Socioeconomic Position, Type 2 Diabetes and Long-Term Risk of Death

<div><p>Background</p><p>Both socioeconomic position (SEP) and type 2 diabetes have previously been found to be associated with mortality; however, little is known about the association between SEP, type 2 diabetes and long-term mortality when comorbidity is taken into account.</p><p>Methods</p><p>We conducted a population-based cohort study of all Danish citizens aged 40-69 years with no history of diabetes during 2001-2006 (N=2,330,206). The cohort was identified using nationwide registers, and it was followed for up to 11 years (mean follow-up was 9.5 years (SD: 2.6)). We estimated the age-standardised mortality rate (MR) and performed Poisson regression to estimate the mortality-rate-ratio (MRR) by educational level, income and cohabiting status among people with and without type 2 diabetes.</p><p>Results</p><p>We followed 2,330,206 people for 22,971,026 person-years at risk and identified 139,681 individuals with type 2 diabetes. In total, 195,661 people died during the study period; 19,959 of these had type 2 diabetes. The age-standardised MR increased with decreasing SEP both for people with and without diabetes. Type 2 diabetes and SEP both had a strong impact on the overall mortality; the combined effect of type 2 diabetes and SEP on mortality was additive rather than multiplicative. Compared to women without diabetes and in the highest income quintile, the MRR’s were 2.8 (95%CI 2.6, 3.0) higher for women with type 2 diabetes in the lowest income quintile, while diabetes alone increased the risk of mortality 2.0 (95%CI 1.9, 2.2) times and being in the lowest income quintile without diabetes 1.8 (95%CI 1.7,1.9) times after adjusting for comorbidity. For men, the MRR’s were 2.7 (95%CI 2.5,2.9), 1.9 (95%CI 1.8,2.0) and 1.8 (95%CI 1.8,1.9), respectively.</p><p>Conclusion</p><p>Both Type 2 diabetes and SEP were associated with the overall mortality. The relation between type 2 diabetes, SEP, and all-cause mortality was only partly explained by comorbidity.</p></div

Comprehensive Evaluation of TFF3 Promoter Hypomethylation and Molecular Biomarker Potential for Prostate Cancer Diagnosis and Prognosis

Overdiagnosis and overtreatment of clinically insignificant tumors remains a major problem in prostate cancer (PC) due to suboptimal diagnostic and prognostic tools. Thus, novel biomarkers are urgently needed. In this study, we investigated the biomarker potential of Trefoil factor 3 (TFF3) promoter methylation and RNA expression levels for PC. Initially, by quantitative methylation specific PCR (qMSP) analysis of a large radical prostatectomy (RP) cohort (n = 292), we found that the TFF3 promoter was significantly hypomethylated in PC compared to non-malignant (NM) prostate tissue samples (p &lt; 0.001) with an AUC (area under the curve) of 0.908 by receiver operating characteristics (ROC) curve analysis. Moreover, significant TFF3 promoter hypomethylation (p ≤ 0.010) as well as overexpression (p &lt; 0.001) was found in PC samples from another large independent patient sample set (498 PC vs. 67 NM) analyzed by Illumina 450K DNA methylation arrays and/or RNA sequencing. TFF3 promoter methylation and transcriptional expression levels were inversely correlated, suggesting that epigenetic mechanisms contribute to the regulation of gene activity. Furthermore, low TFF3 expression was significantly associated with high ERG, ETS transcription factor (ERG) expression (p &lt; 0.001), as well as with high Gleason score (p &lt; 0.001), advanced pathological T-stage (p &lt; 0.001), and prostate-specific antigen (PSA) recurrence after RP (p = 0.013; univariate Cox regression analysis). There were no significant associations between TFF3 promoter methylation levels, ERG status, or PSA recurrence in these RP cohorts. In conclusion, our results demonstrated diagnostic biomarker potential of TFF3 promoter hypomethylation for PC as well as prognostic biomarker potential of TFF3 RNA expression. To the best of our knowledge, this is the most comprehensive study of TFF3 promoter methylation and transcriptional expression in PC to date

Characteristics of people with and without diabetes and the general population aged 40–69 years, 2001–06.

<p>Characteristics of people with and without diabetes and the general population aged 40–69 years, 2001–06.</p

MRR for all-cause mortality among people with and without diabetes in the Danish population aged 40–69 years at inclusion, mean follow-up: 9.5 years.

<p>Model 1. Adjusted for age, duration of diabetes, calendar time. Model 2. Further adjusted for CVD and cancer before study start. Model 3. Further adjusted for CVD and cancer before study start and CVD, cancer and no. of other diseases according to Charlson Comorbidity Index during follow-up. Reference: Highest SEP-level among people without diabetes, Interaction between SEP and diabetic status, p<0.001</p><p>MRR for all-cause mortality among people with and without diabetes in the Danish population aged 40–69 years at inclusion, mean follow-up: 9.5 years.</p