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The genes regulating circulating levels of soluble gp130 (sgp130), the antagonist of the inflammatory response in atherosclerosis driven by interleukin 6, are largely unknown. Aims of the present study were to identify genetic loci associated with circulating sgp130 and to explore the potential association between variants associated with sgp130 and markers of subclinical atherosclerosis. The study is based on IMPROVE (n = 3703), a cardiovascular multicentre study designed to investigate the determinants of carotid intima media thickness, a measure of subclinical atherosclerosis. Genomic DNA was genotyped by the CardioMetaboChip and ImmunoChip. About 360,842 SNPs were tested for association with log-transformed sgp130, using linear regression adjusted for age, gender, and population stratification using PLINK v1.07. A p value of 1 × 10−5 was chosen as threshold for significance value. In an exploratory analysis, SNPs associated with sgp130 were tested for association with c-IMT measures. We identified two SNPs significantly associated with sgp130 levels and 24 showing suggestive association with sgp130 levels. One SNP (rs17688225) on chromosome 14 was positively associated with sgp130 serum levels (β = 0.03 SE = 0.007, p = 4.77 × 10−5) and inversely associated with c-IMT (c-IMTmean–max β = −0.001 SE = 0.005, p = 0.0342). Our data indicate that multiple loci regulate sgp130 levels and suggest a possible common pathway between sgp130 and c-IMT measures.

Background/Aim The association between alcohol consumption and subclinical atherosclerosis is still unclear. Using data from a European multicentre study, we assess subclinical atherosclerosis and its 30-month progression by carotid intima-media thickness (C-IMT) measurements, and correlate this information with self-reported data on alcohol consumption. Methods Between 2002–2004, 1772 men and 1931 women aged 54–79 years with at least three risk factors for cardiovascular disease (CVD) were recruited in Italy, France, Netherlands, Sweden, and Finland. Self-reported alcohol consumption, assessed at baseline, was categorized as follows: none (0 g/d), very-low (0 − 5 g/d), low (> 5 to ≤ 10 g/d), moderate (> 10 to ≤ 20 g/d for women, > 10 to ≤ 30 g/d for men) and high (> 20 g/d for women, > 30 g/d for men). C-IMT was measured in millimeters at baseline and after 30 months. Measurements consisted of the mean and maximum values of the common carotids (CC), internal carotid artery (ICA), and bifurcations (Bif) and whole carotid tree. We used quantile regression to describe the associations between C-IMT measures and alcohol consumption categories, adjusting for sex, age, physical activity, education, smoking, diet, and latitude. Results Adjusted differences between median C-IMT values in different levels of alcohol consumption (vs. very-low) showed that moderate alcohol consumption was associated with lower C-IMTmax[− 0.17(95%CI − 0.32; − 0.02)], and Bif-IMTmean[− 0.07(95%CI − 0.13; − 0.01)] at baseline and decreasing C-IMTmean[− 0.006 (95%CI − 0.011; − 0.000)], Bif-IMTmean[− 0.016(95%CI − 0.027; − 0.005)], ICA-IMTmean[− 0.009(95% − 0.016; − 0.002)] and ICA-IMTmax[− 0.016(95%: − 0.032; − 0.000)] after 30 months. There was no evidence of departure from linearity in the association between alcohol consumption and C-IMT. Conclusion In this European population at high risk of CVD, findings show an inverse relation between moderate alcohol consumption and carotid subclinical atherosclerosis and its 30-month progression, independently of several potential confounders.

Background: Health-related quality of life (HRQOL) in nursing home residents is generally low. The purpose of this study was to investigate the associations between HRQOL and two clinically relevant outcome measures, all-cause mortality and successful rehabilitation, in a nursing home population. Methods: In an observational prospective cohort study in a nursing home population, HRQOL was assessed with the RAND-36. A total of 184 patients were included, 159 (86%) completed the RAND-36 and were included in the study. A Cox proportional hazard model was used to investigate the independent association between HRQOL, rehabilitation and mortality with adjustment for confounders. Risk prediction capabilities were assessed with Harrell's C statistics and the proportion of explained variance (R-2). Results: The median age (interquartile range) was 79 (75-85) years. The health dimensions vitality (HR 0.88 (95% CI 0.77-0.99)) and mental health (HR 0.86 (95% CI 0.75-0.98)) were inversely associated and role functioning-physical (HR 1.08 (95% CI 1.02-1.15)) was positively associated with mortality. The Harrell's C value and the R-2 were

Objectives: To study vitamin B-12 concentrations in patients with type 2 diabetes with and without metformin use and to identify risk factors and consequences of low vitamin B-12 concentrations. Research design and methods: This study had a cross-sectional design. During eight weeks all patients with type 2 diabetes visiting the diabetic outpatient clinic of the Isala Clinics in Zwolle were approached for participation. Participation included measurement of haemoglobin, mean corpuscular volume and vitamin B-12 levels. Data on neuropathy were retrospectively searched for in the patient records. Vitamin B-12 deficiency was defined as serum B-12 concentrations Results: In the total cohort (n=298), the overall prevalence of vitamin B-12 concentrations Conclusion: Among patients with type 2 diabetes using metformin, the prevalence of vitamin B-12 deficiency is higher than compared with patients not using metformin. However, metformin use did not predict the chance of having anaemia or neuropathy.

