Plasma levels of soluble urokinase plasminogen activator receptor (suPAR) and high-sensitivity C-reactive protein after Roux-en-Y gastric bypass or sleeve gastrectomy: a 1-year prospective observational study.

PURPOSE: Low-grade inflammation in obesity contributes to the development of cardiovascular disease, diabetes mellitus and cancer, and is associated with increased mortality. The purpose of this 1-year prospective observational study was to examine the weight loss effect of bariatric surgery on plasma concentrations of two inflammatory markers, namely high-sensitivity C-reactive protein (hsCRP) and soluble urokinase-type plasminogen activator receptor (suPAR), in patients with obesity. METHODS: Sixteen subjects without obesity and 32 patients with obesity class III, who had already settled upon Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) were included in the study. Subjects without obesity were examined once, at baseline; patients with obesity were examined preoperatively (baseline) and 3, 6 and 12 months postoperatively. RESULTS: Plasma suPAR and hsCRP concentrations at baseline were higher in patients with obesity than in lean participants (2.68 ± 0.86 vs 1.86 ± 0.34 ng/mL, p < 0.001 and 9.83 ± 9.55 vs 1.36 ± 1.95 mg/dL, p < 0.001). Levels of suPAR following bariatric surgery increased significantly 3 months after either RYGB or SG (3.58 ± 1.58 vs 3.26 ± 0.7 ng/mL, respectively) and declined at 6 (3.19 ± 1.75 vs 2.8 ± 0.84 ng/mL, respectively) and 12 months (2.6 ± 1.5 vs 2.22 ± 0.49 ng/mL, respectively; p < 0.05 for the effect of time on suPAR levels during the study), whereas those of hsCRP declined consistently after bariatric surgery (3 months: 5.44 ± 3.99 vs 9.47 ± 11.98 mg/dL, respectively; 6 months; 5.39 ± 5.6 vs 10.25 ± 17.22 mg/dL, respectively; and 12 months: 2.23 ± 2.5 vs 3.07 ± 3.63 mg/dL, respectively; p < 0.001 for the effect of time on hsCRP levels during the study). 1-year change in BMI was negatively associated with suPAR levels at 12 months. CONCLUSION: Our findings support an association between obesity and low-grade inflammation. Weight loss following bariatric surgery is associated with a consistent decline in plasma hsCRP, while plasma suPAR levels increase at 3 months and decline by 12 months.

Fish intake interacts with TM6SF2 gene variant to affect NAFLD risk: results of a case-control study.

PURPOSE: Non-alcoholic fatty liver disease (NAFLD) is a complex disease, resulting from a variety of genetic and environmental factors. The aim of this case-control study was to evaluate the effect of selected genetic polymorphisms, nutrition aspects and their interaction on the risk of NAFLD. METHODS: The sample consisted of 134 patients with NAFLD and 217 controls. Disease was diagnosed by liver ultrasound and volunteers were clinically and nutritionally assessed. Food groups were extracted from a 172 food-item FFQ questionnaire. Three genetic polymorphisms were assessed: PNPLA3 rs738409, TM6SF2 rs58542926 and GCKR rs780094. RESULTS: We replicated the effect of previously reported risk factors for NAFLD, such as elevated liver enzymes, obesity and metabolic syndrome. Food groups rich in simple sugars, fat and especially saturated fat were positively associated with NAFLD risk, whereas food groups rich in polyunsaturated fatty acids were reversely associated with the possibility of developing the disease (p < 0.05). Only the PNPLA3 genetic variant was statistically significantly associated with the disease (padditive = 0.015). However, it was found that a one-portion increase in fish intake increased the risk of NAFLD in carriers of the risk allele of TM6SF2 rs58542926 polymorphism compared to non-carriers, after adjusting for age, gender, energy intake, pack-years, PAL, TM6SF2 genotype and fish consumption (ORdominant = 1.503, 95% CI 1.094-2.064). CONCLUSIONS: Fish intake exerts an additive effect on NAFLD risk for carriers of the TM6SF2 polymorphism. This novel finding provides further rationale on the need for personalized nutritional advice, based on the genetic background of NAFLD patients.

