Background: Brown adipose tissue (BAT) is abundant in small mammals and in newborns and helps them to survive cold temperatures. In adults, it had long been considered to be absent or at least of no relevance. Recent investigations, however, have fuelled interest in adult BAT. Objective: We aimed at (1) summarizing structural and physiological characteristics of BAT versus white adipose tissue (WAT); (2) discussing the development of the two adipose tissue types; (3) reviewing the data available from human studies on BAT, and (4) discussing the impact of aging. Methods: We summarize recent descriptions of BAT and WAT based on the original literature and reviews in the field, with emphasis on human BAT. Results: WAT and BAT have essentially antagonistic functions: WAT stores excess energy as triglycerides and BAT is specialized in the dissipation of energy through the production of heat. Considerable amounts of BAT are present in a substantial proportion of adult humans and relatively high quantities of BAT are associated with lower body weight. With increasing age, BAT decreases and body weight increases. Conclusions: Although the available cross-sectional data do not allow definite conclusions to be drawn concerning a causal relationship between loss of BAT and increasing body weight with advancing age or obesity-related metabolic disorders of older age, stimulation of BAT appears to be an attractive novel candidate target for the treatment of age-related obesity.

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Aims/hypothesis Sphingolipid synthesis is typically initiated by the conjugation of L-serine and palmitoyl-CoA, a reaction catalysed by serine palmitoyltransferase (SPT). SPT can also metabolise other acyl-CoAs (C 12 to C 18 ) and other amino acids such as L-alanine and glycine, giving rise to a spectrum of atypical sphingolipids. Here, we aimed to identify changes in plasma levels of these atypical sphingolipids to explore their potential as biomarkers in the metabolic syndrome and diabetes.Methods We compared the plasma profiles of ten sphingoid bases in healthy individuals with those of patients with the metabolic syndrome but not diabetes, and diabetic patients (n=25 per group). The results were verified in a streptozotocin (STZ) rat model. Univariate and multivariate statistical analyses were used. Results Deoxysphingolipids (dSLs) were significantly elevated (p ¼ 5 Â 10 À6 ) in patients with the metabolic syndrome (0.11±0.04 μmol/l) compared with controls (0.06±0.02 μmol/l) but did not differ between the metabolic A. Othman and M. F. Rütti contributed equally to this study. Diabetologia (2012) 55:421-431 DOI 10.1007/s00125-011-2384 syndrome and diabetes groups. Levels of C 16 -sphingosinebased sphingolipids were significantly lowered in diabetic patients but not in patients with the metabolic syndrome but without diabetes (p=0.008). Significantly elevated dSL levels were also found in the plasma and liver of STZ rats. A principal component analysis revealed a similar or even closer association of dSLs with diabetes and the metabolic syndrome in comparison with the established biomarkers. Conclusions/interpretation We showed that dSLs are significantly elevated in patients with type 2 diabetes mellitus and non-diabetic metabolic syndrome compared with healthy controls. They may, therefore, be useful novel biomarkers to improve risk prediction and therapy monitoring in these patients.

Bile acids (BAs) regulate glucose and lipid metabolism. In longitudinal and case-control-studies, we investigated the diurnal variation of serum concentrations of the 15 major BAs as well as the biosynthetic precursor 7α-hydroxy-4-cholesten-3-one (C4) and their associations, respectively, with coronary artery disease (CAD), diabetes mellitus type 2 (T2DM), and non-diabetic metabolic syndrome (MetS). In hourly taken blood samples of four healthy probands, the intraindividual 24 h variation of C4, conjugated and unconjugated BAs ranged from 42% to 72%, from 23% to 91%, and from 49% to 90%, respectively. Conjugated BA concentrations mainly increased following food intake. Serum levels of C4 and unconjugated BAs changed with daytime with maxima varying interindividually between 20h00 and 1h00 and between 3h00 and 8h00, respectively. Comparisons of data from 75 CAD patients with 75 CAD-free controls revealed no statistically significant association of CAD with BAs or C4. Comparisons of data from 50 controls free of T2DM or MetS, 50 MetS patients, and 50 T2DM patients revealed significantly increased fasting serum levels of C4 in patients with MetS and T2DM. Multiple regression analysis revealed body mass index (BMI) and plasma levels of triglycerides (TG) as independent determinants of C4 levels. Upon multivariate and principle component analyses the association of C4 with T2DM and/or MetS was not independent of or superior to the canonical MetS components. In conclusion, despite large intra- and interindividual variation, serum levels of C4,are significantly increased in patients with MetS and T2DM but confounded with BMI and TG.

