B.C.T. van Bussel

Fish Consumption in Healthy Adults Is Associated with Decreased Circulating Biomarkers of Endothelial Dysfunction and Inflammation during a 6-Year Follow-Up

A healthy diet rich in fish, fruit, and vegetables, moderate in alcoholic beverages, and low in dairy products has been associated with lower circulating concentrations of biomarkers of endothelial dysfunction (ED) and low-grade inflammation (LGI). It is, however, unknown how consumption of these food groups affects ED and/or LGI over time. We measured diet by the computer-assisted crosscheck dietary history method at 36 ± 0.63 y of age (n = 301, women = 161). At 36 and 42 y of age, we measured von Willebrand factor, soluble intercellular adhesion molecule 1 (sICAM-1), soluble endothelial selectin, soluble vascular cell adhesion molecule 1 and soluble thrombomodulin (circulating biomarkers of ED); and C-reactive protein, serum amyloid A, IL-6, IL-8, TNFα, and sICAM-1 (circulating biomarkers of LGI). We investigated the associations between food groups and changes in combined biomarker Z-scores of ED and LGI [higher scores associated with greater risk of (incident) cardiovascular disease]. After adjustment for sex, energy intake, BMI, physical activity, alcohol consumption, smoking behavior, and other food groups, consumption of fish (per 100 g/wk), but none of the other food groups, was inversely associated with changes in ED [β (95%CI) = -0.06 (-0.10; -0.02); P = 0.003] and LGI [-0.05 (-0.09; -0.003); P = 0.036]. Additionally, EPA+DHA intake was inversely associated with changes in ED [β (95%CI) = -0.13 (-0.19; -0.07); P ≤ 0.001] and LGI [-0.09 (-0.16; -0.02); P = 0.013] and explained 83 and 40% of the association between fish and changes in ED and LGI. In conclusion, fish consumption, but not fruit, vegetable, alcoholic beverage, or dairy product consumption, was associated with decreased ED and LGI in healthy adults.

Adherence to a Mediterranean dietary pattern in early life is associated with lower arterial stiffness in adulthood: the Amsterdam Growth and Health Longitudinal Study

To investigate whether adherence to a Mediterranean dietary pattern during adolescence and early adulthood affects arterial stiffness in adulthood, and the extent to which any such association may be attributed to a beneficial impact of this diet on cardiovascular disease risk factors such as blood pressure, central fatness and dyslipidaemia.

Unhealthy dietary patterns associated with inflammation and endothelial dysfunction in type 1 diabetes: The EURODIAB study

BACKGROUND AND AIMS A healthy diet has been inversely associated with endothelial dysfunction (ED) and low-grade inflammation (LGI). We investigated the association between nutrient consumption and biomarkers of ED and LGI in type 1 diabetes. METHODS AND RESULTS We investigated 491 individuals. Nutrient consumption and lifestyle risk factors were measured in 1989 and 1997. Biomarkers of ED (von Willebrand factor, soluble vascular cell adhesion molecule-1 and soluble endothelial selectin) and LGI (C-reactive protein, interleukin 6 and tumour necrosis factor α) were measured in 1997 and averaged into Z-scores. The nutrient residual method was used to adjust individual nutrient intake for energy intake. Data were analysed with generalised estimation equations. We report increments/decrements in nutrient consumption, averaged over time, per +1 standard deviation (SD) of 1997 ED or LGI Z-scores, after adjustment for sex, age, duration of diabetes, investigation centre, body mass index, energy intake, smoking behaviour, alcohol consumption, and each of the other nutrients. One SD elevation in ED Z-score was associated with a diet lower in fibre [β(95%CI);-0.09(-0.18;-0.004)], polyunsaturated fat [-0.18(-0.31;-0.05)] and vegetable protein [-0.10(-0.20;-0.001)]. For the LGI Z-score results showed associations with fibre [-0.09(-0.17;-0.01)], polyunsaturated fat [-0.14(-0.24;-0.03)] and cholesterol [0.10(0.01; 0.18)]. CONCLUSION In type 1 diabetes, consumption of less fibre, polyunsaturated fat and vegetable protein, and more cholesterol over the study period was associated with more ED and LGI. Following dietary guidelines in type 1 diabetes may reduce cardiovascular disease risk by favourably affecting ED and LGI.

Polymorbidity in diabetes in older people: consequences for care and vocational training

Objective: To investigate the prevalence of complicating and concurrent morbidities in older diabetic patients and to evaluate to what extent their occurrence affects the burden of disease and use of medical healthcare. Study design: Cross-sectional analysis of retrospectively obtained data on comorbidities and use of medical healthcare. Healthcare registration systems were used to retrieve data on 300 patients with diabetes aged ⩾60 years who, according to the severity of their disease and intensity of care required, were treated in a regional general practitioner (GP), diabetes nurse specialist (DNS) or medical specialist (MS) practice. Results: Complicating and concurrent morbidities were often found irrespective of the type of practice involved. After adjustments for differences in sex, age and glycosylated haemoglobin (HbA1c), the extent of complicating comorbidities showed sequential increases in patients managed by GP, DNS and MS (mean number of 3.6, 4.7 and 6.7, respectively; ptrend<0.001). However, the mean number of concurrent comorbidities was similar across all three settings (2.1, 1.8 and 2.0, respectively). Both complicating and concurrent comorbidities were similarly associated with the extent of drug use (β = 0.49 (95% CI 0.40 to 0.58) and β = 0.57 (95% CI 0.52 to 0.72), respectively) and the number of consultations with specialists other than the main care giver (β = 1.19 (95% CI 1.15 to 1.24) and β = 1.21 (95% CI 1.14 to 1.28), respectively). However, the mean number of different specialists involved in a patient’s care per additional concurrent comorbidity was twice as high as per any additional complicating comorbidity (β = 0.60 (95% CI 0.48 to 0.71) vs β = 0.31 (95% CI 0.24 to 0.39)). Conclusions: The use of healthcare facilities by older patients with diabetes is substantial, irrespective of the complexity of the disease and the kind of practice involved. The common manifestation of complicating and concurrent comorbidities and their varying complexity in individual patients requires a patient-oriented rather than a disease-oriented approach and vocational training programmes for care givers that are tailored to the complexity of multiple chronic diseases.

