Effect of nano-curcumin supplementation on angina status, and traditional and novel cardiovascular risk factors in overweight or obese patients with coronary slow flow phenomenon: a randomized double-blind placebo-controlled clinical trial.

BACKGROUND: Cardiovascular events and poor quality of life are frequently observed in patients with coronary slow flow phenomenon (CSFP). This trial evaluated the effect of nano-curcumin supplement containing curcuminoids, as multifunctional nutraceuticals, on angina status, and some traditional and novel cardiovascular risk factors in overweight or obese patients with CSFP. METHODS: In this double-blind, randomized, placebo-controlled clinical trial, 42 overweight or obese patients with CSFP received either 80 mg/day of nano-curcumin or placebo for 12 weeks. Seattle angina questionnaire (SAQ) as a clinical measure of angina status, circulating endocan, adropin, homocysteine, lipid profile, and the novel scores of visceral adiposity index (VAI) and waist-triglyceride index (WTI) were assessed before and after the intervention. The independent samples t-test, Mann-Whitney test, analysis of covariance, Chi-square, and Fisher's exact tests were used where appropriate. RESULTS: All domains of SAQ including physical limitation, angina stability, angina frequency-severity, treatment satisfaction, and disease perception and quality of life improved significantly in the nano-curcumin compared with the placebo group. No significant changes were observed in serum endocan, adropin, and homocysteine following the intervention. Triglycerides, triglyceride/high-density lipoprotein cholesterol ratio, WTI and VAI values improved significantly only within the nano-curcumin group. CONCLUSIONS: Supplementation with 80 mg/day nano-curcumin (containing curcuminoids) for 12 weeks significantly improved clinically important disease-specific aspects of health in patients with CSFP. Some traditional and novel cardiovascular risk factors improved significantly only compared with the baseline values, which need further investigation. TRIAL REGISTRATION: This study was approved by the Ethics Committee of Tehran University of Medical Sciences (IR.TUMS.VCR.REC.1398.794). The study protocol was registered at Iranian Registry of Clinical Trials by IRCT20131125015536N8 registration ID at 19.06.2019.

Effects of hydrolyzed collagen alone or in combination with fish oil on the gut microbiome in patients with major burns.

Burns are associated with gut dysbiosis. Collagen peptides and omega-3 fatty acids (FAs) are suggested to improve wound healing and the inflammatory response. These are also correlated with microbiome colonization. Therefore, the present study aimed to investigate the effect of hydrolyzed collagen alone or in combination with fish oil on specific species of the gut microbiome in patients with major burns. In this randomized double-blind clinical trial, 57 adults (aged 18-60 years) with 20-45% total body surface area burns were randomised into three groups to receive either 40 gr hydrolyzed collagen +10 ml sunflower oil, 40 g hydrolyzed collagen +10 ml fish oil or placebo, divided into two daily drinks, for two weeks. Gut bacteria were measured using the real-time quantitative polymerase chain reaction (qPCR) method. The mean concentration of Bifidobacterium was significantly reduced in the control (P = 0.002) and collagen (P = 0.005) groups compared with the baseline values, whereas no significant change was observed in the collagen omega-3 group. The Firmicutes to Bacteroidetes ratio decreased significantly in the collagen group (p = 0.002) after supplementation compared to baseline . No significant changes in concentration of Lactobacillus, Enterobacteriaceae, and F.prausnitzii were observed between or within the study groups. Two weeks of supplementation with collagen and omega-3 FAs in patients with major burns did not result in a significant difference in the concentration of bacteria measured between the study groups. However, the addition of omega-3 FAs prevented a significant reduction in gut Bifidobacterium. Future studies are suggested to investigate the potential efficacy of these nutrients in improving the gut microbiota and clinical outcomes in major burns. REGISTRATION NUMBER: IRCT20131125015536N9.

Implications of the Serum Concentrations of Neuregulin-4 (Nrg4) in Patients with Coronary Artery Disease: A Case-Control Study.

