Baris Akinci

Biomarkers and cytokines of bone turnover: extensive evaluation in a cohort of patients with ankylosing spondylitis

BackgroundAnkylosing spondylitis (AS) is a chronic inflammatory disease of spine and sacroiliac joints; it is characterized by new bone formation, and the disease processes can be accompanied by osteoporosis. In the present study, we investigated changes in bone mineral density (BMD) and in the levels of various bone turnover-related biomarkers and cytokines in a cohort of AS patients, with regard to clinical parameters, disease activity, and treatment regimen.Methods55 AS patients and 33 healthy controls included in the study. Spinal mobility was assessed by the Bath Ankylosing Spondylitis Metrology Index (BASMI), and radiologic changes were scored by the Bath Ankylosing Spondylitis Radiologic Index (BASRI). Patients were also evaluated with the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Bone mineral density (BMD) assessed by dual energy X-ray absorptiometry. Various biomarkers and cytokines of bone turnover including osteoprotegerin (OPG), serum band 5 tartrate-resistant acid phosphatase (TRAP-5), soluble receptor activator of nuclear factor kappa-B ligand (sRANKL), secreted frizzled-related protein 1 (sFRP-1), Dickkopf-related protein 1 (DKK-1), and sclerostin were studied.ResultsThe levels of TRAP-5, NTX, sRANKL, sclerostin, sFRP-1, DKK-1, and IFNγ, were similar between the patients and controls (p > 0.05), while BMD of femoral neck, and OPG levels were significantly lower in AS patients (p < 0.05). In a subgroup analysis, patients with active disease had significantly higher concentrations of OPG compared with the inactive group. Rest of the biomarkers and cytokines of bone turnover were similar between the active and inactive disease groups. Subgroup analysis of patients receiving anti-TNFα agents and conventional therapy revealed that OPG concentrations were significantly lower in the patients receiving biological drugs, while BAP and DKK-1 were significantly higher in the patients treated with conventional agents.ConclusionsIn this cross-sectional study we showed that OPG levels were significantly lower in AS patients compared to healthy subjects. On the other hand, the levels of wingless (Wnt) signal pathway inhibitors seem not altered. Ectopic bone formation in AS may be related to dysfunction of these molecules at the cellular level.

Prediction of developing metabolic syndrome after gestational diabetes mellitus

OBJECTIVE To determine the predictors of subsequent development of metabolic syndrome (MS) in women with previous gestational diabetes mellitus (GDM). DESIGN Controlled clinical study. SETTING University hospital. PATIENT(S) One hundred sixty-four consecutive women with previous GDM were evaluated after a mean follow-up of 40.54 months from index pregnancy. Sixty-five lean women with negative screening for GDM were included as a control group. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Subjects were evaluated for diagnosis of MS according to criteria of the National Cholesterol Education Program and the International Diabetes Federation. Tests were performed including a 75-g oral glucose tolerance test (OGTT), fasting insulin, lipids, plasma fibrinogen, blood pressure, and body measurements. The homeostasis model assessment score was calculated. RESULT(S) The MS prevalence was higher in women with previous GDM, according to both definitions. Univariate analysis showed that prepregnancy obesity, weight gain during follow-up, and fasting glucose level at the OGTT of the index pregnancy were predictors of developing MS. Multivariate analysis showed that fasting glucose level >100 mg/dL at the OGTT of the index pregnancy was an independent predictor of the MS development. CONCLUSION(S) We suggest that early prediction of women with previous GDM who are at high risk for developing MS is possible, and it is vital to prevent MS-related complications.

Serum osteoprotegerin is associated with carotid intima media thickness in women with previous gestational diabetes

Circulating levels of osteoprotegerin (OPG) have been shown to be increased in patients with cardiovascular disorders and diabetes. The aim of this study was to determine serum OPG levels in women with previous gestational diabetes (GDM), and to investigate the relationship between OPG and carotid intima media thickness (IMT) and circulating cardiovascular risk factors. Serum OPG was measured in 46 women with previous GDM and 30 age-matched healthy controls. Carotid IMT was evaluated. Serum lipid, insulin and hsCRP levels, plasma fibrinogen, vWF and PAI-1 levels were measured. Serum OPG levels tended to be increased in women with previous GDM (p=0.058). Carotid IMT was increased in the study group. Women with previous GDM had elevated levels of hsCRP and PAI-1. OPG levels were positively correlated with age, fasting and post-load glucose levels, hsCRP, and carotid IMT. Multiple regression analysis showed that serum OPG was a statistically significant predictor for elevated carotid IMT. Our results revealed that OPG levels tended to be elevated in women with previous GDM. Significant association of OPG with carotid IMT suggested that OPG might play a role in the pathogenesis of endothelial dysfunction in women with previous GDM.

