Estudio de polimorfismos y biomarcadores de remodelado óseo y de inflamación en la diabetes mellitus

Resumen

Study of polymorphisms and biomarkers of bone remodeling and inflammation in Diabetes Mellitus ABSTRACT Introduction: Chronic hyperglycemia in diabetes mellitus induces the overproduction of macrophage colony stimulating factor, RANKL and certain proinflammatory cytokines that activate osteoclastic proliferation and differentiation, as well as suppress osteoblast function and proliferation, decreasing mineralization and expression of several markers. All this adversely affects the skeleton and is associated with an increased risk of osteoporosis and fragility fractures. Aim: To evaluate the bone state of the diabetic patient and to evaluate the possible loss of bone mass throughout the study by determining the bone mineral density, the quantification of biochemical markers of bone remodeling and resorption and the evaluation of the inflammation state through interleukin 6 in both types of DM. To determine the genotypic frequency of polymorphisms of genes associated with bone loss. To study the most appropriate combination of markers and polymorphisms with clinical variables for the diagnosis and follow-up of bone disease in the diabetic patient. Methods: A one-year prospective longitudinal study was conducted in 53 patients with type 1 diabetes and 112 with type 2 diabetes. Clinical data were collected and fracture risk was calculated using the FRAX¿ questionnaire. Bone mineral density was determined at baseline and 1 year later. The concentrations of biochemical parameters were measured to evaluate phosphocalcic metabolism, renal function and lipid and hydrocarbon metabolism. Biochemical markers of bone resorption and formation remodeling (osteocalcin, aminoterminal propeptide of collagen type 1 and beta-crosslaps) were quantified, the inflammation status through interleukin 6 was evaluated in both types of diabetes and frequency genotype of the polymorphisms of the VDR, ESR1, OPG, RANKL and IL-6 genes. Results: Type 2 diabetes shows a higher risk of fracture (p = 0,001). In both types of diabetes, values of osteocalcin lower than the reference range are found, being these values lower in type 2 diabetes (12,28 ± 6,09 ng / ml vs 16,47 ± 6.32 ng / ml, (p <0,001). osteocalcin correlated inversely with obesity and lumbar bone mineral density data.In terms of inflammation parameters, interleukin 6 values increased throughout the study, with higher values in patients with type 2 diabetes (p < 0,001). There is association with bone mineral density in type 1 diabetes in the interleukin 6 polymorphism and in the case of type 2 diabetes in the BsmI, ApaI and FokI polymorphisms of the VDR. Conclusions: We can say that bone disease is one of the complications of diabetes, although the mechanisms by which they occur differ between both types of diabetes and that despite the increased lumbar T-score in type 2 diabetes, these patients have increased risk of fractures due to deterioration of bone quality. Bone markers decrease in patients with diabetes, suggesting that diabetes is a pathology with low bone turnover, associated, in the case of type 2 diabetes to a low-grade proinflammatory state, which can lead to a more fragile bone. It is therefore necessary to evaluate the clinical variables, markers of bone remodeling and inflammation and genetic polymorphisms to assess bone status and to be able to perform an appropriate therapeutic intervention.