Increased thioredoxin levels are related to insulin resistance in familial combined hyperlipidaemia.

BACKGROUND: Thioredoxins (TRX) are major cellular protein disulphide reductases that are critical for redox regulation. Oxidative stress and inflammation play promoting roles in the genesis and progression of atherosclerosis, but until now scarce data are available considering the influence of TRX activity in familial combined hyperlipidaemia (FCH). Since FCH is associated with high risk of cardiovascular disease, the objective of the present study was to assess oxidative stress status in FCH patients, and evaluate the influence of insulin resistance (IR). MATERIALS AND METHODS: A cohort of 35 control subjects and 35 non-related FCH patients were included, all of them nondiabetic, normotensive and nonsmokers. We measured lipid profile, glucose and insulin levels in plasma, and markers of oxidative stress and inflammation such as oxidized glutathione (GSSG), reduced glutathione (GSH) and TRX. RESULTS: Familial combined hyperlipidaemia subjects showed significantly higher levels of GSSG, GSSG/GSH ratio and TRX than controls. In addition, FCH individuals with IR showed the worst profile of oxidative stress status compared to controls and FCH patients without IR (P < 0·01). TRX levels correlated with higher insulin resistance. CONCLUSION: Familial combined hyperlipidaemia patients showed increased TRX levels. TRX was positively correlated with IR. These data could partially explain the increased risk of cardiovascular events in primary dyslipidemic patients.

Contribution of hyperammonemia and inflammatory factors to cognitive impairment in minimal hepatic encephalopathy.

To assess the contribution of hyperammonemia and inflammation to induction of mild cognitive impairment (or MHE). We analyzed the presence of mild cognitive impairment (CI) by using the PHES battery of psychometric tests and measured the levels of ammonia and of the inflammatory cytokines IL-6 and IL-18 in blood of patients with different types of liver or dermatological diseases resulting in different grades of hyperammonemia and/or inflammation. The study included patients with 1) liver cirrhosis, showing hyperammonemia and inflammation; 2) non-alcoholic fatty liver disease (NAFLD) showing inflammation but not hyperammonemia; 3) non-alcoholic steatohepatitis (NASH) showing inflammation and very mild hyperammonemia; 4) psoriasis, showing inflammation but not hyperammonemia; 5) keloids, showing both inflammation and hyperammonemia and 6) controls without inflammation or hyperammonemia. The data reported show that in patients with liver diseases, cognitive impairment may appear before progression to cirrhosis if hyperammonemia and inflammation are high enough. Five out of 11 patients with NASH, without liver cirrhosis, showed cognitive impairment associated with hyperammonemia and inflammation. Patients with keloids showed cognitive impairment associated with hyperammonemia and inflammation, in the absence of liver disease. Hyperammonemia or inflammation alone did not induce CI but the combination of certain levels of hyperammonemia and inflammation is enough to induce CI, even without liver disease.

Anthropometric parameters and permanent remission of comorbidities 10 years after open gastric bypass in a cohort with high prevalence of super-obesity.

BACKGROUND AND AIM: Roux-en-Y gastric bypass (RYGB) is an effective treatment for weight loss in patients with morbid obesity. However, few studies have assessed its long-term efficacy in super-obese patients. The study objective was to analyse the long-term effectiveness of RYGB and its effect on improvement of comorbidities after 10 years of follow-up, and to compare the results depending on baseline BMI (<50kg/m2 vs ≥50kg/m2). PATIENTS AND METHODS: A retrospective study was conducted in 63 patients referred for RYGB with a 10-year or longer follow-up period. Mean BMI before surgery was 55kg/m2. RESULTS: Mean BMI decreased to 38.1kg/m2 at 10 years of follow-up. The success rates according to Reinhold criteria modified by Christou and to Biron's criteria were 30.2% and 54% respectively. The corresponding rates in super-obese patients were 21.4% and 57.1%. Significant, stable improvement was seen in diabetes, dyslipidemia, hypertension, and sleep apnea. CONCLUSIONS: Sustained weight loss was achieved after gastric bypass, with a mean excess weight loss of 50.6% after 10 years despite the high prevalence of super-obesity. Comorbidity improvement was maintained.

Xanthine oxidase is involved in free radical production in type 1 diabetes: protection by allopurinol.

