Pedro Rozas-Moreno

Circulating Levels of Sclerostin Are Increased in Patients with Type 2 Diabetes Mellitus

CONTEXT Diabetes mellitus is a risk factor for osteoporotic fractures. Sclerostin is an inhibitor of bone formation. However, there are no data about sclerostin levels in type 2 diabetes mellitus (T2DM). OBJECTIVES The aims were to evaluate serum sclerostin in T2DM patients and to analyze its relationship with bone metabolism. DESIGN, SETTING, AND PATIENTS This was a cross-sectional study. We compared serum sclerostin in the T2DM group (n = 74) and control group (n = 50), and we analyzed its relationship with calciotropic hormones, bone turnover markers, bone mineral density (BMD), and morphometric vertebral fractures. RESULTS Sclerostin levels were significantly higher in T2DM patients than control subjects (P < 0.001) and in T2DM males than in T2DM females (P < 0.001). Serum sclerostin was positively correlated with age in males T2DM (P = 0.031). In linear regression analysis, gender, study group, and age were predictive of sclerostin levels (P < 0.05). Sclerostin concentrations were positively associated with duration of T2DM (P = 0.064) and glycated hemoglobin (P = 0.074) independently of age in T2DM patients. Sclerostin was inversely related to bone turnover markers (P < 0.05) and positively related to lumbar spine, femoral neck, and total hip BMD (P < 0.05) in the T2DM group. Sclerostin was significantly lower in osteoporotic than nonosteoporotic patients with T2DM (P = 0.048). CONCLUSIONS Circulating sclerostin is increased in T2DM independently of gender and age. Serum sclerostin is also correlated with duration of T2DM, glycated hemoglobin, bone turnover markers, and BMD in T2DM patients. Additional studies are needed to evaluate the role of sclerostin on bone metabolism in this population.

Atherosclerotic Disease in Type 2 Diabetes Is Associated With an Increase in Sclerostin Levels

OBJECTIVE Wnt/β-catenin signaling is related to the pathogenesis of several diseases. Sclerostin is an inhibitor of Wnt/β-catenin signaling. However, there are few data regarding the sclerostin levels and vascular disease. Our aim was to examine the relationship between serum sclerostin and atherosclerotic disease (AD) in type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS We performed a cross-sectional study including 78 T2DM patients (45.3% females, mean age 59 ± 5.7 years; 54.7% males, 57.4 ± 6.7 years). RESULTS Serum sclerostin concentrations of T2DM patients in the AD group were significantly higher than in the non-AD group (P = 0.006). For each increase of 1 pmol/L in sclerostin level, there was a 4% increase of the risk of AD in T2DM patients. A concentration of ≥42.3 pmol/L showed a sensitivity of 69% and a specificity of 54.8% to detect an increased risk of AD. In males, sclerostin levels were higher in those with AD (P = 0.04), abnormal intima-media thickness (IMT) (P = 0.004), carotid plaques (P < 0.001), and aortic calcification (P < 0.001). In females, higher levels of sclerostin were related to abnormal IMT (P = 0.03) and aortic calcifications (P = 0.004). Homocysteine (β = 0.319 [95% CI 0.561–2.586], P = 0.003) and IMT (β = 0.330 [14.237–67.693], P = 0.003) were positively correlated with sclerostin. CONCLUSIONS Circulating sclerostin is increased in T2DM patients with atherosclerotic lesions. Although the sample size of our study was small, these data suggest that sclerostin levels could be a major modulator of Wnt signaling in AD with implications in T2DM patients.

Osteocalcin as a marker of metabolic risk in healthy postmenopausal women.

Objective: Several studies have reported the role of osteocalcin on glucose and fat metabolism. In this study, we analyzed the relationship between the concentration of osteocalcin and metabolic risk factors in healthy postmenopausal women. Methods: Cross-sectional analyses of 54 postmenopausal women aged 56 ± 3.5 years were conducted. We recorded clinical and biochemical data of metabolic risk including fasting plasma glucose (FPG) level and evaluated the relationship between serum osteocalcin and bone formation markers. Results: Serum osteocalcin concentration was negatively correlated with FPG (&bgr; = −0.328, P = 0.035). When osteocalcin levels were divided into tertiles, we found significant differences in FPG between the highest and the lowest tertiles (84 ± 11 vs 98 ± 30 mg/dL, respectively; P = 0.029). We found significantly lower osteocalcin levels in women with impaired fasting glucose levels than in those with normoglycemia (10.7 ± 6.1 vs 17.1 ± 7.4 ng/mL, respectively; P = 0.006). We also found lower concentrations of osteocalcin in obese women versus nonobese women (14.4 ± 8.8 vs 17.3 ± 6.2 ng/mL; P = 0.034) and women with increased low-density lipoprotein cholesterol levels versus those with low LDL-c levels (14.1 ± 5.4 vs 18.9 ± 9.1 ng/mL; P = 0.045). A concentration of 13.5 ng/ mL or lower showed a sensitivity of 85.7% and a specificity of 63.8% to detect increased risk for diabetes (FPG ≥100 mg/dL). In contrast, serum levels of bone alkaline phosphatase did not correlate with any variable. Conclusions: In this population, there is a consistent association between osteocalcin and markers of metabolic syndrome. We suggest potential usefulness of serum osteocalcin as a predictor for increased risk of diabetes in postmenopausal women.

