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Background: The aim of this study is to assess for the change in progression of inflammatory, adiposity, and atherosclerotic markers in first degree relatives of type 2 diabetes mellitus patients. Methods: Normal glucose tolerant (NGT) individuals (20–40 years) who had positive family history of T2DM (FHP) were enrolled in this prospective study based on ADA 2015 criteria. Age, sex, and BMI matched controls without any history of diabetes in their parents referred as family history negative (FHN) were taken for comparison. At baseline, detailed clinical assessment and requisite blood/imaging investigations were done. All the available subjects from the original cohort (FHN-32 and FHP-46) were studied after 2 years with recording of the clinical, biochemical and imaging parameters. Results: A total of 64 cases (FHP) and 42 controls (FHN) were enrolled at baseline. FHP group had significantly higher hsCRP (p = 0.039) and cIMT (p = 0.003) than that of FHN group. No significant difference in the rate of conversion of NGT to prediabetes (using multiple criteria) was found after 2 years between the two groups. cIMT was increased significantly from baseline in FHP group than FHN group at the end of the study(0.02 ± 0.03 vs. 0.01 ± 0.02 mm, p = 0.002). But there was no significant difference for changes in glycemic status, lipid parameters, HOMA IR, hsCRP, and adiposity markers between the two groups at the end of the study. Conclusion: Despite no significant differences in change in glycemic parameters or rates of conversion from NGT to pre diabetes, cIMT increased significantly in the normoglycemic offspring of T2DM subjects than those without history of T2DM in their parents. [ABSTRACT FROM AUTHOR]

Background:LIGHT (lymphotoxin-like inducible protein that competes with glycoprotein D for herpesvirus entry on T cells) is a member of the tumor necrosis factor (TNF) family, primarily expressed in lymphocytes, which was associated with the induction of pro-inflammatory cytokines and alterations of lipid homeostasis in animal models. We aimed to analyze whether LIGHT has a role in the human obesity-associated inflammatory status.Methods:The association between circulating LIGHT concentrations and clinical variables was studied in 190 subjects with different degrees of obesity and glucose tolerance. The expression and release of 21 different cytokines, and the expression of genes involved in lipid metabolism were also evaluated after stimulation with LIGHT in cultured human differentiated adipocytes.Results:Serum LIGHT concentrations positively associated with body mass index (BMI), fat mass, glycated hemoglobin and fasting triglycerides, and negatively with high-density lipoprotein cholesterol. Circulating LIGHT concentrations were significantly increased in morbidly obese subjects and in patients with type 2 diabetes. LIGHT induced the secretion of several cytokines and upregulated the expression and secretion of interleukin-6 (IL-6), IL-8, Growth Regulated Oncogene (GRO) and monocyte chemotactic protein-1 (MCP-1). These observations were concomitant with the activation of nuclear factor (NF)-κB signalling in human differentiated adipocytes. LIGHT also upregulated the expression and synthesis of its own receptor (herpesvirus entry mediator (HVEM)) and decreased the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) and fatty acid synthase.Conclusion:These data suggest that LIGHT may have a role in mediating chronic inflammation and alterations of lipid metabolism in obese subjects. [ABSTRACT FROM AUTHOR]

Objective:To determine whether increased expression of macrophage markers and of inflammatory markers in subcutaneous adipose tissue is associated with liver fat in human obesity. We also determined whether expression of TNF (gene encoding TNF-α), HSD11B1 (gene encoding 11β-HSD-1) and RETN (gene encoding resistin) in cultured monocyte-derived macrophages differs between obese/overweight and non-obese subjects.Design:Cross-sectional comparison of obese/overweight and non-obese subjects with respect to adipose tissue gene expression, gene expression in monocyte-derived macrophages, liver fat content and in vivo insulin sensitivity.Subjects:Adipose tissue gene expression, gene expression in monocyte-derived macrophages, liver fat content and in vivo insulin sensitivity: 10 healthy non-obese (24.2±1.0 kg/m2) and 10 healthy obese/overweight (33.1±1.7 kg/m2) women. Gene expression in monocyte-derived macrophages: seven healthy non-obese (22.1±0.7 kg/m2) and seven healthy obese/overweight (36.9±2.2 kg/m2) women.Measurements:Adipose tissue biopsies and blood samples for isolation of peripheral mononuclear cells were taken after an overnight fast. Liver fat content was measured using magnetic resonance proton spectroscopy. Whole body insulin sensitivity was measured using the hyperinsulinemic euglycemic clamp technique. Expression levels of TNF, HSD11B1, RETN and the macrophage markers CD68 and ITGAM were determined by real-time PCR.Results:In adipose tissue, expression of HSD11B1, ITGAM and CD68 was significantly increased in the obese/overweight as compared to the non-obese group. Expression of all these genes was closely positively correlated with liver fat content and inversely correlated with whole body insulin sensitivity. The associations between expression of CD68, ITGAM and HSD11B1 and liver fat were independent of obesity. There were no differences in TNF, HSD11B1, RETN or CD68 gene expression basally or after stimulation with lipopolysaccharide in monocyte-derived macrophages between obese/overweight and non-obese subjects.Conclusion:Accumulation of fat in the liver is associated with increased adipose tissue inflammation independent of obesity.International Journal of Obesity (2007) 31, 1617–1625. doi:10.1038/sj.ijo.0803635; published online 24 April 2007 [ABSTRACT FROM AUTHOR]

