Metabolic Syndrome and Related Disorders

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ISSN / EISSN : 1540-4196 / 1557-8518
Published by: Mary Ann Liebert Inc (10.1089)
Total articles ≅ 1,273
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Reyan Ghany, , Gordon Chen, Elissa Dawkins, Emancia Forbes, Thiago Tajiri, Ana Palacio
Metabolic Syndrome and Related Disorders; https://doi.org/10.1089/met.2021.0006

Abstract:
Background: Prediabetes is a novel risk factor recently associated with changes in the left ventricle. Our aim is to determine if prediabetes is associated with heart failure (HF) and structural heart disease. Methods: We conducted a cross-sectional study and performed screening echocardiograms to consecutive primary care patients. We calculated the hemoglobin A1c (HbA1c) within 3 months of the echocardiogram and classified patients as having normal glucose, low-risk or high-risk prediabetes or diabetes. Our primary outcome was HF defined as an ejection fraction (EF) <50% and HF with preserved EF. Our secondary outcome was structural heart disease defined as having either a large atrium, left ventricular hypertrophy, or low EF. Results: We included 15,056 patients who underwent a screening echocardiogram and had a recorded HbA1c. Only 2794 patients had a normal blood glucose, 4201 had low-risk prediabetes, 2499 had high-risk prediabetes, and the remainder had diabetes. The adjusted odds ratio (ORs) of HF for low-risk prediabetes, high-risk prediabetes and diabetes were 1.38 [confidence interval (95% CI) 1.07–1.78] (P = 0.01), 1.47 (95% CI 1.05–2.01) (P = 0.01), and 1.60 (95% CI 1.16–2.01) (P < 0.01), respectively, when compared with normoglycemic patients. The adjusted OR of HF with preserved EF for low- and high-risk prediabetes and diabetes were 1.17 (95% CI 0.86–1.60) (P = 0.30), 1.60 (95% CI 1.15–2.21) (P < 0.01), and 1.63 (95% CI 1.24–2.13) (P < 0.01), respectively, when compared with normoglycemic patients. Conclusions: Prediabetes is a prevalent condition associated with structural heart disease and HF.
Yanxin Xiao, Yan Liu, Liwei Zhao, Yaru Zhou
Metabolic Syndrome and Related Disorders; https://doi.org/10.1089/met.2022.0014

Abstract:
Background: The prevalence of nonalcoholic fatty liver disease (NAFLD) is rapidly growing in China, especially in patients with type 2 diabetes mellitus (T2DM). Weight loss strategies have been shown to treat NAFLD effectively. We conducted a 24-week, prospective, randomized study in T2DM patients with NAFLD to evaluate the effects of a 5:2 fasting diet on liver fat content. Methods: Sixty-one T2DM patients with NAFLD were enrolled and randomly divided into a 5:2 fasting diet intervention group (5:2 diet group, n = 31) and 1.8 mg/day liraglutide intervention group (Lira group, n = 30). The study was performed for 24 weeks. Data of the body weight, waist circumference, plasma lipids and glucose profile, fasting plasma insulin, and liver function parameters were collected. Controlled attenuation parameter (CAP) was measured to assess the liver fat content. Superoxide dismutase (SOD) and malondialdehyde (MDA) were measured to evaluate oxidative stress status. Results: At 24 weeks after intervention, compared with those at baseline, CAP was significantly decreased in both the 5:2 diet group and Lira group, which was 7.4% and 5.5%, respectively. Body weight, plasma lipids and glucose profile, and liver function parameters improved significantly, while homeostasis model assessment-β (HOMA-β) was significantly increased in both groups (all P < 0.05). Stepwise linear regression showed that increased HOMA-β and SOD, as well as reduced body mass index (BMI), were the independent predictors of CAP decrease in the Lira group (P = 0.000, 0.000, 0.015). In contrast, reduced BMI and MDA were the independent influencing factors of CAP decrease in the 5:2 diet group (P = 0.011, 0.043). The common side effects in the 5:2 diet group were hunger (60%), weakness (10%), and constipation (0.3%). Conclusions: A 5:2 fasting diet achieved comparable effects with liraglutide on liver fat content in patients with T2DM with NAFLD by reducing BMI and oxidative stress. Both treatment strategies were safe and effective for glucose control.
, Ali Aminian, Sangeeta R. Kashyap
Metabolic Syndrome and Related Disorders; https://doi.org/10.1089/met.2022.0039