FGF23 in type 2 diabetic patients: relationship with bone metabolism and vascular disease.

The relationship between fibroblast growth factor (FGF) 23 and vascular disease is well established in chronic kidney disease (CKD). Regarding serum FGF23 and bone fragility, there is contradictory data. Type 2 diabetes (T2D) is associated with higher rates of cardiovascular disease and fractures despite high bone mineral density (BMD), so the evaluation of FGF23 and its relationship with bone and cardiovascular disease in T2D is of interest. Our hypothesis was that serum FGF23 may be related to cardiovascular disease and bone metabolism (BMD, osteoporosis, and fractures) in T2D. We performed a cross-sectional study including 68 T2D subjects and 45 subjects without diabetes. We analyzed the relationship between circulating FGF23, bone metabolism, cardiovascular events, and intima-media thickness (IMT). There were no differences in FGF23 according to group. In the …

Metabolomic profile related to cardiovascular disease in patients with type 2 diabetes mellitus: A pilot study.

Type 2 diabetes mellitus (T2DM) patients have an increased risk of cardiovascular disease (CVD) that represents one of the main causes of mortality in this population. The knowledge of the underlie factors involved in the development of CVD and the discovery of new biomarkers of the disease could help to early identification of high-risk patients. Using liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS) we analyzed the serum metabolomic profile of 30 subject distributed according three groups: (i) T2DM patients with CVD; (ii) T2DM patients without CVD; (iii) non-diabetic subjects as controls (C) in order to identify potential biomarkers of the CVD related to T2DM. A partial least squares discriminant analysis (PLS-DA) and one-way analysis of variance (ANOVA) were applied to identify differential metabolites between different groups. Four glycerophospholipids were further identified as potential biomarkers of CVD in T2DM patients. Specifically, a reduction in phosphatidylcholine, lysophosphatidylcholine and lysophosphatidylethanolamine (LPE) serum levels were found in T2DM patients compared to controls, presenting the patients with CVD the lowest serum levels of these metabolites. These results show a generalized reduction of circulating phospholipids species in T2DM patients which is more pronounced in those with CVD providing information of the pathways involved in the pathogenesis and progression of CVD associated to T2DM.

Relationship of Dickkopf1 (DKK1) with Cardiovascular Disease and Bone Metabolism in Caucasian Type 2 Diabetes Mellitus

Objectives Dickkopf-1 (DKK1) is a potent inhibitor of Wnt signalling, which exerts anabolic effects on bone and also takes part in the regulation of vascular cells. Our aims were to evaluate serum DKK1 in type 2 diabetes (T2DM) patients and to analyze its relationships with cardiovascular disease (CVD). We also evaluated the relationship between DKK1 and bone metabolism. Design We conducted a cross-sectional study in which we measured serum DKK1 (ELISA, Biomedica) in 126 subjects: 72 patients with T2DM and 54 non-diabetic subjects. We analysed its relationship with clinical CVD, preclinical CVD expressed as carotid intima media thickness (IMT), and bone metabolism. Results T2DM patients with CVD (P = 0,026) and abnormal carotid IMT (P = 0,038) had higher DKK1 concentrations. DKK1 was related to the presence of CVD in T2DM, independently of the presence of risk factors for atherosclerosis. Therefore, for each increase of 28 pg/ml of serum DKK1 there was a 6,2% increase in the risk of CVD in T2DM patients. The ROC curve analysis to evaluate the usefulness of DKK1 as a marker for high risk of CVD showed an area under the curve of 0,667 (95% CI: 0,538–0,795; P = 0,016). In addition, there was a positive correlation between serum DKK1 and spine bone mineral density in the total sample (r = 0,183; P = 0,048). Conclusion In summary, circulating DKK1 levels are higher in T2DM with CVD and are associated with an abnormal carotid IMT in this cross-sectional study. DKK1 may be involved in vascular disease of T2DM patients.