OBJECTIVE:: This study sought to determine the relationship between levels of the inflammatory marker, C-reactive protein (CRP), cardiovascular risk factors and oral contraceptive use in young adults. DESIGN:: Cross-sectional study of a community cohort. SUBJECTS:: A total of 822 men and women aged 26?y. MEASUREMENTS:: CRP, body mass index (BMI), blood pressure, lipid and lipoprotein levels, smoking status, socioeconomic status, health status, and hormonal contraceptive use in women. RESULTS:: Multiple regression analysis showed that obesity was independently related to CRP with an increase in ratio CRP of 1.03 (95% CI 1.01, 1.05) for men and 1.07 (1.05, 1.09) for women associated with a 1?kg/m2 increase in BMI. In women, combined oral contraceptive use was associated with a ratio change in CRP of 1.52 (1.27, 1.82) compared with nonusers. Other independent determinants of CRP in men and women were apolipoprotein B level, systolic blood pressure and apolipoprotein A1 in men. Univariate analysis showed that the relationship between CRP and BMI, systolic blood pressure and apolipoprotein B was significantly stronger in women than men. CONCLUSION:: These findings suggest that obesity is associated with inflammation independent of other cardiovascular risk factors that may contribute to an increased risk for cardiovascular disease in men and women. Elevated CRP related to combined oral contraceptive use may influence the rate of cardiovascular events in young women.International Journal of Obesity (2004) 28, 998-1003. doi:10.1038/sj.ijo.0802713 Published online 22 June 2004 [ABSTRACT FROM AUTHOR]

Obesity and diabetes are associated with chronic inflammation. Specialized pro-resolving lipid mediators (SPMs)—resolvins (Rv), protectins (PD) and maresins (MaR)—actively resolve inflammation. Bariatric surgery achieves remission of diabetes, but mechanisms are unclear. We measured SPMs and proinflammatory eicosanoid levels using liquid chromatography-tandem mass spectrometry in 29 morbidly obese subjects (13 with diabetes) and 15 nondiabetic, mildly obese subjects. Compared to the mildly obese, the morbidly obese had higher levels of SPMs—RvD3, RvD4 and PD1—and white blood cells (WBC) and platelets. Post-surgery, SPM and platelet levels decreased in morbidly obese nondiabetic subjects but not in diabetic subjects, suggesting continued inflammation. Despite similar weight reductions 1 year after surgery (44.6% vs. 46.6%), 8 diabetes remitters had significant reductions in WBC and platelet counts whereas five non-remitters did not. Remitters had a 58.2% decrease (p = 0.03) in 14-HDHA, a maresin pathway marker; non-remitters had an 875.7% increase in 14-HDHA but a 36.9% decrease in MaR1 to a median of 0. In conclusion, higher levels of RvD3, PD1 and their pathway marker, 17-HDHA, are markers of leukocyte activation and inflammation in morbid obesity and diabetes and diminish with weight loss in nondiabetic but not diabetic subjects, possibly representing sustained inflammation in the latter. Lack of diabetes remission after surgically-induced weight loss may be associated with reduced ability to produce MaR1 and sustained inflammation. [ABSTRACT FROM AUTHOR]

The article focuses on inflammation and cardiovascular disease. Several lipid-lowering trials have clearly established the importance of targeting LDL-cholesterol in order to reduce the risk of a first or recurrent coronary heart disease (CHD) event. A substantial proportion of CHD patients do not have LDL-cholesterol levels that are different from the healthy asymptomatic population, suggesting that there is a need to go beyond the lipid hypothesis and classical risk factors in order to properly assess and manage a significant proportion of high-risk individuals. Most studies have failed to properly control for abdominal fat accumulation when reporting the apparently independent association between CRP and the risk of myocardial infarction.