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Sex-Specific Regulation of Inflammation and Metabolic Syndrome in Obesity.
Ter Horst, R, van den Munckhof, ICL, Schraa, K, Aguirre-Gamboa, R, Jaeger, M, Smeekens, SP, Brand, T, Lemmers, H, Dijkstra, H, Galesloot, TE, et al
Arteriosclerosis, thrombosis, and vascular biology. 2020;(7):1787-1800
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Abstract
OBJECTIVE Metabolic dysregulation and inflammation are important consequences of obesity and impact susceptibility to cardiovascular disease. Anti-inflammatory therapy in cardiovascular disease is being developed under the assumption that inflammatory pathways are identical in women and men, but it is not known if this is indeed the case. In this study, we assessed the sex-specific relation between inflammation and metabolic dysregulation in obesity. Approach and Results: Three hundred two individuals were included, half with a BMI 27 to 30 kg/m2 and half with a BMI>30 kg/m2, 45% were women. The presence of metabolic syndrome was assessed according to the National Cholesterol Education Program-ATPIII criteria, and inflammation was studied using circulating markers of inflammation, cell counts, and ex vivo cytokine production capacity of isolated immune cells. Additionally, lipidomic and metabolomic data were gathered, and subcutaneous fat biopsies were histologically assessed. Metabolic syndrome is associated with an increased inflammatory profile that profoundly differs between women and men: women with metabolic syndrome show a lower concentration of the anti-inflammatory adiponectin, whereas men show increased levels of several pro-inflammatory markers such as IL (interleukin)-6 and leptin. Adipose tissue inflammation showed similar sex-specific associations with these markers. Peripheral blood mononuclear cells isolated from men, but not women, with metabolic syndrome display enhanced cytokine production capacity. CONCLUSIONS We identified sex-specific pathways that influence inflammation in obesity. Excessive production of proinflammatory cytokines was observed in men with metabolic syndrome. In contrast, women typically showed reduced levels of the anti-inflammatory adipokine adiponectin. These different mechanisms of inflammatory dysregulation between women and men with obesity argue for sex-specific therapeutic strategies.
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Vitamin D Deficient Older Adults Are More Prone to Have Metabolic Syndrome, but Not to a Greater Number of Metabolic Syndrome Parameters.
Pott-Junior, H, Nascimento, CMC, Costa-Guarisco, LP, Gomes, GAO, Gramani-Say, K, Orlandi, FS, Gratão, ACM, Orlandi, AADS, Pavarini, SCI, Vasilceac, FA, et al
Nutrients. 2020;(3)
Abstract
This study investigated the relationship between metabolic parameters and low serum 25-hydroxyvitamin D (25(OH)D) levels in older adults (n = 265). They were assessed for anthropometrics and metabolic measurements, including 25(OH)D, insulin, glucose, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and other inflammatory markers. Vitamin D deficiency was defined as a 25(OH)D level below 50 nmol/L. Comparisons between groups were performed using Wilcoxon-Mann-Whitney or Pearson's Chi-squared test. A multivariate adjusted Poisson regression was used to model the number of metabolic parameters as a function of a set of explanatory variables. Subjects with 25(OH)D deficiency were predominantly females and presented higher body weight, body mass index, waist circumference, triglycerides and Tumor Necrosis Factor-α (TNF-α), and higher insulin resistance. Metabolic syndrome was also more prevalent among 25(OH)D-deficient subjects. In those without metabolic syndrome, 25(OH)D deficiency was related only to obesity and higher insulin resistance. Female sex, hypertension, higher waist circumference and higher levels of hemoglobin A1C (%), HDL-C, and TG were significantly associated with an increased number of metabolic syndrome parameters after adjusting for covariates, but 25(OH)D was not. The fact that serum 25(OH)D concentration was inversely associated with metabolic syndrome and insulin resistance not only reaffirms the relevance to consider serum 25(OH)D concentration as an influencing factor for insulin resistance, but also the need to actively screen for hypovitaminosis D in all patients with this condition.
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Metabolic syndrome in patients with type 2 diabetes and atherosclerotic cardiovascular disease: a post hoc analyses of the EMPA-REG OUTCOME trial.