Background: Relative mortality differences between educational level in mortality have been reported among diabetic as well as among non-diabetic subjects in Europe, but data on absolute differences are lacking. We studied the effect of educational disparities on mortality in a Dutch prospective cohort of type 2 diabetes mellitus (T2DM) patients. Methods: This study was part of the ZODIAC study, a prospective observational study of patients with T2DM. Data on educational level were first collected on 19 May 1998, and from this date on, 858 patients were included in 1998; educational level was known for 656 patients. Vital status was assessed in 2009. The relationship between mortality and educational level was studied using a Cox proportional hazard model, the relative index of inequality (RII), slope index of inequality (SII) and the population attributable risk (PAR). Educational level was divided into four categories; the highest educational level was used as reference. Results: After a median follow-up time of 9.7 years, 365 out of 858 patients had died. The hazard ratio of primary education for total mortality was 3.02 (95% CI 1.44-6.34). The RII was 2.85 (95% CI 1.21-6.67), the absolute difference in the risk for mortality (SII) was 384 deaths (95% CI 49-719) per 10,000 follow-up years. PAR for patients with the lowest level of education was 51.4%. Conclusions: A low educational level had a higher impact on mortality than having a macrovascular complication. Given the substantial differences in mortality between educational levels in T2DM, more understanding of underlying (modifiable) mechanisms is necessary.

Background: Patients' adherence to guidelines regarding self-monitoring of blood glucose (SMBG) is limited. However, there are no previous reports about the recommendations that are given in clinical practice concerning SMBG. The aim of this study was to investigate what healthcare providers recommend to insulin-treated patients with diabetes regarding frequency and timing of SMBG. Methods: In this cross-sectional descriptive study, primary care assistants, diabetes specialised nurses and doctors in the Netherlands were invited via e-mail to complete an internet survey. Results: A total of 980 (14%) professionals returned the questionnaire. Insulin pump users and patients with type 1 diabetes (T1DM) on 4 injections a day were advised to perform SMBG daily by 96% and 63% of the professionals, respectively. The majority of the professionals advised these patients to perform 3-4 measurements per day. There was less agreement on the timing (pre-and/or postprandial). Patients with type 2 diabetes (T2DM) on four injections were advised to perform SMBG less frequently. There was a wide variation in recommendations that were given to patients with T2DM on less intensive insulin regimens. Conclusion: This study investigated SMBG from a professional's perspective. A considerable and relevant variation in the recommendations about the number and timing of SMBG was observed. The most striking differences were found in patients with T2DM on less intensive insulin regimes, also with respect to the frequency of SMBG. Well-designed studies are necessary in order to give a more evidence-based advice on the basic frequency and timing of SMBG.

Background: Patients with type 2 diabetes mellitus (T2DM) as well as patients with obesity have increased cancer mortality. In a previous paper we suggested that there was a trend for decreased mortality in obese individuals with T2DM. The aim of the new analyses was to investigate the same relationship after increasing our sample size and extending our follow-up period. Patients and Methods: 1353 patients were followed prospectively as part of the ZODIAC study. The cancer mortality rate was evaluated using standardized mortality ratio (SMR) and its association with BMI (kg/m(2)) and obesity (>30 kg/m(2)) with Cox proportional hazard analysis. Results: After a median follow-up time of 9.8 years, 570 patients had died, of whom 122 died front malignancy. The SMR for cancer mortality was 1.47 (95%CI 1.22-1.76). BMI and obesity were not associated with cancer death. Conclusion: The trend towards an inverse relationship between obesity and cancer mortality, as reported previously disappeared after increasing sample size and follow-up to 9.6 years.

Background: Whether self-monitoring of blood glucose (SMBG) improves glycaemic control in patients with type 2 diabetes mellitus (T2DM) not using insulin is questionable. Our aim was to investigate the effects of SMBG in patients with T2DM who were in persistent moderate glycaemic control whilst not using insulin. Methods: Patients were eligible when between 18 and 70 years of age, with an HbA1c between 7 and 8.5%, using one or two oral blood glucose lowering agents. Forty-one of the anticipated 52 patients were randomly assigned to receive either SMBG added to usual care, or to continue with usual care for one year. A fasting glucose value and three postprandial glucose values were measured twice weekly (including a Saturday or a Sunday). The primary efficacy parameter was HbA1c. Furthermore, health-related quality of life and treatment satisfaction were assessed using the Short-form 36 Health Survey Questionnaire (SF-36), the Type 2 Diabetes Symptom Checklist (DSC-r), the Diabetes Treatment Satisfaction Questionnaire (DTSQ) and the WHO-Wellbeing Index (WHO-5). Results: Change in HbA1c between groups was -0.05% (95% CI: -0.51, 0.41; p=0.507). Also, there were no significant changes between groups on the DTSQ, DSC type 2, WHO-5 or SF-36, except for the SF-36 dimension 'health change' which was lower in the SBMG group (mean difference: -12 (95% CI: -20.9, -3.1). Conclusion: On top of the absence of a clinical benefit, tablet-treated T2DM patients experienced some worsening of their health perception. We therefore argue that the use of SMBG in this patient group is questionable, and its unlimited use and promotion should be reconsidered.