Hypoglycaemia requiring medical assistance in patients with diabetes: a prospective multicentre survey in tertiary hospitals.

AIM: Hypoglycaemia is considered a factor contributing to morbidity and mortality in patients with diabetes. The aim of the present study was to examine the frequency, clinical characteristics, predisposing factors and outcomes of iatrogenic hypoglycaemia requiring medical assistance. METHODS: Eight hospitals participated in this prospective survey of documented iatrogenic hypoglycaemia at their emergency departments. Cases with type 2 diabetes (T2D) were compared with a control group, consisting of patients visiting the outpatients' diabetes clinics of the same hospitals during the same time period. RESULTS: Median survey duration was 16.5 months, and 295 episodes of iatrogenic hypoglycaemia were recorded. Frequency varied across centres from 0.25 to 0.78 cases per 100 presenting patients. Most cases (90.8%) were observed in patients with T2D (mean age: 76.7±10.1 years), while 8.1% of events were recorded in patients with type 1 diabetes (mean age: 42.7±18.3 years). Total in-hospital mortality was 3.4%, and all involved patients with T2D. In T2D patients, advanced age (OR: 1.3 [1.20-1.45] for 5-year increase), use of sulphonylureas (OR: 4.0 [2.5-6.36]), use of insulin (OR: 2.35 [1.42-3.95]), lower estimated GFR (OR: 1.15 [1.07-1.23] at 10mL/min) and number of comorbidities (OR: 1.74 [1.34-2.27]) were each independently associated with hypoglycaemia requiring medical assistance. CONCLUSION: Hypoglycaemia requiring medical assistance in patients with diabetes is a moderately common condition seen in emergency departments and has a mortality rate of 3.4%. The majority of cases involve elderly individuals with T2D who are suffering from serious comorbidities and treated with insulin and/or sulphonylureas.

Stress management can facilitate weight loss in Greek overweight and obese women: a pilot study.

BACKGROUND: Stress and negative emotions have been shown to be critical factors in inducing overeating as a form of maladaptive coping in obese people. METHODS: The present study aimed to evaluate the efficacy of an 8-week stress management programme that includes progressive muscle relaxation (PMR) and diaphragmatic breathing on weight loss and eating behaviour in a sample of overweight and obese women who started a weight-loss programme. A total of 34 women with a mean (SD) body mass index of 38.17 (7.19) kg m(-) ² and mean (SD) age 47.35 (11.64) years were recruited from the outpatients Obesity Clinic of a public hospital in Athens. Participants were randomly assigned into a Stress Management (SM) and a control group. Anthropometric measurements were taken before and after the intervention, and the participants completed the following questionnaires: Dutch Eating Behaviour Questionnaire (DEBQ), Eating Attitudes Test (Eat-26), Health Locus of Control (HLC) and Perceived Stress Scale (PSS) before and after the intervention. RESULTS: The findings indicated a significant improvement in weight loss in the SM group [4.44 (0.83) kg] after intervention compared to the control group [1.38 (0.78) kg] (P < 0.05). A higher restrained eating behaviour was observed in the SM group after intervention compared to the control group, although there was no significant difference in perceived stress levels. CONCLUSIONS: The intervention group showed greater weight reduction, possibly because of the stress management programme, and a greater dietary restraint was demonstrated by them compared to the control group. It is likely that stress management could facilitate weight loss in obese women; however, more studies are needed to confirm this hypothesis.

Acute hyperhomocysteinemia impairs endothelium function in subjects with type 2 diabetes mellitus.

The objective of the present study was to examine the effect of acute, methionine-induced hyperhomocysteinemia (HHCY) on endothelial function and indices of arterial stiffness in subjects with type 2 diabetes mellitus (T2DM). A total of 30 subjects with T2DM, free of macrovascular disease were examined in a crossover study. L-methionine (M) (0.1 g/kg) and water (W) load were given in random order with an interval of about 1 week in between. Endothelial function was assessed by flow-mediated vasodilation (FMD). Arterial stiffness was assessed by determination of augmentation index (AI). Measurements were performed in the fasting state, 1, 2 and 3 h after the M or the W load. Total plasma homocysteine (HCY) levels did not change after W administration, while M administration resulted in a significant increase in HCY concentrations at 3 h. FMD throughout the experiment expressed as area under the curve (AUC) was significantly lower after the M than after the W load. Consistent with impairment in endothelial function, the AUC of AI was significantly higher after the M than after the W administration. Acute HHCY impairs endothelial function and increases arterial stiffness in patients with T2DM. This effect is probably mediated by a reduction of nitric oxide bioavailability in endothelium.