Ferreira, JP, Verma, S, Fitchett, D, Ofstad, AP, Lauer, S, Zwiener, I, George, J, Wanner, C, Zinman, B, Inzucchi, SE
Cardiovascular diabetology. 2020;(1):200
Abstract
BACKGROUND Patients with type 2 diabetes (T2D) and metabolic syndrome (MetS) are at greater cardiovascular risk than those with T2D without MetS. In the current report we aim to study the characteristics, cardio-renal outcomes and the effect of empagliflozin in patients with MetS enrolled in the EMPA-REG OUTCOME trial. METHODS A total of 7020 patients with T2D and atherosclerotic cardiovascular disease were treated with empagliflozin (10 mg or 25 mg) or placebo for a median of 3.1 years. The World Health Organization MetS criteria could be determined for 6985 (99.5%) patients. We assessed the association between baseline MetS and multiple cardio-renal endpoints using Cox regression models, and we studied the change in the individual component over time of the MetS using mixed effect models. RESULTS MetS at baseline was present in 5740 (82%) patients; these were more often white and had more often albuminuria and heart failure, had lower eGFR and HDL-cholesterol, and higher blood pressure, body mass index, waist circumference, and triglycerides. In the placebo group, patients with MetS had a higher risk of all outcomes including cardiovascular death: HR = 1.73 (95% CI 1.01-2.98), heart failure hospitalization: HR = 2.64 (95% CI 1.22, 5.72), and new or worsening nephropathy: HR = 3.11 (95% CI 2.17-4.46). The beneficial effect of empagliflozin was consistent on all cardio-renal outcomes regardless of presence of MetS. CONCLUSIONS A large proportion of the EMPA-REG OUTCOME population fulfills the criteria for MetS. Those with MetS had increased risk of adverse cardio-renal outcomes. Compared with placebo, empagliflozin improved cardio-renal outcomes in patients with and without MetS. Trial registration Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01131676.
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Effect of Treatment of Mild Gestational Diabetes on Long-Term Maternal Outcomes.
Casey, BM, Rice, MM, Landon, MB, Varner, MW, Reddy, UM, Wapner, RJ, Rouse, DJ, Biggio, JR, Thorp, JM, Chien, EK, et al
American journal of perinatology. 2020;(5):475-482
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Abstract
OBJECTIVE The main purpose of this article is to evaluate whether identification and treatment of women with mild gestational diabetes mellitus (GDM) during pregnancy affects subsequent maternal body mass index (BMI), anthropometry, metabolic syndrome, and risk of diabetes. STUDY DESIGN This is a follow-up study of women who participated in a randomized controlled treatment trial for mild GDM. Women were enrolled between 5 and 10 years after their index pregnancy. Participants underwent blood pressure, height, weight, and anthropometric measurements by trained nursing personnel using a standardized approach. A nurse-assisted questionnaire regarding screening and treatment of diabetes or hypercholesterolemia, diet, and physical activity was completed. Laboratory evaluation included fasting serum glucose, fasting insulin, oral glucose tolerance test, and a lipid panel. Subsequent diabetes, metabolic syndrome, obesity, and adiposity in those diagnosed with mild GDM and randomized to nutritional counseling and medical therapy (treated) were compared with those who underwent routine pregnancy management (untreated). Multivariable analyses were performed adjusting for race/ethnicity and years between randomization and follow-up visit. RESULTS Four-hundred fifty-seven women with mild GDM during the index pregnancy were included in this analysis (243 treated; 214 untreated) and evaluated at a median 7 years after their index pregnancy. Baseline and follow-up characteristics were similar between treatment groups. Frequency of diabetes (9.2 vs. 8.5%, p =0.80), metabolic syndrome (32.2 vs. 34.3%, p =0.63), as well as adjusted mean values of homeostasis model assessment for insulin resistance (2.5 vs. 2.3, p =0.11) and BMI (29.4 vs. 29.1 kg/m2, p =0.67) were also not different. CONCLUSION Identification and treatment of women with mild GDM during pregnancy had no discernible impact on subsequent diabetes, metabolic syndrome, or obesity 7 years after delivery.
