Homeostasis Assessment Of Insulin Resistance Research Articles

Anti-Diabetic and Antioxidant Effects of Methanolic Flower Head Extract of Tagetes Patula in Streptozotocin and Dexamethasone Induced Diabetic Rats


 Diabetes is a chronic metabolic disorder characterized by a high blood glucose concentration, i.e., hyperglycemia or caused by insulin deficiency, often combined with insulin resistance. In the Present study, the antidiabetic and antioxidant activity of the methanolic extract of Tagetes patula flower heads was screened out in rodent models. The pharmacological evaluation was carried out using 200 and 400 mg/kg, b.w. The in-vivo antidiabetic activity was performed in streptozotocin, dexamethasone- induced diabetic models and oral glucose tolerance test. Metformin hydrochloride was used as a standard. The parameters like blood glucose levels, insulin levels, homeostasis assessment of insulin resistance, insulin sensitivity, and fasting glucose-insulin ratio were estimated in these models. The in-vitro antioxidant activity of methanolic extract of Tagetes patula was performed by using hydroxyl radical scavenging assay and Ascorbic acid was used as a standard. The preliminary phytochemical screening of Tagetes patula revealed the presence of phytoconstituents like alkaloids, flavonoids, saponins, steroids, phenols, carbohydrates, triterpenoids, and tannins. The extract showed a significant decrease in the elevated blood glucose levels in streptozotocin, dexamethasone-induced diabetic models, and also in the oral glucose tolerance test. The extract prevented insulin resistance and significantly increased insulin sensitivity in the dexamethasone-induced model. The various phytochemical constituents like alkaloids, flavonoids, saponins, steroids, and phenols might be responsible for lowering the blood glucose levels in the animal models mentioned above. The extract showed significant scavenging activity against hydroxyl free radicals. From the above outcomes, it is flawless that the methanolic extract of Tagetes patula has antidiabetic and antioxidant activities.

Metabolic profile and adipokine levels in overweight and obese dogs

Obesity in dogs is increasingly present in the veterinary practice. In humans, it is known that there is a significant correlation between obesity and the development of hypertension and insulin resistance (IR), a clinical picture called metabolic syndrome. In dogs, however, there are only anecdotes about the syndrome. The objectives of this study were to determine serum levels of adiponectin, leptin, triglycerides, cholesterol, insulin, glucose, homeostasis assessment of B cell function (HOMA-B), homeostasis assessment of insulin resistance (HOMA-IR), and systolic blood pressure (SBP) in dogs with different body conditions (BC) and body fat (BF) without endocrine disease. For this purpose, 76 healthy dogs were submitted to evaluation of body conditions score (BCS) and morphometry. The dogs were separated into 3 groups: optimal BC [BCS 3,4, or 5 of 9 and BF% of 13 to 27-Group 1 (G1)], overweight [BCS 6 and 7 of 9 and BF% of 14 to 38- Group 2 (G2)], obese [BCS 8 and 9 of 9 and BF% greater than or equal to 34-Group 3 (G3)]. G3 presented higher serum levels of total protein, triglycerides, glucose, insulin, and HOMA-IR. Adipokines did not correlate to any other parameter, but the occurrence of hyperinsulinemia was higher in G3. The results have shown that obese dogs presented IR and alterations in fat metabolism.

Serum Nesfatin-1 in patients with type 2 diabetes mellitus: A cross sectional study

Background and objective: Nesfatin-1 is a newly described peptide, derived from nucleobindin2. Nesfatin-1 suppresses food intake and it is involved in regulating insulin secretion. The aim of this study was to compare serum levels of Nesfatin-1 in patients having type 2 diabetes and non-diabetic subjects. Methods: This cross-sectional study included 90 participants; 64 patients with type 2 diabetes mellitus (32 males and 32 females) and 26 control subjects (13 males and 13 female). Body mass index, fasting serum level of glucose, fasting serum level of insulin, and glycated hemoglobin were estimated. Homeostasis model assessment of insulin resistance was calculated. Nesfatin-1 level was measured using enzyme-linked immune-sorbent assay kit. The data was analyzed using Graphpad prism 7.04 for windows. Results: Type 2 diabetes patients aged from 33-78 years and the control group aged from 32-75 years. Nesfatin-1 level in the diabetic group was significantly lower than controls. The median interquartile range (IQR) of Nesfatin-1 was 0.765 (0.4-1.173) in diabetes and 1.02 (0.775-1.458) in controls. The diabetes group has significantly higher homeostasis model assessment of insulin resistance compared with non-diabetics. Serum Nesfatin-1 was correlated negatively with body mass index, fasting serum glucose, fasting serum insulin, glycatedhemoglobin, and homeostasis assessment of insulin resistance. Conclusion: Serum Nesfatin-1 level is negatively correlated with fasting serum glucose, fasting serum insulin, and glycated hemoglobin. This association supports the role of Nesfatin-1 in increased insulin resistance in patients with type 2 diabetes.

