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Cardiometabolic risk factors may be of key importance in the development of future brain diseases like dementia or depression. However, it remains unclear how these risk factors exactly affect the brain. Advanced MR imaging methods such as, diffusion weighted and functional MRI, can provide detailed insights into subtle brain changes, and potentially into early development of disease. In this narrative review, we summarize the available evidence on the associations of cardiometabolic risk factors with subtle changes in brain MRI measures. We found clear evidence that hyperglycemia, physical inactivity, central obesity, and hypertension are associated with both structural and functional brain alterations, while the role of dyslipidemia is far less clear. However, longitudinal evidence that assesses temporality of the associations with more advanced and thus more precise brain imaging methods is needed to improve our insights into the complex etiology of brain diseases.

Background and Objectives: An inter-arm systolic blood pressure difference (IASBPD) is defined as a blood pressure (BP) disparity of ≥10 mmHg between arms. IASBPDs are associated with an increased risk of cardiovascular disease (CVD). Similarly, visceral fat accumulation (VFA) is clinically important because it is associated with higher cardiovascular disease risk. Accordingly, this study compared the body composition parameters of IASBPD individuals with individuals who did not express an IASBPD. Materials and Methods: The analysis included 104 patients. The blood pressures of all participants were measured simultaneously in both arms using automated oscillometric devices. Then patients were divided into two groups according to their IASBPD status: Group 1 (IASBPD- (&lt, 10 mmHg)), Group 2 (IASPPD+ (≥10 mmHg)). Body composition parameters were measured using bioelectrical impedance analysis. Results: In 42 (40%) patients, the simultaneously measured IASBPD was equal to or higher than 10 mmHg. The right brachial SBP was higher in 63% of patients. There were no differences between the groups in terms of demographic and clinical characteristics. Regarding the two groups’ body composition parameter differences, VFA was significantly higher in group 2 (p = 0.014). Conclusions: The IASBPD is known to be associated with an increased risk of cardiovascular events. Although the body mass indexes (BMIs) of the two groups were similar, VFA levels in those with a greater than 10 mmHg IASBPD were found to be significantly higher. This finding may explain the increased cardiovascular risk in this group.

Context Obesity prevalence has increased in type 1 diabetes (T1D). However, the relationship between body composition and severe diabetic eye disease (SDED) is unknown. Objective To investigate the associations between body composition and SDED in adults with T1D. Methods From 5401 adults with T1D in the Finnish Diabetic Nephropathy Study, we assessed 3468, and 437 underwent dual-energy X-ray absorptiometry for body composition analysis. The composite outcome was SDED, defined as proliferative retinopathy, laser treatment, antivascular endothelial growth factor treatment, diabetic maculopathy, vitreous hemorrhage, and vitrectomy. Logistic regression analysis evaluated the associations between body composition and SDED. Multivariable Cox regression analysis assessed the associations between the anthropometric measures and SDED. Subgroup analysis was performed by stages of albuminuria. The relevance ranking of each variable was based on the z statistic. Results During a median follow-up of 14.5 (interquartile range 7.8-17.5) years, 886 SDED events occurred. Visceral/android fat ratio was associated with SDED [odds ratio (OR) 1.40, z = 3.13], as well as the percentages of visceral (OR 1.80, z = 2.45) and android fat (OR 1.28, z = 2.08) but not the total body fat percentage. Waist-height ratio (WHtR) showed the strongest association with the SDED risk [hazard ratio (HR) = 1.28, z = 3.73], followed by the waist (HR 1.01, z = 3.03), body mass index (HR 1.03, z = 2.33), and waist-hip ratio (HR 1.15, z = 2.22). The results were similar in normo- and microalbuminuria but not significant in macroalbuminuria. A WHtR ≥ 0.5 increased the SDED risk by 28% at the normo- and microalbuminuria stages. Conclusions WHtR, a hallmark of central obesity, is associated with SDED in individuals with T1D.

