The ratio of equol non-producers in overweight or obese populations might be higher than generally reported. Natural S-equol might have a role in glycaemic control and in the prevention of cardiovascular disease by its effects to lower LDL-C levels and CAVI scores in overweight or obese individuals.

Effect of pioglitazone T he monocyte-macrophage system exists in at least two distinct phenotypes of differentiation: proinflammatory (M1) and anti-inflammatory (M2) (1,2). Macrophages, when infiltrated into obese adipose tissue, exhibit a phenotypic switch from M2 to M1 polarization, thereby contributing to obesity-induced adipose tissue inflammation and insulin resistance (1). Expression of both M1 and M2 markers is detected in circulating peripheral blood mononuclear cells as well as in atherosclerotic plaques (3). However, there have been no detailed studies on the M1/M2 phenotype of monocytes and their association with cardiovascular risks in obese subjects with type 2 diabetes. On the other hand, we demonstrated that pioglitazone, a thiazolidinedione class of insulin sensitizer, exerts an antiatherogenic effect independent of its antidiabetic effect (4). Here, we investigated the M1/M2 phenotype of peripheral blood monocytes and pulse wave velocity (PWV), an established index of arterial stiffness, and also the effect of pioglitazone in obese diabetic patients.A total of 161 subjects (95 men and 66 women, mean age 50.4 years), including 45 normal-weight control subjects, 62 obese nondiabetic patients, and 54 obese diabetic patients with or without pioglitazone treatment for 3 months (30 mg daily), were recruited in our clinic. Peripheral blood monocytes were prepared using magnetic-assisted cell sorting and flow cytometry with anti-CD14. Expression of M1/M2 markers was analyzed by real-time quantitative PCR method and flow cytometry. The number and percentage of CD14 ϩ cells among peripheral blood monocytes from obese diabetic patients were significantly increased relative to those of control subjects (P Ͻ 0.05).The CD14 ϩ cells from obese nondiabetic patients showed significantly higher expression of M1 markers, tumor necrosis factor-␣, and interleukin (IL)-6 and lower expression of an M2 marker, IL-10, relative to control subjects (P Ͻ 0.01). This is consistent with a report that peripheral blood mononuclear cells in obesity are in an inflammatory state (5). In addition, expression of IL-10 and CD163 in CD14 ϩ cells from obese diabetic patients was significantly decreased relative to that of obese nondiabetic patients (P Ͻ 0.01). Multivariate regression analysis showed that expression of tumor necrosis factor-␣ is independently associated with age and BMI and that expression of IL-6 is independently associated with BMI and LDL cholesterol (P Ͻ 0.01); expression of IL-10 was negatively and independently associated with diastolic blood pressure, A1C, and triglycerides, and expression of CD163 was negatively and independently associated with insulin concentration, A1C, and PWV (P Ͻ 0.05). Moreover, only age and CD163 were independently correlated with PWV (P Ͻ 0.05). Interestingly, 3-month treatment with pioglitazone significantly increased IL-10 and CD163 and decreased IL-6 (P Ͻ 0.05) in parallel with the improvement of fasting plasma glucose, A1C, insulin conc e n t r a t i o n , h o m e o s t a s i s m o ...

We assessed whether gut microbial functional profiles predicted from 16S rRNA metagenomics differed in Japanese type 2 diabetic patients. A total of 22 Japanese subjects were recruited from our outpatient clinic in an observational study. Fecal samples were obtained from 12 control and 10 type 2 diabetic subjects. 16S rRNA metagenomic data were generated and functional profiles predicted using “Phylogenetic Investigation of Communities by Reconstruction of Unobserved States” software. We measured the parameters of glucose metabolism, gut bacterial taxonomy and functional profile, and examined the associations in a cross-sectional manner. Eleven of 288 “Kyoto Encyclopedia of Genes and Genomes” pathways were significantly enriched in diabetic patients compared with control subjects (p<0.05, q<0.1). The relative abundance of almost all pathways, including the Insulin signaling pathway and Glycolysis/Gluconeogenesis, showed strong, positive correlations with hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) levels. Bacterial taxonomic analysis showed that genus Blautia significantly differed between groups and had negative correlations with HbA1c and FPG levels. Our findings suggest a novel pathophysiological relationship between gut microbial communities and diabetes, further highlighting the significance and utility of combining prediction of functional profiles with ordinal bacterial taxonomic analysis (UMIN Clinical Trails Registry number: UMIN000026592).