Abstract:
The assessment and management of patient-reported outcomes (PROs) is considered secondary to that of cardiometabolic outcomes. When assessed, health-related quality of life (HRQOL), a PRO, can yield pertinent information that cannot be obtained from cardiometabolic assessments. For instance, physical and mental distress can be quantified and treated. Moreover, treatment convenience and satisfaction can be gaged. Behavioral modification, bariatric surgery, and pharmacotherapy can improve PROs. Typically, HRQOL is responsive to changes in weight. Specifically, weight loss and weight gain are associated with positive and negative changes in quality of life, respectively. In addition, patient satisfaction can be influenced by glycemic control. Therefore, hypoglycemia and hyperglycemic episodes can negatively affect patient satisfaction. When managing type 2 diabetes (T2D), it is important to consider how therapies impact PROs. Generally, changes in clinical outcomes mirror changes in PROs. To best manage T2D, integrating the assessment of PROs with clinical outcomes is needed.
Anyang Li, Cong Lin, Fengfeng Xie, Mengya Jin, Feng Lin
Metabolic Syndrome and Related Disorders; https://doi.org/10.1089/met.2022.0017

Abstract:
Introduction: Berberine is derived from rhizoma coptidis, a well-known Traditional Chinese herbal Medicine that has been found to be effective in the treatment of type 2 diabetes mellitus in recent years. The aim of the present study was to investigate the effects of berberine on a gestational diabetes mellitus (GDM) rat model and the related mechanisms. Methods: GDM was induced in Sprague–Dawley rats using a high-fat diet before and during pregnancy. Berberine (100 mg/kg/day) was administered from the 7th to 20th day of pregnancy. Insulin resistance (IR), glucose tolerance, and maternal, fetal, and placental weight were determined. Liver histopathological analysis, as well as analysis of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), inhibitor kappa B kinaseβ (IKKβ), nuclear factor kappa-B (NF-κB), c-Jun N-terminal kinase (JNK), insulin receptor substrate-1 (IRS-1), and protein kinase B (AKT), was performed at the end of pregnancy. Results: Treatment of GDM rats with berberine markedly decreased IR, the number of dead and absorptive fetuses, maternal body weight gain, and fetal and placental weight compared with GDM without berberine. Furthermore, berberine decreased CRP and TNF-α levels, IKKβ expression, NF-κB P65 nuclear translocation, and changed the phosphorylation of JNK, IRS-1, and AKT in the liver of GDM rats. Conclusions: Berberine improved IR and maternal–fetal outcomes of GDM rats, possibly through modulation of IKK/NF-κB, JNK, and IRS-1/AKT signaling pathways in the liver. Therefore, berberine may be a potential GDM treatment.
Fernando A. Isart, Fernando Jose Isart-Infante, Eric Robert Heidel, Stephanie Sisley
Metabolic Syndrome and Related Disorders; https://doi.org/10.1089/met.2022.0005

Abstract:
Background: Clinical consensus differs as to when blood vitamin D (VD) levels should be measured in children. Obesity and metabolic syndrome are risk factors for low VD levels and are also associated with acanthosis nigricans (AN). Objectives: To test whether the clinical diagnosis of AN is a strong predictor for vitamin D deficiency (VDD) in children. Methods: Within the study period (2015–2020), we identified 677 consecutive individuals (age <18 years) with available calcidiol measurements and compared those with (n = 273) and without (n = 404) AN. Bivariate associations and the occurrence of AN were tested using the chi-squared test. Multivariate logistic regression was performed to control for confounding variables, and adjusted odds ratios with 95% confidence intervals (CI) were reported. Multiple regression analysis was performed, and unstandardized beta coefficients, standard errors, and standardized beta coefficients were reported. Results: Individuals with AN had 3.6 times higher odds of VDD than those without (95% CI: 1.38–9.51, P = 0.009). Males had 0.41 times lower odds of having AN than females (95% CI: 0.21–0.79, P = 0.008). Individuals with vitamin D sufficiency (VDS) were much less likely to be diagnosed with metabolic syndrome compared with those who were vitamin D deficient (P = 0.011), even after adjusting for body mass index z-scores. Conclusion: Children and adolescents with AN are at a higher risk of VDD and should likely be tested for low calcidiol levels.
Vesna Salamun, Manfredi Rizzo, Luca Lovrecic, Keli Hocevar, Tanja Papler Burnik, Andrej Janez, Mojca Jensterle, Eda Vrtacnik Bokal, Borut Peterlin,
Metabolic Syndrome and Related Disorders; https://doi.org/10.1089/met.2021.0149

