Complications Of Metabolic Syndrome Research Articles

Energy expenditure and nutritional complications of metabolic syndrome and rheumatoid cachexia in rheumatoid arthritis: an observational study using calorimetry and actimetry

Altered energy expenditure may contribute to the nutritional complications of RA, metabolic syndrome (MS) and rheumatoid cachexia (RC). The main aim of this study was to evaluate whether the altered resting energy expenditure (REE) and physical activity (PA)-related energy expenditure (EE) are related to the duration of RA and inflammatory activity and nutritional complications in RA. Among patients with well-characterized RA (duration, activity: DAS28 ESR), we measured REE by indirect calorimetry, and PA-EE by actimetry (SenseWear Armband). MS was defined according to the International Diabetes Federation criteria and RC from DXA body composition analysis. The relations between the characteristics and nutritional complications, and EE were analysed by linear regression. Fifty-seven patients were included [73% women, age 57 (10) years] with a wide range of disease duration: 3.8 (3.0) years, and DAS28 ESR: 3.9 (1.4). The mean REE was 1486 (256) kcal/day, associated with the DAS28 ESR (β = +0.21, P = 0.02 after adjusting for gender and fat free mass). The prevalence of MS and RC was, respectively, 24 and 18%, and they were unrelated to each other. The patients with MS and/or RC had double the longstanding RA score (P < 0.05), twice the homeostasis model assessment of insulin resistance values (P = 0.052) and halved levels of PA (P < 0.05 for metabolic equivalent tasks (METs) and number of steps/day). Two modifiable factors were associated with the presence of MS and/or RC: a low level of PA as METs [exp(B) = 0.03, P = 0.009] and the use of glucocorticoids [exp(B) = 4.08, P = 0.046]. Low levels of PA and treatment by glucocorticoids are associated with the nutritional complications of RA, suggesting the potential for therapeutic interventions.

Abstract A01: The efficacy of a diabetic registry to improve survival rates in under-resourced environments

Abstract Purpose: African Americans are disproportionately affected by diabetes and the associated complications of metabolic syndrome compared to Caucasians. Diabetes is the seventh leading cause of death in the United States thus contributing to over 300,000 deaths in the U.S. annually. Thirteen percent of those diagnosed are African Americans. Factors associated with optimally managing diabetes include periodic measures of Fasting Blood Glucose (FBG), Hemoglobin A1c (HgbA1c) and Body Mass Index (BMI). We hypothesize that a Diabetes/ Metabolic Disease Registry is an effective way to assess the management of diabetes and will assist in controlling and ultimately reducing morbidity and mortality rates, particularly in underserved communities. Methods: A diabetes metabolic disease registry was created based on best-practice clinical parameters. Demographic factors, co-morbidities and overall health maintenance were assessed. The instrument was evaluated using 52 de-identified patients' information from local Atlanta hospitals. The registry consisted of a comprehensive questionnaire with content pertinent to the diagnosis and management of diabetes such as BMI, HgbA1c and FBG. After inputting data, Statistical Analysis Software (SAS) was used for analysis. Lastly we evaluated the data input devices (smartphone versus computer) for ease and efficiency. Results: In this study, the mean age of the patients was 59 years of age. Eighty-eight percent were female. Over 60% of the patients were classified as obese or morbidly obese. Greater than 70% had persistently elevated levels of HgbA1C and over 65% had mildly or significantly elevated levels of FBG. Cholesterol and LDL levels were normal for about 80% of patients which indicates that those factors are not pertinent to managing diabetes. Conclusion: A Metabolic Disease Registry is an effective way to analyze diabetes management in underserved communities. Data was accurately entered at the exact same rate for both devices suggesting that both means of data entry (computers and smartphones) are equally as efficient. The elevated levels of HgbA1c and FGB in the majority of patients indicate that the serum glucose was not being controlled effectively, in spite of the fact that the majority of patients were under long-term care of a physician and had well defined care plans. We hope that this study will assist in controlling diabetes and lower the rates among those in underserved areas. Citation Format: Tania Anderson, Alexis Maynor, Derrick beech, Ernest Alema-Mensah. The efficacy of a diabetic registry to improve survival rates in under-resourced environments. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr A01.