ObjectiveTo investigate the association between serum soluble triggering receptor expressed on myeloid cells 2 (sTREM2), a soluble type of an innate immune receptor expressed on the microglia, and the risk of dementia.MethodsA total of 1,349 Japanese community residents aged 60 and older without dementia were followed prospectively for 10 years (2002–2012). Serum sTREM2 levels were quantified by using an enzyme‐linked immunosorbent assay and divided into quartiles. Cox proportional hazards model was used to estimate the hazard ratios (HRs) of serum sTREM2 levels on the risk of dementia.ResultsDuring the follow‐up, 300 subjects developed all‐cause dementia; 193 had Alzheimer's disease (AD), and 85 had vascular dementia (VaD). The age‐ and sex‐adjusted incidences of all‐cause dementia, AD, and VaD elevated significantly with higher serum sTREM2 levels (all p for trend < 0.012). These associations were not altered after adjustment for confounding factors, including high‐sensitive C‐reactive protein. Subjects with the highest quartile of serum sTREM2 levels had significantly higher multivariable‐adjusted risks of developing all‐cause dementia, AD, and VaD than those with the lowest quartile (HR = 2.03, 95% confidence interval [CI] = 1.39–2.97, p < 0.001 for all‐cause dementia; HR = 1.62, 95% CI = 1.02–2.55, p = 0.04 for AD; HR = 2.85, 95% CI = 1.35–6.02, p = 0.006 for VaD). No significant heterogeneity in the association of serum sTREM2 levels with the development of dementia was observed among the other risk factor subgroups (all p for heterogeneity > 0.11).InterpretationThe present findings suggest a significant association between increased serum sTREM2 levels and the risk of developing all‐cause dementia, AD, and VaD in the general elderly Japanese population. ANN NEUROL 2019;85:47–58.

Context Thrombospondin 1 (THBS1 or TSP-1) is an adipose-derived matricellular protein, which has recently been highlighted as a potential mediator of insulin resistance and adipose inflammation in obesity. Objective In this study, we aimed to determine the clinical significance of THBS1 as a novel biological marker of visceral obesity, metabolic syndrome, and diabetes. Methods The THBS1 mRNA level was quantified with real-time PCR in human adipose tissues obtained from 16 non-obese subjects. The relationships between serum THBS1 level and obesity/diabetes traits as well as the diagnostic components of metabolic syndrome were assessed in 164 normal-weight or overweight/obese subjects (78 males and 86 females; mean age, 50.4; mean BMI, 29.8) with analysis of covariance (ANCOVA) and regression analyses. Results THBS1 was predominantly expressed in visceral adipose tissues relative to subcutaneous adipose tissues (P < 0.001). The visceral THBS1 expression was positively associated with the body mass index (BMI; γs = 0.54, P = 0.033). ANCOVA demonstrated that the THBS1 level is associated with abdominal obesity (P < 0.001), hyperglycemia (P = 0.02), and hypertension (P = 0.04). Multivariable regression analysis suggested an association between serum THBS1 and fasting plasma glucose levels. The associations between serum THBS1 levels and obesity/diabetes traits were found preferentially in women (BMI, γs = 0.30, P = 0.05; FPG, γs = 0.26, P = 0.016). Subanalyses demonstrated that the association with obesity traits was predominantly found in premenopausal women (BMI, γs = 0.41, P = 0.007), whereas the association with diabetes traits was predominant in postmenopausal women (HbA1c, γs = 0.38, P = 0.01). During medical weight reduction treatment, the change in the serum THBS1 level was associated with the change in BMI and HbA1c in pre- and postmenopausal women, respectively. Conclusions Serum THBS1 is a useful biological marker of obesity and metabolic syndrome in Japanese subjects, particularly in women. THBS1 may act as a critical circulating factor that couples obesity with metabolic syndrome and diabetes in humans.