Danggui Buxue decoction ameliorates lipid metabolic defects involved in the initiation of diabetic atherosclerosis; identification of active compounds.

To determine the constituent compounds of Danggui buxue decoction (DBD) involved and the potential mechanisms mediating its effects, with specific reference to lipids playing a role in the initiation of diabetic atherosclerosis. Liquid chromatography-tandem mass spectrometry was used to identify and quantify the absorbed bioactive compounds (ABCs) present in DBD. Goto-Kakizaki (GK) rats were randomly allocated to a diabetes atherosclerosis (DA) group, a DBD group, and an ABC group (10 per group), which were all high-fat diet-fed. The treated rats were administered DBD (4 g/kg) or ABCs (in amounts equal to those present in DBD) once daily for 28 d, and a control group of Wistar rats were administered vehicle. Body mass gain, fasting blood glucose, and homeostasis assessment of insulin resistance (HOMA- IR) were measured. Serum triglyceride (TG), cholesterol (CHOL), high density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL- C) and tumor necrosis factor-α (TNF-α) concentrations were determined. Hematoxylin and eosin staining and microscopy were used to characterize the abdominal aorta and the expression of lipogenic genes was quantified in this vessel. Seven ABCs were identified in rat serum: ferulic acid, formononetin, calycosin, astragaloside, caffeic acid, ligustilide, and butyphthalide. DBD significantly reduced HOMA-IR, the serum concentrations of TG, CHOL, and LDL-C, and the expression of the lipogenic genes monocyte chemotactic protein 1, Fas, intercellular adhesion molecule 1, and Cd36 in aorta; and significantly increased the mRNA expression of Scd1 in aorta. DBD affects lipid metabolism in the early stage of atherosclerosis in diabetic GK rats, with the mechanism likely involving the regulation of lipid metabolic genes in vessels. The contribution of ABCs to the effect of DBD on lipid metabolism was 24%-101%.

3574 Effect modification between kidney function and adiposity in the association with central and peripheral insulin sensitivity among Nondiabetic patients with moderate Chronic Kidney Disease and Healthy Controls

OBJECTIVES/SPECIFIC AIMS: The main aim of this study was to investigate the interaction between glomerular filtration rate (GFR) and body mass index (as well as serum leptin) as determinants of peripheral and central insulin sensitivity (IS). METHODS/STUDY POPULATION: This was a cross-sectional investigation of 140 nondiabetic participants – 56 with CKD (GFR = 15-59 ml/min/1.73m2) and 94 with normal GFR (≥ 60 ml/min/1.73m2) – recruited as part of the relationship of insulin sensitivity in kidney disease and vascular health (RISKD) study. Peripheral (skeletal muscle) and central (hepatic) IS were assessed with the hyperinsulinemic euglycemic glucose clamp (HEGC) and homeostasis assessment of insulin resistance (HOMA-IR) respectively. Creatinine-based estimated GFR (eGFR) was obtained using the CKD-EPI equation and body mass index (BMI) was computed from baseline weight and height measurements. Linear regression models with robust standard errors (to relax homoscedasticity assumptions) and interaction terms were used to investigate GFR and BMI as predictors of HEGC-derived insulin sensitivity index (ISI) and HOMA-IR. RESULTS/ANTICIPATED RESULTS: The mean (SD) age was 53.9 (14.5) years; 50.7% were female and 36.7% were African-American. Compared to controls, CKD patients had significantly lower mean (SD) ISI [5.4 (3.2) vs. 3.1 (1.6), p < 0.0001]. Log ISI was positively correlated (r = 0.39, p < 0.0001) with eGFR and inversely correlated (−0.30, p < 0.0001) with BMI and log leptin (−0.42, p < 0.0001). In multivariable models adjusted for age, sex and race, a 10 ml/min/1.73m2 lower eGFR was associated with a greater decrease in ISI among non-obese (0.48; 95% CI: −0.25, −0.70) compared to obese participants (−0.18; 95% CI: −0.02, −0.35) (p-interaction = 0.04). Patients with low eGFR (in particular, the lower margin of the CKD stage 3 range, 30ml/min) had lower ISI even with BMI within normal range (Figure 1a). At higher eGFR, BMI had a greater impact on ISI. P-interaction = 0.046, for differential BMI effects at lower vs. higher eGFR. Log HOMA-IR was inversely correlated with eGFR (r = - 0.49, p < 0.0001) and positively correlated with BMI (r = 0.52, p < 0.0001) and log leptin (0.46, p < 0.0001). HOMA-IR was lower for persons with higher GFR compared to lower GFR, at any BMI value. For example, at a BMI of 30 and a GFR of 120, HOMA-IR was 1.2 compared to 4.8 at a GFR of 30 (Figure 1b). Also, persons with high GFR had low HOMA-IR even with BMI in the obese range. BMI had a greater effect on HOMA-IR at lower eGFR. P-interaction = 0.005, for differential BMI effects at lower vs. higher eGFR. Similar findings were obtained when using log leptin in lieu of BMI in models for ISI and HOMA-IR. DISCUSSION/SIGNIFICANCE OF IMPACT: Measures of adiposity (BMI and leptin) and GFR were independently predictive of insulin sensitivity (IS) but the magnitude of the effect of BMI (or leptin) on IS varied significantly across GFR levels and type of IS (peripheral versus central). The effect of BMI on central IS (HOMA-IR) was more pronounced at lower GFR with small changes in BMI translating into greater variations in IS. Conversely, at low GFR, peripheral IS (ISI) is less affected by BMI. Persons with GFR at the lower margin of the CKD stage 3 range were significantly insulin resistant (low ISI) regardless of their BMI. More studies are required to further elucidate these interaction patterns for central and peripheral IS.

