These data suggest that increased CCL3L1 expression may enhance inflammatory responses and increase the chance of autoimmune disease. Genetic interaction data were consistent with a biologically plausible model; CCR5Delta32 protects against RA and T1D by blocking signalling through the CCR5 pathway, mitigating the pro-inflammatory effects of excess CCL3L1.
Vitamin C (ascorbate) is an essential micronutrient in humans, being required for a number of important biological functions via acting as an enzymatic cofactor and reducing agent. There is some evidence to suggest that people with type 2 diabetes mellitus (T2DM) have lower plasma vitamin C concentrations compared to those with normal glucose tolerance (NGT). The aim of this study was to investigate plasma vitamin C concentrations across the glycaemic spectrum and to explore correlations with indices of metabolic health. This is a cross-sectional observational pilot study in adults across the glycaemic spectrum from NGT to T2DM. Demographic and anthropometric data along with information on physical activity were collected and participants were asked to complete a four-day weighed food diary. Venous blood samples were collected and glycaemic indices, plasma vitamin C concentrations, hormone tests, lipid profiles, and high-sensitivity C-reactive protein (hs-CRP) were analysed. A total of 89 participants completed the study, including individuals with NGT (n = 35), prediabetes (n = 25), and T2DM managed by diet alone or on a regimen of Metformin only (n = 29). Plasma vitamin C concentrations were significantly lower in individuals with T2DM compared to those with NGT (41.2 µmol/L versus 57.4 µmol/L, p < 0.05) and a higher proportion of vitamin C deficiency (i.e. <11.0 µmol/L) was observed in both the prediabetes and T2DM groups. The results showed fasting glucose (p = 0.001), BMI (p = 0.001), smoking history (p = 0.003), and dietary vitamin C intake (p = 0.032) to be significant independent predictors of plasma vitamin C concentrations. In conclusion, these results suggest that adults with a history of smoking, prediabetes or T2DM, and/or obesity, have greater vitamin C requirements. Future research is required to investigate whether eating more vitamin C rich foods and/or taking vitamin C supplements may reduce the risk of progression to, and/or complications associated with, T2DM.
A cohort of 50-year-olds from Canterbury, New Zealand (N = 404), representative of midlife adults, undertook comprehensive health and dietary assessments. Fasting plasma vitamin C concentrations (N = 369) and dietary vitamin C intake (N = 250) were determined. The mean plasma vitamin C concentration was 44.2 µmol/L (95% CI 42.4, 46.0); 62% of the cohort had inadequate plasma vitamin C concentrations (i.e., <50 µmol/L), 13% of the cohort had hypovitaminosis C (i.e., <23 µmol/L), and 2.4% had plasma vitamin C concentrations indicating deficiency (i.e., <11 µmol/L). Men had a lower mean plasma vitamin C concentration than women, and a higher percentage of vitamin C inadequacy and deficiency. A higher prevalence of hypovitaminosis C and deficiency was observed in those of lower socio-economic status and in current smokers. Adults with higher vitamin C levels exhibited lower weight, BMI and waist circumference, and better measures of metabolic health, including HbA1c, insulin and triglycerides, all risk factors for type 2 diabetes. Lower levels of mild cognitive impairment were observed in those with the highest plasma vitamin C concentrations. Plasma vitamin C showed a stronger correlation with markers of metabolic health and cognitive impairment than dietary vitamin C.
Background:This study investigated the relationship of obesity, insulin resistance, inflammation and angiogenesis with cancer progression and survival in a colorectal cancer cohort.Methods:Clinical and pathological data, along with anthropometric and follow-up data, were collected from 344 consecutive colorectal cancer patients. Serum samples at diagnosis were analysed by immunoassay for adiponectin, C-reactive protein (CRP), vascular endothelial growth factor-A (VEGF-A), angiopoietin-2 (Ang-2), insulin-like growth factor-1 (IGF-1), insulin and C-peptide.Results:Serum Ang-2 and VEGF-A levels increased with tumour T stage (P=0.007 and P=0.025, respectively) and N stage (P=0.02 and P=0.03, respectively), and correlated with CRP levels (r=0.43, P<0.001 and r=0.23, P<0.001, respectively). Angiopoietin-2 correlated with C-peptide (r=0.14, P=0.007) and VEGF-A with IGF-1 in males (r=0.25, P=0.001). Kaplan–Meier analysis showed that patients with high serum levels of CRP and Ang-2 had significantly reduced survival (both P⩽0.001). After adjusting for tumour stage and age, Ang-2 remained a significant predictor of survival. The CRP levels were inversely associated with survival in American Joint Committee on Cancer stage II patients (P=0.038), suggesting that CRP could be used to support treatment decisions in this subgroup. Serum markers and anthropometric measures of obesity correlated with each other, but not with survival.Conclusion:Our study supports the concept that obesity-related inflammation, rather than obesity itself, is associated with colorectal cancer progression and survival. The study confirms serum Ang-2 as a predictive marker for outcome of colorectal cancer.
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