Easing of America’s Healthcare Burden: The Case for Aggressive Prevention of the Metabolic Syndrome

The term “metabolic syndrome” was used in 1977 by Herman Haller who was studying the risk factors associated with atherosclerosis. In the same year, Dr. Singer used the term to describe the associations between hyperlipoprotenemia and obesity, gout, diabetes mellitus, and hypertension. In1988, Gerald Reaven hypothesized that insulin resistance could be the underlying factor linking this constellation of abnormalities, which he went on to name “syndrome X or Reaven’s syndrome”. Regardless of the clinical term that is utilized, the global impact on health care resources and humanity is massive. 47 million adult patients meeting the criteria for metabolic syndrome which represent over 24% of the adults in the United National inpatient hospital costs for metabolic syndrome with complications were nearly $400 billion in With appropriate primary care for the complications of metabolic syndrome, nearly $17 billion in hospital costs might have been averted, with significant potential savings obtained in US government health care programs. Non-pharmacological approaches to fight the risk factors associated with metabolic syndrome have been known for The scientific evidence supports the efficacy of nutritional Metabolic syndrome is a preventable life threatening disease process. With its roots in childhood, this vicious cycle slowly destroys lives while we spend billions in the process. Delegating responsibility of financing our health and wellness to the insurance industry, Americans are ill prepared to deal with the reality that health is neither a luxury nor an entitlement. The impact of accepting the responsibility of prevention through nutritional counseling and education combined with regular exercise could save billions of dollars annually. More importantly aggressively preventing metabolic syndrome would save millions of lives.

SIRT3-AMP-Activated Protein Kinase Activation by Nitrite and Metformin Improves Hyperglycemia and Normalizes Pulmonary Hypertension Associated With Heart Failure With Preserved Ejection Fraction.

Pulmonary hypertension associated with heart failure with preserved ejection fraction (PH-HFpEF) is an increasingly recognized clinical complication of metabolic syndrome. No adequate animal model of PH-HFpEF is available, and no effective therapies have been identified to date. A recent study suggested that dietary nitrate improves insulin resistance in endothelial nitric oxide synthase null mice, and multiple studies have reported that both nitrate and its active metabolite, nitrite, have therapeutic activity in preclinical models of pulmonary hypertension. To evaluate the efficacy and mechanism of nitrite in metabolic syndrome associated with PH-HFpEF, we developed a 2-hit PH-HFpEF model in rats with multiple features of metabolic syndrome attributable to double-leptin receptor defect (obese ZSF1) with the combined treatment of vascular endothelial growth factor receptor blocker SU5416. Chronic oral nitrite treatment improved hyperglycemia in obese ZSF1 rats by a process that requires skeletal muscle SIRT3-AMPK-GLUT4 signaling. The glucose-lowering effect of nitrite was abolished in SIRT3-deficient human skeletal muscle cells, and in SIRT3 knockout mice fed a high-fat diet, as well. Skeletal muscle biopsies from humans with metabolic syndrome after 12 weeks of oral sodium nitrite and nitrate treatment (IND#115926) displayed increased activation of SIRT3 and AMP-activated protein kinase. Finally, early treatments with nitrite and metformin at the time of SU5416 injection reduced pulmonary pressures and vascular remodeling in the PH-HFpEF model with robust activation of skeletal muscle SIRT3 and AMP-activated protein kinase. These studies validate a rodent model of metabolic syndrome and PH-HFpEF, suggesting a potential role of nitrite and metformin as a preventative treatment for this disease.

Metabolic syndrome in rural Kerala: a hospital based study

Background: Metabolic syndrome refers to a cluster of various interrelated cardio-metabolic risk factors that promote the development of atherosclerotic cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). Identifying at risk individuals is necessary for early medical management, thereby reducing the economic burden on the patient and the society. The objective of this study was to assess the prevalence of metabolic syndrome in patients presenting to medicine clinics of our institute. Methods: This cross-sectional hospital based study was carried out at department of medicine, DM Wayanad institute of medical sciences, Wayanad, Kerala and included 432 patients attending the general medicine outpatient department. Patients’ demographic details and anthropometric measurements including height, weight, waist and hip measurements were taken. Clinical data including blood pressure, blood sugars and fasting lipid profile was also collected. The NCEP ATP III (National cholesterol education program - adult treatment panel III) criteria for diagnosis of metabolic syndrome were used to make a diagnosis of metabolic syndrome. Results: On applying the modified NCEP ATP III guidelines with the waist circumference specific to Asian population, we found that the prevalence of metabolic syndrome in our study population was 60.9%. The prevalence was more in females than in males and the difference was statistically significant (p = 0.049). Abdominal obesity and decreased HDL was more in females as compared to males and the difference was also found to be statistically significant. 27% of the study population with metabolic syndrome was normal or underweight. Conclusions: The prevalence of metabolic syndrome in the present studied population was high as they represent patients presenting to hospital. This data is more like the tip of an iceberg. Larger population based studies and intervention in the form of aggressive lifestyle modification is the need of the hour to prevent the cardio-metabolic complications of metabolic syndrome.