Heterogeneity in effects of genetically determined adiposity on insulin resistance and type 2 diabetes: The atherosclerosis risk in communities study

BackgroundA recent genome-wide association study has identified 12 genetic variants robustly associated with body fat percentage (BF%) with diverse cardiometabolic consequences. We developed three genetic risk scores (GRSs) according to the associations of the 12 individual variants with type 2 diabetes (T2D) and test the GRSs' associations with insulin resistance and T2D in the Atherosclerosis Risk in Communities Study. MethodsIn 6895 European-American participants, we calculated GRS-I as the number of BF%-increasing alleles from variants associated with increased risk of T2D, GRS-D from variants associated with decreased risk of T2D, and GRS-ALL from all 12 variants. Linear and logistic regression models were used to evaluate associations of the GRSs with insulin resistance and risk of T2D, respectively, adjusted for age, sex, smoking, and drinking, and additionally for body mass index (BMI). ResultsGRS-D was significantly associated with decreased levels of fasting insulin (P = 0.014) and homeostasis assessment of insulin resistance (P = 0.023). While GRS-I was not associated with insulin resistance measures, it was with T2D (P = 0.002). Further adjustment for BMI did not substantially change the above associations. GRS-ALL was inversely associated with insulin resistance after controlling for covariates including BMI; GRS-ALL was not associated with T2D. ConclusionGenetically determined BF% has differential effects on cardiometabolic risk, which may partly explain the heterogeneity in obesity-induced cardiometabolic risk and have implications for developing new strategies mitigating obesity-induced cardiometabolic consequences.

The association of the lipidomic profile with features of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) affects up to 18% of reproductive-aged women with reproductive and metabolic complications. While lipidomics can identify associations between lipid species and metabolic diseases, no research has examined the association of lipid species with the pathophysiological features of PCOS. The aim of this study was to examine the lipidomic profile in women with and without PCOS. This study was a cross-sectional study in 156 age-matched pre-menopausal women (18-45 years, BMI >20 kg/m2; n = 92 with PCOS, n = 64 without PCOS). Outcomes included the association between the plasma lipidomic profile (325 lipid species (24 classes) using liquid chromatography mass spectrometry) and PCOS, adiposity, homeostasis assessment of insulin resistance (HOMA), sex hormone-binding globulin (SHBG) and free androgen index (FAI). There were no associations of the lipidomic profile with PCOS or testosterone. HOMA was positively associated with 2 classes (dihydroceramide and triacylglycerol), SHBG was inversely associated with 2 classes (diacylglycerol and triacylglycerol), FAI was positively associated with 8 classes (ceramide, phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, lysophosphatidylethanolamine, phosphatidylinositol, diacylglycerol and triacylglycerol) and waist circumference was associated with 8 classes (4 positively (dihydroceramide, phosphatidylglycerol, diacylglycerol and triacylglycerol) and 4 inversely (trihexosylceramide, GM3 ganglioside, alkenylphosphatidylcholine and alkylphosphatidylethanolamine)). The lipidomic profile was primarily related to central adiposity and FAI in women with or without PCOS. This supports prior findings that adiposity is a key driver of dyslipidaemia in PCOS and highlights the need for weight management through lifestyle interventions.

