Journal of Metabolic Syndrome

Alzheimer Disease is a global epidemic; every 3 seconds someone in the world develops dementia. An estimated 50 million people are living with a disease that cannot be prevented, treated or cured. Without novel breakthroughs, AD is predicted to exceed 130 million by 2050. Pharmaceuticals offer minimal relief with dismal evidence of reversing neurodegeneration. Research focuses on β-amyloid plaques and tau tangles; but, in a clinical trial, medications designed to sop-up toxic proteins in the brain fail to impede neural decline. Instead, plaques and tangles appear to be late-arrivers in the insidious progression of dementia. The recent explosion of comorbid metabolic pathologies (global prevalence of T2DM estimated @ 463 million) invites researchers into a deeper discussion of bioenergetics regulating cognitive impairment and metabolic dysregulation. Age-related energy deficits, driven by peripheral insulin resistance, exacerbate Aβ/tau accumulation, increase oxidative stress and impede mitochondrial function; work by Sergi et al. and Mastroeni et al. suggest that mitochondrial dysfunction with epigenetic impairment in oxidative respiration appear to be the earliest offenders in the progression of T2DM and AD [1,2]. This case report highlights a novel, integrated intervention with a 69-year-old male dually diagnosed with T2DM and Mild Cognitive Impairment (MCI). Physiological biomarkers were measured pre/mid/post-intervention; the MoCA (Montreal Cognitive Assessment) measured cognitive function, pre/post. Statistically significant results were observed in the metabolic risk biomarkers, memory was restored to normal ranges, and the HbA1c normalized out of the diabetic range Furthermore, the metabolic and cognitive improvements were sustained @ 3 months postintervention. These promising results suggest that dietary ketogenesis restores peripheral insulin sensitivity, mitigates T2DM and improves cognition by circumventing neural starvation via the restoration of metabolic flexibility

Background: Alcohol abuse is common in people with sedentary lifestyles, unbalanced diets, and metabolic syndrome (MS). Both, alcohol abuse and MS have negative effects on the CNS inducing cognitive impairment and impaired brain oxidative status. Considering that a few studies have focused on the combined effects of both conditions in the brain, the aim of this work is to elucidate the effects of alcohol intake in a mouse model of MS, at the behavioral and biochemical levels. Methodology: Control (B6.V-Lep ob/+ JRj) and MS (B6.V-Lep ob/obJRj) male mice aging 4 weeks were used in the study, divided into four groups: control (C), ethanol (E), obese (Ob), obese-ethanol (Ob-E). 10% ethanol consumption model was used for 6 weeks. c, insulinemia and a glucose overload test were evaluated at the end of the study. An object recognition test was used to assess short- and long-term memory. The antioxidant enzyme glutathione peroxidase (GPX) activity and the lipid peroxidation product, malondialdehyde (MDA) were analyzed in mice cortex samples. 

Results: No significant differences were found among groups in long- and short-term memory. No significant differences between C and E groups were found in the basal glycemia and the glucose overload test. However, the Ob group presented a significant increase in both parameters when compared to the C and E groups. These values were significantly decreased in the Ob-E group when compared to the Ob group. Insulinemia was increased in both, Ob and Ob-E when compared to C and E groups. The activity of GPX was burst in the E, Ob, and Ob-E groups when compared to C animals. No significant differences were observed in MDA concentration.

Conclusion: Four weeks of ethanol administration do not induce significant behavioral or biochemical brain impairments in Ob mice, although it was able to modulate glucose metabolism.