Exosomes as the source of biomarkers of metabolic diseases

Exosomes are extracellular vesicles that contain molecules that regulate the metabolic functions of adjacent or remote cells. Recent in vitro, in vivo and clinical studies support the hypothesis that exosomes released from various cell types play roles in the progression of metabolic disorders including type 2 diabetes. Based on this concept and advances in other diseases, the proteins, mRNA, microRNA and lipids in exosomes isolated from biological fluids have been proposed as biomarkers in metabolic disorders. However, several problems with the development of clinically applicable biomarkers have not been resolved. In this review, the biologic functions of exosomes are briefly introduced, and we discuss the technical and practical pros and cons of different methods of exosome isolation for the identification of exosomal biomarkers of metabolic disorders. Standardization of preanalytical variables and isolation of high-purity exosomes from fully characterized biological fluids will be necessary for the identification of useful exosomal biomarkers that can provide insights into the pathogenic mechanisms of complications of metabolic syndrome and of whole-body metabolism.

Abstract 15694: Roles of Nitrite and Metformin in Severe Pulmonary Arterial Hypertension (PAH) and Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction (PH-HFpEF)

Background: PAH (Group I) is a disease of the small pulmonary arteries, characterized by vasoconstriction, vascular proliferation and remodeling. PH-HFpEF (Group II) is known to occur secondary to the LV diastolic dysfunction and is recognized as a clinical complication of metabolic syndrome, with no currently approved therapies. Since the use of conventional therapies for PAH in PH-HFpEF patients is often ineffective, targeting both pulmonary vascular disease and metabolic disorders appears to be a key strategy for the treatment of PH-HFpEF. We, as well as others, have reported that nitrite exhibits therapeutic efficacy in moderate PAH models and improves glucose metabolism. In addition, metformin, the canonical AMPK activator and the first-line anti-diabetic drug, has been found to prevent the development of moderate PAH. In this work, we examined the effects of nitrite and metformin in PH-HFpEF, and compared their effects in severe PAH. Methods and Results: Nitrite (100mg/L) and metformin (300mg/kg) were given in drinking water to rats with Su5416/hypoxia-induced severe PAH or to rats with Su5416/metabolic syndrome-induced PH-HFpEF for 6 and 14 weeks, respectively. In the PH-HFpEF rats, our data showed that both nitrite and metformin treatments reduced pulmonary pressures and pathological vascular remodeling and limited hyperglycemia, which correlated with increased SIRT3-AMPK activation in skeletal muscles and AMPK activation in pulmonary vessels. Similar protective effect of nitrite was also observed in Su5416/hypoxia rats, together with increased activation of SIRT3 and AMPK in skeletal muscles. However, metformin failed to reduce pulmonary pressures and vascular remodeling in Su5416/hypoxia rats, with unchanged activation levels of SIRT3 and AMPK, suggesting metformin may favorably affect PH only in the presence of metabolic disorders. In addition, the AMPK agonist AICAR was found incapable of limiting PAH in Su5416/hypoxia rats. Conclusions: Our findings indicate that oral nitrite treatment limits PH-HFpEF, as well as PAH, while metformin treatment more preferentially improves PH-HFpEF. Our findings also indicate that activation of SIRT3-AMPK may represent a potential therapeutic route in the treatment of both PAH and PH-HFpEF.

Bariatric surgery as a means to decrease mortality in women with type I endometrial cancer — An intriguing option in a population at risk for dying of complications of metabolic syndrome