OBJECTIVE Nonalcoholic fatty liver disease (NAFLD), insulin resistance, and liver fibrosis are prevalent in individuals co-infected with human immunodeficiency virus type 1 (HIV-1)/hepatitis C virus (HCV), even after HCV eradication. Our aim was to evaluate single nucleotide polymorphisms (SNPs) associated with advanced liver fibrosis in HIV-1/HCV co-infected patients. DESIGN/METHODS In a cohort of 102 participants, we genotyped 16 SNPs in 10 genes previously associated with NAFLD and the innate immune response and correlated the genotypes with liver fibrosis and fat accumulation. RESULTS Multinomial logistic regression analysis identified three metabolic parameters that were significantly associated with advanced liver fibrosis (stage F3-4): albumin (odds ratio [OR] 0.80, 95% confidence interval [CI] 0.69-0.91, p = 0.001), percentage of visceral fat area (PVFA) (OR 1.06, 95% CI 1.01-1.12, p = 0.03), and body mass index (BMI) (OR 1.47, 95% CI 1.22-1.77, p

The clinical importance of assessment of metabolic syndrome lies in the selection of individuals with multiple risk factors based on visceral fat accumulation, and helping them to reduce visceral fat. Behavioral modification by population approach is important, which adds support to the personal approach. The complexity of visceral fat accumulation requires multicomponent and multilevel intervention. Preparation of food and physical environments could be useful strategies for city planners. Furthermore, actions on various frameworks, including organizational, community, and policy levels, have been recently reported. There are universal public health screening programs and post-screening health educational systems in Japan, and diseases management programs in Germany. Understanding one’s own health status is important for motivation for lifestyle modification. The U.S. Preventive Services Task Force recommends that primary care practitioners screen all adults for obesity and offer behavioral interventions and intensive counseling. Established evidence-based guidelines for behavioral counseling are needed within the primary care setting.

We investigated whether the difference in miso consumption between the Japanese diets of 1975 and 2010 has influenced the observed increase in diet-induced obesity. To recreate the 2010 and 1975 Japanese high-fat diets with the corresponding proportions of miso, freeze-dried miso was added to high-fat mouse feed at 1.6% and 2.6%, respectively. When 5-week-old male Institute of Cancer Research (ICR) mice were provided each of these diets ad libitum for 8 weeks, it was found that the white adipose tissue weight and adipocyte area were lower in mice receiving the 1975 diet than in those receiving the 2010 diet. Therefore, high miso consumption is one reason why the 1975 Japanese diet tended to not lead to obesity. Next, the combined effects of treadmill exercise and miso consumption were investigated. The mice were divided into three groups, which were provided either a high-fat diet (group C), a high-fat diet with exercise (group C + E), or a miso-supplemented high-fat diet with exercise (group M + E) for 8 weeks. In this experiment, the white adipose tissue weight and adipocyte area in group M + E were lower than in group C. When the mRNA expression of lipid metabolism-associated genes in adipose tissue was measured, we found that expression of Hsl (lipase, hormone sensitive), which is involved in lipolysis, and Ppar&gamma, (peroxisome proliferator activated receptor gamma), which regulates adipocyte differentiation upstream of Hsl, was increased in group M + E. These results clearly demonstrated that lipid accumulation in the adipose tissues is suppressed by miso consumption in combination with exercise.

