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Objective: The aim of the current study was to evaluate the short-term effects of anti-tumour necrosis factor alpha (infliximab) therapy on serum cartilage oligomeric matrix protein (COMP) levels, a possible biomarker of cartilage destruction. Methods: Nine consecutive patients with active psoriatic arthritis (PsA) were treated with infliximab for 6 weeks. Serum COMP levels were measured and correlated to pre-established disease activity outcome variables: pain as assessed by the patient, using the 100 mm visual analogue scale (VAS), duration of morning stiffness (MGST), swollen joint count (SJC), tender joint count (TJC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Results: Significant improvements in MGST, VAS, SJC and TJC values were observed after 6 weeks of therapy. Similar significant improvements were demonstrated in the ACR response rate and in eight (89%) patients the ACR20 was achieved. ESR and CRP decreased significantly over 6 weeks. Serum COMP levels also decreased significantly after 6 weeks of treatment (12.99 +/- 1.71 baseline, 10.22 +/- 1.1 after 6 weeks, P

Objective: To compare the effects of a 4-month strength training (ST) versus aerobic endurance training (ET) program on metabolic control, muscle strength, and cardiovascular endurance in subjects with type 2 diabetes mellitus (T2D). Design: Randomized controlled trial. Setting: Large public tertiary hospital. Participants: Twenty-two T21) participants (I I men, I I women; mean age +/- standard error, 56.2 +/- 1.1 y; diabetes duration, 8.8 +/- 3.5y) were randomized into a 4-month ST program and 17 T2D participants (9 men, 8 women; mean age, 57.9 +/- 1.4y; diabetes duration, 9.2 +/- 1.7y) into a 4-month ET program. Interventions: ST (up to 6 sets per muscle group per week) and ET (with an intensity of maximal oxygen consumption of 60% and a volume beginning at 15min and advancing to a maximum of 30min 3X/wk) for 4 months. Main Outcome Measures: Laboratory tests included determinations of blood glucose, glycosylated hemoglobin (Hb A(1c)), insulin, and lipid assays. Results: A significant decline in Hb A, was only observed in the ST group (8.3% +/- 1.7% to 7.1% +/- 0.2%, P=.001). Blood glucose (204 +/- 16mg/dL to 147 +/- 8mg/dL, P

Background: Hereditary hemochromatosis is an autosomal recessive disorder of iron metabolism that is characterized by excess accumulation of iron in various organs and often leads to diabetes mellitus (DM). To study whether mutations in the hemochromatosis gene (HFE) could be a risk factor for the development of gestational diabetes mellitus (GDM), the prevalence of HFE mutations in patients with GDM was compared to that of healthy pregnant controls. Methods: GDM was diagnosed in 208 of 2,421 pregnant woman screened between the 24th and 28thweek of gestation over a period of 18 months. Patients and 170 matched control subjects were screened for the HFE gene mutations C282Y and H63D. Results: In North and Central European GDM patients, the allele frequency of the C282Y mutation (7.7%) was higher than in pregnant controls (2.9%; p = 0.04), while the frequency of the H63D mutation was not different (p = 0.45). Three patients with GDM were homozygous for H63D (3.1%), 1 patient was homozygous for C282Y (1.0%), 2 patients were compound heterozygous (2.0%) and 26 were heterozygous [11 C282Y (11.2%) and 15 H63D (15.3%)]. C282Y and H63D allele frequencies were not different between controls and GDM patients of Southern European or non-European origin. Irrespective of the HFE-mutation status, serum ferritin levels were increased in patients with GDM compared to healthy pregnant controls (p = 0.01), while transferrin saturation was similar in both groups. Conclusions: In North and Central European patients with GDM, the C282Y allele frequency is higher than in healthy pregnant women, suggesting a genetic susceptibility to the development of GDM.

