Maciej Owecki

The role of adipocytokines in the pathogenesis of knee joint osteoarthritis.

Osteoarthritis (OA) is one of the most common causes of musculoskeletal disability in the world. Traditionally, it has been thought that obesity contributes to the development and progression of OA by increased mechanical load of the joint structures. Nevertheless, studies have shown that adipose tissue-derived cytokines (adipocytokines) are a possible link between obesity and OA. Furthermore, according to recent findings, not only articular cartilage may be the main target of these cytokines but also the synovial membrane, subchondral bone and infrapatellar fat pad may be encompassed in the process of degradation. This review presents the most recent reports on the contribution of adipocytokines to the knee joint cartilage degradation, osteophyte formation, infrapatellar fat pad alterations and synovitis.

Leptin, Soluble Leptin Receptors, Free Leptin Index, and Their Relationship with Insulin Resistance and BMI: High Normal BMI is the Threshold for Serum Leptin Increase in Humans

Leptin binds to the soluble form of its receptor (sOB-R). Leptin and sOB-R balance (free leptin index, FLI) reflect leptin activity. Leptin correlates with obesity and insulin resistance, but it remains uncertain whether sOB-R and FLI also do the same. Therefore, the aim of this study was to measure serum leptin, sOB-R, and FLI, and evaluate their associations with BMI and insulin resistance. We studied 145 obese and 49 nonobese humans. Obesity was defined according to WHO (BMI >30 kg/m (2)). Results are given as: median and interquartile range, obese vs. nonobese, respectively. Leptin (ng/ml): 30.83, 37.27 vs. 8.31, 10.04; sOB-R (ng/ml): 17.62, 17.05 vs. 27.25, 11.30; FLI: 231.2, 310.0 vs. 30.85, 27.77; HOMA: 5.99, 6.64 vs. 3.92, 4.52; p<0.001 for all. Serum leptin, sOB-R, and FLI did not correlate with insulin resistance separately in obese and nonobese humans. Leptin and FLI, but not sOB-R, were associated with insulin resistance in obese and nonobese subjects examined together. Leptin, sOB-R and FLI differed between obese and nonobese humans, and, except sOB-R, correlated with BMI. In piecewise linear regression, BMI threshold where leptin increased was 24.6 (r=0.5969, p=0.00016 and <0.00001). Leptin and its free index, but not sOB-R, correlate with BMI only in a mixed obese and nonobese human cohort, and not in isolated obese or nonobese groups. Moreover, BMI threshold where leptin starts to increase is 24.6 kg/m (2), which is lower than the cutoff for overweight. Under the conditions, metabolic abnormalities may occur in parallel to much lower BMI levels as expected so far.

Atypical features in depression: Association with obesity and bipolar disorder.

OBJECTIVES Depression with atypical features amounts to a significant proportion of depressed patients. Studies have shown its association with bipolarity and, recently, with obesity. In this study, we investigated atypical features of depression in relation to overweight/obesity in three diagnostic categories: unipolar depression, bipolar depression and dysthymia. METHODS Out of 512 depressed patients screened, we recruited 182 research subjects, consisting of 91 pairs, matched by age, gender and diagnosis, in which one member of the pair was within the normal weight range (BMI≤25) and the other was either overweight or obese (BMI>25). There were 35 pairs with unipolar depression, 27 with bipolar depression and 29 with dysthymia. Symptoms of atypical depression, such as increased appetite, hypersomnia, leaden paralysis, longstanding pattern of interpersonal rejection sensitivity, and, a significant weight gain in the past 3 months, were assessed. RESULTS All the symptoms of atypical depression were significantly more pronounced in those depressed patients with a BMI>25, compared with depressed subjects with a normal weight. Except for hypersomnia, these symptoms scored significantly higher in women compared to men. Among the diagnostic categories, symptoms of atypical depression were significantly higher in patients with bipolar disorder compared with both major depressive disorder and dysthymia. LIMITATIONS The preponderance of women, the assessment of atypical depression by adaptation of the DSM criteria, entirely Polish population, specificity of selection criteria. CONCLUSIONS The results demonstrated a higher intensity of atypical depressions symptoms in overweight/obese depressed patients. They also confirm the association between obesity and bipolarity.