Background: The objective of this study was to determine whether the management of type 2 diabetes (DM2) can be transferred from an internist to a nurse specialised in diabetes (NSD). Methods: Ninety-three patients with DM2 referred by their general practitioner were randomised; 84 patients completed the study. The intervention group received care from an NSD who treated glycaemia, blood pressure and lipid profile by protocol. The control group received care from an internist. The primary endpoint was the main decrease in HbA1c. Secondary endpoints included blood pressure, lipid profile, healthcare costs, QOL, and patient satisfaction. Results: HbA1c, total cholesterol, LDL cholesterol and cholesterol/HDL ratio decreased significantly in both study populations after a follow-up time of 12 months. Cholesterol/HDL ratio decreased by 0.4 and 0.9 in the NSD and control group respectively (P=0.034 for the difference between groups). The decreases (95% confidence interval) in systolic blood pressure were 8.6 mmHg (2.6, 14.7) in the NSD group and 4.0 mmHg (-0.9, 8.9) in the control group, without a significant difference between groups. After one year, 33.3% of the patients in the NSD group achieved an HbA1c level Conclusion: NSDs using treatment protocols are able to provide effective care for patients with DM2, comparable with the care provided by an internist, with respect to clinical parameters, and superior with respect to healthcare costs and patient satisfaction.

Background: It is unclear whether there is a relationship between type two diabetes and cancer mortality. It also is unclear whether obesity and body mass index (BMI) are associated with cancer in type 2 diabetes patients. Patients and Methods: In 1998, 1,145 patients with type two diabetes mellitus were enrolled in the Zwolle Outpatient Diabetes project Intergrating Available Care (ZODIAC) study. In this project, general practitioners (GPs) were assisted by hospital-based diabetes specialist nurses. Vital status was assessed in September 2004. The cancer mortality rate was evaluated using standardized mortality ratio (SMR) and its association with BMI (kg/m(2)) and obesity (> 30 kg/m(2)) with the Cox proportional hazard ratio. Results: The median follow-up time was 5.8 years. A total of 335 patients had died, of whom 70 died from malignancy. The SMR for cancer mortality was 1.38.(95% CI 1.07-1.75). BM[ and obesity were not associated with cancer death. Conclusion: An increased cancer mortality rate was found in type two diabetes mellitus patients but there was no significant association between BM[ or obesity and cancer mortality.

The effect of a daily supplementation of 6 g fish oil (30% C20:5 omega-3 = EPA and 20% C22:6 omega-3 = DHA) for 1 month on renal function variables was investigated in a placebo-controlled (6 g coconut oil), prospective, randomized, double-blind study in acute postoperative cyclosporin A (CyA)-treated renal transplant recipients. Seventeen patients ingested placebo capsules (EPA-) and 14 patients fish oil (EPA +). Renal function tests were performed using the simultaneous determination of 1251-iothalamate and 1311-hippuran clearances for glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), respectively. Renal reserve filtration capacity was assessed by dopamine infusion, amino acid infusion, and a combination of both stimuli. After 1 month there were no significant differences in rejection episodes, CyA dose, or CyA levels. In contrast to our earlier observations, serum creatinine, creatinine clearance, GFR, and ERPF did not differ between the EPA-and EPA + groups. Filtration fraction (FF) differed significantly, being 0. 21 in the EPA-group versus 0. 26 in the EPA+ group. To exclude the possible influence of a rejection episode, the nonrejecting patients were analyzed separately, creating the subgroups EPA + re-and EPA-re-. These two groups were comparable in age, donor age, and GFR. The EPA + regroup had a significantly lower ERPF (164 ml/min per 1. 73 nr) than the EPA-re-group (262 ml/min per 1. 73 m2). FF was significantly higher in the EPA + re-group (0. 26) than in the EPA-re-group (0. 21). Following dopamine, no significant differences in the percentage increase of GFR and ERPF between both groups were observed, while FF fell to the same extent in both groups. Following amino acids, the fish oil-treated patients had a significantly better response on GFR (EPA + re-15. 3 versus EPA-re-10. 6%; P < 0. 05). The near-normal FF and the better response on amino acid infusion strongly suggest that at 1 month postoperatively, the CyA-and fish oil-treated patients have more balanced renal hemodynamics than the CyA-and coconut oil-treated patients.