No abstract

Metabolic syndrome (MetS) is as a cluster of cardio-metabolic factors that greatly increase the risk of chronic diseases such as type II diabetes mellitus and atherosclerotic cardiovascular disease. In the United States, obesity, physical inactivity, aging, and genetics (to a minor extent) have arisen as risk factors for developing MetS. Although 35% of American adults suffer from MetS, its pathogenesis largely remains unknown. Worse, there is a lack of screening and optimum therapy for this disease. Researchers have consequently turned towards metabolomics to identify biomarkers to better understand MetS. The purpose of this review is to characterize various metabolites and their potential connections to MetS. Numerous studies have also characterized MetS as a disease of increased inflammation, and therefore this review also explores how metabolites play a role in various inflammatory pathways. Our review explores a broad range of metabolites including biogenic amines, branched chain amino acids, aromatic amines, phosphatidylcholines, as well as a variety of other molecules. We will explore their biochemical pathways and their potential role in serving as biomarkers.

BackgroundMetabolic syndrome (MetS) continues to be a significant problem globally, affecting nearly 35% of adults in the USA. Whilst there is no ideal biomarker that captures this disorder, high sensitivity C-reactive protein (hsCRP) appears to be most widely accepted. We examined the ratios between neutrophils (PMNs) and monocytes to high-density lipoprotein (HDL)-cholesterol and adiponectin, two anti-inflammatory proteins, in patients with nascent MetS without the confounding of diabetes, atherosclerotic cardiovascular diseases (ASCVD), smoking or lipid therapy to determine if they were also valid biomarkers of MetS.Materials and methodsPatients with nascent MetS (n = 58) and matched controls (n = 44) were recruited from Sacramento County. Fasting blood samples were obtained for complete blood counts, basic metabolic panel, lipid profile, insulin and adiponectin. Ratios of PMNs and monocytes to HDL-C and adiponectin were calculated and compared statistically.ResultsThe PMN:HDL-C, monocyte:HDL-C, PMN:adiponectin and monocyte:adiponectin ratios were significantly increased in patients with MetS and increased with increasing severity of MetS. Receiver operating characteristic (ROC) curve analysis showed that both the PMN:HDL-C and monocyte:HDL-C areas under the curve (AUCs) significantly added to the CRP AUC. Also both the ratios correlated with cardio-metabolic features of MetS, hsCRP and insulin resistance.ConclusionsOur data indicates that ratios of neutrophils and monocytes to HDL-C are significantly increased in patients with nascent MetS and both ratios appear to be better predictors of MetS than hsCRP alone. These important preliminary findings need to be confirmed in large prospective databases.

Cutaneous angiosarcoma (CAS) is a rare and aggressive malignant tumor with blood vessel or lymphatic-type endothelial differentiation. It has a poor prognosis with lack of standardized treatment options. This study retrospectively evaluated the clinical characteristics and treatment outcomes of 47 patients with CAS of the head and neck treated at an academic sarcoma center. Patient data were collected from the electronic medical records. 62% of patients were male with the scalp being the most commonly affected area (64%). The majority of patients presented with localized disease (53%). Median overall survival (OS) was 3.4 years with an OS of 36% at 5 years. There was a statistically significant increase in OS for patients who underwent surgery compared to those who did not (5.4 vs. 2.8 years). In contrast, radiotherapy (RT) or chemotherapy did not significantly increase OS. 45% of patients had recurrence of disease during their treatment course with a median time to recurrence of 22.8 months. There was not a significant difference in OS for patients who underwent immunotherapy compared to those who underwent chemotherapy, although only a few patients received immunotherapy. We found that surgery was an effective treatment modality in patients with easily resectable disease, while RT, chemotherapy, and immunotherapy did not significantly improve OS.

Metabolic Syndrome (MetS) continues to be a significant problem globally, affecting nearly 35% of adults in the USA. Whilst there is no ideal biomarker that captures this disorder high sensitivity C-reactive protein (hsCRP) is the most widely accepted measure.We examined the ratios between the phagocytes, neutrophils(PMN)and monocytes, to high density lipoprotein (HDL) and adiponectin, two anti-inflammatory proteins, in patients with nascent MetS without the confounding of T2DM, ASCVD, smoking or lipid therapy to determine if they were valid biomarkers of MetS. Patients with nascent MetS(n=58) and matched controls(n=44) were recruited from Sacramento County. Patients with diabetes, cardiovascular diseases, inflammation (hsCRP >10mg/L or leukocytosis), smoking, anti-inflammatory and hypolipidemic drug therapies were excluded. Fasting blood samples were obtained for complete blood counts, basic metabolic panel, lipid profile, insulin adiponectin, leptin and chemerin. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from glucose and insulin levels. Ratios of PMN and monocytes to HDL-C and Adiponectin were calculated and compared statistically. PMN: HDL-C and Monocyte: HDL-C, increased in patients with MetS compared to controls (p<0.0001 and p=0.001 respectively).Also the PMN: Adiponectin and monocyte: Adiponectin ratios were significantly increased in MetS (p=0.006 and 0.02 respectively). All ratios increased with increasing severity of MetS (p=0.01). Receiver Operating Characteristic (ROC) curve analysis showed that both the PMN/HDL-C and monocyte: HDL-C area under the curve(AUC)(0.85 and 0.84 respectively) significantly added to the CRP AUC(0.75), p=0.01 for both. Neither leukocyte: Adiponectin AUC was significant compared to hsCRP. Also both ratios to HDL-C correlated with cardio-metabolic features of MetS, hsCRP and insulin resistance(HOMA-IR) (p<0.05). Whilst the PMN:HDL-C ratio correlated with leptin, and chemerin the monocyte: HDL-C ratio correlated significantly with chemerin only (p<0.05) Our cross-sectional study indicates that ratios of neutrophils and monocytes to HDL-C are significantly increased in patients with nascent MetS, increase with severity of MetS, correlate positively with inflammation and insulin resistance and both ratios appear to be better predictors of MetS than hsCRP. In conclusion, they provide a cost-effective measure of Metabolic Syndrome and should be confirmed in larger data bases and prospective studies.