Weight reduction after gastric bypass surgery has been attributed to a decrease of the orexigenic peptide ghrelin, which may be regulated by insulin and leptin. This study examined effects of long-term weight loss after laparoscopical adjustable gastric banding on plasma ghrelin and leptin concentrations and their relationship with insulin action. Severely obese patients (15 women, three men, 36 ± 12 yr) underwent clinical examinations every 3 months and modified oral glucose tolerance tests to assess parameters of insulin sensitivity and secretion every 6 months. After surgery, body mass index fell from 45.3 ± 5.3 to 37.2 ± 5.3 and 33.6 ± 5.5 kg/m2 at 6 and 12 months, respectively (P < 0.0001). This was associated with lower (P < 0.0001) plasma glucose, insulin, insulin resistance, waist circumference, and blood pressure. Plasma leptin decreased from 27.6 ± 9.5 to 17.7 ± 9.8 (P = 0.0005) and 12.7 ± 5.1 ng/ml (P < 0.0001). Plasma ghrelin was comparable before and at 6 months (234 ± 53; 232 ± 53 pmol/liter) but increased at 12 months (261 ± 72 pmol/liter; P = 0.05 vs. 6 months). At 6 and 12 months, ghrelin levels correlated negatively with fasting plasma insulin levels and hepatic insulin extraction but not with body mass or insulin action.In conclusion, prolonged weight loss results in a rise of fasting ghrelin concentrations that correlates with fasting insulin concentrations but not improvement of insulin sensitivity.

Aims Obesity and type 2 diabetes are associated with increased cardiovascular risk and elevation of traditional and non-traditional risk markers. As bariatric surgery reduces overweight and improves metabolic derangement, we examined a cluster of established and emerging cardiovascular risk factors, such as soluble CD40 ligand (sCD40L) and lipoprotein-associated phospholipase A2 (Lp-PLA2), which might improve prediction of future cardiovascular events because of their more direct involvement in plaque destabilization. Methods and results Obese patients [ n = 32, body mass index (BMI) 46.1 ± 5.9 kg/m2] underwent clinical examinations and blood sampling for measurement of glucose and lipid parameters as well as non-traditional cardiovascular risk markers, i.e. high-sensitivity C-reactive protein, plasminogen activator inhibitor-1 (PAI-1), soluble cellular adhesion molecules (CAM), MMP-2, MMP-9, CD40L, and Lp-PLA2 before and after 1 year following laparoscopic adjustable gastric banding (LAGB), respectively. In patients undergoing LAGB, blood pressure ( P < 0.0001) and blood glucose ( P = 0.02) were significantly lowered by approximately 16% as well as triglyceride levels by approximately 29% ( P = 0.002). In addition to a decrease of the inflammatory and pro-thrombotic marker PAI-1 ( P = 0.001), CAMs, and MMP-9 ( P = 0.004) were reduced, whereas no change was observed for plasma levels of MMP-2, sCD40L, and Lp-PLA2 after LAGB, respectively. Individual changes in (ICAM-1) intercellular adhesion molecule-1 (ΔICAM-1) were related to changes in insulin (Δfasting insulin) before and after LAGB ( r = 0.36 and r = 0.38; both P = 0.04). E-selectin correlated positively with changes in BMI ( r = 0.38; P = 0.04 and r = 0.36; P = 0.05), while Lp-PLA2 concentration was negatively correlated with BMI ( r =−0.41; P = 0.02) after 1 year. Changes were comparable in both overweight diabetic and non-diabetic subjects. Conclusion LAGB not only induced weight loss but also an improvement in the subclinical pro-inflammatory state. However, concentrations of most of the non-traditional risk factors for plaque instability, i.e. MMP-9, sCD40L, and Lp-PLA2 remained unchanged.

INTRODUCTION: Surgically induced weight loss results in reduction of comorbidities in severely obese humans. Reversal of abnormal secretion of appetite-regulating gut hormones such as peptide YY (PYY) could be contributing to the improvement of cardiovascular risk factors. METHODS: Severely obese patients (n = 42, BMI = 45.7 ± 5.3 kg/m2) underwent clinical examination and blood sampling for measurement of PYY, plasma lipids, oral glucose tolerance testing and assessment of insulin secretion (HOMA-%B) and action (HOMA-R, QUICKI) before and during 12 months following gastric banding. Comparisons were made at each time point of the study as well as across the total study period. RESULTS: Weight loss after bariatric surgery resulted in improvement of insulin resistance by 54% (p < 0.03) and plasma triglycerides by 26% (p < 0.01) without changes in fasting PYY (16.2 ± 8.7 pmol/l at baseline, 15.1 ± 6.3 pmol/l at 12 months). Fasting PYY correlated negatively with plasma total cholesterol at baseline (p = 0.02) but was not associated with body weight, body mass or abdominal diameter. Individual changes in PYY (ΔPYY) related to changes in insulin (Δfasting insulin) at 12 months (r = −0.582, p = 0.02) and HOMA-B at 6 months (r = −0.677, p = 0.006) and 12 months (r = −0.660, p = 0.007). Diabetic status had no impact on these correlations. DISCUSSION: PYY correlates with a major cardiovascular risk factor and surrogate parameters of insulin secretion but not to weight loss or body mass in severe obesity.