Ischemic preconditioning fails to confer additional protection against ischemia-reperfusion injury in the hypothyroid rat heart.

There is accumulating evidence showing that ischemic preconditioning (PC) may lose its cardioprotective effect in the diseased states. The present study investigated whether PC can be effective in hypothyroidism, a clinical condition which is common and often accompanies cardiac diseases such as heart failure and myocardial infarction. Hypothyroidism was induced in rats by 3-week administration of 6n-propyl-2-thiouracil in water (0.05 %). Normal and hypothyroid hearts (HYPO) were perfused in Langendorff mode and subjected to 20 min of zero-flow global ischemia and 45 min of reperfusion. A preconditioning protocol (PC) was also applied prior to ischemia. HYPO hearts had significantly improved post-ischemic recovery of left ventricular developed pressure, end-diastolic pressure and reduced lactate dehydrogenase release. Furthermore, phospho-JNK and p38 MAPK levels after ischemia and reperfusion were 4.0 and 3.0 fold lower in HYPO as compared to normal hearts (P<0.05). A different response to PC was observed in normal than in HYPO hearts. PC improved the post-ischemic recovery of function and reduced the extent of injury in normal hearts but had no additional effect on the hypothyroid hearts. This response, in the preconditioned normal hearts, resulted in 2.5 and 1.8 fold smaller expression of the phospho-JNK and phospho-p38 MAPK levels at the end of reperfusion, as compared to non-PC hearts (P<0.05), while in HYPO hearts, no additional reduction in the phosphorylation of these kinases was observed after PC. Hypothyroid hearts appear to be tolerant to ischemia-reperfusion injury. This response may be, at least in part, due to the down-regulation of ischemia-reperfusion induced activation of JNKs and p38 MAPK kinases. PC is not associated with further reduction in the activation of these kinases in the hypothyroid hearts and fails to confer added protection in those hearts.

Increased plasma ghrelin levels in chronic renal failure are not associated with hemodynamic parameters.

BACKGROUND/AIMS: Hardly anything is known about the effect of renal function on plasma ghrelin levels. Ghrelin is an orexigenic hormone with important hemodynamic effects. We examined differences in plasma ghrelin levels between chronic renal failure (CRF) patients and healthy subjects, and ghrelin's relationship with indices of left ventricular (LV) function. METHODS: Fasting total plasma ghrelin levels were measured in 122 CRF patients (57 on, 65 not on hemodialysis) and 57 control subjects. Indices of LV function were evaluated using echocardiography. RESULTS: Total plasma ghrelin levels were higher in patients with CRF compared to controls, but were not different between patients on and those not on hemodialysis. In a multivariate linear regression model, presence of kidney dysfunction explained 41 % of the variability of ghrelin values. The etiology of renal failure (diabetic nephropathy or not) had no influence on ghrelin levels in the renal patients. Ghrelin levels were not associated with indices of LV systolic function or blood pressure in these patients. CONCLUSION: Fasting plasma ghrelin concentrations are higher in CRF patients regardless of their need for hemodialysis compared to controls. The etiology of renal failure does not have any effect on plasma ghrelin levels. In addition, ghrelin levels are not associated with hemodynamic parameters in patients with CRF.

Viscoelastic properties of cartilage-subchondral bone complex in osteoarthritis.