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Coronary Artery Disease in Adults With a History of Juvenile Arthritis.
Sule, S, Fontaine, K
Arthritis care & research. 2020;(12):1790-1793
Abstract
OBJECTIVE To define the risk of coronary artery disease (CAD) in adults with a history of juvenile arthritis (JA). METHODS We used the National Health and Nutrition Examination 2007-2014 surveys. Two comparison groups were identified: a random sample of patients without arthritis, and respondents with reported having rheumatoid arthritis (RA). CAD was defined as a "yes" response to the survey question, "Have you ever been told you had congestive heart failure, coronary heart disease, angina/angina pectoris, heart attack, or stroke?" Potential confounders for CAD included age, sex, race, smoking status, and any component of metabolic syndrome. RESULTS A total of 232 respondents reported having JA. We randomly selected 1,028 without arthritis and 1,105 who reported having RA. In simple logistic regression, the JA group had a 3-fold increased odds of CAD compared to those without arthritis (odds ratio [OR] 3.2 [95% confidence interval (95% CI) 2.1-4.8], P < 0.0001). Controlling for confounders, the odds of CAD in JA continued to be increased (OR 4.2 [95% CI 4.7-10.5], P = 0.002). When comparing the JA and RA groups, in simple logistic regression, the JA group had a lower odds of CAD (OR 0.7 [95% CI 0.5-0.9], P = 0.03). Controlling for confounders, there was no significant difference in the odds of CAD between groups (OR 0.8 [95% CI 0.5-1.3], P = 0.4). CONCLUSION Adults with a history of JA have a higher risk of CAD compared to adults without arthritis. Providers should be aware of the increased risk of CAD in adults with JA and aggressively screen these patients for modifiable risk factors.
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Serum Vitamin D Concentration ≥75 nmol/L Is Related to Decreased Cardiometabolic and Inflammatory Biomarkers, Metabolic Syndrome, and Diabetes; and Increased Cardiorespiratory Fitness in US Adults.
Ganji, V, Tangpricha, V, Zhang, X
Nutrients. 2020;(3)
Abstract
A serum vitamin D [25-hydroxyvitamin D, 25(OH)D] concentration of ≥75 nmol/L is recommended for optimal health. We investigated the relationship between serum 25(OH)D and metabolic syndrome (MetS), diabetes, cardiometabolic biomarkers, and cardiorespiratory fitness (CRF) in US adults using clinical cut points recommended by health organizations. Data from USA's National Health and Nutrition Examination Surveys were used. Prevalences and likelihood of having MetS and diabetes according to clinical cut points for serum 25(OH)D (<30 nmol/L, 30-<50 nmol/L, 50-<75 nmo/L, and ≥75 nmol/L) were determined with multivariate logistic regression. Relations between serum 25(OH)D and various cardiometabolic biomarkers, CRF, MetS, and diabetes were tested using multivariable adjusted regression. Prevalence of MetS and diabetes were significantly lower in individuals with serum 25(OH)D ≥75 nmol/L (MetS, 21.6%; diabetes, 4.1%) compared to those with 25(OH)D <30 nmol/L (MetS, 45.5%; diabetes, 11.6%) (p < 0.0001). Individuals with serum 25(OH)D ≥75 nmol/L had significantly lower waist circumference (p < 0.0001), C-reactive protein (p = 0.003), glycated hemoglobin (p < 0.0002), fasting triglycerides (p < 0.0001), total homocysteine (p < 0.0001), and insulin resistance (p = 0.0001) and had significantly higher HDL-cholesterol (p < 0.0001) and maximal oxygen uptake (marker for CRF) (p< 0.0009) compared to those with 25(OH)D <30 nmol/L. In conclusion, serum 25(OH)D ≥75 nmol/L is associated with positive indicators related to cardiometabolic diseases in US adults.
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Impact of a Three-Week in-Hospital Multidisciplinary Body Weight Reduction Program on Body Composition, Muscle Performance and Fatigue in a Pediatric Obese Population with or without Metabolic Syndrome.
