Vitamin D deficiency, serum leptin and osteoprotegerin levels in older diabetic patients: an input to new research avenues.

The aim of this study was to assess the effects of single oral bolus of 300,000 IU Vitamin D3 on serum levels and on bone and metabolic parameters in diabetic patients. This study is a Phase IV, randomized, double-blind, placebo-controlled, monocenter clinical trial. Thirty patients, 60 years or older, with type 2 diabetes mellitus, and diabetic foot complications, were enrolled and monitored for 24 weeks: 14 were treated with Vitamin D3 and 16 with placebo. Parameters including glucose, adiponectin, leptin, osteoprotegerin (OPG), 25-hydroxyvitamin D [25(OH)D], beta-CrossLaps, osteocalcin, bone-specific isoenzyme of alkaline phosphatase, tumor necrosis factor-α and parathyroid hormone were measured at screening and baseline and 12 and 24 weeks after treatment. Analysis of covariance was used to compare treatment groups. Analysis of the data detected a significant increase in 25(OH)D serum levels both at 12 and 24 weeks with respect to baseline values only in the treated patients. Significant variations with respect to baseline values were noted in OPG (P = 0.0085) and in leptin (P = 0.0442) levels: these were lower in the placebo group at week 24 but higher in the treated group. Vitamin D3 supplementation significantly increased serum leptin and OPG levels. Further, large-scale clinical trials are warranted to confirm these results.

Deep venous thrombosis after surgery for inflammatory bowel disease: is standard dose low molecular weight heparin prophylaxis enough?

BACKGROUND: Inflammatory bowel disease (IBD) and colorectal surgery are risk factors for deep venous thrombosis (DVT). The aim of this prospective study was to evaluate the effectiveness of standardized prophylactic low molecular weight heparin (LMWH) therapy in patients who underwent surgery for ulcerative colitis (UC) and Crohn's disease (CD). PATIENTS AND METHODS: Since 1999 all patients operated on for colorectal diseases in our institute have received 4,000 IU/day LMWH from the day of operation to discharge. The complete series of patients who had major colorectal surgery from 1999 until 2006 were reviewed for overt DVT episodes. Furthermore, 60 consecutive patients who were admitted for surgery for IBD were prospectively enrolled in the 2004-2006 period. Each patient underwent venous color Doppler ultrasound scan at admission and at discharge. Demographic data, disease activity, and clotting parameters were collected. Data were analyzed with Spearman's correlation test, multiple regression, and receiver operating characteristics (ROC) curves analysis. RESULTS: The rate of DVT in UC patients was significantly higher than in colorectal cancer patients (p = 0.009), and the odds ratio (OR) for postoperative DVT in UC patients was 7.4 (95% CI 1.4-44.4; p = 0.017). Female gender, UC diagnosis, active rectal bleeding, aPTT value, aCL IgM, abeta2 IgM, and pANCA levels significantly correlated with postoperative DVT. At multivariate analysis only aCL IgM levels were found to be independently associated with postoperative DVT (p = 0.05). CONCLUSIONS: In conclusion, our study showed that prophylactic therapy with 4,000 IU/day LMWH was not completely effective for the prevention of postoperative DVT in patients with CD, and even less so in those with UC. In these patients, a more tailored prophylactic therapy should be considered, and further randomized controlled trials testing the effectiveness of different prophylactic protocols would be advisable. Furthermore, aCL IgM serum levels might be helpful in identifying IBD patients who are at higher risk of postoperative DVT.

Bariatric surgery improves atherogenic LDL profile by triglyceride reduction.

BACKGROUND: Small dense low-density lipoprotein (LDL) are atherogenic particles frequently observed in obese patients. Fatty acids modulate LDL. Objective of this study was to determine the relations between plasma phospholipid fatty acid composition and the presence of small dense LDL particles in morbidly obese patients treated with laparoscopic gastric banding (LAGB). METHODS: Small dense LDL, plasma lipids, lipoproteins, apoproteins, and phospholipid fatty acid composition (a marker of dietary fatty acid intake) were quantified before and 12 months after surgery in four men and 11 women who were morbidly obese and (BMI > 40 kg/m(2)) eligible for surgery, consecutively treated with LAGB at the Department of Medical and Surgical Sciences of the University of Padova. RESULTS: BMI was 48.3 +/- 4.8 kg/m(2) before and 36.1 +/- 5.5 kg/m(2) after LAGB. Plasma triglycerides and apoprotein E levels significantly decreased, while HDL cholesterol significantly increased after LAGB. A reduction of small dense LDL with an increase of LDL relative flotation (0.34 +/- 0.04 before vs 0.38 +/- 0.03 after LAGB, p < 0.001) was also observed. These modifications were neither related to weight reduction nor to changes in phospholipid fatty acid composition, but they were associated to triglyceride reduction, which explained 76.7% of the LDL relative flotation variation. CONCLUSION: Weight loss obtained by LAGB in morbidly obese subjects was accompanied by triglyceride reduction, high-density lipoprotein increase, and an improvement of the atherogenic LDL profile. Triglyceride reduction, but not the extent of weight loss or dietary fatty acid modifications, is the determinant of modifications of LDL physical properties in these patients.