The prevalence of type 2 diabetes mellitus (T2DM) has been developed in the last three decades. Discover an effective solution is necessary to manage and prevent this disease. Physical activity and exercise training is an effective way for metabolic syndrome risk factors in type 2 diabetes mellitus (T2DM) patients. However, there are some uncertainties in effects of Circuit Resistance Training (CRT) program on patients T2DM. The purpose of this study is to investigation the effect of 8 weeks of Circuit resistance training (CRT) on metabolic syndrome and body composition in women over age 50 with T2DM.Twenty women over 50 years old with diabetes Referred to diabetes Center of 17 Shahrivar hospital in Amol and they were divided randomly into two groups; Circuit resistance (n=10) and Control (n=10). Resistance training consisted of 10 stations for 8 weeks and 3 sessions per week (Intensity 60-80% 1RM). Levels of Lipid profile and body composition before and after eight weeks training in both groups were measured. Statistical analysis of the data was carried out by SPSS (v. 22).Fasting Blood Sugar (FBS) levels (P=0.021), Triglycerides (0.010), high-density lipoprotein cholesterol (0.042), significant decreased in CRT. Also after 8 weeks circuit resistance training, BMI (P= 0.003), WHR (P=0.004) and body fat present (0.019) significant decreased in CRT.According to our results, CRT was an effective approach to improve the Anthropometrics, FBS, lipid profile in women over age 50 with diabetes mellitus type 2. Moreover, CRT did have influence on LDL level.

OBJECTIVE -To evaluate the atherogenicity of lipids in coronary patients with normal fasting glucose (NFG), impaired fasting glucose (IFG), and type 2 diabetes. RESEARCH DESIGN AND METHODS -Serum lipid values, the presence of angiographic coronary artery disease (CAD) at baseline, and the incidence of vascular events over 2.3 years were recorded in 750 consecutive patients undergoing coronary angiography.RESULTS -Triglycerides significantly (P Ͻ 0.001) increased and HDL cholesterol (P Ͻ 0.001) as well as LDL particle diameter (P Ͻ 0.001) significantly decreased from subjects with NFG Ͻ5.6 mmol/l (n ϭ 272) over patients with IFG Ն5.6 mmol/l (n ϭ 314) to patients with type 2 diabetes (n ϭ 164). Factor analysis revealed two factors in the lipid profiles of our patients: triglycerides, HDL cholesterol, apolipoprotein A1, and LDL particle diameter loaded high on an HDL-related factor, and total cholesterol, LDL cholesterol, and apolipoprotein B loaded high on an LDL-related factor. In patients with type 2 diabetes, the HDL-related factor (odds ratio 0.648 [95% CI 0.464 -0.904]; P ϭ 0.011), but not the LDL-related factor (0.921 [0.677-1.251]; P ϭ 0.597), was associated with significant coronary stenoses Ն50%. Consistently, in the prospective study, the HDL-related factor (0.708 [0.506 -0.990]; P ϭ 0.044), but not the LDL-related factor (1.362 [0.985-1.883]; P ϭ 0.061), proved significantly predictive for vascular events in patients with type 2 diabetes. CONCLUSIONS -The low HDL cholesterol/high triglyceride pattern is associated with the degree of hyperglycemia. In coronary patients with type 2 diabetes, this pattern correlates with the prevalence of CAD and significantly predicts the incidence of vascular events. Diabetes Care 28:108 -114, 2005E pidemiologic data from the Framingham Study (1) and the Multiple Risk Factor Intervention Trial (2) indicate that the risk for cardiovascular death is increased two-to threefold in type 2 diabetic individuals. Moreover, after a first myocardial infarction, cardiovascular morbidity and mortality are increased in patients with diabetes compared with nondiabetic patients (3). In the U.K. Prospective Diabetes Study, protocols targeted to optimize glycemic (4) or blood pressure control (5) failed to significantly reduce the incidence of myocardial infarction. Therefore, and because in the U.K. Prospective Diabetes Study plasma levels of LDL cholesterol and low levels of HDL cholesterol were strong predictors of myocardial infarction (6), the main interest for risk intervention now focuses on lipids. However, it is still not clear which lipoprotein abnormality predominantly endangers diabetic patients.Typically, patients with type 2 diabetes are characterized by hypertriglyceridemia and low HDL cholesterol levels (7), whereas levels of LDL cholesterol have been reported to be normal (7), higher (8) or lower (9) than those in nondiabetic control subjects. Moreover, compositional changes of lipoproteins have been demonstrated: both LDL and HDL are smaller and denser than average (10)...