Rigamonti, AE, Tringali, G, Micheli, R, Col, A, Tamini, S, Saezza, A, Cella, SG, Sartorio, A
Nutrients. 2020;(1)
Abstract
Metabolic syndrome is a combination of cardiometabolic risk factors, frequently detected in obese children and adolescents. To date, few clinical studies have evaluated the effectiveness of multidisciplinary body weight reduction programs on body mass index, body composition, muscle performance and fatigue in pediatric obese subjects suffering from metabolic syndrome, which might represent a sub-population that is more difficult to be treated and worthy of more intensive interventions than a population less metabolically complicated. The aim of the present study was to compare the impact of a three-week in-hospital multidisciplinary integrated body weight reduction program (BWRP) on body mass index (BMI), body composition (particularly, fat mass (FM) and fat-free mass (FFM)), motor control (evaluated by one-leg standing balance (OLSB) test), muscle performance (evaluated by the stair climbing test (SCT)) and fatigue (evaluated by fatigue severity scale (FSS)) in a pediatric obese population with or without metabolic syndrome. A pediatric population of 548 obese subjects without metabolic syndrome (F/M = 312/236; age range: 8-18 years; BMI: 36.3 ± 6.7 kg/m2) and 96 obese subjects with metabolic syndrome (F/M = 53/43; age range: 9-18 years; BMI: 38.3 ± 6.9 kg/m2) was recruited. The BWRP significantly reduced BMI, FM (expressed as %), SCT time and FSS score, and increased OLSB time in all subgroups of obese subjects, independent of sex and metabolic syndrome, with preservation of FFM. No significant differences in |ΔBMI|, |ΔFM|, |ΔOLSB| or |ΔSCT| times and |ΔFSS| score were found when comparing subjects (males and females) with or without metabolic syndrome, apart from obese females without metabolic syndrome, who exhibited a lower weight loss and FM (expressed as %) reduction when compared to the corresponding male counterpart. In conclusion, the beneficial effects of a three-week BWRP on BMI, body composition, muscle performance and fatigue in a pediatric obese population were not found to be different in patients with or without metabolic syndrome, thus indicating that the more metabolically compromised patient is as responsive to a short-term BWRP as the patient without metabolic syndrome. More prolonged follow-up studies are, however, necessary in order to verify whether the adherence to the multidisciplinary recommendations at home and the long-term maintenance of the positive effects in the two subgroups of patients will remain similar or not.
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Plasmatic lipocalin-2 levels in chronic low-grade inflammation syndromes: Comparison between metabolic syndrome, total and partial adult growth hormone deficiency.
Currò, D, Vergani, E, Bruno, C, Comi, S, D'Abate, C, Mancini, A
BioFactors (Oxford, England). 2020;(4):629-636
Abstract
Lipocalin-2 (LCN2) is a secreted glycoprotein involved in several chronic inflammatory processes. Metabolic syndrome (MetS) and adult growth hormone deficiency (GHD) are known as chronic inflammatory conditions. The primary objective of this observational cross-sectional study was to compare LCN2 plasmatic levels in these clinical settings, whereas the secondary objective was to investigate any possible correlation between LCN2 and BMI and/or indexes of insulin sensitivity/resistance. Seventy-four patients were divided as follows: Group A, MetS (18 patients, 13 females and 5 males, mean ± SEM age 45.1 ± 4.11 years, BMI 31.22 ± 1.73 kg/m2 ); Group B, total GHD (18 patients, 8 females and 10 males, age 52.44 ± 2.61 years, BMI 30.49 ± 1.87 kg/m2 ); Group C, Partial GHD (pGHD; 19 patients, 13 females and 6 males, age 48.63 ± 2.19 years, BMI 29.11 ± 1.85 kg/m2 ); Group D, Controls (19 patients, 13 females and 6males, age 40.26 ± 2.87 years, BMI 23.25 ± 0.95 kg/m2 ). They were evaluated for glucose and insulin, HOMA-index, QUICKI-index, Total/low-density lipoprotein/high-density lipoprotein cholesterol, triglycerides, uric acid, IGF-1, and LCN2. LCN2 plasmatic levels were significantly increased in MetS, while no significant differences with controls were found in total and pGHD. LCN2 levels did not correlate with BMI. A significant positive correlation between LCN2 and HOMA-index was found in controls, while a trend-like, yet not significant, a positive correlation was observed in pGHD. Our data show an increase in LCN2 plasmatic levels in MetS. Different inflammatory patterns characterize MetS and GHD. The correlation between HOMA index and LCN2 in normal subjects and possibly in pGHD ones suggests a modulatory action of LCN2 on insulin resistance.