Background: Neuregulin-4 (Nrg4), a novel brown fat-enriched factor, has been reported to play a crucial role in developing metabolic disorders. The current case-control study aimed to investigate the association between serum Nrg4 and coronary artery disease (CAD). Methods: This study enrolled 43 patients with CAD and 43 subjects with normal coronary arteries diagnosed by coronary angiography. Anthropometric and biochemical parameters were measured and recorded. The serum Nrg4 level was determined using the enzyme-linked immunosorbent assay. The relationships between circulating Nrg4 and CAD and other clinical parameters were analyzed. A receiver operating characteristic analysis was applied to assess the utility of Nrg4 in identifying CAD. Results: The study population comprised 86 patients, including 64 men (74.4%), at a mean age of 57.83±6.01 years. Patients with CAD had significantly lower serum Nrg4 than the control group (P<0.001). The serum Nrg4 level was negatively correlated with anthropometric variables, including the body mass index, waist circumference, and the waist-to-hip ratio, fasting blood glucose, and the triglyceride-glucose index (P<0.05). In multivariable-adjusted regression analysis, the odds of CAD decreased by 46% per 1 SD elevation in the serum Nrg4 level (OR, 0.54; 95% CI, 0.40 to 0.73; P<0.001) after controlling for potential confounders. Nrg4 showed a significantly high area under the curve value (AUC, 0.85; 95% CI, 0.75 to 0.94) with 81.4% sensitivity and 95.3% specificity to identify CAD. Conclusion: Generally, the serum level of Nrg4 declines in patients with CAD, which might be an independent risk factor for CAD.

The relationship of circulating neuregulin 4 and irisin, and traditional and novel cardiometabolic risk factors with the risk and severity of coronary artery disease.

BACKGROUND AND AIMS: Neuregulin 4 (NRG4) and irisin are adipokines that have been suggested to be associated with cardiometabolic risk factors and coronary artery disease (CAD), but the data are inconclusive. This study aimed to investigate the relationship between circulating NRG4 and irisin and cardiometabolic risk factors with CAD risk and severity. METHODS AND RESULTS: In this cross-sectional study, the presence of CAD and the severity of stenosis (gensini score) were documented based on coronary angiography in 166 adults. Circulating NRG4 and irisin, glucose homeostasis markers, hs-CRP, lipid profiles, blood pressure, and anthropometric measurements were assessed as well. Age (p = 0.005), sex (p = 0.008), SBP (p = 0.033), DBP (p = 0.04), MAP (p = 0.018), FBG (p = 0.012), insulin (p = 0.039) and HOMA-IR (p = 0.01) were significantly associated with odds of having CAD. The final logistic regression model showed that age, sex, HOMA-IR, and MAP were the most important determinants of having CAD. There were no significant associations between circulating irisin and NRG4 with odds of having CAD. The final general linear model showed that being men (ß = 17.303, 95% CI: 7.086-27.52, P = 0.001), age (Aß = 0.712, 95% CI: 0.21-1.214, P = 0.006), HOMA-IR (Aß = 2.168, 95% CI: 0.256 to 4.079, P = 0.027), and NRG4 level (ß = 1.836, 95% CI: 0.119-3.553, P = 0.036) were directly associated with higher gensini score. Participants with the three-vessel disease had a mean increase of about 5 units in circulating irisin compared to those with no clinical CAD (ß = 5.221, 95% CI: 0.454-9.987, p = 0.032). CONCLUSIONS: This study showed that the adipokines NRG4 and Irisin might be associated with the severity of coronary stenosis.

Effect of a collagen-enriched beverage with or without omega-3 fatty acids on wound healing, metabolic biomarkers, and adipokines in patients with major burns.

BACKGROUND & AIMS: This study investigated the effects of collagen hydrolysate and omega-3 fatty acids (FAs) on the rate and quality of wound healing, metabolic disorders, and adipose-derived peptides in patients with major burns. METHODS: In this randomized clinical trial, 66 patients with 20-45% deep partial or full-thickness burns were randomly assigned to three groups to receive either a beverage containing collagen (40 gr/d), collagen (40 gr/d) plus 3 gr/d omega-3 (ω-3) FAs, or placebo for four weeks. Wound healing rate, Vancouver scar scale (VSS), as well as baseline, weeks two and three serum concentrations of adiponectin, fibroblast growth factor 21 (FGF21), neuregulin 4 (NRG4), transforming growth factor (TGF)-ß1, and pre-albumin/hs-CRP ratio were assessed. RESULTS: The wound healing rate during the weeks post-burn (p = 0.006 and p = 0.01), and days of 95% (21.3 ± 6.8 and 22.9 ± 8.7 vs. 34.3 ± 14.8 days, p = 0.003 and p = 0.03) and complete (26 ± 7.7 and 27.4 ± 9.4 vs. 41.1 ± 16.6 days, p = 0.003 and p = 0.01) wound healing were significantly better with Collagen and Collagen. ω-3 compared to the placebo group. The VSS was significantly lower, indicated better scar status, in the both intervention groups compared to the placebo (p = 0.02 and p = 0.01). Wound healing outcomes were not statistically different between the Collagen and Collagen. ω-3 groups. Hs-CRP/pre-albumin ratio was significantly lower in the Collagen. ω-3 than the placebo group at week three (1.2 ± 1.9 vs. 4.8 ± 7.7 dl/l, p = 0.03). The significant decrease in serum adiponectin seen during the trial course within the placebo (10 ± 8.8 to 5.8 ± 4.9 mg/l, p = 0.03) and Collagen (11.8 ± 14 to 8.6 ± 11.7 mg/l, p = 0.03) groups was prevented in the Collagen. ω-3 group (p = 0.4). Circulating FGF21 decreased significantly within the Collagen (p = 0.005) and Collagen. ω-3 (p = 0.02) groups at the end of week three compared to the baseline. CONCLUSIONS: Adding collagen hydrolysate as part of adjunctive therapy improved wound healing rate and quality. These findings as well as the efficacy of omega-3 FAs need to be further confirmed in larger populations. This study was registered with the Iranian Registry of Clinical Trials (IRCT20090901002394N42).