OBJECTIVE -The International Diabetes Federation (IDF) has recently established a worldwide consensus definition of the metabolic syndrome. No prospective data are available on the cardiovascular risk associated with this new metabolic syndrome definition. RESEARCH DESIGN AND METHODS-In a prospective study of 750 coronary patients, we recorded vascular events over 4 years.RESULTS -From our patients, 37.3% (n ϭ 280) had the metabolic syndrome according to the Adult Treatment Panel III (ATPIII) definition and 45.5% (n ϭ 341) according to the IDF definition. The metabolic syndrome as defined by the ATPIII criteria significantly predicted vascular events (adjusted hazard ratio 1.745 [95% CI 1.255-2.427]; P ϭ 0.001), but the metabolic syndrome as defined by IDF criteria did not (1.189 [0.859 -1.646]; P ϭ 0.297). Accordingly, event-free survival was significantly lower among patients who fulfilled the ATPIII but not the IDF criteria than among those who met the IDF but not the ATPIII criteria (P ϭ 0.012). The metabolic syndrome as defined by ATPIII criteria remained significantly predictive of vascular events after adjustment for type 2 diabetes but not after additional adjustment for the metabolic syndrome components high triglycerides and low HDL cholesterol. These lipid traits in turn proved significantly predictive of vascular events even after adjustment for the metabolic syndrome.CONCLUSIONS -The ATPIII definition of the metabolic syndrome confers a significantly higher risk of vascular events than the IDF definition. However, among angiographied coronary patients, even the ATPIII definition of the metabolic syndrome does not provide prognostic information beyond its dyslipidemic features. Diabetes Care 29:901-907, 2006T he term metabolic syndrome refers to a cluster of cardiovascular risk factors associated with insulin resistance (1,2). During the past decade, there have been various attempts to standardize the definition of the metabolic syndrome as a diagnostic category, with several institutions proposing various criteria (3-7).The definition of the metabolic syndrome that has most often been used in the literature was proposed by the National Cholesterol Education Program's Adult Treatment Panel III (ATPIII) 4 years ago (4). According to this definition, the metabolic syndrome is diagnosed in the presence of any three of five markers: central obesity, high triglycerides, low HDL cholesterol, high fasting glucose, and high blood pressure.Recently, the concept of the metabolic syndrome as an entity with clinical implications over and above its single constituents has been challenged (8,9). However, efforts continue to integrate the individual metabolic syndrome traits into an overall diagnosis, and the International Diabetes Federation (IDF) has now established a worldwide consensus definition of the metabolic syndrome (10,11).This new definition basically agrees with the component features of the ATPIII definition but introduces some important changes: the cutoff for a waist circumference defining central o...

BACKGROUND AND AIMS Sodium–glucose co-transporter 2 inhibition reduces the risk of hospitalisation for heart failure and for death in patients with symptomatic heart failure. However, trials investigating the effects of this drug class in patients following acute myocardial infarction are lacking. METHODS In this academic, multicentre, double-blind trial, patients (n = 476) with acute myocardial infarction accompanied by a large creatine kinase elevation (>800 U/L) were randomly assigned to empagliflozin 10 mg or matching placebo once-daily within 72 hours of percutaneous coronary intervention. The primary outcome was the N-terminal pro-hormone of brain natriuretic peptide (NT-proBNP) change over 26 weeks. Secondary outcomes included changes in echocardiographic parameters. RESULTS Baseline median (interquartile range) NT-proBNP was 1,294 (757–2,246) pg/ml. NT-proBNP reduction was significantly greater in the empagliflozin group, compared with placebo, being 15% lower (95% confidence interval [CI] -4.4% to -23.6%) after adjusting for baseline NT-proBNP, sex and diabetes status (p = 0.026). Absolute left ventricular ejection fraction improvement was significantly greater (1.5%, 95% CI 0.2% to 2.9%, p = 0.029), mean E/e’ reduction was 6.8% (95% CI 1.3% to 11.3%, p = 0.015) greater, and left ventricular end-systolic and end-diastolic volumes were lower by 7.5 ml (95% CI 3.4 to 11.5 ml, p = 0.0003) and 9.7 ml (95% CI 3.7 to 15.7 ml, p = 0.0015), respectively, in the empagliflozin group, compared with placebo. Seven patients were hospitalised for heart failure (three in the empagliflozin group). Other predefined serious adverse events were rare and did not differ significantly between groups. CONCLUSIONS In patients with a recent myocardial infarction, empagliflozin was associated with a significantly greater NT-proBNP reduction over 26 weeks, accompanied by a significant improvement in echocardiographic functional and structural parameters.