Lead Exposure Induces Weight Gain in Adult Rats, Accompanied by DNA Hypermethylation.

ObjectivePrevious studies have revealed the association of lead (Pb) exposure with obesity. DNA methylation alteration has been suggested to be one of the regulatory mechanisms of obesity. We aimed to explore whether Pb exposure is related with weight gain and DNA methylation alteration.MethodsMale adult 8 week Wistar rats were divided into 5 groups: the normal chow diet (NCD); the NCD+0.05%Pb; the NCD+0.15%Pb; the NCD+0.45%Pb and the high fat diet. Rats were exposed to different dosages of Pb through drinking water for 21 weeks. Body weight, fasted blood glucose level, fasted insulin level, homeostasis assessment of insulin resistance (HOMA-IR) index and lipid profile were detected. Intra-peritoneal glucose tolerance test (IPGTT) was constructed to evaluate the glucose tolerance. Lipid accumulation of liver was detected and liver DNA underwent whole genome bisulfite sequencing.ResultsThe NCD+0.05%Pb group had significantly greater weight, HOMA-IR and triglycerides, and lower glucose intolerance than the NCD group (P <0.05). This group also showed hepatic lipid accumulation. These metabolic changes were not observed in the other two Pb dosage groups. Furthermore, DNA hypermethylation extended along pathways related to glucose and lipid metabolism in NCD+0.05%Pb group.ConclusionPb exposure resulted in dose-specific weight gain in adult Wistar rats, accompanied by alteration of DNA methylation.

Nephroprotective potential of Quercus infectoria galls against experimentally induced diabetic nephropathy in rats through inhibition of renal oxidative stress and TGF-β

ABSTRACTDiabetic nephropathy (DN) is the leading cause of death in diabetic patients and the current treatment options available have a limited significance. The insect galls of Quercus infectoria are traditionally important in the treatment of numerous diseases including diabetes. Hence, the present study was undertaken to evaluate the effect of Q. infectoria gall extract (QIGE) against experimental DN. Type 2 diabetes was induced by feeding rats with a high-fat diet (HFD) initially for 5 weeks, followed by a single intraperitoneal injection of streptozotocin (STZ, 35 mg/kg bw/day). QIGE was administered to the rats orally at doses of 100 and 200 mg/kg bw/day, respectively. At the end of the experimental period, various glycemic and renal function parameters were evaluated in the serum, urine and kidney tissues. The QIGE treatment significantly (p < .001) reduced the levels of fasting blood glucose, serum lipid profile, glycated hemoglobin (HbA1c) and homeostasis assessment of insulin resistance in treated rats as compared to diabetic control rats. Markers of oxidative stress and the expression of transforming growth factor-β (TGF-β) in the kidneys of diabetic rats were significantly (p < .001) normalized by QIGE administration. QIGE prevents the development of DN via the inhibition of hyperglycemia-induced oxidative stress and renal TGF-β expression and is, therefore, a potential therapeutic agent in the treatment of diabetic complications, especially DN.

Association of Metabolic Syndrome with Serum Adipokines in Community-Living Elderly Japanese Women: Independent Association with Plasminogen Activator-Inhibitor-1.

Associations between metabolic syndrome (MetS) with serum adipokines and basal lipoprotein lipase mass (serum LPL) have not been extensively studied in elderly Asians, who in general have lower body mass index than European populations. A cross-sectional analysis was conducted including 159 community-living elderly Japanese women whose age averaged 77 years. MetS was defined by the modified National Cholesterol Education Program Adult Treatment Panel III criteria, but using a body mass index ≥25 kg/m(2) instead of waist circumference. Serum LPL, leptin, adiponectin, plasminogen activator inhibitor 1 (PAI-1), interleukin-6, tumor necrosis factor-alpha, and high-sensitivity C-reactive protein were measured. Both the presence of MetS and the number of MetS components were associated with higher homeostasis assessment of insulin resistance, serum levels of leptin, PAI-1, and tumor necrosis factor-alpha and with lower serum levels of LPL and adiponectin (all P < 0.05), but not with high-sensitivity C-reactive protein and interleukin-6. Among six biomarkers of MetS, PAI-1 remained associated with MetS independent of fat mass index and insulin resistance. Although proinflammatory, prothrombotic, and anti-inflammatory states were associated with MetS, higher PAI-1 was associated with MetS independent of fat mass index and insulin resistance in elderly Japanese women, in whom obesity is rare.