Relationship between Proinflammatory and Antioxidant Proteins with the Severity of Cardiovascular Disease in Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus patients are at significant risk of cardiovascular disease, however, the pathophysiology of these complications is complex and incompletely known in this population. The aim of this study was to compare the serum proteome of patients with type 2 diabetes mellitus presenting or not presenting cardiovascular disease with non-diabetic subjects to find essential proteins related to these cardiovascular complications. This cross-sectional study compares the serum proteome by a combination of protein depletion with 2D-DIGE (2-dimension Difference Gel Electrophoresis) methodology. The proteins differentially expressed were identified by MALDI TOF/TOF (Matrix-assisted laser desorption/ionization and Time-Of-Flight ion detector) or LC-MS/MS (Liquid Chromatography coupled to Mass-Mass Spectrometry). Type 2 diabetes mellitus patients with cardiovascular disease showed higher expression of plasma retinol binding protein and glutathione peroxidase-3 compared to those without cardiovascular disease and non-diabetic controls. These results show that proteins related to the inflammatory and redox state appear to play an important role in the pathogenesis of the cardiovascular disease in the type 2 diabetes mellitus patients.

Adiponectin and leptin serum levels in osteoporotic postmenopausal women treated with raloxifene or alendronate.

ObjectiveClinical studies evaluating the role of leptin and adiponectin on bone metabolism had shown conflicting results, and data about the effect of anticatabolic drugs on these adipokines are scarce. Our aims were to determine adiponectin and leptin levels in osteoporotic postmenopausal women and their relationship with bone mass and bone turnover and to analyze changes on adiponectin and leptin levels after treatment with raloxifene or alendronate. MethodsWe selected 53 women (mean ± SD age, 63 ± 7 y) with postmenopausal osteoporosis divided into two treatment groups: raloxifene (60 mg/d; n = 20) or alendronate (70 mg/wk; n = 33) during a period of 1 year. Bone mineral density by dual-energy x-ray absorptiometry and serum levels of leptin, adiponectin, and bone turnovers markers were determined at baseline and at 1 year after treatment. ResultsBaseline levels of leptin were correlated to body mass index (r = 0.47; P < 0.01), waist circumference (r = 0.38, P = 0.01), and estradiol (r = 0.4, P = 0.003). Adiponectin was inversely related to bone-specific alkaline phosphatase (r = −0.41, P < 0.01) and serum crosslaps (r = −0.35; P < 0.01). There was no correlation between bone mineral density, leptin, and adiponectin. After 12 months, no changes were observed in leptin and adiponectin in the alendronate group; however, a significant increase in leptin levels (973.5 ± 637.4 pM/mL vs 1,305.7 ± 793.5 pM/mL; P = 0.031) was detected in the raloxifene group, whereas adiponectin levels showed no significant changes (P = 0.46). ConclusionsIn postmenopausal women with osteoporosis, raloxifene induces a significant increase in leptin levels without significant changes in adiponectin serum levels. The antiresorptive effect of raloxifene and alendronate is not substantially influenced by changes in leptin or adiponectin levels.

Serum 25 OH vitamin D concentrations and calcium intake are low in patients with prostate cancer

OBJECTIVE To evaluate dietary calcium intake (DCI) and vitamin D serum concentrations in patients with prostate cancer. METHODS We conducted a cross-sectional study including 91 subjects with prostate cancer. We determined DCI by a questionnaire, 25 OH vitamin D levels and bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA). RESULTS According to current guidelines (1000 mg/day), calcium intake was low in patients with prostate cancer (394±201 mg/day). Twenty-two percent (20) of patients had adequate levels of vitamin D, whereas 29.7% (27) of patients were vitamin D deficient and 48.3% (44) were classified as vitamin D insufficiency. Vitamin D levels were not different in patients with or without androgen-deprivation therapy. There were no correlation between DCI, 25 OH vitamin and BMD. CONCLUSIONS In summary, in our group of prostate cancer patients DCI was low and vitamin D deficiency is highly prevalent. Although this is a common condition in other populations, in this group of patients especially prone to osteoporosis could have more relevance. Additional research is needed to establish the consequences of low calcium intake and vitamin D deficiency in prostate cancer patients.

Encuesta sobre práctica clínica en el hiperparatiroidismo primario

Una reciente conferencia de consenso, promovida por los National Institutes of Health y la Endocrine Society, ha establecido un conjunto de recomendaciones para el tratamiento del hiperparatiroidismo primario en la practica clinica. Sin embargo, no se conoce los grados de conocimiento y de cumplimiento de estas recomendaciones por parte de los endocrinologos espanoles. En este articulo se revisan las recomendaciones del consenso y se presenta una encuesta elaborada por el Grupo de Trabajo de Metabolismo Mineral Oseo de la SEEN.