Alcohol and red wine consumption, but not fruit, vegetables, fish or dairy products, are associated with less endothelial dysfunction and less low-grade inflammation: the Hoorn Study

PurposeEndothelial dysfunction and low-grade inflammation are key phenomena in the pathobiology of cardiovascular disease (CVD). Their dietary modification might explain the observed reduction in CVD that has been associated with a healthy diet rich in fruit, vegetables and fish, low in dairy products and with moderate alcohol and red wine consumption. We investigated the associations between the above food groups and endothelial dysfunction and low-grade inflammation in a population-based cohort of Dutch elderly individuals.Methods Diet was measured by food frequency questionnaire (n = 801; women = 399; age 68.5 ± 7.2 years). Endothelial dysfunction was determined (1) by combining von Willebrand factor, and soluble intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1, endothelial selectin and thrombomodulin, using Z-scores, into a biomarker score and (2) by flow-mediated vasodilation (FMD), and low-grade inflammation by combining C-reactive protein, serum amyloid A, interleukin 6, interleukin 8, tumour necrosis factor α and sICAM-1 into a biomarker score, with smaller FMD and higher scores representing more dysfunction and inflammation, respectively. We used linear regression analyses to adjust associations for sex, age, energy, glucose metabolism, body mass index, smoking, prior CVD, educational level, physical activity and each of the other food groups.Results Moderate [β (95% CI) −0.13 (−0.33; 0.07)] and high [−0.22 (−0.45; −0.003)] alcohol consumption, and red wine [−0.16 (−0.30; −0.01)] consumption, but none of the other food groups, were associated with a lower endothelial dysfunction biomarker score and a greater FMD. The associations for FMD were, however, not statistically significant. Only red wine consumption was associated with a lower low-grade inflammation biomarker score [−0.18 (−0.33; −0.04)].ConclusionsAlcohol and red wine consumption may favourably influence processes involved in atherothrombosis.

Diets poor in fibre, vegetable protein and polyunsaturated fat are associated with inflammation and endothelial dysfunction in type 1 diabetes mellitus: the EURODIAB study

Background and aims: TCF7L2 is both an activator and an inhibitor of transcription and the most highly associated type 2 diabetes gene known to date. It influences beta cell survival and function, i.e. incretin hormonal effects, insulin processing and secretion. However, its target genes in pancreatic islets are not fully described and the molecular mechanism whereby it propagates its effects on islet function is not known. The aim of this study is to identify the molecular mechanisms through which TCF7L2 influence beta cell survival and function. Materials and methods: Wister rat primary islets and INS-1 (832/13) cells were incubated with siRNA against Tcf7l2, both Tcf7l2 and TP53INP1 or both TCF7L2 and TP53 in 5.5 mM and 14.3 mM glucose. TCF7L2 activity, p53 activity and target gene expression (using qPCR) were measured after siRNA treatment. INS-1 cell apoptosis was measured by DNA degradation levels, caspase-3/7 levels and by using antibodies against Annexin V, and 7-AAD, visualized using confocal microscopy. Rat islet viability was estimated measuring metabolic rate. Rat islet apoptosis was estimated by measuring Caspase-3/7 level. Results: The type 2 diabetes associated genes TP53INP1, FTO, GIPR and ADAMTS9 were identified as TCF7L2 potential target gene using chromatin immunoprecipitation on microarrays. In INS-1 cells, siRNA mediated Tcf7l2 knock down (69.5 %) resulted in decreased TCF7L2 activity (91%) and differential expression of the target genes: Tp53 (14.5% increase), TP53INP1 (65.9% increase) and ADAMTS9 (82.8% decrease). TCF7L2 knockdown also lead to reduced cell viability (65%) and increased apoptosis (113%). The TCF7L2 induced cell death was replicated in rat primary islets. When restoring (decreasing) the Tp53inp1 expression level in TCF7L2 depleted islets, the decrease in cell viability and increase in apoptosis were prevented, suggesting that the Tcf7l2 effect is mediated via Tp53inp1. Furthermore, p53 depletion prohibited TCF7L2 down regulation induced cell death and elevation of Tp53inp1 expression in both INS-1 cells and rat primary islets. Conclusion: The type 2 diabetes associated genes TP53INP1 and ADAMTS9 are target genes of TCF7L2 in pancreatic islets. TCF7L2 induced apoptosis and decreased cell viability are mediated through activation of p53 and increased p53INP1 expression.