The Effects of Allopurinol on the Carotid Intima-media Thickness in Patients with Type 2 Diabetes and Asymptomatic Hyperuricemia: A Three-year Randomized Parallel-controlled Study.

The aim of this study was to investigate the long-term effective control of serum uric acid by allopurinol on the carotid intima-media thickness (IMT) in patients with type 2 diabetes (T2DM) and asymptomatic hyperuricemia (HUA). This was a randomized open parallel-controlled study. In this study, 176 patients with T2DM and asymptomatic HUA were randomly allocated to the conventional or allopurinol treatment groups on the basis of a computer-generated random number table. Changes in the carotid IMT, biochemical indexes, high sensitive C-reactive protein (hs-CRP) and the incidence of hypertension in patients before and after three years of treatment were examined and compared between the groups. There were no statistically significant differences in the baseline characteristics of the study participants between the two treatment groups (p>0.05 for all). Nevertheless, the serum uric acid, triglyceride, and hs-CRP levels and the homeostasis assessment for insulin resistance (HOMA-IR), systolic blood pressure, diastolic blood pressure and the carotid IMT in the allopurinol group were significantly lower than those in the conventional group after three years of treatment (p<0.01 for all). The intention-to-treat analysis indicated that the incidence of new-onset hypertension in the allopurinol group showed a declining trend compared to that in the conventional treatment group (6.8% vs. 13.6%, p>0.05). The long-term effective control of serum uric acid by allopurinol may improve insulin resistance, decrease the serum levels of hs-CRP, reduce the carotid IMT, and may delay the development of atherosclerosis in patients with T2DM and asymptomatic HUA.

Circulating cf-DNA: A promising, noninvasive tool for assessment of early cardio-metabolic risk

In 1948, Mandel and colleagues were the first group to report the presence of circulating nucleic acids in the human bloodstream [1]. The origin of cell-free DNA (cf-DNA) is not fully understood, but apoptosis, necrotic death, cell lysis and active release are possible mechanisms of cf-DNA release into the blood circulation [2]. Circulating cf-DNA is a recent area of increased research interest, with nearly 9000 related papers in the PubMed library. This research has explored a wide range of topics, including the uses of circulating cf-DNA as a cancer prognostic factor, an indicator for intensive care unit admission, and a diagnostic marker of carcinogenesis, injury, sepsis and autoimmune disease [2e5]. The pathophysiological significance of circulating cf-DNA in cardiovascular disease has not received much attention until recently. However, scattered experimental and clinical studies have shed light upon this interesting issue [6e8]. Ten years ago, a clinical study by Chang et al. showed elevated circulating cf-DNA in patients with myocardial infarction [6]. Recently, an observational cohort study clearly demonstrated that plasma cf-DNA levels are a useful biomarker for predicting the outcome after out-of-hospital

Top Single Nucleotide Polymorphisms Affecting Carbohydrate Metabolism in Metabolic Syndrome: From the LIPGENE Study

Metabolic syndrome (MetS) is a high-prevalence condition characterized by altered energy metabolism, insulin resistance, and elevated cardiovascular risk. Although many individual single nucleotide polymorphisms (SNPs) have been linked to certain MetS features, there are few studies analyzing the influence of SNPs on carbohydrate metabolism in MetS. A total of 904 SNPs (tag SNPs and functional SNPs) were tested for influence on 8 fasting and dynamic markers of carbohydrate metabolism, by performance of an intravenous glucose tolerance test in 450 participants in the LIPGENE study. From 382 initial gene-phenotype associations between SNPs and any phenotypic variables, 61 (16% of the preselected variables) remained significant after bootstrapping. Top SNPs affecting glucose metabolism variables were as follows: fasting glucose, rs26125 (PPARGC1B); fasting insulin, rs4759277 (LRP1); C-peptide, rs4759277 (LRP1); homeostasis assessment of insulin resistance, rs4759277 (LRP1); quantitative insulin sensitivity check index, rs184003 (AGER); sensitivity index, rs7301876 (ABCC9), acute insulin response to glucose, rs290481 (TCF7L2); and disposition index, rs12691 (CEBPA). We describe here the top SNPs linked to phenotypic features in carbohydrate metabolism among approximately 1000 candidate gene variations in fasting and postprandial samples of 450 patients with MetS from the LIPGENE study.