Abstract:
Introduction and Aim: Obese women with polycystic ovarian syndrome (PCOS) have a reduced rate of spontaneous conception even when their cycles are ovulatory. Endometrial receptivity is an important factor for poor implantation and increased miscarriage rates. Mechanisms in which both pathologies modify the endometrium are not fully clarified. The aim of our study was to compare the endometrial transcriptomic profiles between infertile obese PCOS (O-PCOS) women and infertile normal weight subjects during the window of implantation in ovulatory menstrual cycles. Methods: We conducted a prospective transcriptomic analysis of the endometrium using RNA sequencing. In this way, potential endometrial mechanisms leading to the poor reproductive outcome in O-PCOS patients could be characterized. Endometrial samples during days 21–23 of the menstrual cycle were collected from infertile O-PCOS women (n = 11) and normal weight controls (n = 10). Subgroups were defined according to the ovulatory/anovulatory status in the natural cycles, and O-PCOS women were grouped into the O-PCOS ovulatory (O-PCOS-ovul) subgroup. RNA isolation, sequencing with library reparation, and subsequent RNAseq data analysis were performed. Results: Infertile O-PCOS patients had 610 differentially expressed genes (DEGs), after adjustment for multiple comparisons with normal weight infertile controls, related to obesity (MXRA5 and ECM1), PCOS (ADAMTS19 and SLC18A2), and metabolism (VNN1 and PC). In the ovulatory subgroup, no DEGs were found, but significant differences in canonical pathways and the upstream regulator were revealed. According to functional and upstream analyses of ovulatory subgroup comparisons, the most important biological processes were related to inflammation (TNFR1 signaling), insulin signaling (insulin receptor signaling and PI3/AKT), fatty acid metabolism (stearate biosynthesis I and palmitate biosynthesis I), and lipotoxicity (unfolded protein response pathway). Conclusions: We demonstrated that endometrial transcription in ovulatory O-PCOS patients is deranged in comparison with the control ovulatory endometrium. The most important pathways of differentiation include metabolism and inflammation. These processes could also represent potential mechanisms for poor embryo implantation, which prevent the development of a successful pregnancy. ClinicalTrials.gov ID: NCT03353948.
Ee Vien Low, Miryoung Lee, , Susan P. Fisher-Hoch, Joseph B. McCormick, Susan Abughosh, Ekere J. Essien, Jessica Rodriguez,
Metabolic Syndrome and Related Disorders; https://doi.org/10.1089/met.2021.0151

Abstract:
Background: This retrospective cohort study aimed to examine the interaction effect between puberty stage and weight status on individual and clustering of cardiometabolic risk factors (CMRFs) among Mexican American children and adolescents. A total of 333 children and adolescents (aged 8–18 years) enrolled in the Cameron County Hispanic Cohort (CCHC) from 2014 to 2020 were included in the study. Methods: CCHC is a longitudinal, randomly recruited cohort based on the United States Census tracts/blocks of Mexican Americans living on the Texas-Mexico border. Individual CMRFs, including high blood pressure, central obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol, and insulin resistance (IR) were assessed. Clustering of CMRFs is defined as the presence of three or more individual CMRFs. Puberty stages were assessed using the Tanner criteria. Multivariable logistic regressions were conducted to assess the association of puberty, weight status, and the interaction of the two main exposures with individual and clustering of CMRFs. Results: We observed that weight status had a dominant effect on all CMRF measures. The effect was especially prominent on central obesity and clustering of CMRFs. There were 95.4% of children with central obesity and 98.4% of those with clustering of CMRF were either overweight or obese. Entering puberty was associated with an increased risk of having IR [Tanner stage 2 vs. 1: odds ratio (OR) = 3.25, 95% confidence interval (95% CI) 1.28–8.27; Tanner stage 3 vs. 1: OR = 3.50, 95% CI 1.45–8.46] and hypertriglyceridemia (Tanner stage 2 vs. 1: OR = 2.67, 95% CI 1.11–6.45). However, the effects were not observed among those reaching the end of puberty (Tanner stage 4 and 5). Conclusions: A significant interaction effect between weight status and puberty was not detected on any individual CMRF and in the clustering of CMRFs. Other factors positively associated with individual CMRFs, especially IR, were being female and having a family history of diabetes.
A. Lum Han,
Metabolic Syndrome and Related Disorders; https://doi.org/10.1089/met.2022.0013

Abstract:
Background: No study has examined whether serum uric acid/creatinine (sUA/Cr) is associated with the newly defined metabolic-associated fatty liver disease (MAFLDs). Furthermore, studies on other factors influencing their relationship have not been conducted. Aim: To investigate the relationship between sUA/Cr and newly defined MAFLD, and to identify any factors that affect this relationship. Methods: We retrospectively reviewed the data of patients who underwent abdominal computed tomography (CT) at the Hospital Health Promotion Center. Participants were divided into the healthy (no evidence of liver disease; n = 707), MAFLD+non-heavy drinking (steatosis diagnosed by CT and drinking 140 and 70 grams/week for men and women, respectively; n = 61) groups. The relationship between sUA/Cr and MAFLD among the three groups were compared using multivariate logistic regression. Results: After adjusting for age, it was observed that when the sUA/Cr ratio increased by 1, the risk of MAFLD increased by 1.205 times the risk in the normal group. After adjusting for age, an increase by 1 in the sUA/Cr ratio increased the probability of non-heavy drinking+MAFLD and heavy drinking+MAFLD by 1.302 and 1.556 times, respectively, compared with healthy individuals. For those who smoked, the probability of heavy drinking+MAFLD was 9.901 times higher compared with healthy individuals. Conclusion: The newly defined MAFLD is related to sUA/Cr. The amount of alcohol consumption and smoking influenced the association between sUA/Cr and MAFLD.
Zehra Calis, Dervis Dasdelen, Abdulkerim Kasim Baltaci,
Metabolic Syndrome and Related Disorders; https://doi.org/10.1089/met.2022.0028