Background Although both strength training (ST) and endurance training (ET) seem to be beneficial in type 2 diabetes mellitus (T2D), little is known about post-exercise glucose profiles. The objective of the study was to report changes in blood glucose (BG) values after a 4-month ET and ST programme now that a device for continuous glucose monitoring has become available. Materials and methods Fifteen participants, comprising four men age 56.5 +/- 0.9 years and 11 women age 57.4 +/- 0.9 years with T2D, were monitored with the MiniMed (Northridge, CA, USA) continuous glucose monitoring system (CGMS) for 48 h before and after 4 months of ET or ST. The ST consisted of three sets at the beginning, increasing to six sets per week at the end of the training period, including all major muscle groups and ET performed with an intensity of maximal oxygen uptake of 60% and a volume beginning at 15 min and advancing to a maximum of 30 min three times a week. Results A total of 17 549 single BG measurements pretraining (619.7 +/- 39.8) and post-training (550.3 +/- 30.1) were recorded, correlating to an average of 585 +/- 25.3 potential measurements per participant at the beginning and at the end of the study. The change in BG-value between the beginning (132 mg dL(-1)) and the end (118 mg dL(-1)) for all participants was significant (P = 0.028). The improvement in BG-value for the ST programme was significant (P = 0.02) but for the ET no significant change was measured (P = 0.48). Glycaemic control improved in the ST group and the mean BG was reduced by 15.6% (Cl 3-25%). Conclusion In conclusion, the CGMS may be a useful tool in monitoring improvements in glycaemic control after different exercise programmes. Additionally, the CGMS may help to identify asymptomatic hypoglycaemia or hyperglycaemia after training programmes.

Marathon running is growing in popularity, and many diabetic patients are participating in various marathon races all over the world each year. This study aimed to investigate the prevalence and extent of glycemic excursions (hypo- and hyperglycemic) during a marathon run in patients with well-controlled diabetes mellitus using a continuous glucose monitoring system (CGMS). Five subjects with type 1 and one patient with type 2 diabetes mellitus were monitored with the Medtronic MiniMed CGMS during the 2002 Vienna City Marathon (n = 3) or the "Fernwarme run" (n = 3) long distance runs of 42.19/15.8 km. All six patients finished their course. The CGSM system was well tolerated in all patients over an average duration of 34 +/- 4.0 hours and it did not limit the patients' activities. The mean running time for the Vienna city marathon was 257 +/- 8 min (247 to 274 min) and for the Fernwarme run 134 +/- 118 min (113 to 150 min). A total of 1470 blood glucose measurements (mean 245 readings per subject) were performed. During and after the marathons frequent hypo- and hyperglycemic episodes with and without clinical symptoms were measured. Our data confirm that the CGMS may help to identify asymptomatic hypoglycemia or hyperglycemia during and after a long distance run. The system may also be helpful to improve our understanding about the individual changes of glucose during and after a marathon and may protect hypoglycemic or hyperglycemic periods in future races.

The effectiveness of physical exercise in the management of diabetes mellitus type 2 is well established. The purpose of this investigation was to evaluate the effect of long term exercise on glycemic and metabolic control measured after eight months in contrast to patients who had ceased their training after four months.After an effective 4 months' strength training or endurance training period, ten patients (5 male and 5 female, mean age +/- SE:57.1 +/- 1.6 yr) were randomised to a further 4 months of combined endurance and strength training, while a control group of 10 patients (5 male and 5 female, mean age +/- SE:56.9 +/- 1.6 yr) ceased training.Long term glycemic control improved and HbA1C values fell from 6.9 +/- 0.4 to 6.2 +/- 0.2 in active patients and increased from 7.5 +/- 0.4 to 8.7 +/- 0.6 in control patients (p = 0.002). Baseline levels of total cholesterol significantly decreased in training group (205.5 mg/dl +/- 14.1 to 177.5 +/- 13.3) and increased in controls (185.9 +/- 14.1 to 220.2 +/- 15.8) [p = 004]. In addition, significant decreases in LDL-cholesterol and triglyceride levels (both p05) were observed in the training group compared to controls.This study showed that in addition to a 4 month training period, continuation of training proved highly beneficial with further reductions in fasting blood glucose, HbA1C, total cholesterol, LDL-cholesterol, triglyceride, and an elevation in HDL-cholesterol concentrations in diabetes mellitus type 2 patients, thus resulting in a reduced atherogenic lipid profile. In contrast, patients who ceased training after 4 months developed an atherogenic lipid profile and a worsened glycemic control. The results of this study indicate that long term exercise plays an important role in the treatment of diabetes mellitus type 2 and may protect against the development of cardiovascular diseases.

