Aims/hypothesisSoluble tumor necrosis factor receptors 1 and 2 (sTNFR1 and sTNFR2) contribute to experimental diabetic kidney disease, a condition with substantially increased cardiovascular risk when present in patients. Therefore, we aimed to explore the levels of sTNFRs, and their association with prevalent kidney disease, incident cardiovascular disease, and risk of mortality independently of baseline kidney function and microalbuminuria in a cohort of patients with type 2 diabetes. In pre-defined secondary analyses we also investigated whether the sTNFRs predict adverse outcome in the absence of diabetic kidney disease.MethodsThe CARDIPP study, a cohort study of 607 diabetes patients [mean age 61 years, 44 % women, 45 cardiovascular events (fatal/non-fatal myocardial infarction or stroke) and 44 deaths during follow-up (mean 7.6 years)] was used.ResultsHigher sTNFR1 and sTNFR2 were associated with higher odds of prevalent kidney disease [odd ratio (OR) per standard deviation (SD) increase 1.60, 95 % confidence interval (CI) 1.32–1.93, p < 0.001 and OR 1.54, 95 % CI 1.21–1.97, p = 0.001, respectively]. In Cox regression models adjusting for age, sex, glomerular filtration rate and urinary albumin/creatinine ratio, higher sTNFR1 and sTNFR2 predicted incident cardiovascular events [hazard ratio (HR) per SD increase, 1.66, 95 % CI 1.29–2.174, p < 0.001 and HR 1.47, 95 % CI 1.13–1.91, p = 0.004, respectively]. Results were similar in separate models with adjustments for inflammatory markers, HbA1c, or established cardiovascular risk factors, or when participants with diabetic kidney disease at baseline were excluded (p < 0.01 for all). Both sTNFRs were associated with mortality.Conclusions/InterpretationsHigher circulating sTNFR1 and sTNFR2 are associated with diabetic kidney disease, and predicts incident cardiovascular disease and mortality independently of microalbuminuria and kidney function, even in those without kidney disease. Our findings support the clinical utility of sTNFRs as prognostic markers in type 2 diabetes.

Diabet. Med. 29, 1119–1125 (2012) Abstract Aims  The aim of this study was to explore the association between pedometer‐determined physical activity versus measures of obesity, inflammatory markers and arterial stiffness in people with Type 2 diabetes. Methods  We analysed data from 224 men and 103 women with Type 2 diabetes, aged 54–66 years. Physical activity was measured with waist‐mounted pedometers during three consecutive days and the number of steps/day were calculated and classified in four groups: < 5000 steps/day, 5000–7499 steps/day, 7500–9999 steps/day and ≥ 10000 steps/day. Blood samples were analysed for lipids, HbA1c, inflammatory markers including C‐reactive protein and interleukin‐6. Nurses measured blood pressure and anthropometrics. Aortic pulse wave velocity was measured with applanation tonometry over the carotid and femoral arteries. Results  Mean steps/day was 7683 ± 3883 (median 7222, interquartile range 4869–10 343). There were no differences in age, diabetes duration, blood pressure, lipids or glycaemic control between the four groups of pedometer‐determined physical activity. Subjects with higher steps/day had lower BMI (28.8 vs. 31.5 kg/m2, P < 0.001), waist circumference (101.7 vs. 108.0 cm, P < 0.001), lower levels of C‐reactive protein (1.6 vs. 2.6 mg/l, P = 0.007), lower levels of interleukin‐6 (1.9 vs. 3.8 pg ml, P < 0.001) and lower pulse wave velocity (10.2 vs. 11.0 m/s, P = 0.009) compared with less physically active people. Conclusions  We conclude that physical activity measured with pedometer was associated not only with less abdominal obesity, but also with decreased systemic low‐grade inflammation as well as with low arterial stiffness, in people with Type 2 diabetes.

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BackgroundLow levels of vitamin D have been related to increased mortality and morbidity in several non-diabetic studies. We aimed to prospectively study relationships between serum 25-OH vitamin D3 (vitamin D) and of serum parathyroid hormone (PTH) to total mortality in type 2 diabetes. We also aimed to compare the levels of these potential risk-factors in patients with and without diabetes.MethodsThe main study design was prospective and observational. We used baseline data from 472 men and 245 women who participated in the “Cardiovascular Risk factors in Patients with Diabetes—a Prospective study in Primary care” study. Patients were 55–66 years old at recruitment, and an age-matched non-diabetic sample of 129 individuals constituted controls for the baseline data. Carotid-femoral pulse-wave velocity (PWV) was measured with applanation-tonometry and carotid intima-media thickness (IMT) with ultrasound. Patients with diabetes were followed for all-cause mortality using the national Swedish Cause of Death Registry.ResultsLevels of vitamin D were lower in patients with diabetes than in controls, also after correction for age and obesity, while PTH levels did not differ. Nine women and 24 men died during 6 years of median follow up of the final cohort (n = 698). Vitamin D levels were negatively related to all-cause mortality in men independently of age, PTH, HbA1c, waist circumference, 24-h systolic ambulatory-blood pressure (ABP) and serum-apoB (p = 0.049). This finding was also statistically significant when PWV and IMT were added to the analyses (p = 0.028) and was not affected statistically when medications were also included in the regression-analysis (p = 0.01). In the women with type 2 diabetes, levels of PTH were positively related with all-cause mortality in the corresponding calculations (p = 0.016 without PWV and IMT, p = 0.006 with PWV and IMT, p = 0.045 when also adding medications to the analysis), while levels of vitamin D was without statistical significance (p >0.9).ConclusionsSerum vitamin D in men and serum PTH in women give prognostic information in terms of total-mortality that are independent of regular risk factors in addition to levels of ABP, IMT and PWV.Trial registrationClinicalTrials.gov: NCT01049737

We found that a high level of pedometer-determined physical activity was associated with a slower progression of arterial stiffness over 4 years in middle-aged people with Type 2 diabetes.