Abstract:
Background: Hyperuricemia (HU) is a metabolic disease characterized by high uric acid levels in the blood. HU is a risk factor for diabetes, cardiovascular complications, metabolic syndrome, and chronic kidney disease. Purpose: The present study was performed to determine the effect of experimental HU on xanthine oxidase (XO), tumor necrosis factor-alpha (TNF-α), nuclear factor-kappa B (NF-κB), interleukin-17 (IL-17), cytochrome C, glutathione peroxidase (GPx), caspase-3, and 8-hydroxydeoxyguanosine (8-OHdG) levels in liver tissues of rats. Study Design: Thirty-five, male, Wistar albino-type rats were used for this study. Experimental groups were formed as follows: Group 1: control group; Group 2: potassium oxonate (PO) group; group 3: PO+NAR (naringenin; 2 weeks) group; and Group 4: PO (2 weeks)+NAR (2 weeks) group (total of 4 weeks). Methods: The first group was not given anything other than normal rat food and drinking water. In the second group, a 250 mg/kg intraperitoneal dose of PO was administered for 2 weeks. In the third group, 250 mg/kg intraperitoneal PO (application for 2 weeks) and 100 mg/kg NAR intraperitoneally 1 hr after each application were administered. In the fourth group, intraperitoneal PO administration was applied for 2 weeks, followed by intraperitoneal administration of NAR for 2 weeks (4 weeks in total). At the end of the experimental period, XO, TNF-α, NF-κB, IL-17, cytochrome C, GPx, caspase-3, and 8-OHdG levels were determined in liver tissues. Results: HU increased XO, TNF-α, NF-κB, IL-17, cytochrome C, caspase-3, and 8-OHdG levels in liver tissues. However, both 2 and 4 weeks of NAR supplementation decreased these values, and also NAR supplementation led to an increase in GPx levels in tissues. Conclusions: The results of the study show that increased inflammation, apoptosis, and DNA damage in experimental HU can be prevented by administration of NAR due to inhibition of cytochrome C, NF-κB, caspase-3, and 8-OHdG.
, Nasser J. Issa, Shereef B. Elhalwagi, Hilda T. Draeger, Joyce G. Schwartz, Jonathan A. Gelfond
Metabolic Syndrome and Related Disorders; https://doi.org/10.1089/met.2022.0015

Abstract:
Background: Patients with metabolic syndrome components were frequently noted to have increased nasal and parotid activity on clinically referred scintigraphic whole-body blood pool scans. This increase in activity was not observed in patients without metabolic syndrome. Increased nasal blood pool activity in patients with elevated body mass indices (BMIs) has implications for (1) sleep apnea, (2) risk of nasal infection, and (3) possible impaired nasal lymphatic drainage of brain waste proteins. Methods: To follow-up this clinical observation, a retrospective study was performed on 200 patients having whole-body blood pool scans referred over a 3-year period. The whole-body blood pool scans were evaluated for an association between nose and parotid region of interest (ROI) to heart ROI maximum (max) pixel ratios as correlated with clinical conditions, including obesity, diabetes, hypertension, and sleep apnea. Continuous variables of BMI, hemoglobin A1c (HbA1c), blood glucose, and blood lipids were also correlated with these ratios. Results: A direct association of nose to heart max ratio (NHMR) with diabetes, sleep apnea, and hypertension was found with an increase in the ratio of +0.10 (P = 0.002), +0.13 (P = 0.0002), +0.08 (P = 0.0123), respectively. Correlation of NHMR with continuous variables had moderate correlation with BMI (r = 0.36, P < 0.0001), glucose (r = 0.27, P = 0.0001), HbA1c (r = 0.25, P = 0.0008) and less association with the number of diabetes medications (r = 0.22, P = 0.0021). Similar associations were found for parotid to heart max ratios but were weaker than the NHMR. Conclusions: Patients with metabolic syndrome components have significantly increased nasal and parotid activity on blood pool scans. These associations have implications for the treatment of sleep apnea, for nasal infections involving such agents as Covid-19, and for the risk of dementias related to decreased clearance of brain waste proteins through nasal turbinate lymphatics in patients with metabolic syndrome. If further studies support these findings, the nasal turbinates and the increased parasympathetic activity controlling their dilation could become a new therapeutic target.
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