RESUMEN
AIMS/HYPOTHESIS: Earlier studies have shown that skin autofluorescence measured with an AGE reader estimates the accumulation of AGEs in the skin, which increases with ageing and is associated with the metabolic syndrome and type 2 diabetes. In the present study, we examined whether the measurement of skin autofluorescence can predict 4 year risk of incident type 2 diabetes, cardiovascular disease (CVD) and mortality in the general population. METHODS: For this prospective analysis, we included 72,880 participants of the Dutch Lifelines Cohort Study, who underwent baseline investigations between 2007 and 2013, had validated baseline skin autofluorescence values available and were not known to have diabetes or CVD. Individuals were diagnosed with incident type 2 diabetes by self-report or by a fasting blood glucose ≥7.0 mmol/l or HbA1c ≥48 mmol/mol (≥6.5%) at follow-up. Participants were diagnosed as having incident CVD (myocardial infarction, coronary interventions, cerebrovascular accident, transient ischaemic attack, intermittent claudication or vascular surgery) by self-report. Mortality was ascertained using the Municipal Personal Records Database. RESULTS: After a median follow-up of 4 years (range 0.5-10 years), 1056 participants (1.4%) had developed type 2 diabetes, 1258 individuals (1.7%) were diagnosed with CVD, while 928 (1.3%) had died. Baseline skin autofluorescence was elevated in participants with incident type 2 diabetes and/or CVD and in those who had died (all p < 0.001), compared with individuals who survived and remained free of the two diseases. Skin autofluorescence predicted the development of type 2 diabetes, CVD and mortality, independent of several traditional risk factors, such as the metabolic syndrome, glucose and HbA1c. CONCLUSIONS/INTERPRETATION: The non-invasive skin autofluorescence measurement is of clinical value for screening for future risk of type 2 diabetes, CVD and mortality, independent of glycaemic measures and the metabolic syndrome.
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Enfermedades Cardiovasculares/diagnóstico por imagen , Diabetes Mellitus Tipo 2/diagnóstico por imagen , Imagen Óptica/métodos , Piel/diagnóstico por imagen , Adulto , Anciano , Glucemia , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/mortalidad , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/mortalidad , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de RiesgoRESUMEN
PURPOSE: Advanced glycation endproducts (AGEs) and their precursors α-dicarbonyls are implicated in the progression of diabetic retinopathy. The purpose of this study was to assess AGEs and α-dicarbonyls in the vitreous of patients with type 2 diabetes mellitus (T2DM) with early stages or absence of diabetic retinopathy. METHODS: We examined vitreous samples obtained during vitrectomy from 31 T2DM patients presenting themselves with rhegmatogenous retinal detachment and compared these to 62 non-diabetic rhegmatogenous retinal detachment patients, matched on age, estimated glomerular filtration rate, smoking, intra-ocular lens implantation, and proliferative vitreoretinopathy. AGEs (pentosidine, Nε-(carboxymethyl)lysine, Nε-(carboxyethyl)lysine, and 5-hydro-5-methylimidazolone) and α-dicarbonyls (3-deoxyglucosone, methylglyoxal, and glyoxal) were measured by ultra performance liquid chromatography or high performance liquid chromatography. Skin autofluorescence was measured by the AGE Reader. RESULTS: Mean age was 64 ± 7.6 years for T2DM patients and 63 ± 8.1 years for controls. For T2DM patients, median diabetes duration was 2.2 (0.3-7.4) years. Non-proliferative diabetic retinopathy was present in 1 patient and classified as absent or background retinopathy in 30 patients. Vitreous levels of pentosidine (2.20 vs. 1.59 µmol/mol lysine, p = 0.012) and 3-deoxyglucosone (809 vs. 615 nmol/L, p = 0.001) were significantly elevated in T2DM patients compared to controls. Other AGEs and α-dicarbonyls in the vitreous were not significantly different. There was a trend for increased skin autofluorescence in T2DM patients as compared to controls (p = 0.07). CONCLUSIONS: Pentosidine and 3-deoxyglucosone concentrations were increased in the vitreous of rhegmatogenous retinal detachment patients with a relatively short duration of diabetes compared to non-diabetic rhegmatogenous retinal detachment patients.
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Diabetes Mellitus Tipo 2/complicaciones , Retinopatía Diabética/etiología , Retinopatía Diabética/metabolismo , Productos Finales de Glicación Avanzada/metabolismo , Desprendimiento de Retina/etiología , Desprendimiento de Retina/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Arginina/análogos & derivados , Arginina/metabolismo , Biomarcadores , Estudios de Casos y Controles , Desoxiglucosa/análogos & derivados , Desoxiglucosa/metabolismo , Femenino , Humanos , Lisina/análogos & derivados , Lisina/metabolismo , Masculino , Persona de Mediana EdadRESUMEN
Purpose: Advanced glycation endproducts (AGEs) have been suggested to play a role in retinal redetachment by promoting proliferative vitreoretinopathy (PVR). The purpose of this study was to investigate whether AGEs, in combination with other clinical characteristics, were able to identify patients at high risk for redetachment after vitrectomy for rhegmatogenous retinal detachment (RRD). Methods: In this prospective cohort study, 410 RRD patients were included. Skin autofluorescence (SAF), as a reflection of tissue AGE accumulation, was measured by the AGE Reader. In a subgroup of 90 patients, the well characterised AGEs Nε-(carboxymethyl)lysine (CML), Nε-(carboxyethyl)lysine (CEL), 5-hydro-5-methylimidazolone (MG-H1), and pentosidine, and the α-dicarbonyls methylglyoxal, glyoxal, and 3-deoxyglucosone were measured in vitreous biopsies using ultra- or high-performance liquid chromatography. The main outcome was retinal redetachment within 3 months after surgery. Results: Fifty-three patients developed a redetachment (aged 64 ± 9.6, 64% male) and were compared with 352 patients without a redetachment (aged 61 ± 9.4, 69% male); five patients were excluded for various reasons. Univariable analysis revealed that SAF, vitreous AGEs, and vitreous α-dicarbonyls were not significantly elevated in patients with a redetachment. Multivariable logistic regression analysis showed that surface area of detachment greater than 50% (odds ratio [OR] 2.74, confidence interval [CI] 1.45-5.17), PVR grade C (OR 4.57, CI 1.68-12.42), and pulse pressure (OR 1.37, CI 1.03-1.83 per SD) were independently associated with the occurrence of redetachment. Conclusions: Skin autofluorescence and vitreous AGEs are not suitable to identify patients at high risk for redetachment after vitrectomy surgery. Surface area of detachment greater than 50%, PVR grade C, and pulse pressure were associated with redetachment.
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Presión Sanguínea/fisiología , Productos Finales de Glicación Avanzada/metabolismo , Desprendimiento de Retina/diagnóstico , Agudeza Visual , Vitrectomía , Vitreorretinopatía Proliferativa/diagnóstico , Cuerpo Vítreo/patología , Biopsia , Cromatografía Líquida de Alta Presión , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Recurrencia , Desprendimiento de Retina/metabolismo , Desprendimiento de Retina/cirugía , Vitreorretinopatía Proliferativa/metabolismo , Vitreorretinopatía Proliferativa/cirugía , Cuerpo Vítreo/metabolismoRESUMEN
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.