ObjectiveTo estimate the cost-effectiveness and utility of a strategy of offering weight loss surgery (WLS) to women with low risk stage I endometrial cancer (EC) and BMI≥40kg/m2. MethodsA modified Markov state transition model was designed to compare routine care to WLS for women with low risk stage I endometrioid EC, age<70, with a mean BMI 40. A time horizon of 15years was used to simulate the overall survival (OS) of 96,232 women treated from 1988–2010 from SEER*Stat data. To simulate the effects of WLS on OS, a hazard ratio (0.76, 95% CI 0.59–0.99) representing the OS improvement achieved from this intervention (derived from a prospective trial) was modeled. We assumed that 90% of women undergoing bariatric procedures would experience a reduction in BMI. We assumed that 5% of women not undergoing WLS would achieve weight loss to a BMI of 35. Costs of treatment for obesity-related chronic diseases and quality of life (QOL)-related utilities were modeled from published reports. ResultsThe mean cost-effectiveness for each strategy was: $69,295 and 8.10 quality-adjusted life years (QALYs) for routine care versus $100,675 and 9.30 QALYs for WLS. WLS had an incremental cost-effectiveness ratio (ICER) of $26,080/QALY compared to routine care. At a willingness to pay threshold of $50,000/QALY, WLS was the strategy of choice in 100% of simulations. ConclusionsWLS is a potentially cost-effective intervention in women with low risk, early stage EC, at least in part due to improved quality of life with weight reduction.

Haplotype analysis of the Apolipoprotein A5 gene in Moroccan patients with the metabolic syndrome.

BackgroundIn this case–control study we investigated the relative contribution of commons APOA5 polymorphisms and haplotypes to the risk of metabolic syndrome in Moroccan patients.MethodsUsing the International Diabetes Federation (IDF) criteria for metabolic syndrome, the study included 176 patients and 105 controls. We genotyped APOA5 polymorphisms (−1131 T > C, c.56C > G, c.553G > T and c.1259 T > C) by PCR-RFLP analysis. The effects of APOA5 polymorphisms and constructed haplotypes on metabolic syndrome were estimated using logistic regression analyses.ResultsThe statistical analysis showed a significant association between APOA5 -1131 T > C and APOA5 c.56C > G polymorphisms with metabolic syndrome in both Codominant and Dominant models. The APOA5 -1131 T > C polymorphism was associated with increased fasting glucose (p = 0.0295) and reduced HDL levels (p = 0.0091). Carriers of the APOA5 c.56G allele had increased triglyceride levels (p = 0.0435) and waist circumference (p = 0.0122). Similarly the APOA5 1259 T > C variant was associated with increased waist circumference (p = 0.0463). The haplotypes CCGT (OR = 3.223; p = 0.00278) and CGGT (OR = 8.234; p = 0.00534) were significantly associated with susceptibility to metabolic syndrome.ConclusionsOur results confirms the association of APOA5 -1131 T > C and c.56C > G variants with the predisposition to metabolic syndrome complications.

Beneficial effects of melatonin on serum nitric oxide, homocysteine, and ADMA levels in fructose-fed rats

Context: Melatonin, a pineal hormone and a potent antioxidant, has important roles in metabolic regulation.Objective: This study investigated serum asymmetric dimethylarginine (ADMA), homocysteine (Hcy), nitric oxide (NO) levels, known to be reliable markers of cardiovascular diseases, and determined possible protective effects of melatonin in fructose-fed rats.Materials and methods: Sprague–Dawley rats were divided into four groups: control, fructose, melatonin, and fructose plus melatonin. Metabolic syndrome was induced in rats by 20% (w/v) fructose solution in tap water, and melatonin was administered at the dose of 20 mg/kg bw per day by oral gavage. After 8 weeks, serum lipids, glucose, insulin, ADMA, Hcy, and NOx (the stable end products of NO) levels were quantified.Results: Fructose administration caused a statistically significant increase in systolic blood pressure (SBP), serum insulin, triglycerides, and very low-density lipoprotein (VLDL)–cholesterol levels compared with the control group and the metabolic syndrome model was successfully demonstrated. In comparison with the control group, fructose caused a significant increase in serum ADMA, Hcy, and NOx levels. Melatonin counteracted the changes in SBP, serum ADMA, and Hcy levels found in rats both alone and administered with fructose.Discussion and conclusion: These results show that high fructose consumption leads to elevated SBP, atherogenic lipid profile, increased serum ADMA, and Hcy levels and melatonin treatment has beneficial effects on these biochemical parameters in rats. Melatonin might be beneficial for the prevention and/or treatment of the cardiovascular complications of metabolic syndrome not only by reducing the well-known risk factors of the disease but also by diminishing blood ADMA and Hcy levels.