20-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome p450-derived eicosanoid that stimulates endothelial dysfunction and inflammation via binding to its receptor, GPR75 (GPCR-Gαq/11). Increased 20-HETE in animals and humans is associated with hypertension, stroke, myocardial infarction (MI), metabolic syndrome (MetS), and increased reactive oxygen species (ROS). However, investigated effectiveness of 20-HETE antagonists on ROS generation and MI size has been limited by short-term follow-up and administration of inhibitors prior to the onset of MI only in healthy animals. Here, we evaluated the effect of a 20-HETE antagonist, 20-SOLA, administered at the onset of reperfusion on post-MI remodeling 48 hours and 8 weeks after reperfusion in normal (SD) and MetS (JCR: LA-cp) rats. 20-HETE was elevated in response to ischemia and more so during reperfusion; this elevation was greater in MetS (ischemia: 2-fold SD and JCR; reperfusion: 3-fold SD, 4-fold JCR). MI size was markedly greater in JCR vs. SD rate (50% vs. 25% of LV). Treatment with 20-SOLA significantly decreased MI size in both SD (~50%) and JCR (~65%) rats. Equivalent results were obtained in animals treated with GPR75-shRNA-Lnv at the onset of reperfusions. 20-SOLA improved coronary blood flow (1.00 ± 0.01 to 1.84 ± 0.03 mg/ml/g in SD to 0.99 ± 0.03 to 1.75±0.01 mg/ml/g in JCR).   Mechanistically, a smaller MI size in 20-SOLA-treated animals correlated with decreased ROS production in JCR rats (90%). Furthermore, survival and left ventricular (LV) function were preserved 8 weeks post-MI in 20-SOLA-treated animals (ejection fraction (EF) = 80.5% (SD, 100% survival) and 82.5% (JCR, 100% survival))This correlated with decreased ROS, preserved myocyte morphology, and preserved intact collagen. Differential activation of MMPs in SD vs. JCR rats vs. 20-SOLA-treated animals underlie the observed morphological, structural and functional changes. ROS production was decreased in JCR rats treated with a NOX inhibitor (~60%); NOX inhibition also markedly reduced MI size at 48h (60%) and preserved LV function at 8 weeks (EF = 74%, 85% survival) vs. non-treated rats demonstrating an important role for NOX-derived ROS in determining MI size and long-term post-MI remodeling. In the aggregate, these results indicated that targeting 20-HETE actions may be an important consideration in the prevention of detrimental LV remodeling and mortality post-MI. Funding: HL093052.

Background: Obesity is a serious medical condition affecting more than 30 % of Indiana, and 25 % of Unites States pregnant women. Obesity is related to maternal complications and significantly impacts the health of pregnant women. Objective: The objective of this study was to describe the relationship between maternal complications and pre-pregnancy maternal weight. Methods: Using logistic regression models, we analyzed 2008 to 2010 birth certificate data, for 255,773 live births abstracted from the Indiana Vital Statistics registry. We examined the risk of reproductive factors, obstetrical complications, and perinatal (intrapartum) complications for underweight, healthy weight, overweight and obese women for this population. Results: Women who received prenatal care were more likely to be obese [Adjusted Odds Ratio (AOR)=1.82 (1.56??? 2.13)], women with parity of zero (0) were less likely to be obese [AOR=0.89, 95% CI (0.86??? 0.91)]. Women giving birth to twins [AOR=1.25, 95% CI (1.17-1.33)], women delivering by Caesarean section [AOR=2.31, 95% CI (2.26??? 2.37)] and women who previously had a Caesarean section [AOR=1.95, 95% CI (1.88??? 2.02)] were more likely to be obese. Obesity was significantly associated with obstetrical conditions of the metabolic syndrome, including pre-pregnancy diabetes, gestational diabetes Prepregnancy hypertension, pregnancy-induced hypertension and eclampsia [AOR=5.12, 95% CI (4.47??? 5.85); AOR=3.87, 95% CI (3.68??? 4.08); AOR=7.66, 95% CI (6.77??? 8.65); AOR=3.23, 95% CI (3.07??? 3.39) and AOR=1.77, 95% CI (1.31??? 2.40), respectively. Maternal obesity modestly increased the risk of induction, epidural, post-delivery bleeding an.d prolonged labor [AOR=1.26, 95% CI (1.23???1.29); AOR=1.15, 95% CI (1.13???1.18); AOR=1.20, 95% CI (1.12???1.28) and AOR=1.44, 95% CI (1.30???1.61)], respectively. Conclusions: Our results suggest that maternal obesity in Indiana, like other populations in the USA, is associated with high risks of maternal complications for pregnant women. Pre-pregnancy obesity prevention efforts should focus on targeting children, adolescents and young women, if the goal to reduce the risk of maternal complications related to obesity, is to be reached

