a simulation model of lifestyle disease and tested it using data from DPP and a low carb-low fat diet crossover study. Here we used the model to analyze data from J-DOIT1 to understand the causes of variability and to optimize diet therapy. Methods: J-DOIT1 is a large-scale intervention study of 2,607 subjects with a 5.5 year follow-up. We selected 60 baseline-matched individuals from placebo and intervention arms. Model was calibrated to each subject’s body weight, FPG, HbA1c time courses to estimate physiology and lifestyle parameters (e.g., RMR, diet intake). Simulation analysis was used to optimize individual diet. Results: Individuals with the most and least improved biomarkers showed no significant difference in model-estimated energy balance or in self-reported lifestyle at baseline. Neither caloric deficit nor linear combinations of model-estimated parameters were predictive of outcomes, showing the value of our complex physiological model for prediction. The model suggests that unique sets of optimal diets exist for achieving individual health goals (Fig. 1). Fig. 1. Optimized changes in fat and carbohydrate intake for two individuals to reduce body weight by 5-7%. Fig. 1. Optimized changes in fat and carbohydrate intake for two individuals to reduce body weight by 5-7%. Disclosure J.H. Chen: None. M. Fukasawa: None. Q. Chen: None. S.P. Burns: None. K. Kumar: None. S. Nirengi: None. K. Takahashi: None. A. Suganuma: None. H. Kuzuya: None. N. Sakane: Research Support; Spouse/Partner; Pwc. G. Dwivedi: None.

Objective: The aim of this study was to evaluate the stages of change toward healthier behavior by telephone-delivery intervention in prediabetic individuals. Research Design and Methods: A total of 2607 participants aged 20-65 years with impaired fasting glucose were randomized to a one-year telephone-intervention intervention arm (n=1240) or a self-directed control arm with weighing scale and pedometer (n=1367). Stages of change were assessed using a self-administered questionnaire. Results: At the baseline, 5.9% were in the precontemplation stage, 50.6% were in the contemplation stage, and 25.5% were in the preparation stage in the change to healthy eating. At the baseline, 9.4% were in the precontemplation stage, 50.2% were in the contemplation stage, and 12.0% were in the preparation stage in the change toward adopting exercise habits. For participants who were in the precontemplation stage, the proportions of those progressing to the action/maintenance stage for a healthy eating after 1-year intervention and at the end of the trial were increased (17.5 and 16.1-percentage-point increase, respectively), but there was small increase for exercise habits (5.4 and 2.7-percentage-point increase, respectively). For participants who were in the precontenplation stage, the odds of progressing to the action/maintenance stage for the intervention vs. control arm for healthy eating after 1-year intervention and at the end of the trial were 3.07 (95% CI=1.23, 8.13) and 2.21 (95% CI=1.04, 4.67), respectively. The corresponding odds for excise habits were 1.59 (95% CI=0.70, 3.61) and 1.27 (95% CI=0.55, 2.91). The hazard ratio for the development of diabetes on receiving the intervention in the precontenplation stage of healthy eating at the baseline was 0.51. Conclusions: The intervention advanced the stages of changes toward healthy eating and might be effective for preventing diabetes even in the precontemplation stage. Disclosure N. Sakane: Research Support; Spouse/Partner; Pwc. S. Nirengi: None. K. Takahashi: None. A. Suganuma: None. K. Okazaki: Advisory Panel; Self; Eli Lilly and Company. Research Support; Self; Taisho Pharmaceutical Co., Ltd.. Speaker's Bureau; Self; Ono Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk A/S, Astellas Pharma US, Inc., Takeda Development Center Asia, Pte. Ltd., Terumo Medical Corporation, MSD K.K., Sanwa Kagaku Kenkyusho Co., Ltd.. Other Relationship; Self; Aichi prefecture government and Nagoya city government. K. Izumi: None. M. Noda: None. H. Kuzuya: None.

Background Brown adipose tissue (BAT) is sympathetically activated and induces thermogenesis during cold exposure, thereby influencing energy expenditure and body fat levels. The very low frequency (VLF) components of pulse rate variability could be a form of thermogenic sympathetic nervous activity, but no clear relationship has yet been reported between VLF activity and BAT density. We therefore aimed to evaluate the association between them. Methods We enrolled 20 adults in winter and 20 matched adults in summer. We assessed BAT densities based on total hemoglobin concentrations ([total-Hb]) measured with near-infrared time-resolved spectroscopy. We calculated VLF activity from pulse rate variability measurements. Results BAT density ([total-Hb]; winter 70.5 ± 17.0 μM, summer 57.8 ± 18.3 μM) and VLF activity (winter 6.7 ± 0.8, summer 6.1 ± 0.9) were significantly higher in winter than in summer (P