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Early-Life Famine Exposure and Risk of Cardiovascular Diseases in Later Life: Findings From the REACTION Study.
Du, R, Zheng, R, Xu, Y, Zhu, Y, Yu, X, Li, M, Tang, X, Hu, R, Su, Q, Wang, T, et al
Journal of the American Heart Association. 2020;(7):e014175
Abstract
Background Previous studies reported that early-life exposure to undernutrition is associated with the risk of diabetes mellitus and metabolic syndrome in adulthood, but the association with risk of cardiovascular disease (CVD) later in life remains unclear. The current study aimed to investigate whether exposure to Chinese famine in early life is associated with risk of CVD. Methods and Results We used data from REACTION (Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal Study), which recruited a total of 259 657 community-dwelling adults aged 40 years or older from 25 centers across mainland China between 2011 and 2012. Compared with the nonexposed participants, those who had been exposed to famine in early life had a significantly increased risk of total CVD, myocardial infarction, stroke, and coronary heart disease. In the multivariable-adjusted logistic regression model, the odds ratios (95% CI) for total CVD, myocardial infarction, stroke, and coronary heart disease in fetal famine exposure were 1.35 (1.20-1.52), 1.59 (1.08-2.35), 1.40 (1.11-1.78), and 1.44 (1.26-1.65), respectively; those odds ratios in childhood famine exposure were 1.59 (1.40-1.81), 2.20 (1.52-3.20), 1.82 (1.45-2.28), and 1.80 (1.56-2.09), respectively; and those in adolescent famine exposure were 1.52 (1.27-1.81), 2.07 (1.28-3.35), 1.92 (1.42-2.58), and 1.83 (1.50-2.24), respectively. The main finding of our study is that, compared with those who lived in the less severely affected famine area, individuals in the severely affected famine area had significantly increased risk of total CVD in all 3 exposed groups. Conclusions Early-life exposure to undernutrition is associated with significantly increased risk of CVD in later life, especially among those who were in the severely affected famine area.
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Energy-restricted Central-European diet stimulates liver microsomal function in obese postmenopausal women - a randomized nutritional trial with a comparison to energy-restricted Mediterranean diet.
Szczepanik, M, Malesza, IJ, Bajerska, J, Chmurzyńska, A, Muzsik, A, Bermagambetova, S, Mądry, E, Walkowiak, J, Lisowska, A
European review for medical and pharmacological sciences. 2020;(21):11165-11171
Abstract
OBJECTIVE Obesity and metabolic syndrome are risk factors for liver diseases like non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. A healthy food pattern is vital for managing these health problems, therefore, this study investigated how two calorie-restricted diets, the Central European diet (CED) and Mediterranean diet (MED), altered microsomal liver function in obese postmenopausal women with a risk of metabolic syndrome. PATIENTS AND METHODS One-hundred-forty-four subjects were randomly assigned to the CED (n=72) or the MED (n=72) groups. A 13C-methacetin breath test was performed, before and after the intervention to assess CPDR (Cumulative Percentage Dose Recovery at 120 minutes of the test), TTP (Time to Peak - maximal momentary recovery of 13C) and Vmax (the maximum momentary 13C recovery). RESULTS There was a statistically significant increase in TTP and Vmax in the CED group only (p=0.0159 and p=0.0498, respectively). Changes in CPDR and TTP due to intervention were significantly higher in the CED group than in the MED group (p=0.0440 and p=0.0115, respectively). CONCLUSIONS This is the first study to document a stimulatory effect of the energy-restricted CED on liver microsomal function as compared to MED. The relatively short dietary intervention led to a significant difference in the CYP1A2 activity between groups. The trial was registered in the German Clinical Trials Register (DRKS-ID: DRKS00012958; URL: https://www.germanctr.de/).