Kemal Agbaht

Circulating adiponectin represents a biomarker of the association between adiposity and bone mineral density

An association exists between adiposity, insulin resistance, and osteoporosis; however, the mechanism of this relationship remains enigmatic. We aimed to determine whether the insulin resistance index (HOMA-IR), serum adiponectin, or leptin levels are associated with bone mineral density (BMD). A cross-sectional, observational study was designed. Eighty-four postmenopausal ambulant women [52.5 (50.0–58.0) years; body mass index (BMI): 29.4 (25.9–33.8) kg/m2] referred for osteoporosis screening were enrolled. Anthropometric measures, fasting serum adiponectin and leptin levels, and the HOMA-IR were determined. The relationships between these variables and lumbar, hip, and forearm BMD measured by dual-energy X-ray absorptiometry (DXA) were analyzed. Considering all 84 participants, the HOMA-IR index was 1.82 (1.17–2.86), serum adiponectin was 13.25 (10.49–16.88) μg/ml, and serum leptin was 19.26 (14.94–24.90) ng/ml. BMI, waist circumference, and leptin positively correlated with hip and lumbar BMD, whereas adiponectin negatively correlated. Multivariate analysis confirmed an inverse relation between serum adiponectin level and femoral neck and lumbar BMD measurements. In total hip and forearm areas, there was no independent association of adipocytokines with BMD measurements. Instead, waist circumference was independently associated with BMD measurements. In conclusion, adiponectin may represent a biomarker in the relationship between visceral fat mass and BMD. However, this association is probably confounded by the specific body composition parameters (i.e., waist circumference, BMI) in postmenopausal women.

Changes in inflammatory and metabolic parameters after periodontal treatment in patients with and without obesity.

BACKGROUND Non-surgical periodontal treatment decreases serum levels of inflammatory cytokines in patients with and without obesity. However, the changes in metabolic parameters in association with these decreases in levels of inflammatory markers by periodontal treatment have not been evaluated in patients with obesity. The aim of this study is to evaluate the short-term changes in systemic inflammatory, lipid, and glucose parameters in the presence of obesity after periodontal treatment. METHODS The study included 22 dyslipemic patients with obesity and 24 healthy individuals without obesity with generalized chronic periodontitis. The periodontal parameters, anthropometric measurements, and serum levels of triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and lipoprotein-a, high-sensitive C-reactive protein, fasting blood glucose, insulin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and leptin were measured. A homeostasis model assessment of the insulin resistance (HOMA-IR) score was calculated before and 3 months after non-surgical periodontal treatment. RESULTS Both groups responded well to the periodontal treatment in terms of periodontal parameters. The treatment was also associated with a decrease in serum TNF-α and IL-6 levels and HOMA-IR scores in individuals with obesity and with a decrease in IL-6 levels in patients without obesity. Conversely, there were insignificant decreases in lipid profiles and serum fasting glucose of patients with obesity. CONCLUSION The non-surgical periodontal treatment causes a decrease in the levels of some circulating proinflammatory cytokines and may be associated with a decrease in insulin resistance in the obese population.

High frequency of aspirin resistance in patients with nephrotic syndrome

BACKGROUND Aspirin has a beneficial role in prevention of cardiovascular and thromboembolic events. Patients may experience thromboembolic events despite aspirin treatment, a phenomenon called aspirin resistance. We evaluated the frequency of aspirin resistance and its correlation with clinical and biochemical parameters among patients with nephrotic syndrome (NS). METHODS A total of 83 patients (50 males, 33 females, age range 18-79 years) with NS using aspirin 100 mg/day were included in the study. Demographic information and aetiology of NS based on the histology of a renal biopsy were recorded for each patient. Blood samples were drawn to investigate the association of aspirin resistance with inflammation and thrombotic risk factors. Aspirin resistance was defined as a normal collagen/epinephrine closure time<159 s using a platelet function analyzer (PFA-100). RESULTS Aspirin resistance was determined in 51 patients (61.4%). The number of patients exposed to azathioprine therapy was significantly higher in the aspirin-sensitive group (P=0.043), whereas patients exposed to cyclosporine therapy were significantly higher in the aspirin-resistant group (P=0.017). More patients in the aspirin-resistant group were on angiotensin-converting enzyme inhibitor therapy compared with the aspirin-sensitive group (P=0.024). The aspirin-resistant group showed significantly higher serum low-density lipoprotein cholesterol (LDL-C) (151±47 versus 104±21 mg/dL; P<0.001), triglyceride levels (192±116 versus 134±82 mg/dL; P=0.015) and glomerular filtration rates (91.8±43.0 versus 74.0±35.6 mL/min/1.73 m2; P=0.044) compared with the aspirin-sensitive group. In multivariate analysis, LDL-C was the only parameter associated independently with aspirin resistance [odds ratio (OR) 1.04, 95% confidence interval (CI) 1.02-1.06; P=0.004]. CONCLUSIONS A significant number of patients with NS are resistant to aspirin therapy. Serum LDL-C level is closely associated with aspirin resistance in NS.