The aim of this work was to study the mechanism of free radical formation in type 1 diabetes and its possible prevention. We have found oxidation of blood glutathione and an increase in plasma lipoperoxide levels in both human type 1 diabetes and experimental diabetes. Peroxide production by mitochondria does not increase in diabetes. On the contrary, the activity of xanthine oxidase, a superoxide-generating enzyme, increases in liver and plasma of diabetic animals. The increase in plasma xanthine oxidase activity may be explained by the increase in the hepatic release of this enzyme, which is not due to nonspecific membrane damage: release of other hepatic enzymes, such as the amino transferases, does not increase in diabetes. Superoxide formation by aortic rings of rabbits increases significantly in diabetes. This is completely inhibited by allopurinol, an inhibitor of xanthine oxidase. Heparin, which releases xanthine oxidase from the vessel wall, also decreases superoxide formation by aortic rings of diabetic animals. Treatment with allopurinol decreases oxidative stress in type 1 diabetic patients: hemoglobin glycation, glutathione oxidation, and the increase in lipid peroxidation are prevented. These results may have clinical significance in the prevention of late-onset vascular complications of diabetes.

Outcome of esophageal function and 24-hour esophageal pH monitoring after vertical banded gastroplasty and Roux-en-Y gastric bypass.

BACKGROUND: One of the co-morbidities frequently associated with morbid obesity is gastro-esophageal reflux disease (GERD), present in >50 % of morbidly obese individuals. We compared the anti-reflux effect of vertical banded gastroplasty (VBG) and Roux-en-Y gastric bypass (RYGBP), and their effect on esophageal function. METHODS: 10 patients underwent VBG and 40 patients underwent RYGBP. Anthropometric parameters, symptomatology of GERD, esophageal manometry (EM), isotopic esophageal emptying (IEE) and 24 hr esophageal pH monitoring were recorded in all patients preoperatively, and at 3 months and 1 year postoperatively. RESULTS: Preoperatively, there was a high prevalence of GERD, symptomatic and pH-metric in both groups (57% and 80% respectively). The preoperative values of EM and IEE parameters were within the normal range in most patients. After surgery, there was an improvement at 3 months postoperatively in both groups. 1 year after surgery, the VBG group presented symptomatic GERD in 30% and pH-metric reflux in 60% of patients while the RYGBP group presented symptomatic GERD and pH-metric reflux in 12.5% and 15% of patients, respectively. There was an increase in postoperative sensation of dysphagia in both groups (70% VBG, 30% RYGBP) one year after operation. After surgery, differences in all EM parameters were minimal, and never reached statistical significance for any group (VBG and RYGBP). The IEE showed a significantly higher percentage of esophageal retention after surgery, but this retention was always within the normal range. Both groups had an improvement in anthropometric parameters, but 1 year after surgery the results were significantly better in RYGBP patients (70% excess weight loss) than in VBG patients (46% excess weight loss). CONCLUSION: >50% of morbidly obese individuals suffer from GERD. We did not find changes in esophageal function of morbidly obese patients to explain their gastroesophageal reflux preoperatively and postoperatively. EM and IEE studies are not indicated as standard preoperative tests, except in patients with significant symptoms of gastroesophageal reflux. RYGBP is significantly better than VBG as an anti-reflux procedure, and had better weight loss.

Abdominal obesity, insulin resistance, and metabolic syndrome in a southern European population.

BACKGROUND: Our objective was to investigate the relationship between abdominal obesity (AO), as measured by waist circumference (WC), insulin resistance (IR), and components of the metabolic syndrome (MS). METHODS: A cross-sectional study was carried out with 283 subjects (130 males and 153 females aged 25-65 years) from a primary care outpatient clinic in Valencia (Spain) over a period of 1 year. Body mass index (BMI), waist circumference (WC), blood pressure (BP), total cholesterol, triglycerides, HDL-C, glucose, and insulin were measured by standard methods. IR was defined as HOMA-IR equal to or greater than 3.8. RESULTS: The prevalence of IR was 39.6%. Subjects were divided into groups according to WC. A 'normal' WC was defined as below 88 cm in women and below 102 cm in men; 'AO' was defined as a WC equal to or above 88 cm in women and equal to or above 102 cm in men. The prevalence of IR was 31.7% in the group with normal WC and 54.6% in the AO group (P<0.001). The percentage of subjects with the MS (high BP, dyslipemia or abnormal glucose tolerance) significantly increased (P<0.001) in subjects with AO (48.4 vs. 18.8% in normal WC subjects). AO is an indicator of IR with an odds ratio of 2.59 (95% CI 1.55-4.29). CONCLUSIONS: AO, expressed as WC, appears to be a good indicator of risk for IR and the MS, particularly in non-obese subjects (BMI<30). The main independent parameters of risk for IR are WC and TG, whereas those for the MS are IR, WC, and age.

Validity of subjective global assessment as a screening method for hospital malnutrition. Prevalence of malnutrition in a tertiary hospital.