Background Catch-up growth in adult (CUGA) is characterized by visceral fat accumulation, ectopic lipid deposition and insulin resistance (IR). Here, we investigated the determinants of these pathophysiological consequences of CUGA. Methods Rats were divided into different groups: control rats were offered normal chow ad libitum (AL), while experimental rats were put on 4-week caloric restriction (CR) initially, followed by regaining weight-matched normal chow (RN) in the RN group. General characteristics of lipid metabolism, expression level of genes in visceral adipose tissue (VAT), and glucose infusion rate (GIR60–120) by the hyperinsulinemic-euglycemic clamp were examined. Results After CR, percentage of abdominal fat mass (AFM%) was lower in the RN group than in the AL group but no difference was observed in serum non-esterified fatty acid (NEFA). Expression of fat-specific protein 27 (FSP27) was decreased in the RN group, while the expression of peroxisome proliferator-activated receptors γ (PPARγ), the key lipogenic gene, was increased. After refeeding, AFM% increased over time and serum NEFA persistently elevated in the RN group. Ectopic triglyceride contents were increased whereas insulin sensitivity was impaired. The expression of FSP27 did not follow the increase in the expression of PPARγ. Additionally, we observed a sustained increase in the expression of ATGL and CGI-58 in VAT in the RN group compared with the AL group after CR and refeeding, and a persistent shift-to-the-left of adipocyte size distribution accompanied by enhanced lipogenesis during CUGA. Conclusion The persistent CR-induced imbalance of lipogenesis/fat storage capacity might be responsible for the CUGA-associated metabolic disorders.

Background Although obesity-related type 2 diabetes mellitus (T2DM) and sarcopenia in the elderly have been increasing worldwide, the associations among visceral fat accumulation, skeletal muscle indices (mass, strength, and quality) and cardiovascular diseases in T2DM remain poorly investigated. Methods We enrolled 183 Japanese T2DM inpatients (126 men, 57 women; mean age 64.7 ± 12.6 years, ± SD). The estimated-visceral fat area (eVFA) and skeletal muscle mass were measured by each device using bioelectrical impedance analysis method. We also measured grip strength by dynamometer and motor nerve conduction velocity (MCV). We analyzed the difference in skeletal muscle indices between T2DM patients with and without visceral fat accumulation, and examined the impact of skeletal muscle indices on cardiovascular diseases in patients with visceral fat accumulation. Results The prevalence of sarcopenia defined by the Consensus of Asian Working Group for Sarcopenia and low skeletal muscle mass were both lower in the visceral fat accumulation (+) group than in (−) group. However, the prevalence of weak hand grip strength was similar in the visceral fat accumulation (−) and (+) groups, indicating that considerable patients with visceral fat accumulation had weak grip strength in spite of fair skeletal muscle mass. Muscle quality [grip strength (kg)/arm muscle mass (kg)] was significantly lower in patients with visceral fat accumulation. Multiple regression analysis identified eVFA, MCV and sex as significant and independent determinants of muscle quality. In visceral fat accumulation (+) group, the patients with low muscle quality had longer duration of diabetes, lower eGFR, higher serum adiponectin, lower MCV and higher prevalence of cardiovascular diseases, compared to the patients with high muscle quality. Finally, sex- and age-adjusted models showed significant association between low muscle quality and cardiovascular diseases in all subjects (odds ratio 2.28, p = 0.012), especially in patients with visceral fat accumulation (odds ratio 2.72, p = 0.018). Conclusions T2DM patients with visceral fat accumulation had low muscle quality, and patients with low muscle quality were more affected with cardiovascular diseases. Electronic supplementary material The online version of this article (10.1186/s12933-018-0755-3) contains supplementary material, which is available to authorized users.

Obesity is a causal factor of type 2 diabetes (T2D); however, people without obesity (including lean, normal weight, or overweight) may still develop T2D. Non-obese T2D is prevalent in Asia and also frequently occurs in Europe. Recently, multiple evidences oppose the notion that either obesity or central obesity (visceral fat accumulation) promotes non-obese T2D. Several factors such as inflammation and environmental factors contribute to non-obese T2D. According to the data derived from gene knockout mice and T2D clinical samples in Asia and Europe, the pathogenesis of non-obese T2D has been unveiled recently. MAP4K4 downregulation in T cells results in enhancement of the IL-6+ Th17 cell population, leading to insulin resistance and T2D in both human and mice. Moreover, MAP4K4 single nucleotide polymorphisms and epigenetic changes are associated with T2D patients. Interactions between MAP4K4 gene variants and environmental factors may contribute to MAP4K4 attenuation in T cells, leading to non-obese T2D. Future investigations of the pathogenesis of non-obese T2D shall lead to development of precision medicine for non-obese T2D.