DISCORDANCE BETWEEN GH AND IGF-1 LEVELS IN TURKISH ACROMEGALIC PATIENTS

OBJECTIVE Discordance between insulin-like growth factor-1 (IGF-1) and growth hormone (GH) levels is an important problem in the follow-up of patients diagnosed with acromegaly. Our aims were to evaluate the discordance between IGF-1 and GH levels and compare the performance of different cut-off levels for the nadir in GH (GHn) in acromegalic patients. METHODS The study included 63 acromegalic patients in a follow-up at a tertiary care university hospital facility. Levels of IGF-1, IGF binding protein-3 (IGFBP-3), and GH were investigated. The baseline GH and GHn levels were evaluated after an oral glucose tolerance test (cut-offs of 0.4 and 1 ng/mL, respectively). The discordance rates between GHn and IGF-1 levels, and IGF-1/IGFBP-3 ratios were determined. RESULTS We first adopted a GHn cut-off value of 1 ng/mL and found that 27 patients (42.9%) exhibited biochemical remission (BR) (IGF-1 <95th percentile, GH <1), and 25 patients (39.7%) had no BR (NBR) (IGF-1 ≥95th percentile, GH >1). Discordance in the presence of normal IGF-1 and nonsuppressed GH (DC1) occurred in 2 of 63 (3.2%) patients; discordance in the presence of high IGF-1 and suppressed GH (DC2) occurred in 9 of 63 (14.3%) patients. If the GHn cut-off value adopted was 0.4 ng/mL, the distributions were 17 of 63 (27.0%) patients in BR, 29 of 63 (46.0%) patients in NBR, 12 of 63 (19.0%) in DC1, and 5 of 63 (7.9%) patients in DC2. If only the baseline GH values were considered, the distributions were very similar to those with a GHn cut-off value of 0.4 ng/mL. The IGF-1/IGFBP-3 ratio was lowest in the BR group. CONCLUSION Adopting a GHn cut-off value of 0.4 ng/mL did not increase the test performance compared with baseline GH only. In contrast, in the follow-up of acromegalic patients, the IGF-1/IGFBP-3 ratio might be a useful measurement when discordance between IGF-1 and GH levels occurs. We propose that these values be considered in clinical practice. ABBREVIATIONS BR = biochemical remission DC1 = discordance group 1 DC2 = discordance group 2 DM = diabetes mellitus GH = growth hormone GHn = nadir in GH IGF-1 = insulin-like growth factor-1 IGFBP-3 = IGF binding protein-3 LAR = long-acting release NBR = not in biochemical remission OGTT = oral glucose tolerance test.

Catastrophic Bone Deformities Associated With Primary Hyperparathyroidism in a Middle-Aged Man

In March 2008, a 43-year-old male presented with generalized leg aches and gait disturbances associated with multiple pathological fractures in both upper (Figure 1, left) and lower (Figure 1, right) extremities. His medical records documented that in March 2001, he presented with leg aches to another hospital. With the suspicion of malignancy, total spine magnetic resonance imaging had been performed, and lytic lesions in cervical, thoracic, and lumbar vertebrae were detected. A total-body skeletal scintigraphy had demonstrated widespread lytic lesions. He had had pathological fractures in the right femur, and humerus, and he had been operated for those fractures. The histopathological examination of bone biopsy suggested an increase in both osteoclastic and osteoblastic activities. Thereafter, he had been diagnosed with primary hyperparathyroidism (corrected serum calcium 18.5 [8.4–10.2] mg/dL, PTH 400 [8–76] pg/mL). A right inferior parathyroid adenoma (28 20 mm in diameter), probably unrecognized parathyroid carcinoma, had been excised. Early after the surgery, serum calcium levels were noted as 8.4 mg/dL. The patient was lost in the interval between 2001 and 2008. His serum calcium, creatinine, PTH, and 25-hydroxyvitamin D levels were 15.6 mg/dL, 2.6 mg/dL, 1700 pg/mL, and 24.8 g/L, respectively. Neck ultrasound showed multinodular goiter and multiple hypoechoic lesions adjacent to thyroid. Total parathyroidectomy and thyroidectomy performed. Histopathological and immunohistochemical examinations revealed a parathyroid carcinoma in 3 different loci, with an invasion to the adjacent perineural, vascular, and lymphatic tissues (Figure 2, right sections), and benign nodular goiter. He was discharged from the hospital with serum calcium and PTH levels of 7.6 mg/dL and 430 pg/mL, respectively, and rehospitalization as soon as possible was advised to perform neck dissection. He disappeared and lost his follow-up once again until October 2010, when he presented with malaise, fatigue, gait disturbances, and marked renal insufficiency (calcium 16.5 mg/dL, PTH 1497 pg/mL, and serum creatinine 5.5 mg/dL). Radiography of the right femur demonstrated generalized brown tumors that were huge and incorporated in distal femur giving it the form bent bone, associated with osteitis fibrosa cystica (Figure 2, upper image). Neck ultrasonography showed an irregularly shaped parathyroid lesion (17 14 mm, Figure 2, lower left image), with a surrounding pathological lymph node (14 8 mm, Figure 2, middle image). He died of myocardial infarction when he was being prepared for neck exploration surgery and while he was awaiting for bureaucratic procedures that were started to import cinacalcet from other European countries. Some of the radiologic findings in the last admission were calcifications in Waldeyer’s ring, bilateral cervical lymph nodes 18 to 20 mm in diameter (neck computed tomography), atrophic kidneys with lobulated contours, indistinguishable cortex and medulla within the kidneys, opacities (probably cristaloids) within the collecting tubes of the urinary system (urinary system ultrasonography), mitral valve calcifications, myocardial hypertrophy (echocardiography), and 95% constriction within the left anterior descending artery (coronary angiography). Although the clinical spectrum of primary hyperparathyroidism has changed during the last decades (1), still severe bone deformities may be observed in cases with severe and long-lasting hyperparathyroidism, especially in