The relationship between low-carbohydrate diet score, dietary insulin index and load with obesity in healthy adults.

PURPOSE: Carbohydrate intake and insulinemic potential of diet are suggested to be correlated with the development of different chronic diseases. Considering the limited research on obesity, this study aimed to investigate the association of dietary insulin index (DII), dietary insulin load (DIL), and low-carbohydrate diet score (LCDS) with body weight and obesity in healthy adults. METHODS: In this cross-sectional study, DII, DIL, and LCDS were calculated using relevant formulas based on dietary intakes obtained by a valid 168-item food frequency questionnaire, in 393 otherwise healthy adults of either normal-weight, overweight, or obese. RESULTS: Individuals in the highest tertile of DIL and DII had respectively 73% (OR: 0.27, 95% CI 0.08-0.94, p = 0.049) and 50% (OR: 0.5, 95% CI 0.26-0.96, p = 0.038) lower odds of being overweight compared to the lowest tertile, after adjusting the effects of age, sex, and dietary energy intake. Participants in the highest tertile of DIL had 92% greater odds of being obese compared to the lowest tertile, but this association did not remain significant after adjusting the effect of energy intake. Individuals in the highest tertile of LCDS had about 2 times odds of being overweight compared with those in the lowest tertile (OR: 2.04, 95% CI 1.04-4.01, p = 0.049). There was no relationship between being obese and tertiles of LCDS. CONCLUSION: Higher dietary carbohydrate intake and insulinemic potential of diet could not be considered independent dietary risk factors for overweight or obesity. LEVEL OF EVIDENCE: Level III: evidence obtained from an observational study.

Effect of Collagen Hydrolysate and Fish Oil on High-Sensitivity C-Reactive Protein and Glucose Homeostasis in Patients with severe Burn; a Randomized Clinical Trial.

INTRODUCTION: Collagen and omega-3 fatty acids (FAs) are suggested to have anti-inflammatory, anti-oxidant, and insulin-sensitizing properties. The aim of this study was to investigate the effect of collagen hydrolysate and omega-3 FAs on inflammation and insulin resistance in patients with major burns. METHODS: In this double-blind randomized clinical trial, 66 patients with 20-45% burns were assigned to either of the three groups of collagen (40 gr/d), collagen (40 gr/d) plus fish oil (10 ml/d), or control. High-sensitivity C-reactive protein (hs-CRP), fasting blood glucose (FBG) and insulin concentrations, and homeostatic model assessment for insulin resistance (HOMA-IR) were assessed at baseline, as well as end of weeks two and three. RESULTS: Based on post-hoc analyses, hs-CRP levels were significantly lower in the collagen (p=0.026) and collagen+omega-3 (p=0.044) groups compared to the control group, at week three. However, pre- to post- (week three) changes of hs-CRP were significantly higher only in the collagen+omega-3 group compared to the control group (173.2 vs. 103.7 mg/l, p=0.024). After three weeks of the intervention, insulin (11.3 and 11.9 vs. 22.8 µIU/ml) and HOMA-IR (2.9 and 2.8 vs. 7.9) values seemed to be clinically, but not statistically, lower in both intervention groups compared to the control group. Pre- to post- (week three) values of FBG decreased significantly in the collagen (p=0.002) and collagen+omega-3 (p=0.036) groups. Insulin (p=0.008) and HOMA-IR (p=0.001) decreased significantly only in the collagen+omega-3 group at week three compared to the baseline. CONCLUSIONS: Supplementation with collagen hydrolysate and omega-3 FAs can improve hs-CRP concentration and probably insulin resistance in patients with severe burns. Omega-3 FAs had additional effects on modulating inflammation. Larger clinical trials are needed to confirm the current findings especially in terms of glucose homeostasis.