Lipid and phospholipid profile after bowel resection for Crohn's disease.

BACKGROUND AND AIM: Chronic inflammation, impaired intestinal adsorption, and bowel resection may have an impact on lipid metabolism before and after intestinal surgery for Crohn's disease (CD). The aim of this prospective study was to define the impact of intestinal surgery for CD on plasma phospholipid fatty acid (FA) composition and of serum plasma lipoprotein concentrations and to investigate the role of CD recurrence on lipid parameters. MATERIALS AND METHODS: Twenty-four consecutive patients who had intestinal surgery for CD since December 2004 to March 2006 were enrolled in this prospective study. The total amount of calorie intake and the quality of the aliments, systemic inflammatory activity, and plasma lipoproteins and phospholipid fatty acid composition were determined at operation and at follow-up. Statistical analysis was performed with pair-matched tests. RESULTS: The median follow-up was 6 (4-20) months. During the follow-up, no significant modification of body mass index was observed. An increase of high-density lipoprotein (HDL) cholesterol (p=0.02) without other modifications in the plasma phospholipid FA composition were evidenced after surgery. The comparison between colectomy and ileo-colonic or ileal resection groups did not show any significant difference in the lipoprotein concentration and phospholipid FA profile. The length of resected bowel did not show any significant correlation with any relevant difference in lipid, phospholipid profile, or in inflammatory parameters. Patients who experienced a recurrence of CD reported significantly higher levels of total (p<0.01), HDL (p=0.01), and low-density lipoprotein cholesterol (p=0.01) were observed in patients in remission than in those with recurrent active disease. CONCLUSIONS: Patients who are submitted to intestinal resection for CD improve their inflammatory status as well as their lipid metabolism, and CD recurrence, but not the extent of bowel resection, is the main predictor of alteration of serum lipid concentration.

Cytokine network in rectal mucosa in perianal Crohn's disease: relations with inflammatory parameters and need for surgery.

BACKGROUND: Nowadays anti-TNF-alpha antibodies are used for the treatment of perianal Crohn's disease (CD). Nevertheless, this treatment is effective in only a part of these patients and recent studies suggested a role for other cytokines in chronic bowel inflammation. The aim of this study was to assess the cytokine profile in the rectal mucosa of patients affected by perianal CD and to understand its relations with the systemic cytokine profile and inflammatory parameters and the need for surgery. METHODS: Seventeen patients affected by perianal CD, 7 affected by CD without perianal involvement, and 17 healthy controls were enrolled and underwent blood sampling and endoscopy. During endoscopy rectal mucosal samples were taken and the expression of TNF-alpha, IL-6, IL-1 beta, IL-12, and TGF-beta1 was quantified with enzyme-linked immunosorbent assay (ELISA). Local cytokine levels were compared and correlated with diagnosis, therapy, phenotype (fistulizing and stenosing), and disease activity parameters. RESULTS: In the group with perianal CD, rectal mucosal IL-1 beta, IL-6, and serum IL-6 and TNF-alpha were higher than in patients with small bowel CD and healthy controls. IL-12 and TGF-beta1 mucosal levels did not show any differences among the 3 groups. Mucosal IL-6 significantly correlated with the Perianal Crohn's Disease Activity Index and mucosal TNF-alpha and IL-1 beta. Mucosal TNF-alpha and IL-1 beta showed a direct correlation with the histological grade of disease activity. CONCLUSIONS: The cytokines network analysis in perianal CD shows the important involvement of IL-1 beta, IL-6, and TNF-alpha. Furthermore, mucosal levels of IL-6 and IL-12 are predictors of recurrence and of need for surgery in perianal CD patients.

Metabolic syndrome and cardiovascular disease in the elderly: the Progetto Veneto Anziani (Pro.V.A.) study.