The prevalence of obesity is rising worldwide dramatically, affecting up to 50 percent of the population. The epidemic of obesity leads to a marked increase in the metabolic syndrome, a cluster of cardiovascular risk factors characterized by visceral obesity, insulin resistance, low HDL-Cholesterol, hypertriglyceridemia, and a subclinical proinflammatory state. In the last years, the NCEP and the WHO highlighted and defined the key features of the metabolic syndrome to facilitate the clinical diagnosis and preventive interventions. The conservative therapy of obesity and the metabolic syndrome by life style intervention and pharmacological interventions leads only to moderate weight loss with inconstant long-term success. Intervention by bariatric surgery can serve as a model for the metabolic effects of permanent weight loss. In several studies the pronounced weight loss induced a reduction of almost all components of the metabolic syndrome, including glucose and lipid status and is followed by an improvement in the quality of life. Recent research suggested a decrease in mortality rate in addition to cost effectiveness of bariatric surgery.

Background: Mild stages of heart failure might be difficult to diagnose in severely obese individuals with a body mass index (BMI) >40 kg/m2. Measurement of the N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) is feasible for detecting cardiac impairment. The aims of our study were to measure NT-proBNP in plasma of severely obese patients and to compare the results with results for patients in different stages of manifest cardiac dysfunction. Methods: In 61 severely obese individuals (median BMI, 43.2 kg/m2) and 96 nonobese patients with existing heart failure [classified into New York Heart Association (NYHA) classes I–IV], NT-proBNP was measured in the fasting condition. A medical history, physical examination, electrocardiography, blood chemistry, and chest x-ray were performed in the obese group. In addition, echocardiography was performed in the NYHA group. Results: In obese individuals, NT-proBNP was increased to a median of 356 (interquartile range, 221–458) pmol/L [854 (530–1099) ng/L] and was comparable (P >0.05) to the median value for NYHA I patients {289 (258–451) pmol/L [694 (619–1082) ng/L]}, but was significantly lower than in the other NYHA groups (P Conclusion: The prognostic relevance of increased NT-proBNP for risk of developing cardiac insufficiency in severely obese patients needs to be further evaluated.

Objective: To evaluate the effect of massive weight loss on insulin sensitivity, soluble adhesion molecules, and markers of the insulin resistance syndrome (IRS). Research Methods and Procedures: Eighteen morbidly obese patients underwent gastric banding and were evaluated before and 6 and 12 months after surgery. Total insulin secretion, hepatic insulin extraction, and insulin sensitivity were analyzed by oral glucose-tolerance test model analysis. In addition, soluble intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, leptin, high-sensitivity C-reactive protein, plasminogen activating factor-1 (PAI-1), and tissue plasminogen activator were measured. Results: BMI dropped from 45.22 ± 5.62 to 36.99 ± 4.34 kg/m2 after 6 months and 33.72 ± 5.55 kg/m2 after 12 months (both p < 0.0001). This intervention resulted in a significant reduction of blood pressure (p < 0.00001), triglycerides (p < 0.01), fasting blood glucose (p = 0.03), basal insulin (p < 0.001), and basal C-peptide (p = 0.008) levels. Total insulin secretion decreased (p < 0.05), whereas hepatic insulin extraction (p < 0.05) and oral glucose insulin sensitivity index (p < 0.0001) increased compared with baseline. Leptin (p < 0.0001) and E-selectin levels decreased significantly after 6 and 12 months (p = 0.05), whereas significantly lower levels of intercellular adhesion molecule-1 and PAI-1 were only seen after 6 months. Subclinical inflammation, measured by high-sensitivity C-reactive protein, was lowered to normal ranges. No changes were observed in vascular cell adhesion molecule-1 and tissue plasminogen activator levels. Discussion: Although gastric banding ameliorates several features of the IRS, including 29.05% improvement in insulin sensitivity and blood pressure and reduction of soluble adhesion molecules and PAI-1, considerable weight loss did not normalize all components of the IRS in morbidly obese patients.