Association of overweight and obesity with the prevalence and incidence of pressure ulcers: A systematic review and meta-analysis.

BACKGROUND & AIM: Pressure ulcers challenge the health status, complicate medical conditions, and affect quality of life. The aim of this systematic review and meta-analysis was to investigate the role of obesity and body weight status, as potentially modifiable risk factors, in the incidence and prevalence of pressure ulcers. METHODS: A systematic search of observational studies was performed to assess documents published between January 1990 and December 2019 in PubMed and Scopus. Finally, 17 articles with total sample size of 2228724 in the prevalence and 218178 in the incidence study were included in the meta-analysis. RESULTS: The pooled data analysis showed no significant effect of obesity on odds of pressure ulcers' prevalence (OR 0.91, 95% CI 0.65 to 1.27, P = 0.579, I2 = 84.8%) or incidence (OR 0.97, 95% CI 0.56 to 1.66, P = 0.905, I2 = 89.8%) compared with non-obese individuals. Overweight was associated with significantly lower odds of prevalence of pressure ulcers compared to non-overweight individuals (OR 0.54, 95% CI 0.33 to 0.88, P = 0.014, I2 = 90.2%). The subgroup analyses showed significantly higher odds of prevalence (OR 2.38, 95% CI 1.72 to 3.29, P < 0.001, I2 = 63.4%) and incidence (OR 2.28, 95% CI 1.77 to 2.94, P < 0.001, I2 = 27.9%) of pressure ulcers in the underweight compared to normal weight groups. Pooled data analyses showed significantly lower odds of prevalence (OR 0.6, 95% CI 0.37 to 0.96, P = 0.034, I2 = 82%) and incidence (OR 0.72, 95% CI 0.53 to 0.98, P = 0.039, I2 = 67.1%) of pressure ulcers in the overweight than normal weight individuals. The findings showed no significant differences in the odds of prevalence or incidence of pressure ulcers in the obese and morbidly obese compared to normal weight individuals. CONCLUSION: This systematic review and meta-analysis showed no significant effect of obesity or morbid obesity on the odds of pressure ulcers. Additionally, overweight was associated with lower odds of pressure ulcers while underweight significantly increased the odds of pressure injuries.

Association between the dietary inflammatory index and obesity in otherwise healthy adults: Role of age and sex.

AIM: The dietary inflammatory index (DII® ) can estimate the overall inflammatory potential of diet. This study aimed to assess the association between DII score and other diet quality parameters with weight status among normal weight, overweight and obese otherwise healthy adults. METHODS: This retrospective observational study investigated DII, energy-adjusted DII (E-DIITM ), dietary energy density (DED) and mean adequacy ratio (MAR) scores, based on a valid 168-item food frequency questionnaire, in 100 normal weight, 100 overweight and 100 obese healthy adults (age > 18yr). RESULTS: Normal-weight participants had higher DII scores than obese participants (mean difference (MD): 0.67, 95% confidence interval (CI): 0.004 - 1.33, P = .048). Body mass index (BMI) had an effect on DII score after adjusting for age (P = .03). A statistically significant interaction was observed between BMI and age on E-DII (P = .03) and MAR (P = .004). E-DII scores were lower (more anti-inflammatory) and MAR was higher with increasing age in the obese compared with normal-weight participants. Additionally, male participants had higher DII (MD: -0.53, 95% CI: -0.97 - -0.09, P = .02), E-DII (MD: -0.76, 95% CI: -1.12 - -0.35, P < .001), DED (MD: -0.09, 95% CI: -0.15 - -0.03, P = .004) and lower MAR (MD: 0.04, 95% CI: 0.02 - 0.06, P = .001), after adjusting for BMI. Obesity (Adjusted odds ratio (AOR) = 0.48, 95% CI: 0.26 - 0.91, P = .02) and DED (AOR =5.81, 95% CI: 2.28 - 14.81, P < .001) were the most important factors associated with high DII. CONCLUSIONS: This study showed that having a normal body weight is not necessarily indicative of less inflammatory potential of diet and better diet quality. Male sex and increasing age were important determinants of diet quality across BMI subgroups.

Association of obesity with mortality and clinical outcomes in children and adolescents with transplantation: A systematic review and meta-analysis.