 Background: Metabolic syndrome is defined by a constellation of abnormal metabolic factors that directly increase the risk for type 2 diabetes and cardiovascular disorders. In the Gulf Cooperation Council region, the prevalence of metabolic syndrome in the population is higher than in most developed countries, with generally greater rates for women, often higher than 40%. Thus, early clinical identification of patients is important to adequately implement treatments to reduce their risk of subsequent metabolic disease. Aim: The aim of this study was to investigate the hypothesis that in sedentary subjects, postprandial hyperinsulinemia, despite normal levels of glucose, is an indicator of incipient diabetes. Further, this lesion is associated with markers of adipose and hepatic dysfunction. Methods: 42 apparently clinically healthy residents of Qatar were studied. After a 10-hour overnight fast, subjects underwent a detailed clinical assessment, including body composition by bio-impedance, anthropometry measurements (height, weight, and BMI), and blood pressure. A liquid mixed meal was administered (200 ml of 18 g proteins, 17.4 g fats, and 40 g carbohydrates: the total energetic value of 400 kcal) and blood sampling carried out prior to and 30 and 120 minutes after the meal. The study was approved by the Institutional Research Ethics Committee and all subjects provided written informed consent prior to participation. Fasting serum levels of lipids {high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, and triglycerides}; liver function markers [gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), direct bilirubin (DB), albumin (ALB)] and; plasma glucose, insulin and pro-insulin were also determined. HOMA-IR (Homeostasis model of assessment-insulin resistance) was calculated using the following formula: (fasting insulin in mIU/L*fasting glucose in mmol/L)/22.5. Serum levels of leptin and adiponectin were measured using human 2-site ELISAs. All inter-and intra-assay CVs were less than 10%. Results: There was no difference in age, blood pressure, and body composition between the two groups. However, 48% of this population showed hyperinsulinemia in the fasting state, as well as relative hyperglycemia, hyperinsulinemia, and hyperproinsulinemia 2 hours after the meal challenge.

Background: Metabolic Syndrome (MetS) is a cluster of established cardiovascular risk factors that collectively increase predisposition to major chronic diseases including heart diseases and diabetes mellitus. Citizens of developing countries such as Saudi Arabia are at risk for MetS secondary to industrialization and accessibility to fast foods. In this epidemiologic study, the kingdom-wide prevalence of MetS is determined. Methods: A total of 4578 Saudis aged 15-64 were randomly selected from 20 regions all over Saudi Arabia. Anthropometrics were collected and fasting blood samples collected ascertaining fasting blood glucose and lipid profile. Components of full MetS as defined by the International Diabetes Federation (IDF) were used for screening. Results: The overall prevalence of MetS is 28.3%. Males had a significantly higher prevalence than females (31.4 versus 25.2%; p=0.001). Prevalence of MetS showed a parallel increase with age, and inversely with educational status as well as income. The region also played a significant contributor to MetS. Conclusion: Despite accumulating evidence of an epidemic, MetS remains largely unresolved in the kingdom. Aggressive public campaigns and policies should be implemented to control future damage of MetS in the kingdom. Methods: A total of 4578 Saudis aged 15-64 were randomly selected from 20 regions all over Saudi Arabia. Anthropometrics were collected and fasting blood samples collected ascertaining fasting blood glucose and lipid profile. Components of full MetS as defined by the International Diabetes Federation (IDF) were used for screening. Results: The overall prevalence of MetS is 28.3%. Males had a significantly higher prevalence than females (31.4 versus 25.2%; p=0.001). Prevalence of MetS showed a parallel increase with age, and inversely with educational status as well as income. The region also played a significant contributor to MetS. Conclusion: Despite accumulating evidence of an epidemic, MetS remains largely unresolved in the kingdom. Aggressive public campaigns and policies should be implemented to control future damage of MetS in the kingdom.