INTRODUCTION: Hospital malnutrition is a highly prevalent problem that affects patient morbidity and mortality resulting in longer hospital stays and increased healthcare costs. Although there is no single nutritional screening method, subjective global assessment (SGA) may be a useful, inexpensive, and easily reproducible tool. METHODS: A cross-sectional, observational, randomized study was conducted in 197 patients in a tertiary hospital. SGA, anthropometric data, and biochemical parameters were used to assess the nutritional status of study patients. RESULTS: Fifty percent of subjects were malnourished according to SGA. A higher prevalence of malnutrition was found in medical (53%) as compared to surgical departments (47%). Half the subjects (50%) had malnutrition by SGA, but only 37.8% received nutritional treatment during their hospital stay. Mean hospital stay was longer for patients malnourished (13.5 days) or at risk of malnutrition (12.1 days) as compared to well nourished subjects (6.97 days). SGA significantly correlated (P<.012) with anthropometric and biochemical malnutrition parameters. CONCLUSIONS: Prevalence of hospital malnutrition is very high in both medical and surgical departments and is inadequately treated. SGA is a useful tool for screening hospital malnutrition because of its high degree of correlation with anthropometric and biochemical parameters.

Alterations in adipocytokines and cGMP homeostasis in morbid obesity patients reverse after bariatric surgery.

OBJECTIVE: Obesity-associated nonalcoholic fatty liver disease (NAFLD), covering from simple steatosis to nonalcoholic steatohepatitis (NASH), is a common cause of chronic liver disease. Aberrant production of adipocytokines seems to play a main role in most obesity-associated disorders. Changes in adipocytokines in obesity could be mediated by alterations in cyclic GMP (cGMP) homeostasis. The aims of this work were: (1) to study the role of altered cGMP homeostasis in altered adipocytokines in morbid obesity, (2) to assess whether these alterations are different in simple steatosis or NASH, and (3) to assess whether these changes reverse in obese patients after bariatric surgery. DESIGN AND METHODS: In 47 patients with morbid obesity and 45 control subjects, the levels in blood of adipocytokines, cGMP, nitric oxide (NO) metabolites, and atrial natriuretic peptide (ANP) were studied. Whether weight loss after a bariatric surgery reverses the changes in these parameters was evaluated. RESULTS: NO metabolites and leptin increase (and adiponectin decreases) similarly in patients with steatosis or NASH, suggesting that these changes are due to morbid obesity and not to liver disease. Inflammation and cGMP homeostasis are affected both by morbid obesity and by liver disease. The increases in interleukin 6 (IL-6), interleukin 18 (IL-18), plasma cGMP, ANP, and the decrease in cGMP in lymphocytes are stronger in patients with NASH than with steatosis. All these changes reverse completely after bariatric surgery and weight loss, except IL-18. CONCLUSION: Altered cGMP homeostasis seems to contribute more than inflammation to changes in leptin and adiponectin in morbid obesity.

Effects of a controlled program of moderate physical exercise on insulin sensitivity in nonobese, nondiabetic subjects.

OBJECTIVE: To study the effect of a moderate, aerobic physical exercise program on insulin resistance and its accompanying metabolic changes in a group of healthy, middle-age, nonobese subjects, without modifying oxygen consumption and body weight. DESIGN: The inclusion of subjects was carried out among volunteers from the health personnel of our center, who complied with the inclusion criteria. PARTICIPANTS: Twelve subjects (age 30-60 years, 5 females), nonsmokers, body mass index (BMI) <27 kg/m2 and fasting plasma glucose <6.1 mmol/L. INTERVENTIONS: Insulin resistance was assessed using the Bergmann minimal model modified with insulin, and basal and maximum metabolic rate were measured with standard methods. All subjects completed a 2-month program of aerobic exercise using the American College of Sports Medicine guidelines, consisting of aerobic exercise of moderate, regular, and continual intensity (3 times per week), with a duration of 45 to 50 minutes per session. RESULTS: Following controlled exercise, no significant differences in BMI, waist-hip ratio, blood pressure, lipids, free fatty acids, and leptin plasma values were observed. Plasma glucose and insulin values decreased significantly (-0.37 mmol/L and -16.5 pmol/L, respectively). Insulin sensitivity showed an increase of 2.1 x 10(-4) mU L(-1) min(-1) (P = 0.001). Basal and maximum metabolic rate showed no significant differences after the exercise program. CONCLUSIONS: Moderate aerobic exercise increases insulin sensitivity in nonobese, nondiabetic subjects in the absence of significant changes in weight, BMI, waist-hip ratio, lipid profile, and oxygen consumption.