Obesity might be associated with mortality and clinical outcomes following transplantation; however, the direction of this relationship has not been well-recognized in youth. The aim of this systematic review and meta-analysis was to investigate the association of obesity with post-transplant mortality and clinical outcomes in children and adolescents. Following a systematic search of observational studies published by December 2018 in PubMed, Scopus, Embase, and Cochrane library, 15 articles with total sample size of 50,498 patients were included in the meta-analysis. The main outcome was mortality and secondary outcomes included acute graft versus host disease (GVHD), acute rejection, and overall graft loss. The pooled data analyses showed significantly higher odds of long term mortality (OR 1.30, 95% CI 1.15-1.48, P < 0.001, I2 = 50.3%), short term mortality (OR 1.79, 95% CI 1.19-2.70, P = 0.005, I2 = 59.6%), and acute GVHD (OR 2.13, 95% CI 1.5-3.02, P < 0.001, I2 = 1.7%) in children with obesity. There were no significant differences between patients with and without obesity in terms of acute rejection (OR 1.07, 95% CI 0.98-1.16, P = 0.132, I2 = 7.5%) or overall graft loss (OR 1.04, 95% CI 0.84-1.28, P = 0.740, I2 = 51.6%). This systematic review and meta-analysis has stated higher post-transplant risk of short and long term mortality and higher risk of acute GVHD in children with obesity compared to those without obesity. Future clinical trials are required to investigate the effect of pre-transplant weight management on post-transplant outcomes to provide insights into the clinical application of these findings. This may in turn lead to establish guidelines for the management of childhood obesity in transplantations.

Effect of l-arginine on cardiac reverse remodeling and quality of life in patients with heart failure.

BACKGROUND & AIMS: Heart failure (HF), as a major cardiac disease, is associated with considerable mortality, morbidities and poor quality of life. The aim of this study was to investigate the effect of l-arginine supplementation on cardiac outcomes and quality of life in patients with ischemic HF. METHODS: This double-blind randomized controlled clinical trial was conducted in 50 patients with ischemic HF. Patients were randomly assigned to receive either 3 gr/d l-arginine or placebo, for 10 weeks. Cardiac function (based on echocardiography and six-minute walk test), blood pressure, and quality of life (based on the Minnesota living with heart failure questionnaire) were assessed. RESULTS: The results showed significant improvements in ejection fraction (-6.5 ± 8.7 vs. -0.7 ± 7.8%, P = 0.037), left ventricular function (P = 0.043), diastolic dysfunction (P = 0.01) and marginally improvement in changes of left ventricular dimension during diastole (LVDd) (4 ± 6 vs. 0.3 ± 6.9 mm, P = 0.065) in the l-arginine compared to the placebo group. At the end of the study, physical aspect (5.7 ± 3.3 vs. 1.2 ± 6.1, P = 0.002) and total score (10 ± 6.7 vs. 4.1 ± 9.4, P = 0.011) of quality of life improved significantly in the l-arginine compared with the placebo group. Additionally, pre-to post-values of diastolic blood pressure, mean arterial pressure, LVDd, LV ejection fraction, left ventricular function, diastolic dysfunction as well as physical and total scores of quality of life improved significantly within the intervention, but not the placebo, group (all P < 0.05). CONCLUSION: This study showed that 3 gr/d l-arginine supplementation for 10 weeks could improve cardiac recovery and function, and quality of life in patients with HF. This study was registered at the Iranian Clinical Trial Registration Center (www.irct.ir) with IRCT20170202032367N4 code.

Dietary Inflammatory Index Is a Better Determinant of Quality of Life Compared to Obesity Status in Patients With Hemodialysis.

OBJECTIVES: This study aimed to investigate the relationships among obesity, anthropometries, and the dietary inflammatory index (DII) with different aspects of quality of life (QoL) in patients undergoing hemodialysis. DESIGN AND METHODS: In 83 patients representing a range of body weights, QoL (based on short form 36), DII (extracted from dietary recalls), malnutrition-inflammation score, and anthropometric measurements were assessed. RESULTS: Obese patients had lower physical health score (mean difference [MD] 9.1, 95% confidence interval [CI] 0.3-17.8, P = .04), physical functioning (MD 10.5, 95% CI 0.7-20.2, P = .04), and bodily pain scores (MD 16.0, 95% CI 3.6-28.4, P = .01) than normal weight group. Patients with abdominal obesity and those with the highest body fat percentage had also lower QoL in many aspects, irrespective of body mass index. The physical (MD 13.2, 95% CI 2.05-24.3, P = .02) and mental (MD 18.4, 95% CI 7.51-29.2, P = .001) health scores, and physical functioning (MD 13.5, 95% CI 1.8-25.2, P = .02), role-physical (MD 25.8, 95% CI 3.0-48.6, P = .03), role-emotional (MD 22.1, 95% CI 5.4-52.8, P = .02), vitality (MD 18.4, 95% CI 7.6-29.3, P = .001), mental health (MD 11.7, 95% CI 3.06-20.4, P = .009), and social functioning (MD 14.2, 95% CI 1.13-27.2, P = .03) were considerably lower in patients with the highest versus the lowest DII. QoL did not differ between normal-weight and obese patients with low DII (P = .26), and between normal-weight and obese patients with high DII (P = .13). Obese patients with low DII also had better QoL than normal-weight subjects with high DII scores. CONCLUSIONS: A diet with higher proinflammatory potential was associated with decreased QoL, irrespective of obesity status. Adherence to a low-DII diet might protect against some obesity-associated complications, a finding that needs further investigations.