Changes in endothelial function and depression scores are associated following long-term dietary intervention: A secondary analysis

ObjectiveCross-sectional studies show associations between depression and endothelial function (as measured by endothelium-dependent brachial artery flow-mediated dilatation [FMD]); but it is not known whether changes in these parameters are associated following dietary management. We have previously reported that compared with consumption of a high-carbohydrate (HC) diet, despite comparable weight loss, a very low-carbohydrate (LC diet) impaired FMD and increased depression. The purpose of this study was to conduct a secondary analysis to examine whether there was an association between changes in FMD and depression. MethodsForty-seven overweight men and women (body mass index 26–43 kg/m2 and ages 24–64 y) completed a 12-mo randomized controlled trial during which participants consumed either an energy-restricted, isocaloric LC or HC diet. Weight, body composition, Homeostasis Assessment of Insulin Resistance (HOMA), depression (Beck Depression Inventory [BDI]), Anxiety (Spielberger State-Trait Anxiety Inventory [STAI]) and FMD were assessed before and after the intervention. This secondary analysis focused on multiple regression analysis of these parameters. ResultsChanges in BDI were independently predicted by changes in FMD (β = −0.356; P = 0.026) but not by diet intervention assignment or changes in weight or HOMA. No variables were significant predictors of the change in STAI. ConclusionsOver time, impairments in FMD were independently associated with increased depression, independent of diet composition, or changes in weight and insulin resistance. This data supports a mechanistic association between depression and endothelial function, which may influence long-term health.

Changes in serum aldosterone are associated with changes in obesity-related factors in normotensive overweight and obese young adults.

Recent data suggest excess circulating aldosterone promotes cardiometabolic decline. Weight loss may lower aldosterone levels, but little longitudinal data is available in normotensive adults. We aimed to determine whether, independent of changes in sodium excretion, reductions in serum aldosterone are associated with favorable changes in obesity-related factors in normotensive overweight/obese young adults. We studied 285 overweight/obese young adult participants (body mass index ≥ 25 and<40 kg m⁻², age 20-45 years) in a clinical trial examining the effects of a 1-year diet and physical activity intervention with or without sodium restriction on vascular health. Body weight, serum aldosterone, 24-h sodium and potassium excretion and obesity-related factors were measured at baseline, 6, 12 and 24 months. Weight loss was significant at 6 (7%), 12 (6%) and 24 months (4%; all P<0.0001). Decreases in aldosterone were associated with decreases in C-reactive protein, leptin, insulin, homeostasis assessment of insulin resistance, heart rate, tonic cardiac sympathovagal balance and increases in adiponectin (all P<0.05) in models adjusting for baseline age, sex, race, intervention arm, time since baseline, and sodium and potassium excretion. Weight loss and reductions in thigh intermuscular fat (intermuscular adipose tissue area; IMAT) were associated with decreases in aldosterone in the subgroup (n=98) with metabolic syndrome (MetS) at baseline (MetS × weight loss, P=0.04; MetS × change in IMAT, P=0.04). Favorable changes in obesity-related factors are associated with reductions in aldosterone in young adults with no risk factors besides excess weight, an important finding, given aldosterone's emergence as an important cardiometabolic risk factor.

The association between chemerin and homeostasis assessment of insulin resistance at baseline and after weight reduction via lifestyle modifications in young obese adults

BackgroundChemerin is a recently discovered adipocytokine, associated with adiposity and insulin sensitivity. The current study investigated the effects of lifestyle intervention on circulating chemerin level and its association with insulin resistance and adiponectin in human. MethodsForty male and 20 female obese adults (mean age: 29.7±5.7y, mean BMI: 29.3±4.5kg/m2) completed an 8-week lifestyle intervention program, which consisted of a home-based diet and exercise program. Anthropometric measurements and biomarkers were assessed at the baseline and at the end of the study. ResultsEight weeks of lifestyle intervention reduced body weight, visceral fat and subcutaneous fat by 3.8%, 15.3% and 11.5%, respectively. The lifestyle intervention further reduced fasting insulin (10.9±6.6 vs. 7.6±5.3μU/ml, p<0.001) and homeostasis assessment of insulin resistance (HOMA-IR) (2.3±1.5 vs. 1.6±1.2, p<0.001), chemerin (103.3±20.7 vs. 96.5±19.5ng/ml, p<0.001) and hs-CRP levels (1.3±1.8 vs. 0.2±0.2mg/dl, p<0.001) while it increased fasting pentraxin (PTX) 3 (0.6±0.7 vs. 0.7±0.4ng/ml, p=0.049) level. The Δ chemerin levels correlated with Δ insulin (r=0.349, p=0.024) and HOMA-IR (r=0.333, p=0.36) even after adjusting for age and gender. ConclusionThe lifestyle intervention reduced circulating chemerin levels independent of visceral fat mass and adiponectin. Chemerin levels are associated with insulin resistance at the baseline and after the lifestyle intervention.