OBJECTIVE: This study examines viscoelastic properties of the 'unaffected' tibial condyle in unicompartmental osteoarthritic knees, in order to determine whether to preserve it or not in knee replacement operations. DESIGN: The viscoelastic properties of longitudinal strips of cartilage and subchondral bone from osteoarthritic and healthy knees were studied. METHODS: Nine medial compartment osteoarthritic and nine cadaveric knees, all age- and gender-matched, were studied. Samples from polyethylene and methacrylate cement were also obtained and all then tested in the DMA (Dynamic Mechanical Analysis) testing apparatus. The dynamic modulus of elasticity (E(dyn)) and the loss factor (tan delta) were measured. RESULTS: The medial compartment in osteoarthritic knees had lost its viscoelastic properties, having a significantly higher E(dyn) compared to the lateral one, and lower values of loss factor. In healthy knees there was no significant difference (p=0.18) in viscoelastic properties between both compartments and with the unaffected side of the osteoarthritic knee. Polyethylene and cement appear to have a high modulus of elasticity compared to both the healthy and the osteoarthritic knees. CONCLUSIONS: The 'unaffected' (lateral) tibial condyles in medial compartment osteoarthritic knees seem to preserve their viscoelastic properties; it is worth considering a hemiarthroplasty. The significant modulus of elasticity difference between the condyles-polyethylene-cement results in different deformation in the interface between them and induces micromotion and loosening.

Differential effects of high-fat and high-carbohydrate content isoenergetic meals on plasma active ghrelin concentrations in lean and obese women.

AIM: To study the effect of two different isoenergetic meals, one rich in carbohydrates and one rich in fat, on plasma active ghrelin levels in lean or obese subjects. METHODS: Eight obese and eight lean women, strictly matched for age, were fed two isoenergetic meals of different composition, one rich in fat and one rich in carbohydrates (CHO), on separate days. Plasma active ghrelin levels were measured just before and at 1, 2 and 3 hours after meal consumption. RESULTS: Overall, plasma active ghrelin levels were significantly lower in the obese compared to the lean women (71.7 +/- 29.7 vs. 222.2 +/- 127.2 pmol/liter respectively, p < 0.0001). Furthermore, ghrelin levels decreased significantly by 30 % from baseline values in the lean subjects in the first hour after the CHO-rich meal (mean difference +/- SD): -66.2 +/- 49.0 pmol/liter (p = 0.03), returning to near-baseline levels by 2 hours, while no significant change was observed in the obese subjects. After the fat-rich meal, active ghrelin levels did not change significantly in either group (p > 0.05). CONCLUSIONS: A fat-rich meal does not suppress plasma active ghrelin levels in either lean or obese women. Moreover, in obese, unlike lean women, a high carbohydrate meal also fails to suppress plasma ghrelin levels, which are already quite low. This suggests that ghrelin-induced satiety mechanisms may be compromised in these subjects.

Effect of gamma-radiation on migration behaviour of dioctyladipate and acetyltributylcitrate plasticizers from food-grade PVC and PVDC/PVC films into olive oil.

Food-grade PVC and PVDC/PVC films containing 28.3% dioctyladipate (DOA) and 5.0% acetyltributylcitrate (ATBC) plasticizers, respectively, were brought into contact with olive oil and were irradiated with gamma-radiation [60Co] at doses equal to 4 kGy and 9 kGy corresponding to "cold pasteurization". Irradiation was carried out at 8-10 degrees C and samples were subsequently stored at 4-5 degrees C. Contaminated oil samples were analysed for DOA and ATBC at intervals between 7 h and 97 h of contact, using an indirect GC method. Identical nonirradiated (control) samples were also analysed for DOA and ATBC content. Results showed no statistically significant differences in migrated amounts of DOA and ATBC between irradiated and non-irradiated samples. Neither were differences observed between samples irradiated at 4 kGy and 9 kGy. This was supported by identical IR spectra recorded for irradiated and non-irradiated samples and leads to the conclusion that at such intermediate radiation doses (< or = 9 kGy) the migration characteristics of both PVC and PVDC/PVC films are not affected. The amount of DOA that migrated into olive oil was dependent on time, reaching equilibrium after approximately 47 h of contact (302.8 mg/l). The amount of ATBC that migrated into olive oil was non-detectable (< 1 mg/l) for all samples stored at 4-5 degrees C after 97 h. In non-irradiated samples (PVDC/PVC in contact with oil) stored at 20 degrees C, small amounts of migrated ATBC were determined (3.3 and 5.1 mg/l after 29 h 94 h of contact respectively).(ABSTRACT TRUNCATED AT 250 WORDS)