The relationship between serum adipokines and glucose homeostasis in normal-weight and obese patients on hemodialysis: a preliminary study.

PURPOSE: Insulin resistance (IR) is a prevalent disorder in advanced renal failure irrespective of diabetes. Adipokines might play a role in IR, which has not been well-documented in uremic conditions. This study investigated the relationship of Zinc-α2-glycoprotein (ZAG), adipose triglyceride lipase (ATGL), and adipolin with glucose-insulin homeostasis in normal weight (NW) and obese (OB) patients with hemodialysis. METHODS: In this cross-sectional study, 59 patients (29 NW; 18.5 ≤ BMI < 25 kg/m2, and 30 OB; BMI ≥ 30 kg/m2) were studied. Anthropometries, circulating ZAG, adipolin, ATGL, free fatty acids (FFAs), fasting blood glucose (FBG), insulin, and homeostasis model assessment of IR (HOMA)-IR were assessed. RESULTS: There were no significant differences in age, gender, hemodialysis duration, dialysis adequacy and diabetes between the two groups. ZAG (100.9 ± 37.1 vs. 107.5 ± 30.5 ng/mL, P = 0.03) and adipolin (12.4 ± 1.6 vs. 13.2 ± 2.8 ng/mL, P = 0.002) concentrations were significantly lower, and FFAs (228.1 ± 112.6 vs. 185 ± 119 ng/mL, P = 0.014) were significantly higher in the OB than NW group. No significant differences were observed in ATGL, FBG, insulin and HOMA-IR between the two groups. Patients with lower IR had higher ZAG (112.9 ± 31.7 vs. 94.9 ± 34.5 ng/mL; P = 0.046), lower FFAs (167.8 ± 98.4 vs. 249.9 ± 120.8 ng/mL; P = 0.004), and marginally lower ATGL (9.1 ± 5.2 vs. 12.3 ± 9.6 mIU/mL; P = 0.079) concentrations than those with higher IR. ZAG was negatively (r = - 0.323, P = 0.018 and r = - 0.266, P = 0.054) and FFAs were positively (r = 0.321, P = 0.019 and r = 0.353, P = 0.009) correlated with insulin and HOMA-IR, respectively. ATGL was directly correlated with FFAs (r = 0.314, P = 0.018). CONCLUSIONS: Novel adipokines, ZAG and ATGL, might contribute to glucose-insulin homeostasis in hemodialysis. Understanding potential causative, diagnostic or therapeutic roles of adipokines in IR require further studies.

White adipose tissue browning in critical illness: A review of the evidence, mechanisms and future perspectives.

Observational studies suggest better clinical outcomes following critical illness in patients with overweight and obesity (obesity paradox). An understanding of the morphologic, physiologic and metabolic changes in adipose tissue in critical illness may provide an explanation. Recent studies have demonstrated the transformation of white to brown-like adipocytes due to the "browning process," which has been of interest as a potential novel therapy in obesity during the last decade. The characteristics of the browning of white adipose tissue (WAT) include the appearance of smaller, multilocular adipocytes, increased UCP1 mRNA expression, mitochondrial density and respiratory capacity. These changes have been identified in some critical illnesses, which specifically refers to burns, sepsis and cancer cachexia in this study. The pathophysiological nature of WAT browning, underlying mechanisms, main regulators and potential benefits and harms of this process are interesting new areas that warrants further investigations. In this review, we discuss emerging scientific discipline of adipose tissue physiology in metabolic stress, available data, gaps of knowledge and future perspectives. Future investigations in this field may provide insights into the underlying mechanisms and clinical aspects of browning that may further our understanding of the proposed obesity paradox following critical illness, which may in turn open up opportunities for novel therapies to save lives and improve recovery.

Effect of fish oil on circulating asymmetric dimethylarginine and adiponectin in overweight or obese patients with atrial fibrillation.