Objective: Aminoterminal pro-brain natriuretic peptide (NT-proBNP), like brain natriuretic peptide, might have diagnostic utility in detecting left ventricular hypertrophy and/or left ventricular dysfunction. The aim of the study was to investigate the relationship between morbid obesity and NT-proBNP and the effect of weight reduction on this parameter. Research Methods and Procedures: A total of 34 morbidly obese patients underwent laparoscopic adjustable gastric banding (LAGB). NT-proBNP levels were measured before and 12 months after the surgery. Results: Metabolic features and systolic and diastolic blood pressure were significantly decreased (p < 0.00001 for both) after a cumulative weight loss of 19.55 kg 1 year after LAGB. NT-proBNP concentration was significantly higher in morbidly obese patients before LAGB than in normal-weight control subjects (341.15 ± 127.78 fmol/mL vs. 161.68 ± 75.78 fmol/mL; p < 0.00001). After bariatric surgery, NT-proBNP concentration decreased significantly from 341.15 ± 127.78 fmol/mL to 204.87 ± 59.84 fmol/mL (p < 0.00, 001) and remained statistically significantly elevated (204.88 ± 59.84 fmol/mL vs. 161.68 ± 75.78 fmol/mL; p = 0.04) compared with normal-weight subjects. Discussion: This investigation demonstrates higher levels of NT-proBNP in morbidly obese subjects and a significant decrease during weight loss after laparoscopic adjustable gastric banding. In obesity, NT-proBNP might be useful as a routine screening method for identifying left ventricular hypertrophy and/or left ventricular dysfunction.

To the Editor: It has been suggested that the reduction in plasma ghrelin concentrations in five morbidly obese patients after treatment with a proximal Roux-en-Y gastric bypass contributed to the weight-reducing effect of the surgery.1 This hypothesis has been questioned,2 because decreased plasma ghrelin concentrations are present in obese people before any intervention and were documented approximately 1.4 years after gastric bypass surgery, when weight loss of approximately 36 percent had occurred. Bariatric surgery is becoming more common — particularly, laparoscopic adjustable gastric banding. This procedure, which was recently approved by the Food and Drug Administration, causes less dramatic weight . . .

We investigated the effect of Infliximab, an anti TNF-alpha antibody, on plasma lipids and lipoproteins in patients with rheumatoid arthritis and psoriatic arthritis.Five male and 10 female patients with a mean age of 56.7 years were included in this study. Seven of the patients were diagnosed with rheumatoid arthritis and 8 patients with psoriatic arthritis. All patients received infusions of 3 mg/kg Infliximab (at week 0, 2 and 6). Lipids, lipoproteins and standard clinical parameters were assessed at baseline (0 week), after 2 weeks, and in 4 patients after 6 weeks.There was a significant increase in triglyceride levels during treatment with Infliximab (112 +/- 48 versus 133 +/- 53 mg/dl, p0.01). In contrast, HDL-cholesterol levels were significantly lowered (56 +/- 12 versus 50 +/- 13 mg/dl, p0.006) by the treatment. There was no significant difference in total cholesterol (209 +/- 25 versus 205 +/- 36 mg/dl) or in LDL-cholesterol (131 +/- 24 versus 118 +/- 43 mg/dl) before and after treatment. Similarly, lipoprotein(a) levels did not alter during treatment (median: 1.1 versus 1.4 mg/dl).This study shows that intravenous Inflixmab therapy leads to changes in plasma lipid and lipoprotein levels in patients with rheumatoid and psoriatic arthritis and may result in a more atherogenic lipid and lipoprotein profile. Although larger patient numbers need to be studied to confirm our findings, these results suggest that lipid levels should be checked and monitored in patients receiving infliximab therapy, particularly in patients with vascular disease.

Objective. The aim was to evaluate the efficacy and safety of multiple infusions with achimeric, anti-tumor necrosis factor (TNF)α monoclonal antibody (infliximab) in patients with psoriatic arthritis (PsA) and psoriasis vulgaris. Methods. Over 22 weeks, nine patients with both active psoriasis and PsA received five infusions of 3 mg/kg infliximab. The endpoints included changes in the swollen and tender joints counts, American College of Rheumatology (ACR) preliminary criteria for improvement response rates 20, 50, and 70, and improvement in the psoriasis area and severity index (PASI). Results. The swollen count (SJC) and tender joint count (TJC) fell from means of 5.33±2.22 and 17.80±4.21 to 1.44±1.09 and 9.77±0.92, respectively, by week 2 (P=0.02, P=0.02). This benefit was sustained through week 22 (2.00±1.12/7.77±3.68, P=0.05/P=0.002). The ACR 20/50/70 response was achieved in 89%/56%/22% of cases. The mean PASI score improved from 19.04±5.41 to 4.91±2.51 (P=0.002). Conclusion. Multiple infusions of infliximab were effective and well tolerated in patients with active psoriasis and PsA.