A Review of the Benefits of Satureja Species on Metabolic Syndrome and Their Possible Mechanisms of Action

Metabolic syndrome, also known as insulin resistance disorder, is the simultaneous manifestation of multiple metabolic disorders in an individual. The present-day complementary and alternative therapies suggest several medicinal herbs that may have the potential to improve one or multiple complications of metabolic syndrome. All of them have their own limitations in efficacy and unwanted effects. Therefore, we reviewed species of Satureja as widespread medicinal herbs and potentially good remedies for metabolic syndrome. We reviewed literature found in PubMed and the ISI Web of Knowledge with the key word Satureja in the title. The influence of any species of Satureja on any disease or syndrome, enzymatic, metabolic, or physiological pathways, in human, animals, or in vitro conditions related to any characteristics of metabolic syndrome were considered. The main outcomes of treatment with Satureja species were categorized, and the possible mechanisms of action are discussed in this article.

Beneficial role of bitter melon supplementation in obesity and related complications in metabolic syndrome.

Diabetes, obesity, and metabolic syndrome are becoming epidemic both in developed and developing countries in recent years. Complementary and alternative medicines have been used since ancient era for the treatment of diabetes and cardiovascular diseases. Bitter melon is widely used as vegetables in daily food in Bangladesh and several other countries in Asia. The fruits extract of bitter melon showed strong antioxidant and hypoglycemic activities in experimental condition both in vivo and in vitro. Recent scientific evaluation of this plant extracts also showed potential therapeutic benefit in diabetes and obesity related metabolic dysfunction in experimental animals and clinical studies. These beneficial effects are mediated probably by inducing lipid and fat metabolizing gene expression and increasing the function of AMPK and PPARs, and so forth. This review will thus focus on the recent findings on beneficial effect of Momordica charantia extracts on metabolic syndrome and discuss its potential mechanism of actions.

CLINICOELECTRONEUROMYOGRAPHIC PECULIARITIES OF PERIPHERAL DISTAL POLYNEUROPATHY IN PATIENTS WITH METABOLIC SYNDROME AND HYPOTHYROIDISM

Prevalence of metabolic syndrome in the total population is 14-24%, metabolic syndrome associated with hypothyroidism occurs in 5-10 % of cases. Aim. To study the polyneural disorders in patients with metabolic syndrome using clinicoelectroneuromyographic characteristics. Materials and methods. Clinical and electroneuromyographic examination of patients with metabolic syndrome and hypothyroidism was carried out; peculiarities of the course of peripheral polyneuropathy in this group of patients were singled out. To clarify electroneuromyographic characteristics, stimulation technique for fibular, tibial, sural nerves was used; “F-wave” index was analyzed. Results. According to cumulative clinical and electroneuromyographic data, sensor polyneuropathy was diagnosed in 22 (55 %) patients with metabolic syndrome and sensomotor polyneuropathy - in 16 (40 %), normal parameters - in 2 (5 %) patients. Conclusions. The obtained data have broadened our knowledge on complications of metabolic syndrome and on inclusion of peripheral distal polyneuropathy with metabolic syndrome into the group of dismetabolic polyneuropathies.

Metabolic and oxidative stress markers in Wistar rats after 2months on a high-fat diet.

BackgroundMetabolic syndrome is associated with an increased risk of cardiovascular and hepatic complications. Oxidative stress in metabolic tissues has emerged as a universal feature of metabolic syndrome and its co-morbidities. We aimed to develop a rapidly and easily induced model of metabolic syndrome in rats to evaluate its impact on plasma and tissue oxidative stress.Materials and methodsMetabolic syndrome was induced in rats using a high-fat diet (HFD), and these rats were compared to rats fed a normal diet (ND) for 2 months. Metabolic control was determined by measuring body weight, blood glucose, triglycerides, lipid peroxidation and protein carbonylation in plasma. Insulinemia was evaluated through the measure of C-peptide. Histological analysis was performed on the pancreas, liver and blood vessels.ResultsAfter 2 months, the HFD induced an increase in body weight, insulin and triglycerides. Liver steatosis was also observed in the HFD group, which was associated with an increase in glycogen storage. In the pancreas, the HFD induced islet hyperplasia. Tissue oxidative stress was also increased in the liver, pancreas and blood vessels, but plasma oxidative stress remained unchanged.ConclusionThis paper reports the development of a fast and easy model of rat metabolic syndrome associated with tissue oxidative stress. This model may be a good tool for the biological validation of drugs or antioxidants to limit or prevent the complications of metabolic syndrome.