Obesity and adipose-derived peptides might be involved in the pathogenesis of atrial fibrillation (AF). Adiponectin plays a major role in the modulation of several metabolic pathways, and asymmetric dimethylarginine (ADMA) has been suggested to be predictive of AF and associated adverse events. The aim of this study was to investigate the effect of fish oil supplementation on circulating adiponectin and ADMA in overweight or obese patients with persistent AF. In this randomized, double-blind, placebo-controlled trial, 80 overweight or obese (body mass index (BMI) ≥ 25 kg/m2) patients with persistent AF were randomly assigned to two groups to receive either 2 g/day fish oil or placebo, for 8 weeks. Serum levels of adiponectin and ADMA, and anthropometric indexes were measured. This study showed that serum adiponectin concentrations increased significantly following fish oil supplementation compared with the placebo group (13.15 ± 7.33 vs. 11.88 ± 6.94 µg/ml; p = .026). A significant reduction was also observed in serum ADMA levels in the fish oil compared with the placebo group following the intervention (0.6 ± 0.13 vs. 0.72 ± 0.15 µmol/L; p = .001). The changes in serum adiponectin and ADMA concentrations remained significant after adjustments for baseline values, age, sex, and changes of BMI and waist circumference (p = .011 and p = .001, respectively). In conclusion,  8 weeks supplementation with fish oil increased serum adiponectin and decreased ADMA concentrations in overweight or obese patients with persistent AF. As adiponectin and ADMA are suggested to be involved in many pathways associated with AF, the current findings might be promising in the clinical management of this disease, an issue that needs further investigations.

The effect of a hydrolyzed collagen-based supplement on wound healing in patients with burn: A randomized double-blind pilot clinical trial.

INTRODUCTION: Burn is among the most severe forms of critical illness, associated with extensive and prolonged physical, metabolic and mental disorders. The aim of this study was to assess the effect of an oral, low-cost, and accessible collagen-based supplement on wound healing in patients with burn. METHODS: In this randomized double-blind controlled pilot clinical trial, 31 men, 18-60years, with 20-30% total body surface area burn were studied. Patients were randomly assigned to receive either a collagen-based supplement (1000kcal) or an isocaloric placebo, for 4 weeks. Serum pre-albumin, rate of wound healing, length of hospital stay, and anthropometries were assessed at baseline, and the end of week 2 and 4. RESULTS: Serum pre-albumin was significantly higher at week 2 (29.7±13.6 vs. 17.8±7.5mg/dL, P=0.006) and week 4 (35.1±7.6 vs. 28.3±8.2mg/dL, P=0.023) in collagen than control group. Changes in pre-albumin concentration were also significantly higher in collagen group at week 2 (13.9±9.8 vs. -1.9±10.3mg/dL, P<0.001) and week 4 (19.2±7.5 vs. 8.5±10.1mg/dL, P=0.002). The Hazard ratio of wound healing was 3.7 times in collagen compared to control group (95% CI: 1.434-9.519, P=0.007). Hospital stay was clinically, but not statistically, lower in collagen than control group (9.4±4.6 vs. 13.5±7 days, P=0.063). There were no significant differences in weight, body mass index, dietary energy and protein intakes between the two groups. CONCLUSION: The findings showed that a hydrolyzed collagen-based supplement could significantly improve wound healing and circulating pre-albumin, and clinically reduce hospital stay in patients with 20-30% burn.

Effects of Selenium Supplementation on Asymmetric Dimethylarginine and Cardiometabolic Risk Factors in Patients with Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is characterized by various reproductive and cardiometabolic disorders. Asymmetric dimethylarginine (ADMA) is associated with cardiovascular, metabolic, and hormonal status. Selenium, a micronutrient with antioxidant properties, could affect multiple physiological pathways. This study aimed to investigate the effect of selenium supplementation on ADMA, cardiometabolic risk factors, and hormonal status in women with PCOS. In this randomized, double-blind, placebo-controlled clinical trial, 66 women with PCOS, aged 18-45 years, were randomly assigned to receive either 200 µg/day selenium or placebo, for 12 weeks. Circulating concentrations of ADMA, testosterone, sex hormone-binding globulin (SHBG), lipid profiles, and glycemic parameters were assessed at baseline and following supplementation. ADMA concentration decreased significantly compared to baseline values (85.14 ± 75 to 56.4 ± 38.64 ng/l, p = 0.02) in the selenium group. This change was marginally significant compared with the placebo group (28.74 ± 68.63 vs. - 1.77 ± 52.88 ng/l, p = 0.056). Serum testosterone levels declined significantly in the intervention compared to the placebo group (0.01 ± 0.17 vs. - 0.08 ± 0.18 ng/ml, p = 0.038). Pre- to post-Apo-B100/Apo-A1 ratio declined considerably in the intervention group (0.72 ± 0.16 to 0.65 ± 0.16, p = 0.003). No further differences were observed in SHBG, lipid profiles, Apo-A1, Apo-B100, Apo-B100/Apo-A1 ratio, and glycemic control between the two groups at the end of the study. Selenium supplementation for 12 weeks had beneficial effects on reduction of circulating ADMA and total testosterone levels in women with PCOS. No significant improvements were seen in other cardiometabolic risk factors. The effects of selenium supplementation on hormonal, reproductive, and cardiometabolic disorders, considering the potential mediating role of ADMA, should be further investigated.