Pasireotide - Mechanism of Action and Clinical Applications

BACKGROUND Pasireotide (SOM230) is a multi-receptor ligand somatostatin analogue (SSA) developed as the successor of the first-generation SSAs. Currently, pasireotide is recommended for the treatment of patients with Cushings disease in whom surgery was unsuccessful, and patients with acromegaly who either remain uncontrolled after surgical therapy or in whom tumor resection is not possible. METHODS AND RESULTS Phase II and III clinical trials have shown pasireotide efficacy in these diseases, with a similar rate of adverse events when compared with first-line SSA, although higher incidence of hyperglycemia has been observed. CONCLUSION Pasireotide therapy provides biochemical control, tumor volume reduction, and improves the quality of life in patients with those disorders. Furthermore, pasireotide might be considered as second-line therapy in patients with metastatic neuroendocrine tumors, and it also might be effective in other neoplasms with a high expression of somatostatin receptors. In addition, therapy with this novel agent has been effective in prevention of postoperative complications after pancreatectomy. However, considering the diversified responsiveness to this drug in vivo, future studies should identify factors predicting better clinical response to pasireotide.

New lower cutoff for serum high sensitive C-reactive protein in obese women indicates the risk of metabolic syndrome

Abstract Objective, materials and methods: The aim of this cross-sectional study with a consecutive enrolment was to analyse the role of high sensitive C-reactive protein (hs-CRP) measurement in similarly obese patients with and without the metabolic syndrome (MS). Results: In total, 589 obese patients were screened, of whom 138 aged 50–75 years were enrolled. The others were rejected due to strict criteria of enrolment, so that the group was highly homogenous in numerous clinical aspects. The study group consisted of 96 patients (49 females and 47 males) with MS; 42 patients (20 females and 22 males) had isolated obesity without MS and served as a control group. hs-CRP levels were significantly higher in patients with MS (p = .0012). To find out the CRP cutoff between MS and non-MS obesity, we performed ROC curve analyses: hs-CRP lower than 1.96 mg/l was the best predictor of simple obesity without MS (sensitivity = 66.7%; specificity = 66.7%; AUC = 0.7; p = .0002). In a separate analysis, hs-CRP level lower than 1.96 mg/dl remained statistically significant as a predictor of isolated central obesity only for females. Conclusions: Already a relatively low level of hs-CRP around 2.0 mg/dl is observed in the MS, whereas patients with simple obesity without the accompanying features of MS would have hs-CRP lower than this value.

Anti-thyroidal peroxidase antibodies are associated with thyrotropin levels in hypothyroid patients and in euthyroid individuals

OBJECTIVE The study was designed to evaluate the relationship between thyroid antibodies and gland dysfunction, with the aim of finding a clinically useful threshold value of thyreoperoxidase antibodies, which could prove to be predictive for thyroid failure. MATERIAL AND METHODS The study was conducted on 99 women, ages ranging from 18-91 years (mean age: 45.5 ±17.0), were treated as outpatients in the Department of Endocrinology, Metabolism and Internal Medicine. Analysis of serum samples for TSH concentration and anti-TPO titers was conducted. RESULTS The most common disorder was hypothyroidism. Anti-TPO titers above reference range values were observed in 35 patients (35.4%): 21 (60%) were hypothyroid and 11 (31.4 %) were euthyroid. The anti-TPO and TSH serum levels correlated both in patients with high thyroid antibody titers, and in the anti-TPO negative groups. To find the threshold value of anti- TPO that would help predict hypothyroidism, receiver operating curves were used. With this approach, TPO antibody titers over 17 IU/ml indicated hypothyroidism with a 90% sensitivity and 75% sensibility. CONCLUSIONS It can be postulated that the cutoff values of anti-TPO in the general population should be decreased in order to improve autoimmune thyroid disorder screening. Obviously, using that margin may lead initially to the detection of some false positive subjects. However, with lower cut-off values, more patients can be enrolled into thyroid follow-up groups. In this way, many people could avoid complications of undiagnosed, insidious thyroid failure.

Depression with atypical features in various kinds of affective disorders.