Is fasting glucose level during oral glucose tolerance test an indicator of the insulin need in gestational diabetes

Maintenance of a good metabolic control improves foetal and maternal outcomes in gestational diabetes mellitus (GDM). The aim of this study is to investigate the utility of diagnostic oral glucose tolerance test (OGTT) in prediction of the need of insulin in patients with GDM. One hundred and fifty five consecutive patients with GDM were included in the study. Patients were ordered MNT first. Those who failed to maintain glycemic targets were treated with insulin. Glucose levels obtained from the diagnostic OGTT were evaluated regarding the need of insulin during the rest of pregnancy. Fasting, 1h and 3h post-load glucose levels were significantly elevated in patients who required insulin. Multivariate analysis showed that fasting glucose level on OGTT was an independent predictor for the insulin need. A cut-off value of 105mg/dl had a fair specificity (91.89%) and positive predictive value (80.64%) for the prediction of patients who required insulin during the rest of their pregnancy. Our results suggest that fasting glucose level on OGTT is a predictor of the need for insulin treatment in GDM. A cut-off level of 105mg/dl seems to effectively determine high-risk patients for additional treatment other than MNT in GDM.

Evaluation of postpartum carbohydrate intolerance and cardiovascular risk factors in women with gestational diabetes

We aimed to evaluate the predictors of subsequent development of postpartum carbohydrate intolerance, metabolic syndrome and cardiovascular risk factors in women with previous GDM. Two hundred fifty-two consecutive women with GDM were enrolled. After exclusion of women who did not attend to the hospital for follow-up visits for minimum 1 year, data of 195 patients were evaluated. Seventy-one lean women with negative screening for GDM were included as a control group. The prevalence of diabetes, impaired glucose tolerance and impaired fasting glucose and metabolic syndrome was significantly higher in women with previous GDM than healthy controls. Women with previous GDM were more insulin resistant, had an atherogenic lipid profile and increased carotid IMT. The most important predictors of postpartum diabetes were the need for insulin treatment during index pregnancy and glucose values on antepartum OGTT. Among women with previous GDM, the development of postpartum diabetes and metabolic syndrome was associated with increased carotid IMT. Our data show that women with previous GDM are at high risk for developing carbohydrate intolerance, metabolic syndrome and atherosclerosis. Antepartum prediction of high risk subjects for the subsequent development of postpartum carbohydrate intolerance and metabolic syndrome seems to be vital to prevent cardiovascular outcomes.

Evaluation of markers of inflammation, insulin resistance and endothelial dysfunction in children at risk for overweight.

Objective: Childhood obesity is associated with impaired endothelial function, insulin resistance and inflammation. Being at risk for overweight has been defined as having a body mass index (BMI) between the 85th and 94th percentile for age and sex. In this study, we looked for features linked to cardiovascular risk in children who are at risk for overweight. Design: Twenty-one children who were at risk for overweight (study group) and 20 children with a BMI between the 25th–74th percentiles (controls) were studied. Fasting blood levels of glucose, insulin, total cholesterol, HDL cholesterol, triglycerides, uric acid, fibrinogen and high sensitive C-reactive protein (CRP) were assessed in both groups. LDL-cholesterol, HOMA-IR and QUICKI indices were calculated. Flow-mediated Vasodilatation (FMD) was determined for the evaluation of endothelial function. Results: Increased HOMA-IR was observed in children who were at risk for overweight. Waist circumference was the main predictor of insulin resistance in these children. Higher levels of CRP were found in the study group compared to controls, while plasma fibrinogen did not differ in the two groups. The children who were at risk for overweight had lower FMD values and slightly elevated lipids compared to controls; however, these differences were not statistically significant. Conclusion: Insulin resistance and inflammation indices were higher in children who were at risk for overweight as has been shown for obese children. The data suggest that appropriate treatment strategies for weight control are essential not only for obese children but also for those at risk for overweight.