Обоснование персонифицированного подхода к диагностике, профилактике и лечению метаболического синдрома среди жителей Хакасии

The article gives the justification of the personified approach to diagnostics, prevention and treatment of metabolic syndrome among inhabitants of Khakassia. The article reveals additional data confirming the phenomenon of a population dimorphism of metabolic syndrome referring to a complex clinical laboratory examination of two ethnic populations living in Khakassia – Khakas who represent the indigenous people originating from Mongoloids and non-indigenous population (Caucasians). The authors demonstrate statistically and clinically significant differences in the frequency of their occurrence and intensity of separate symptoms and cardiovascular complica-tions of metabolic syndrome. It is shown that indigenous people suffering from metabolic syndrome have less intensive visceral obesity in comparison with non-indigenous population. Multiagent metabolic syndrome is estab-lished to prevail among both indigenous and non-indigenous people. The combination of only two agents is consi-derably rarer among Khakas with metabolic syndrome than among non-indigenous inhabitants with this disease. The ultrasonic examination of carotids proves that Khakas suffering from metabolic syndrome have more intensive thickening of intima-media in comparison with the non-indigenous, with less intensive visceral obesity among Khakas. Visceral obesity of Khakas associates with high risk of intima-media thickening (OR=2,95).

Обоснование персонифицированного подхода к диагностике, профилактике и лечению метаболического синдрома среди жителей Хакасии

The article gives the justification of the personified approach to diagnostics, prevention and treatment of metabolic syndrome among inhabitants of Khakassia. The article reveals additional data confirming the phenomenon of a population dimorphism of metabolic syndrome referring to a complex clinical laboratory examination of two ethnic populations living in Khakassia – Khakas who represent the indigenous people originating from Mongoloids and non-indigenous population (Caucasians). The authors demonstrate statistically and clinically significant differences in the frequency of their occurrence and intensity of separate symptoms and cardiovascular complications of metabolic syndrome. It is shown that indigenous people suffering from metabolic syndrome have less intensive visceral obesity in comparison with non-indigenous population. Multiagent metabolic syndrome is established to prevail among both indigenous and non-indigenous people. The combination of only two agents is considerably rarer among Khakas with metabolic syndrome than among non-indigenous inhabitants with this disease. The ultrasonic examination of carotids proves that Khakas suffering from metabolic syndrome have more intensive thickening of intima-media in comparison with the non-indigenous, with less intensive visceral obesity among Khakas. Visceral obesity of Khakas associates with high risk of intima-media thickening (OR=2,95).

Bariatric surgery as a means to decrease mortality in women with type I endometrial cancer: An intriguing option in a population at risk of dying from complications of metabolic syndrome

Bariatric surgery as a means to decrease mortality in women with type I endometrial cancer: An intriguing option in a population at risk of dying from complications of metabolic syndrome

Effect of combination treatment of S–amlodipine with peroxisome proliferator-activated receptor agonists on metabolic and cardiovascular parameters in Zucker fa/fa rats

BackgroundType 2 diabetes is a complex metabolic disorder characterized by hyperglycemia, impaired glucose tolerance and insulin resistance associated with dyslipidemia and hypertension. The available drugs are not sufficiently efficacious in reducing cardiovascular risk and restoring normal glucose metabolism associated with type 2 diabetes as a mono- or a combination therapy. The present study examined the combined effects of an antihypertensive (S-Amlodipine) and an insulin-sensitizing agent, peroxisome proliferator-activated receptor (PPAR) agonists (Pioglitazone and Ragaglitazar), on cardiovascular risk factors in aged diabetic and insulin-resistant Zucker fa/fa rats.MethodsFollowing combination treatment for 14 days, blood pressure (BP), serum glucose, total cholesterol and triglycerides were measured. Aortic ring study was conducted to determine the effect of combination treatments on phenylephrine-induced vasoconstriction and acetylcholine (Ach)-induced vasorelaxation.ResultsIn combination, S-Amlodipine and Pioglitazone significantly reduced blood glucose (115.1 ± 6.6 vs. 81.7 ± 4.2), BP (184.4 ± 5.0 vs. 155.1 ± 5.0), serum triglycerides (362.5 ± 47.5 vs. 211.1 ± 23.7) and glucose intolerance when compared with vehicle treated Zucker fa/fa rats. Similar results were observed with the combination of S-Amlodipine and Ragaglitazar (Triglycerides, 362.5 ± 47.5 vs. 252.34 ± 27.86; BP, 184.4 ± 5.0 vs. 159.0 ± 8.0) except for serum glucose. ACh-induced vasorelaxation in aortic rings was also superior with both of the combinations compared to individual treatment. Furthermore, there was less body weight gain and food intake with S-Amlodipine and Pioglitazone combination in Zucker fa/fa rats. S-Amlodipine itself caused significant reduction in glucose (115.1 ± 6.6 vs. 89.7 ± 2.7) and BP (184.4 ± 5.0 vs. 156.1 ± 4.0) with improvement in insulin sensitivity observed through oral glucose tolerance test.ConclusionsThe results suggest that a combination of PPAR agonists and S-Amlodipine has partial benefits in improving the cardiovascular risk factors such as reduction in triglyceride levels, associated with chronic type 2 diabetes, and therefore may be utilized as an approach for addressing some of these devastating metabolic syndrome complications.

