RESUMEN
AIMS: To evaluate and compare the association of four potential insulin resistance (IR) biomarkers (pigment-epithelium-derived factor [PEDF], retinol-binding-protein-4 [RBP-4], chitinase-3-like protein 1 [YKL-40] and brain-derived neurotrophic factor [BDNF]) with objective measures of IR. METHODS: We studied 81 subjects with different metabolic profiles. All participants underwent a 5-point OGTT with calculation of multiple IR indexes. A subgroup of 21 participants additionally underwent a hyperinsulinemic-euglycemic clamp. IR was defined as belonging to the highest quartile of incremental area under the insulin curve (iAUCins), or to the lowest quartile of the insulin sensitivity index (ISI). RESULTS: PEDF was associated with adiposity variables. PEDF and RBP4 increased linearly across quartiles of iAUCins (for PEDF p-trend=0.029; for RBP-4 p-trend=0.053). YKL-40 and BDNF were not associated with any adiposity or IR variable. PEDF and RBP-4 levels identified individuals with IR by the iAUCins definition: A PEDF cutoff of 11.9ng/mL had 60% sensitivity and 68% specificity, while a RBP-4 cutoff of 71.6ng/mL had 70% sensitivity and 57% specificity. In multiple regression analyses simultaneously including clinical variables and the studied biomarkers, only BMI, PEDF and RBP-4 remained significant predictors of IR. CONCLUSIONS: Plasma PEDF and RBP4 identified IR in subjects with no prior diagnosis of diabetes.
Asunto(s)
Biomarcadores/sangre , Factor Neurotrófico Derivado del Encéfalo/sangre , Proteína 1 Similar a Quitinasa-3/sangre , Técnicas de Diagnóstico Endocrino , Proteínas del Ojo/sangre , Resistencia a la Insulina , Factores de Crecimiento Nervioso/sangre , Proteínas Plasmáticas de Unión al Retinol/análisis , Serpinas/sangre , Adulto , Anciano , Femenino , Técnica de Clampeo de la Glucosa , Intolerancia a la Glucosa/sangre , Intolerancia a la Glucosa/complicaciones , Intolerancia a la Glucosa/diagnóstico , Prueba de Tolerancia a la Glucosa , Humanos , Masculino , Persona de Mediana Edad , Obesidad/sangre , Obesidad/complicaciones , Obesidad/metabolismo , Estado Prediabético/sangre , Estado Prediabético/complicaciones , Estado Prediabético/diagnóstico , Proteínas Plasmáticas de Unión al Retinol/metabolismoRESUMEN
Diabetic polyneuropathy (DPN) encompasses multiple syndromes with a common pathogenesis. Glycemic control shows a limited correlation with DPN, arguing in favor of major involvement of other factors, one of which is alterations of lipid and lipoprotein metabolism. Consistent associations have been found between plasma triglycerides/remnant lipoproteins and the risk of DPN. Studies in cultured nerve tissue or in murine models of diabetes have unveiled mechanisms linking lipid metabolism to DPN. Deficient insulin action increases fatty acids flux to nerve cells, inducing mitochondrial dysfunction, anomalous protein kinase C signaling, and perturbations in the physicochemical properties of the plasma membrane. Oxidized low-density lipoproteins bind to cellular receptors and promote generation of reactive oxygen species, worsening mitochondrial function and altering the electrical properties of neurons. Supplementation with specific fatty acids has led to prevention or reversal of different modalities of DPN in animal models. Post hoc and secondary analyses of clinical trials have found benefits of cholesterol reducing (statins and ezetimibe), triglyceride-reducing (fibrates), or lipid antioxidant (thioctic acid) therapies over the progression and severity of DPN. However, these findings are mostly hypothesis-generating. Randomized trials are warranted in which the impact of intensive plasma lipids normalization on DPN outcomes is specifically evaluated.