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Objective: Patients with type 1 diabetes (T1D) have a higher risk of developing chronic kidney disease, cardiovascular events (CVEs), and mortality than the general population. We hypothesized that two previously published biomarkers, namely PRO-C6, a biomarker of collagen type VI formation, and C3M, a biomarker of collagen type III degradation, may be associated with impaired renal function and have prognostic value for adverse renal, CVE, and mortality in patients with T1D., Research Design and Methods: PRO-C6 and C3M in serum (sPRO-C6, sC3M) and urine (uPRO-C6, uC3M) were measured by ELISA in 663 patients with T1D ranging from normoalbuminuric to macroalbuminuric. Association of the biomarkers with mortality, CVEs, heart failure, decline in estimated glomerular filtration rate (eGFR) ≥30%, and end-stage renal disease (ESRD) were tested in Cox proportional hazards models after log 2 transformation and adjusted for relevant clinical characteristics. Hazard ratios (HRs) were reported per doubling of biomarker levels., Results: High levels of sPRO-C6 were independently associated with a higher risk of all-cause mortality (HR 2.26 [95% CI 1.31-3.87], P < 0.0031). There was an association with higher risk of CVEs ( n = 94) and heart failure ( n = 28) but not after adjustment ( P ≥ 0.58). In relation to renal outcomes, adjusted sPRO-C6 was associated with a higher risk of eGFR decline ≥30% in T1D, with eGFR >45 and >30 mL/min/1.73 m 2 , and with a higher risk of ESRD (all P ≤ 0.03). Higher uPRO-C6 was associated with a lower risk of decline in eGFR., Conclusions: In patients with T1D, higher sPRO-C6 was an independent predictor of both decline in eGFR and development of ESRD and of all-cause mortality. Higher uPRO-C6 was also associated with a lower risk of decline in eGFR., (© 2019 by the American Diabetes Association.)

Objective: Previous studies have provided inconclusive results on the role of uric acid (UA) in risk prediction. Here we aimed to improve the power and precision of the predictive value of UA for the risk of decline in kidney function, cardiovascular events (CVEs), and mortality in patients with type 1 diabetes (T1D)., Research Design and Methods: Plasma UA was measured in 670 patients with T1D and various degrees of albuminuria, ranging from normoalbuminuria to macroalbuminuria. Associations of UA with an estimated glomerular filtration rate (eGFR) decline of ≥30%, CVEs, and mortality were analyzed. The median follow-up time was 5.3 years [interquartile range (IQR) 2.7-6.2 years] for a decline in eGFR of ≥30%, 5.8 years (2.5-6.4 years) for progression in albuminuria status, 5.1 years (4.7-5.6 years) for CVE, and 6.2 years (5.8-6.7 years) for mortality. Both univariable and multivariable associations of UA with relevant outcomes and variables were reported. Hazard ratios (HRs) were calculated per doubling of the UA level., Results: A doubling in UA level was associated with a higher risk of decline in eGFR of ≥30% ( n = 89) (HR 3.18 [IQR 1.71-5.93]; P < 0.001), CVE ( n = 94) (HR 2.25 [IQR 1.20-4.21]; P = 0.011), and mortality ( n = 58) (HR 2.58 [IQR 1.12-5.90]; P = 0.025) in adjusted analyses. Adding UA to the adjusted model including conventional risk factors improved the relative integrated discrimination index by 12.6% for a decline in eGFR of ≥30% ( P < 0.001), 6.5% for CVE ( P = 0.010), and 11.8% ( P = 0.003) for mortality. A doubling in UA level was also associated with a steeper decline in eGFR ( P < 0.0026) and a steeper increase in urine albumin-to-creatinine ratio ( P < 0.0027) in adjusted analysis., Conclusions: In individuals with T1D, a higher UA level is associated with a higher risk of decline in kidney function, CVE, and mortality, independently of other risk factors. Our results suggest that UA has a promising role in risk stratification among individuals with T1D., (© 2019 by the American Diabetes Association.)

Background: To examine the association between plasma uric acid (UA) and the presence of diabetic complications including diabetic nephropathy and cardiovascular risk factors in patients with type 1 diabetes., Methods: This study, which is cross-sectional in design, included 676 Caucasian type 1 diabetes patients from the Steno Diabetes Center Copenhagen. Participants with UA within the three lowest sex-specific quartiles were compared with participants with levels in the highest quartile. Unadjusted and adjusted linear regression analyses were applied. Adjustment included sex, age, diabetes duration, body mass index, high-density lipoprotein cholesterol, smoking, haemoglobin A1c, 24-h pulse pressure, urinary albumin excretion rate (UAER), estimated glomerular filtration rate (eGFR) and treatment with renin-angiotensin-aldosterone system blockers., Results: Of the 676 patients, 372 (55%) were male, mean ± SD age was 55 ± 13 years and eGFR was 82 ± 26 mL/min/1.73 m2. The median UA was 0.30 (interquartile range 0.23-0.37) mmol/L. UA in the upper sex-specific quartile was associated with lower eGFR, higher UAER and carotid-femoral pulse wave velocity and lower 24 h and daytime diastolic blood pressure (BP) in unadjusted analyses (P < 0.001). Moreover, UA in the upper sex-specific quartile was associated with higher nighttime systolic BP and the presence of cardiovascular disease in unadjusted analyses (P ≤ 0.01), but significance was lost after adjustment (P ≥ 0.17). UA was higher across the retinopathy groups [nil (n = 142), simplex (n = 277), proliferative (n = 229) and blind (n = 19)] in unadjusted analyses (P < 0.0001), but not after adjustment (P = 0.12). Patients with an accelerated decline in eGFR (≥3 mL/min/year) had significantly higher UA at baseline (P = 0.006) compared with slow decliners (<3 mL/min/year), but significance was lost after adjustment (P = 0.10)., Conclusions: In type 1 diabetes patients, higher UA was associated with lower kidney function and other diabetic complications. The association between higher UA and lower eGFR and lower diastolic BP was independent of traditional risk factors., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Statins are important in the prevention of cardiovascular (CV) disease. However, they are associated with new-onset diabetes in a dose-dependent manner, particularly when the patient is already in risk of contracting diabetes. Meta-analyses estimate that the risk is increased by 9%. In absolute terms one major CV event can be prevented per 155 patients treated with statins per year compared to one new case of diabetes per 498 patients treated per year. However, this new evidence should not affect the guidelines, where the goal of LDL-cholesterol concentration is < 1,8 mmol/l in patients with high CV risk.

Statins are potent inhibitors of cholesterol biosynthesis. Statins are beneficial in the primary and secondary prevention of coronary heart disease. Recent studies indicate that there is an association between statin use and the development of new-onset diabetes mellitus. This article reviews the patophysiological mechanisms by different statins to explain this association.