Management and modelling of diabetes and its complications

Nijpels, M.G.A.A.M. [Promotor]Dekker, J.M. [Promotor]Feenstra, T.L. [Copromotor]Bruijne, M.C. de [Copromotor

HbA(1c) is associated with altered expression in blood of cell cycle- and immune response-related genes

Therapeutic cell differentiatio

Sex- and site-specific differences in colorectal cancer risk among people with type 2 diabetes

Purpose: The prevalence of colorectal cancer is higher among patients with type 2 diabetes mellitus (T2D) than among patients without diabetes. Furthermore, men are at higher risk for developing colorectal cancer than women in the general population and also subsite-specific risks differ per sex. The aim was to evaluate the impact of T2D on these associations. Methods: A population-based matched cohort study was performed using data from the PHARMO Database Network. Patients with T2D were selected and matched (1:4) to diabetes free controls. Cox proportional hazards models were used to estimate hazard ratios (HRs) for CRC and its subsites. HRs were determined per sex and adjusted for age and socioeconomic status. The ratio of distal versus proximal colon cancer was calculated for people with T2D and controls per sex and stratified by age. Results: Over 55,000 people with T2D were matched to > 215,000 diabetes free controls. Men and women with T2D were 1.3 times more likely to develop colorectal cancer compared to controls. Men with T2D were at higher risk to develop distal colon cancer (hazard ratio (95% confidence interval), 1.42 (1.08–1.88)), and women with T2D were at higher risk for developing proximal colon cancer (hazard ratio (95% confidence interval), 1.58 (1.13–2.19)). For rectal cancer, no statistically significant risk was observed for both men and women. Conclusions: Sex-specific screening strategies and prevention protocols should be considered for people with T2D. More tailored screening strategies may optimize the effectiveness of colorectal cancer screening in terms of reducing incidence and mortality

Plasma Metabolomics Identifies Markers of Impaired Renal Function: A Meta-analysis of 3089 Persons with Type 2 Diabetes

CONTEXT: There is a need for novel biomarkers and better understanding of the pathophysiology of diabetic kidney disease. OBJECTIVE: To investigate associations between plasma metabolites and kidney function in people with type 2 diabetes (T2D). DESIGN: 3089 samples from individuals with T2D, collected between 1999 and 2015, from 5 independent Dutch cohort studies were included. Up to 7 years follow-up was available in 1100 individuals from 2 of the cohorts. MAIN OUTCOME MEASURES: Plasma metabolites (n = 149) were measured by nuclear magnetic resonance spectroscopy. Associations between metabolites and estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), and eGFR slopes were investigated in each study followed by random effect meta-analysis. Adjustments included traditional cardiovascular risk factors and correction for multiple testing. RESULTS: In total, 125 metabolites were significantly associated (PFDR = 1.5×10-32 - 0.046; β = -11.98-2.17) with eGFR. Inverse associations with eGFR were demonstrated for branched-chain and aromatic amino acids (AAAs), glycoprotein acetyls, triglycerides (TGs), lipids in very low-density lipoproteins (VLDL) subclasses, and fatty acids (PFDR < 0.03). We observed positive associations with cholesterol and phospholipids in high-density lipoproteins (HDL) and apolipoprotein A1 (PFDR < 0.05). Albeit some metabolites were associated with UACR levels (P < 0.05), significance was lost after correction for multiple testing. Tyrosine and HDL-related metabolites were positively associated with eGFR slopes before adjustment for multiple testing (PTyr = 0.003; PHDLrelated < 0.05), but not after. CONCLUSIONS: This study identified metabolites associated with impaired kidney function in T2D, implying involvement of lipid and amino acid metabolism in the pathogenesis. Whether these processes precede or are consequences of renal impairment needs further investigation

Heritability estimates for 361 blood metabolites across 40 genome-wide association studies

Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify >800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2 total), and the proportion of heritability captured by known metabolite loci (h2 Metabolite-hits) for 309 lipids and

PDB34 A PERSONALIZED SCREENING STRATEGY FOR DIABETIC RETINOPATHY:A COST-EFFECTIVENESS PERSPECTIVE

Objectives: Diabetic retinopathy (DR) is one of the leading causes of visual impairment and blindness. However, only a minority of the type 2 diabetes population is at risk of sight-threatening retinopathy (STR). Most current DR screening programs recommend that these patients should be screened annually or biennially. Recently, a prediction model for DR was developed. Combined with the appropriately chosen STR risk margin this resulted in personalized screening intervals. We examined the cost-effectiveness of using this personalized model compared with annual screening and the most recent Dutch guideline algorithm. Methods: DR screening intervals were determined for STR risk margins ranging from 0.0% to 4.0%, for each individual. Observational data (1998-2017) of the Diabetes Care System, a cohort of people with type 2 diabetes, were used (N=5,514). Missed cases were determined by comparing model based screening to observed grades of DR, then, costs were calculated based on screening and travel costs. Real time to develop STR was missing for 22 percent of STR cases, for these an optimistic and a pessimistic scenario were assumed. Finally, savings per missed case were determined, as compared with annual screening for finding the best risk margin and then this model was compared with the Dutch guideline algorithm. Results: The risk margins that maximized the savings per missed case compared to annual screening were 2.7% (€12,500) and 3.0% (€15,900) for the pessimistic and optimistic scenarios, respectively. Screening patients according to the Dutch guideline led to more missed cases (N=10) as well as higher costs compared to personalized screening (C=€2.1 per patient). Conclusions: A personalized DR screening model with a risk margin of around 3.0% is cheaper and more effective than the Dutch guideline. Assuming 800,000 diabetes patients in the Netherlands, implementing this personalized model could save 8.3 to 8.8 million euros annually

Cultural competency of gp trainees and gp trainers:A cross-sectional survey study

ObjectiveTo assess the cultural competence (CC) of GP trainees and GP trainers.Design and setting: A cross-sectional survey study was conducted at the GP Training Institute of Amsterdam UMC.SubjectsWe included 92 GP trainees and 186 GP trainers.Main outcome measuresWe measured the three domains of cultural competency: 1) knowledge, 2) culturally competent attitudes and 3) culturally competent skills. Regression models were used to identify factors associated with levels of CC. Participants rated their self-perceived CC at the beginning and end of the survey, and the correlation between self-perceived and measured CC was assessed.ResultsApproximately 94% of the GP trainees and 81% of the GP trainers scored low on knowledge; 45% and 42%, respectively, scored low on culturally competent attitudes. The level of culturally competent skills was moderate (54.3%) or low (48.4%) for most GP trainees and GP trainers. The year of residency and the GP training institute were significantly associated with one or more (sub-)domains of CC in GP trainees. Having &gt;10% migrant patients and experience as a GP trainer were positively associated with one or more (sub-) domains of cultural competence in GP trainers. The correlation between measured and self-perceived CC was positive overall but very weak (Spearman correlation coefficient ranging from -0.1-0.3).ConclusionThe level of cultural competence was low in both groups, especially in the knowledge scores. Cultural competence increased with experience and exposure to an ethnically diverse patient population. Our study highlights the need for cultural competence training in the GP training curricula.<br/