OBJECTIVES Assessment of atypical symptoms in various types of depressive disorders, using the authors questionnaire for symptoms of atypical depression. METHODS The study involved 70 patients with a diagnosis of depressive episode in the course of recurrent depression, 54 patients with a diagnosis of depressive episode in bipolar disorder (BD) and 58 patients with a diagnosis of dysthymia. To assess the severity of atypical symptoms, the special questionnaire has been elaborated. In each diagnostic group, half of patients had normal body weight, and half were overweight or obese (BMI > 25). RESULTS Patients with various types of depression did not differ significantly in terms of clinical and demographic factors. Symptoms of atypical depression such as increased appetite, weight gain and leaden paralysis were more common in women. Patients with bipolar depression had significantly increased symptoms such as hypersomnia (compared with dysthymia), and leaden paralysis (vs. recurrent depression and dysthymia). In overweight and obese patients, the severity of atypical symptoms correlated with body mass index and intensity of depression score on the 17-items Hamilton Depression Rating Scale. In this group, all symptoms of atypical depression were significantly more intense in patients with depression in the course of bipolar disorder. CONCLUSIONS The results indicate higher prevalence of symptoms of atypical depression in bipolar disorder compared with recurrent depression and dysthymia. They also suggest the interdependency between the symptoms of atypical depression, bipolar disorder and obesity.

Pulsatility index in carotid arteries is increased in levothyroxine-treated Hashimoto disease.

The aim of this case-control study was to evaluate carotid hemodynamic variables and traditional cardiovascular risk factors in women with Hashimoto thyroiditis (HT). The study group consisted of 31 females with HT on levothyroxine (L-T4) and 26 euthyroid women with HT without L-T4 matched for age and body mass index (BMI) as controls. Carotid intima-media thickness (CIMT), carotid extra-media thickness (CEMT), and pulsatility indexes in common carotid artery (PI CCA) and in internal carotid artery (PI ICA) were measured. BMI, waist circumference, lipid profile, fasting glucose and insulin levels, and parameters of thyroid function [TSH, free thyroxine (FT4) and antithyroperoxidase antibodies (TPOAbs)] were assessed. The study and the control groups did not differ in age, BMI, waist circumference, lipid profile, fasting glucose, and insulin levels. Results are expressed as median (IQR). Treated HT group had higher FT4 levels than nontreated [17.13 (5.11) pmol/l vs. 14.7 (2.27) pmol/l; p=0.0011] and similar TSH [1.64 (2.08) IU/ml vs. 2.07 (3.14) IU/ml; p=0.5915]. PI CCA and PI ICA were higher in the study group than in controls (p=0.0224 and p=0.0477, respectively). The difference remained statistically significant for PI ICA and PI CCA after adjustment for other variables (coefficient=0.09487; standard error=0.04438; p=0.037 and coefficient=0.1786; standard error=0.0870; p=0.0449, respectively). CIMT and CEMT were similar in both groups (p=0.8746 and p=0.0712, respectively). Women with HT on L-T4 replacement therapy have increased PI in common and internal carotid arteries than nontreated euthyroid HT patients. Therefore, it seems that hypothyroidism, but not autoimmune thyroiditis per se, influences arterial stiffness.

The efficacy of octreotide LAR (long acting release) treatment in patients with somatotropinoma, and mixed pituitary tumours

Objective: The efficacy of somatostatin analogues in the treatment of acromegaly is not always equal and therefore we wanted to evaluate the efficacy of therapy with octreotide long acting release (LAR) in patients with monohormonal tumours (somatotropinomas) in comparison to individuals with mixed pituitary tumours secreting alphasubunit.Method: The 35 acromegalic patients (18 males and 17 females), aged 41.8 ± 8.8 years, were divided into 2 groups according to the secreted hormones: 1 with mixed pituitary tumours with elevated growth hormone and alpha-subunit concentrations, the other with isolated growth hormone hypersecretion and normal alpha-subunit levels. The groups included 19 patients (9 males and 10 females), aged 40.1 ± 7.1 years (mean ± SD), and 16 patients (9 males and 7 females) aged 43.8 ± 8.8 years (mean ± SD), respectively.Results: The decrease of GH and IGF-I levels after octreotide LAR treatment were observed in both groups. However, the reduction of GH and IGF-I concentrations was not equal in both groups and the differences between both groups were statistically significant (P=0.01 for GH levels, and P=0.047 for IGF-I levels).Conclusions: After octreotide LAR treatment, the decrease of GH level and of mean IGF-I values was greater in patients with mixed pituitary tumours and high alpha-subunit concentrations than in patients with isolated GH hypersecretion and normal alpha-subunit levels.