Bcl-2 and p53 immunophenotypes in colorectal adenocarcinoma in type 2 diabetes mellitus versus non-diabetic patients.

We aimed to investigate immunohistochemical expression of the p53 tumor suppressor protein, and the B-cell lymphoma-2 (Bcl-2) apoptotic protein in colorectal adenocarcinoma patients with or without type 2 diabetes mellitus (T2DM). Tissue sections from 95 paraffin-embedded colorectal adenocarcinomas, originating from 52 T2DM and 43 non-diabetic patients, were immunostained for p53 [Ventana mouse monoclonal primary antibody (mAb) in vitro diagnostic (IVD) anti-p53, clone Bp53-11] and Bcl-2 (Ventana mAb IVD anti-Bcl-2, clone Bcl-2/124). Immunohistochemistry analysis did not find statistically significant differences between the two groups, but analysis on subgroups of patients in terms of presence or absence of obesity identified overexpression of p53 (>70% of cells) in the T2DM obese patients compared to non-diabetics. Overexpression of p53 was present in 80% of tumor cells coming from T2DM obese patients compared to 37.2% of tumor cells coming from non-diabetics obese and non-obese, and in 36.6% of tumor cells coming from non-diabetic non-obese patients (p=0.024). There was a single non-diabetic obese patient with p53 overexpression. Most cancer cells of T2DM obese patients presented more frequently p53 overexpression by comparison with cancer cells of the T2DM non-obese patients (80% vs 40.5%, p=0.028). Bcl-2/p53 co-expression was an infrequent event in T2DM patients' group. The results of this study suggest that patients with colorectal adenocarcinoma that associate T2DM and obesity exhibit higher p53 protein expression in malignant cells. In conclusion, our research highlights that obesity is a potential key factor in the relationship between T2DM and colorectal cancer.

Effects of lifestyle changes including specific dietary intervention and physical activity in the management of patients with chronic hepatitis C--a randomized trial.

BACKGROUND: In patients with chronic hepatitis C (CHC), obesity is involved in the pathogenesis of insulin resistance, fatty liver disease and progression of fibrosis. The objective of this study was to compare a normoglucidic low-calorie diet (NGLCD) with a low-fat diet (LFD) among participants with CHC. Aimed to measure the impact of dietary changes in reduction of insulin resistance, obesity but also in steatosis and fibrosis. METHODS: Randomized, controlled trial in three medical centers with assessments at baseline, 6 months and 12 months. Participants were patients over 35 years with chronic hepatitis C (n = 120) with BMI over 25 kg/m². We evaluated the effects of NGLCD vs. LFD in weight management and metabolic improvement. The primary endpoint was to measure the impact of dietary changes through nutritional intervention in reversibility of insulin resistance, obesity, steatosis, and fibrosis. We performed anthropometric measurements, fasting glucose profile, serum lipids, liver profile, blood count at baseline, 6 and 12 months. Steatosis was evaluated using ultrasonographic criteria. Liver fibrosis was non-invasively assessed. RESULTS: After 6 and 12 months of intervention, both groups had a significant decrease in caloric consumption. At 6 months, weight loss was greater in the NGLCD group (-5.02 ± 3.43 kg vs. -4.1 ± 2.6 kg; p = 0.002) compared to the LFD group. At 1-year, however, weight loss was similar in both groups (-3.9 ± 3.3 kg vs. -3.1 ± 2.6 kg; p = 0.139). At 12 months, fasting plasma glucose, fasting plasma insulin, and HOMA-IR had significant improvements in both groups. With both diets aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT) decreased with significant differences; also there were significant improvements in AST/ALT ratio, Forns fibrosis index. The two diets were associated with reduction of both the prevalence and the severity of steatosis (all p < 0.001). At 12 months, total cholesterol, HDL-cholesterol, triglycerides improved in both groups (all p < 0.05). CONCLUSIONS: The present study establishes the benefits of low-calorie diet and low-fat diet in management of patients with hepatitis C regarding improvement of insulin resistance, steatosis and also fibrosis.Overweight or obese patients with CHC undergoing a lifestyle intervention (specific dietary intervention and physical activity) for 1-year had significant improvements in body weight, lipid and hepatic profile. TRIAL REGISTRATION: PNCI2-3343/41008/2007.