Role of type 2 diabetes and hemodialysis in serum adipolin concentrations: A preliminary study.

INTRODUCTION: Adipocytokines play a major role in obesity-associated disorders like insulin resistance (IR). IR is prevalent in diabetes and advanced kidney failure. Adipolin is an adipocytokine with major beneficial effects on insulin sensitivity. This study aimed to investigate adipolin concentration and its relationship with IR and other cardiovascular risk factors in patients with diabetes and/or hemodialysis. METHODS: In this preliminary study, 24 obese patients with type 2 diabetes (DM) and 30 with hemodialysis (14 with diabetes and hemodialysis (HD/DM) and 16 with hemodialysis (HD/non-DM)) were studied. Anthropometric indexes, serum concentrations of adipolin, fasting blood glucose (FBG), insulin, homeostatic model assessment of insulin resistance (HOMA-IR), and lipid profile were assessed. FINDINGS: The results showed higher serum adipolin in DM (29 ± 35 ng/mL) than in HD/DM (13 ± 2 ng/mL, P = 0.01) and HD/Non-DM (12 ± 1.6 ng/mL, P = 0.01) groups. Insulin level was lower in DM than HD/DM (P < 0.001) and HD/Non-DM (P < 0.001) groups, and HOMA-IR was also significantly lower in DM compared to HD/DM group (P < 0.001); while, FBG was significantly higher in DM (P < 0.001) and HD/DM (P = 0.006) compared to HD/Non-DM patients. Adipolin was inversely associated with insulin level (r = -0.446, P = 0.001) and HOMA-IR (r = -0.296, P = 0.035). LDL level was higher in DM compared to HD/DM (P = 0.008) and HD/Non-DM (P = 0.005) groups. Adipolin was directly correlated with cholesterol (r = 0.348, P = 0.01) and LDL (r = 0.428, P = 0.001) concentrations. DISCUSSION: Higher adipolin level in DM group might indicate a compensatory elevation in adipolin production or secretion to modulate IR. It might also be due to medications and inflammation. Further studies are required to investigate the precise role of this adipokine in IR.

Effects of zinc supplementation on serum adiponectin concentration and glycemic control in patients with type 2 diabetes.

BACKGROUND: Previous studies have suggested that zinc is involved in insulin homeostasis. Adiponectin is a well-known adipokine with anti-diabetic, anti-atherogenic, and anti-inflammatory properties. The aim of this study was to investigate the effect of zinc supplementation on glycemic control, and the potential mediating role of adiponectin, in patients with type 2 diabetes. METHODS: In this randomized double-blind placebo-controlled clinical trial, 60 patients with diabetes, 30-60 years, were randomized to receive either 30 mg/d zinc (as zinc gluconate) or placebo for 12 weeks. Circulating levels of adiponectin, zinc, glucose homeostasis parameters, and lipid profiles, as well as anthropometric parameters and dietary intakes, were assessed. RESULTS: About 53.3% of the patients had zinc insufficiency at baseline. Serum zinc levels improved significantly in the intervention than control group following 12 weeks supplementation (P < 0.001). Adiponectin (1.23 ± 2.23 µg/ml, P = 0.006) and insulin (3.6 ± 4.66 µIU/ml, P = 0.001) levels increased significantly compared to baseline in the zinc group; but this change was not significant compared with the control group. Following supplementation, there were no significant differences in glycemic control and anthropometric parameters between the two groups. Serum HDL levels increased significantly in the zinc (5.37 ± 14.8 mg/dl) compared to control (-1.53 ± 6.9 mg/dl) group following supplementation (P = 0.039). CONCLUSION: Despite a significant increase in serum zinc level, no improvement was observed in glycemic control, following 12 weeks supplementation with 30 mg/d zinc (as zinc gluconate). Zinc supplementation restored adiponectin concentrations partly within the intervention group, and increased HDL levels compared to the control group. The current findings did not support improvement in glucose homeostasis following zinc supplementation in patients with type 2 diabetes under the present study design.