Quality of life in patients with Takayasu's arteritis is impaired and comparable with rheumatoid arthritis and ankylosing spondylitis patients

The aims of the study were to assess the health-related quality of life (QOL) in patients with Takayasus arteritis (TA) by two different generic QOL instruments and to compare the results with those patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and healthy controls (HC). A cross-sectional study was performed in 51 patients with TA (41 women; mean age 38.4 ± 13.5), 43 RA (36 women; 55.2 ± 9.6), 31 AS (12 women; 41.2 ± 13.1), and 75 HC (53 women; 38.8 ± 10.9). Quality of life was assessed by using Short-Form 36 (SF-36) and Nottingham Health Profile (NHP). Separate dimensions of SF-36 and NHP and physical and mental summary scores of SF-36 as well were compared between patients and control groups. Physical and mental health summary scores and all SF-36 subscales, except for social functioning, were significantly lower in patients with TA than healthy controls. No significant differences between TA, RA, and AS patients were found in all SF-36 subscales and summary scores. NHP scores for energy level, pain, emotional reactions, and physical mobility were significantly higher in TA patients than controls. All NHP subscales, except for pain, were comparable in patients with TA, RA, and AS. Pain score was worse in RA patients. The NHP scores for sleep and social isolation were not different between patients and controls. Many aspects of QOL in patients with TA are significantly impaired in comparison with local healthy controls and similar to those in patients with RA and AS.

Increased osteoprotegerin levels in women with previous gestational diabetes developing metabolic syndrome

Osteoprotegerin (OPG), a novel soluble member of tumour necrosis factor receptor superfamily, has been shown to link cardiovascular disorders. The aim of this study is to investigate the potential relationship between serum OPG levels, cardiovascular risk factors and metabolic syndrome in a relatively large group of women with previous GDM. In this cross-sectional case-control study, 128 women with previous GDM and 67 age-matched controls were enrolled. Subjects were evaluated for the diagnosis of metabolic syndrome according to the criteria of the American Heart Association (AHA). Fasting glucose, insulin, serum lipids, CRP and OPG were assayed. HOMA score was calculated. Carotid intima media thickness (IMT) was measured. There was no significant increase in OPG levels in women with previous GDM when compared to controls. On the other hand, women with previous GDM developing metabolic syndrome had higher OPG levels than those without metabolic syndrome and healthy controls. Serum OPG levels were associated with obesity, insulin resistance, serum CRP and carotid IMT. Serum OPG is related to cardiovascular risk factors and metabolic syndrome, and might be involved in the development of cardiovascular disorders in women with previous GDM.

Allergic reactions to human insulin: a review of current knowledge and treatment options

Although the incidence of insulin allergy decreased after the introduction of recombinant human insulin preparations, it is still a major problem which may be life-threatening in some cases. In this article, we attempted to review current knowledge concerning allergic reactions to human insulin and discuss the available treatment options of insulin allergy.

Hashimoto's Thyroiditis, but not Treatment of Hypothyroidism, Is Associated with Altered TGF-β1 Levels

BACKGROUND Although the role of cytokines in the development of Hashimotos thyroiditis has already been established, its pathogenesis has not yet been clearly elucidated. The aim of our study was to investigate serum transforming growth factor-beta1 (TGF-beta1) levels in patients with Hashimotos thyroiditis as well as the effect of achieving euthyroidism by levothyroxine replacement on TGF-beta1 levels. METHODS Twenty nine female, newly diagnosed hypothyroid Hashimotos thyroiditis patients (16 overt, 13 subclinical hypothyroid) and 25 age- and sex-matched healthy controls were enrolled in the study. RESULTS Serum TGF-beta1 levels were lower in the Hashimotos thyroiditis group when compared with control cases. Although significant differences were noted in lipid levels and in anthropometric measurements following levothyroxine replacement, serum TGF-beta1 levels remained unchanged. CONCLUSIONS Our data suggest that altered TGF-beta1 levels are associated with the presence of Hashimotos thyroiditis, not with the treatment of thyroid dysfunction. Autoimmunity may have been triggered as a result of decreased immunosuppressive effect induced by depressed TGF-beta1 levels in patients with Hashimotos thyroiditis.