BACKGROUND AND AIMS: The prevalence of the metabolic syndrome increases with age, although only few data are available about its prevalence in the general elderly population. This study describes the prevalence of the metabolic syndrome in an elderly population, and its association with cardiovascular diseases. METHODS: The Progetto Veneto Anziani (Pro.V.A.) is an observational study of 3,099 subjects aged 65 and older, randomly selected from the general population of Northern Italy. Cardiovascular diseases and metabolic syndrome according to Adult Treatment Panel III were evaluated in 2,910 subjects. RESULTS: The metabolic syndrome was present in 25.6% of men and 48.1% of women. Its prevalence was mainly due to high blood pressure (93%) in both sexes, and to abdominal obesity in 73% of women. The prevalence of cardiovascular diseases was significantly higher among subjects with metabolic syndrome. Together with age and former smoking habits, the metabolic syndrome was significantly associated with cardiovascular diseases. High blood pressure and low HDL were independently associated with cardiovascular diseases in men, and with high fasting plasma glucose and waist circumference in women. CONCLUSIONS: The metabolic syndrome is frequent, and significantly but not independently associated with prevalent cardiovascular diseases in the elderly. In old people, rather than the metabolic syndrome per se, some of its components are independently associated with cardiovascular diseases.

Restorative proctocolectomy for ulcerative colitis: impact on lipid metabolism and adipose tissue and serum fatty acids.

The aim of this prospective study was to evaluate the changes of the metabolism of circulating and storage lipids in patients with ulcerative colitis after restorative proctocolectomy. Fifteen consecutive patients and 15 sex- and age-matched healthy controls were enrolled. Disease activity, diet, inflammatory parameters, plasma lipoprotein concentrations, and fatty acids (FA) of serum phospholipids and of the subcutaneous adipose tissue were assessed at colectomy and at ileostomy closure. In ulcerative colitis patients, total cholesterol and docosahexaenoic acid were lower than in healthy subjects (p < 0.01 and p < 0.05). The median interval between colectomy and ileostomy closure was 6 (range 2-9) months. During that interval, the inflammatory parameters improved, high-density lipoproteins (HDL) cholesterol increased (p < 0.01), and low-density (LDL) cholesterol decreased (p = 0.01). At ileostomy closure, serum arachidonic acid levels were increased (p = 0.04), whereas serum oleic acid level was decreased (p = 0.02). In this interval, no significant alteration, either in serum n-3 FA precursors or in the FA of subcutaneous adipose tissue, was observed. The increase of serum arachidonic acid after colectomy might suggest a lower utilization for inflammatory process. The reduction of LDL cholesterol is an index of malabsorption probably due to the accelerated transit and to the exclusion of the terminal ileum caused by the covering ileostomy.

Cytokine network in chronic perianal Crohn's disease and indeterminate colitis after colectomy.

Antitumor necrosis factor alpha (anti-TNF-alpha) therapy in perianal Crohn's disease (CD) is widely established but recent studies suggest that the underlying fistula tract and inflammation may persist. Treatment with a monoclonal antibody against interleukin (IL)-12 was reported to induce clinical responses and remissions in patients with active CD. The aim of our study was to analyze the cytokine network (TNF-alpha, IL-12, IL-1beta, and IL-6) in 12 patients with chronic perianal CD and a Crohn's disease activity index (CDAI) score <150 to exclude active intestinal disease, in 7 patients with indeterminate colitis (IC) after restorative proctocolectomy with perianal complications, in 7 patients with active intestinal CD without perianal manifestations, and in 19 healthy controls. Nonparametric Mann-Whitney U test and Spearman's rank correlation test were used. Serum TNF-alpha levels were significantly higher in patients with IC than perianal CD patients and healthy controls. Serum TNF-alpha levels significantly correlated with perianal CDAI score and with the presence of anal fistulas. Serum IL-12 levels correlated with the presence of anal strictures and were similar in all groups. Serum IL-6 levels were significantly higher in the presence of perianal fistulas and lower in the presence of anal strictures. Our study confirmed that TNF-alpha plays a major role in the perianal and intestinal CD. Furthermore, the significantly higher TNF-alpha serum levels in patients with IC suggest the use of anti-TNF-alpha in such patients. On the contrary, according to our results the efficacy of anti-IL-12 antibodies appears doubtful in chronic perianal CD or IC without anal strictures. The role of IL-6 as a systemic mediator for active chronic inflammation was confirmed and a possible role for its monoclonal antibody was suggested.