Cardiovasc Diabetol

BACKGROUND: Advanced glycation end-products play a role in diabetic vascular complications. Their optical properties allow to estimate their accumulation in tissues by measuring the skin autofluorescence (SAF). We searched for an association between SAF and major adverse cardiovascular events (MACE) incidence in subjects with Type 1 Diabetes (T1D) during a 7 year follow-up. METHODS: During year 2009, 232 subjects with T1D were included. SAF measurement, clinical [age, sex, body mass index (BMI), comorbidities] and biological data (HbA1C, blood lipids, renal parameters) were recorded. MACE (myocardial infarction, stroke, lower extremity amputation or a revascularization procedure) were registered at visits in the center or by phone call to general practitioners until 2016. RESULTS: The participants were mainly men (59.5%), 51.5 +/- 16.7 years old, with BMI 25.0 +/- 4.1 kg/m(2), diabetes duration 21.5 +/- 13.6 years, HbA1C 7.6 +/- 1.1%. LDL cholesterol was 1.04 +/- 0.29 g/L, estimated Glomerular Filtration Rates (CKD-EPI): 86.3 +/- 26.6 ml/min/1.73 m(2). Among these subjects, 25.1% were smokers, 45.3% had arterial hypertension, 15.9% had elevated AER (>/= 30 mg/24 h), and 9.9% subjects had a history of previous MACE. From 2009 to 2016, 22 patients had at least one new MACE: 6 myocardial infarctions, 1 lower limb amputation, 15 revascularization procedures. Their SAF was 2.63 +/- 0.73 arbitrary units (AU) vs 2.08 +/- 0.54 for other patients (p = 0.002). Using Cox-model, after adjustment for age (as the scale time), sex, diabetes duration, BMI, hypertension, smoking status, albumin excretion rates, statin treatment and a previous history of MACE, higher baseline levels of SAF were significantly associated with an increased risk of MACE during follow-up (HR = 4.13 [1.30-13.07]; p = 0.02 for 1 AU of SAF) and Kaplan-Meier curve follow-up showed significantly more frequent MACE in group with SAF upper the median (p = 0.001). CONCLUSION: A high SAF predicts MACE in patients with T1D

Skin fluorescence as a clinical tool for non-invasive assessment of advanced glycation and long-term complications of diabetes

Glycation is important in the development of complications of diabetes mellitus and may have a central role in the well-described glycaemic memory effect in developing these complications. Skin fluorescence has emerged over the last decade as a non-invasive method for assessing accumulation of advanced glycation endproducts. Skin fluorescence is independently related to micro- and macrovascular complications in both type 1 and type 2 diabetes mellitus and is associated with mortality in type 2 diabetes. The relation between skin fluorescence and cardiovascular disease also extends to other conditions with increased tissue AGE levels, such as renal failure. Besides cardiovascular complications, skin fluorescence has been associated, more recently, with other prevalent conditions in diabetes, such as brain atrophy and depression. Furthermore, skin fluorescence is related to past long-term glycaemic control and clinical markers of cardiovascular disease. This review will discuss the technique of skin fluorescence, its validation as a marker of tissue AGE accumulation, and its use as a clinical tool for the prediction of long-term complications in diabetes mellitus

Influence of Storage and inter- and intra-Assay Variability on the Measurement of Inflammatory Biomarkers in Population-Based Biobanking

Background: In the present study, we examined the effect of sample storage on the reproducibility of several inflammatory biomarkers, including high-sensitivity C-reactive protein (hsCRP), high-sensitivity interleukin-6 (hsIL6), and high-sensitivity tumor necrosis factor alpha (hsTNFα). In addition, we assessed inter- and intra-assay variability between collaborating biobanks.Methods: In total, 240 fasting plasma samples were obtained from the LifeLines biobank. Samples had been stored for less than 2 or more than 4 years at −80°C. Measurements were performed at three different laboratories. hsCRP was measured by immunonephelometry and ELISA, hsIL6, and hsTNFα samples were measured with ELISAs from two different manufacturers. For confirmation, similar analyses were performed on samples obtained from a subpopulation of 80 obese individuals. Passing–Bablok regression analysis and Bland–Altman plots were used to compare the results.Results: We observed good stability of samples stored at −80°C. hsCRP measured on the day of blood draw was similar to levels measured after more than 4 years of storage. There were small interlaboratory differences with the R&D ELISAs for hsIL6 and hsTNFα. We found a linear correlation between the Bender Medsystems ELISA and the R&D ELISA for hsIL6, with significantly higher levels measured with the R&D ELISA. Over 90% of hsTNFα samples measured with the IBL ELISA were below the detection limit of 0.13 ng/L, rendering this assay unsuitable for large-scale analysis. Similar results were found in the confirmation study.Conclusion: In summary, plasma hsCRP showed good stability in samples stored for either less than 2 years or more than 4 years at −80°C. Both the R&D and Bender Medsystems for hsIL6 measurement yielded similar results. The IBL hsTNFα assay is not suited for use in biobanking samples. Assays for the measurement of inflammatory biomarker assays should be rigorously tested before large sample sets are measured