Risk prediction of complications of metabolic syndrome before and 6 years after gastric bypass

BackgroundRoux-en-Y gastric bypass (RYGB) surgery has been shown to have favorable effects on components of metabolic syndrome. However, the long-term effect of RYGB on predicted risk of end-organ complications is less clear. The objective of this study was to examine long-term changes in predicted risk of metabolic syndrome-related complications after RYGB. MethodsThe predicted risk of metabolic syndrome-related complications in a cohort of 131 diabetic patients was compared between baseline and last follow-up points after RYGB using validated risk assessment tools. ResultsAfter a median postsurgical follow-up time of 6 years (range, 5–9), a mean percent excess weight loss of 60.7±25.1% was associated with a diabetes remission rate of 61%. At long-term follow-up, the levels of glycated hemoglobin, low-density lipoprotein, and blood pressure were within the recommended American Diabetes Association’s goals in 85%, 73%, and 63% of patients, respectively (P<.001). RYGB was associated with a relative risk reduction of 27% for 10-year overall risk of coronary heart disease (CHD), stroke, and peripheral vascular disease; 20% for 10-year risk of CHD; 40% for 10-year risk of myocardial infarction; 42% for 10-year risk of stroke; 47% for 4-year risk of intermittent claudication; 45% for 5-year risk of moderate-severe kidney disease; and 18% for 5-year risk of cardiovascular mortality. Four-year risk of diabetic retinopathy was also significantly decreased. ConclusionRYGB in diabetic patients results in remarkable control of diabetes, dyslipidemia, and hypertension, and is associated with a significant reduction in predicted risk of major complications including nephropathy, retinopathy, and cardiovascular disease and mortality in the range of 18–47% at long-term follow-up.

Risk factors associated with Barrett's epithelial dysplasia.

To elucidate risk factors associated with dysplasia of short-segment Barrett's esophagus (BE). A total of 151 BE patients who underwent endoscopic examination from 2004 to 2008 in Aoyama Hospital, Tokyo Women's Medical University, Japan and whose diagnosis was confirmed from biopsy specimens were enrolled in the study. BE was diagnosed based on endoscopic findings of gastric-appearing mucosa or apparent columnar-lined esophagus proximal to the esophagogastric junction. Dysplasia was classified into three grades - mild, moderate and severe - according to the guidelines of the Vienna Classification System for gastrointestinal epithelial neoplasia. Anthropometric and biochemical data were analyzed to identify risk factors for BE dysplasia. The prevalence of Helicobacter pylori (H. pylori) infection and the expression of p53 by immunohistological staining were also investigated. Histological examination classified patients into three types: specialized columnar epithelium (SCE) (n = 65); junctional (n = 38); and gastric fundic (n = 48). The incidence of dysplasia or adenocarcinoma from BE of the SCE type was significantly higher than that of the other two types (P < 0.01). The univariate analysis revealed that sex, H. pylori infection, body weight, p53 overexpression, and low diastolic blood pressure (BP) were associated with BE dysplasia. In contrast, body mass index, waist circumference, metabolic syndrome complications, and variables related to glucose or lipid metabolism were not associated with dysplasia. Multivariate logistic analysis showed that overexpression of p53 [odds ratio (OR) = 13.1, P = 0.004], H. pylori infection (OR = 0.19, P = 0.066), and diastolic BP (OR = 0.87, P = 0.021) were independent risk factors for epithelial dysplasia in BE patients with the SCE type. Overexpression of p53 is a risk factor for dysplasia of BE, however, H. pylori infection and diastolic BP inversely associated with BE dysplasia might be protective.