Characterization, pharmacokinetics, and hypoglycemic effect of berberine loaded solid lipid nanoparticles

The high aqueous solubility, poor permeability, and absorption of berberine (BBR) result in its low plasma level after oral administration, which greatly limits its clinical application. BBR solid lipid nanoparticles (SLNs) were prepared to achieve improved bioavailability and prolonged effect. Developed SLNs showed homogeneous spherical shapes, small size (76.8 nm), zeta potential (7.87 mV), encapsulation efficiency (58%), and drug loading (4.2%). The power of X-ray diffraction combined with 1H nuclear magnetic resonance spectroscopy was employed to analyze chemical functional groups and the microstructure of BBR-SLNs, and indicated that the drug was wrapped in a lipid carrier. Single dose (50 mg/kg) oral pharmacokinetic studies in rats showed significant improvement (P<0.05) in the peak plasma concentration, area under the curve, and variance of mean residence time of BBR-SLNs when compared to BBR alone (P<0.05), suggesting improved bioavailability. Furthermore, oral administration of both BBR and BBR-SLNs significantly suppressed body weight gain, fasting blood glucose levels, and homeostasis assessment of insulin resistance, and ameliorated impaired glucose tolerance and insulin tolerance in db/db diabetic mice. BBR-SLNs at high dose (100 mg/kg) showed more potent effects when compared to an equivalent dose of BBR. Morphologic analysis demonstrated that BBR-SLNs potentially promoted islet function and protected the islet from regeneration. In conclusion, our study demonstrates that by entrapping BBR into SLNs the absorption of BBR and its anti-diabetic action were effectively enhanced.

Features of social adaptability and autonomic stability of adolescents with metabolic syndrome

Aim. To identify the features of social adaptability and autonomic stability of adolescents with metabolic syndrome. Methods. The parameters of social adaptation and autonomic stability of 300 obese adolescents were studied. The main group included 150 adolescents (mean age 14.0±0.12 years) who were diagnosed with metabolic syndrome. The comparison group consisted of 150 adolescents (mean age 13.9±0.14 years) with primary uncomplicated obesity. A two-factor personality questionnaire of M. Gavlinova («society - autonomic nervous system») was used. Anthropometric indices (body weight, body mass index, height, waist circumference, hip circumference, waist/hip circumference ratio) were evaluated, the blood pressure was measured. General and biochemical blood tests and urine tests were performed (determination of the level of glucose, insulin, triglycerides, cholesterol, lipoproteins of high and low density, uric acid), as well as instrumental investigations. Results. In the group of adolescents with metabolic syndrome the mean body mass index 29.21±0.37 was significantly higher (p 0.001) compared to 26.07±0.46 in the group of patients with uncomplicated obesity. The waist/hip circumference ratio was significantly higher in adolescents with metabolic syndrome: 0.89±0.41 vs. 0.80±0.12 in the control group. In 92.71% of adolescents with metabolic syndrome arterial hypertension was diagnosed. In adolescents of the first group found were and laboratory markers of the metabolic syndrome: dyslipidemia in the form of hypertriglyceridemia (2.04±0.08 mmol/l) and decrease of the concentration of high-density lipoproteins (1.1±0.04 mmol/l). The average fasting blood glucose level was 5.78±0.02 mmol/l, the index of the model of homeostasis assessment for insulin resistance was 6.64±0.21. In the group of adolescents with metabolic syndrome the average score on the scale of social adaptation was low (8.48±0.13), whereas in the group without metabolic syndrome it was 13.51±0.22, which was significantly higher than in the main group (p 0.001), and was evidence of normal social adaptation. Low level of social adaptation was observed more frequently in girls than boys in both groups. Established was a correlation between the body mass index and social adaptability (r=-0.358), and with autonomic stability (r=0.378), p 0.05. Conclusion. Social adaptability and autonomic stability of adolescents with metabolic syndrome depend on the severity of clinical and metabolic changes and on the sex, thus this must be taken into account during treatment and rehabilitation.