Aims/Introduction The aim of the present study was to determine whether weight reduction is associated with improvement of glycemic control in non‐obese and obese subjects with or without visceral fat accumulation, whose hemoglobin A1c (A1C) is 5.6–6.4%. Materials and Methods A total of 798 male subjects whose A1C levels were between 5.6% and 6.4% were divided into subgroups based on body mass index (BMI) and/or estimated visceral fat area (eVFA), and were analyzed with respect to the relationships between 1‐year changes in BMI (ΔBMI) and A1C (ΔA1C). Results In both the BMI ≥25 and BMI 100 cm2 (n = 293, r = 0.256, P

Background Visceral fat accumulation is a major etiological factor in the progression of type 2 diabetes mellitus and atherosclerosis. We described previously visceral fat accumulation and multiple cardiovascular risk factors in a considerable number of Japanese non-obese subjects (BMI

Background Non-shivering thermogenesis (NST) involves a substantial amount of energy expenditure in humans and, thus, contributes to reducing the risk for obesity. Molecular evolutionary studies have reported that SNPs in/near the uncoupling protein 3 gene (UCP3) and the regulatory associated protein of mTOR complex 1 gene (RPTOR) might influence NST and confer adaptive advantages for modern human dispersal into cold environments. In the present study, the impact of these SNPs on obesity-related traits was investigated. Methods Study subjects consisted of 2,834 Japanese adults (percentage of female: 46%, mean age: 51.5). Associations of the UCP3-55C/T and the RPTOR-26934C/T - the 2 potential genetic variations involved in cold adaptation and thermogenic mechanisms in mammals, with quantitative obesity-related traits including body mass index (BMI), waist circumference, visceral fat area (VFA), VFA adjusted for BMI, and selected blood parameters - were tested using multiple linear regression models. Sliding windowsampling analysis was applied to depict seasonal effects of the SNPs on the obesity-related phenotypes. Results UCP3-55C/T and the RPTOR-26934C/T did not show any association with obesity traits and blood chemical parameters in multiple linear regression models consisting of the whole subjects. Moreover, sliding window sampling-based association analyses involving seasonality also failed to find associations between these two SNPs and obesity-related traits. Conclusions UCP3-55C/T and the RPTOR-26934C/T may only have subtle effects on the development of obesity-related traits in the present humans. These two SNPs might be irrelevant to inter-individual variations in energy metabolism and efficiency of NST.

AIMS/INTRODUCTION: Weight reduction improves glycemic control in obese men with glycated hemoglobin (HbA1c) of 5.6-6.4%, suggesting that it can prevent the development of diabetes in these patients. The aim of the present study was to quantify the amount of weight reduction necessary for minimization of diabetes risk in Japanese men with visceral fat accumulation. MATERIALS AND METHODS: The study participants were 482 men with an estimated visceral fat area of ≥100 cm(2), HbA1c of 5.6-6.4%, fasting plasma glucose (FPG) of