Pathological and Behavioral Risk Factors for Higher Serum C-Reactive Protein Concentrations in Free-Living Adults—a Brazilian Community-Based Study

Low-grade chronic systemic inflammation is often associated with chronic non-communicable diseases, and its most frequently used marker, the C-reactive protein (CRP), has become an identifier of such diseases as well as an independent predictor for cardiovascular disorders and mortality. CRP is produced in response to pro-inflammatory signaling and to individual and behavioral factors, leading to pathological states. The aim of this study was to rank the predicting factors of high CRP concentrations in free-living adults from a community-based sample. We evaluated 522 adults (40-84 years old; 381 women) for anthropometric characteristics, dietary intake, clinical and physical tests, and blood analysis. Subjects were assigned to groups, according to CRP concentrations, as normal CRP (G1; <3.0 mg/L; n = 269), high CRP (G2; 3.0-6.0 mg/L; n = 139), and very high CRP (G3; >6.0 mg/dL; n = 116). Statistical comparison between groups used one-way ANOVA or Kruskal-Wallis tests, and prediction of altered values in increasing CRP was evaluated by proportional hazard models (odds ratio). CRP distribution was influenced by gender, body mass index, body and abdominal fatness, blood leukocytes, and neutrophil counts. The higher CRP group was discriminated by the above variables in addition to lower VO(2max), serum metabolic syndrome components (triglycerides, glucose, and HDL cholesterol), higher insulin, homeostasis assessment of insulin resistance, uric acid, gamma-GT, and homocysteine. After adjustments, only fatness, blood leukocytes, and hyperglycemia remained as independent predictors for increased serum CRP concentrations. Intervention procedures to treat low-grade chronic inflammation in overweight women would mainly focus on restoring muscle mass and functions in addition to an antioxidant-rich diet.

Abstract MP009: Changes in Aldosterone are Associated With Changes in Obesity-Related Factors in Normotensive Overweight/Obese Young Adults Undergoing Lifestyle Modification

Background: Elevated aldosterone promotes inflammation, insulin resistance, and hypertension. These effects are particularly important in obesity because adipocytes secrete factors that increase aldosterone production. Weight loss is thought to lower aldosterone levels, but little longitudinal data is available. We aimed to determine if, independent of changes in sodium intake, reductions in circulating aldosterone are associated with weight loss and improvements in inflammation, adipokines, insulin resistance, and blood pressure in normotensive overweight and obese young adults undergoing lifestyle modification. Methods: Participants were overweight/obese adults aged 20–45 years (20% male, 15% black) from the Slow Adverse Vascular Effects of excess weight trial, a study evaluating the relationships between weight loss, dietary sodium, and vascular health. Subjects were randomly assigned to a regular or reduced sodium diet, and all received a one-year nutrition and physical activity intervention. For this study, individuals providing valid baseline 24hr urine collections were included (n=281). Linear mixed models were used to evaluate associations between changes in aldosterone and changes in weight, blood pressure, and obesity-related factors. Results: Weight loss was significant at 6 months (∼7%), 12 months (∼6%), and 24 months (∼4%) (p&lt;0.0001 for all). Within-subject decreases in aldosterone were associated with decreases in C-reactive protein, leptin, and homeostasis assessment of insulin resistance (HOMA-IR) and with increases in adiponectin (p&lt;0.01 for all) in models including baseline age, sex, race, intervention arm, time since baseline, and baseline and concurrent changes in BMI, urinary sodium and potassium, and the obesity-related factor of interest. Decreases in aldosterone were associated with weight loss only in the subgroup (n=98) with metabolic syndrome (MetS) at baseline (MetS x percent weight loss p=0.02); a 10% weight reduction in this subgroup was associated with a 9% (95% CI 1–16) reduction in aldosterone. Though no association was detected between changes in aldosterone and mean arterial pressure (MAP), a significant association was found between reductions in MAP and 24hr urinary sodium in those with MetS (MetS x urinary sodium reduction p=0.02). Independent of weight loss, a 30% reduction in urinary sodium was associated with a 0.9 mm Hg (95% CI 0.2–1.6) decrease in MAP in those with MetS. Conclusions: Changes in aldosterone are associated with changes in obesity-related factors in overweight/obese normotensive young adults. In persons with MetS, weight loss and dietary sodium restriction are particularly useful to reduce aldosterone and MAP respectively. Given the adverse effects of excess aldosterone on cardiac and vascular remodeling, future studies should investigate the benefits of aldosterone antagonists in individuals with MetS.