Background Although many Asian type 2 diabetic patients have been considered to be not obese and have low capacity of insulin secretion, the proportion of obese patients with visceral fat accumulation has increased in recent years. We found previously considerable number of Japanese non-obese subjects (body mass index (BMI) 2) with visceral fat accumulation and multiple cardiovascular risk factors. The aim of the study was to investigate the difference in clinical features of type 2 diabetic patients with and without visceral fat accumulation, focusing on vascular complications and changes in BMI. Methods We enrolled 88 Japanese hospitalized type 2 diabetic patients. Abdominal obesity represented waist circumference (WC) of ≥85 cm for males and ≥90 cm for females (corresponding to visceral fat area of 100 cm2). Subjects were divided into two groups; with or without abdominal obesity. Results Hypertension, dyslipidemia and cardiovascular diseases were significantly more in the patients with abdominal obesity. The prevalence of cardiovascular disease in the non-obese patients (BMI 2) with abdominal obesity were similar in obese patients (BMI ≥25 kg/m2). The mean BMI of the patients with abdominal obesity was 2 at 20 years of age, but reached maximum to more than 30 kg/m2 in the course. Furthermore, substantial portion of the type 2 diabetic patients (52% in males and 43% in females) were not obese at 20 year-old (BMI 2), but developed abdominal obesity by the time of admission. Conclusion These results emphasize the need to control multiple risk factors and prevent atherosclerotic disease in patients with abdominal obesity. The significant weight gain after 20 years of age in patients with abdominal obesity stresses the importance of lifestyle modification in younger generation, to prevent potential development of type 2 diabetes and future atherosclerotic cardiovascular disease.

Background It has been shown that visceral fat accumulation is associated with autonomic dysfunction, though the precise mechanism remains unclear. A recent basic study found that leptin can directly modulate autonomic function through the dorsomedial hypothalamus in relation to obesity. Here, we investigated the mutual relationships among plasma leptin, visceral fat accumulation, and cardiac autonomic dysfunction in patients with type 2 diabetes. Methods This cross-sectional study included 100 diabetic patients, and 100 age- and gender-matched non-diabetic patients with cardiovascular risk factors. Plasma leptin and soluble leptin receptor levels, visceral fat area (VFA), and heart rate variability (HRV) were determined in addition to classical cardiovascular risk factors. Results In the type 2 diabetic patients, VFA was significantly (p

Background Circulating thiobarbituric acid-reacting substance (TBARS) levels, a marker of systemic oxidative stress, are predictive of cardiovascular events. However, they has not been evaluated in Japanese, especially with regard to the factors that contribute to the changes in circulating TBARS levels. We investigated the cross-sectional and longitudinal relationships between circulating TBARS levels and various clinicobiochemical parameters in middle-aged men. Methods In this population-based study (The Amagasaki Visceral Fat Study), 1,178 Japanese male urban workers who had undergone health check-ups in 2006, 2007 and 2008 and were not on medications for metabolic disorders during the follow-up period, were enrolled. Serum TBARS levels were measured by the method of Yagi. The estimated visceral fat area (eVFA) by bioelectrical impedance was measured annually. After health check-ups, subjects received health education with lifestyle modification by medical personnel. Results The number of cardiovascular risk factors (hypertension, hyperglycemia, low HDL-C, hypertriglyceridemia, hyperuricemia, hyper-LDL-C and impaired renal function) augmented with the increases in log-eVFA (p < 0.0001) and log-TBARS (p < 0.0001). The combination of TBARS and eVFA had a multiplicative effect on risk factor accumulation (F value = 79.1, p = 0.0065). Stepwise multiple regression analysis identified log-eVFA, as well as age, log-body mass index (BMI), LDL-C, log-adiponectin, γ-glutamyl transpeptidase (γ-GTP) and uric acid as significant determinants of log-TBARS. Stepwise multiple regression analysis identified one-year changes in eVFA as well as BMI, γ-GTP and estimated glomerular filtration rate (eGFR) as significant determinants of one-year change in TBARS, and biennial changes in eVFA as well as BMI and γ-GTP, eGFR as significant determinants of biennial change in TBARS. Conclusions The present study showed a significant cross-sectional and longitudinal correlation between TBARS and eVFA, as well as BMI and γ- GTP, eGFR. Visceral fat reduction may independently associate with the improvement in systemic ROS in middle-aged Japanese men. Trial Registration The Amagasaki Visceral Fat Study UMIN000002391.