Background. Abnormalities in glucose homeostasis (AGH) frequently occur in kidney transplantation and favor vascular lesions. The purpose of this study was to analyze whether C-reactive protein (CRP), adiponectin, and ghrelin are markers of AGH and indicators of carotid atherosclerosis in kidney transplant patients with fasting plasma glucose below 126 mg/dL. Methods. This was a cross-sectional study of 85 kidney transplant patients (59 men; mean age: 52.4±11.6 years; median posttransplant follow-up 31 (range 3–61) months). All patients underwent an oral glucose tolerance test. Abnormalities in glucose homeostasis were diagnosed following American Diabetes Association criteria. CRP, adiponectin, and ghrelin levels were determined. Doppler ultrasound of the carotid artery was performed to determine intima media thickness (IMT) and atheromatous plaque. Results. A total of 50.5% of patients had AGH (12.9% were diagnosed with new-onset diabetes mellitus after transplantation and 37.7% had impaired glucose tolerance or impaired fasting glucose), whereas 49.4% were normoglycemic. Patients with AGH were older (P=0.002), had greater carotid IMT (P=0.022), and lower ghrelin concentrations (P=0.017) than normoglycemic patients. Logistic regression analyses showed ghrelin to be an independent marker for AGH (P=0.012) and AGH to be related to greater IMT (P=0.041). No differences in adiponectin or CRP were found in relation to AGH or atherosclerosis; however, there was a positive correlation between adiponectin levels and prednisone dose (r=0.240; P=0.044). Conclusions. A total of 50.5% of the study patients had abnormalities in glucose homeostasis. Patients with AGH had a higher percentage of preclinical atherosclerosis (greater carotid IMT). Ghrelin is an independent marker for abnormalities in glucose homeostasis.
New-onset diabetes mellitus after transplantation (NODAT) is a severe complication of kidney transplantation (KTx) with negative effects upon patient and graft survival. Several risk factors for NODAT have been described; however, the search for an early predictive marker is ongoing. It has recently been demonstrated that high concentrations of adiponectin (APN), which is an adipocyte-derived peptide with antiinflammatory and insulin-sensitizing properties, protect against future development of type 2 diabetes in healthy individuals. The purpose of this report was to study pretransplant insulin resistance and analyze pretransplant serum leptin and APN levels as independent risk factors for the development of NODAT.A total of 68 KTx patients were studied [mean age, 48 +/- 11 years; 70% males; body mass index (BMI), 25 +/- 3 kg/m]; 31 KTx patients with NODAT and 37 KTx patients without NODAT (non-NODAT) with similar age, sex, BMI, immunosuppression, and posttransplant time were studied. All patients received prednisone and calcineurin inhibitors (75% tacrolimus and 25% cyclosporine A), and 76% of patients received mycophenolate mofetil. Family history of diabetes mellitus was recorded. Pretransplant homeostasis model assessment for insulin resistance (HOMA-IR) index was calculated from fasting plasma glucose and insulin. Pretransplant serum leptin and APN levels were determined by radioimmunoassay.NODAT patients showed higher pretransplant plasma insulin concentrations [NODAT, 13.4 (11-22.7) microIU/mL; non-NODAT, 10.05 (7.45-18.4) microIU/mL; P=0.049], HOMA-IR index [NODAT, 4.18 (2.49-5.75); non-NODAT, 2.63 (1.52-4.68); P=0.043], and lower pretransplant serum APN concentration [NODAT, 8.78 (7.2-11.38) microg/mL; non-NODAT, 11.4 (8.56-15.27) microg/mL, P=0.012]. Inverse correlations between APN and BMI (r=-0.33; P=0.014) and APN and HOMA-IR index (r=-0.39; P=0.002) and between APN and NODAT (r=-0.31; P=0.011) were observed. Multiple logistic regression analysis showed the patients with lower pretransplant APN concentrations to be those at greater risk of developing NODAT [Odds Ratio=0.832 (0.71-0.96); P=0.01].Pretransplant serum APN concentration is an independent predictive factor for NODAT development in kidney-transplanted patients.
Background: Patients with psoriatic arthritis (PsA) have an increased risk of cardiovascular disease (CVD). The carotid ultrasound, which measures both carotid intima-media thickness (cIMT) and carotid plaque (CP), is a non-invasive tool useful in the detection of subclinical atherosclerosis 1 . However, carotid ultrasound differences between PsA patients and general population have not yet been well described. Objectives: This study aimed to compare the carotid ultrasound characteristics in PsA patients with controls. Methods: This cross-sectional study included 70 PsA patients that fulfilled the CASPAR (Classification Criteria for Psoriatic Arthritis) criteria and 70 controls subjects matched by age and comorbidities. Patients with a history of previous atherosclerotic CVD (ischemic heart disease, cerebrovascular accident or peripheral arterial disease) and pregnancy were excluded. A clinical history and blood tests were performed. Carotid B-mode ultrasonography was used for measurements of cIMT and the presence of plaques. Increased cIMT was defined as ≥0.9 mm to 1.1 mm. CP was defined as a focal narrowing ≥0.5 mm of the surrounding lumen or a cIMT ≥1.2 mm. Descriptive analysis was done with frequencies (%), mean (±SD) and median (q25-q75), and comparisons with Chi square, Student´s t and Mann-Whitney U tests. Results: A total of 138 subjects were included. Clinical and demographic characteristics are shown in Table 1. Increased cIMT and right carotid plaque were significantly more prevalent in PsA patients compared to controls (p= 0.017 and p=0.049, respectively). No significant differences were found in the prevalence of carotid plaque and in the intima-media thickness between the PsA patients and the control group. Table 1. Clinical and demographic characteristics. Variable PsA (n=69) Controls (n=69) P Age(mean±SD) 53.58±10.946 53.86±7.313 NS Women, n (%) 38(55.1) 59(85.5) <0.001 Obese, n (%) 26(37.7) 28(40.6) NS Type 2 Diabetes, n (%) 14(20.3) 9(13) NS Hypertension, n (%) 27(39.1) 19(27.5) NS Dyslipidemia, n (%) 29(42) 24(34.8) NS Active smoker, n(%) 15(21.7) 12(17.4) NS Disease duration, median (q25-q75) 5(2.5-8) - - Methotrexate, n (%) 46(66.7) - - Biologics, n (%) 23(33.3) - - DAS28-ESR, (mean±SD) 3.74±1.477 - - DAS28-CRP, (mean±SD) 2.43±1.088 - - DAPSA, median (q25-q75) 35(27.5-58.5) - - Conclusion: Patients with psoriatic arthritis have a higher cardiovascular risk, as proven by the increased cIMT found on carotid ultrasound results. Therefore, it is advisable to perform a carotid ultrasound in patients with PsA to achieve an optimal management of the disease. The rheumatologist must be aware of the importance of performing a complete cardiovascular evaluation to provide a correct treatment in order to lower possible cardiac events. References: [1]Lucke, M., Messner, W., Kim, E.S.H. et al. The impact of identifying carotid plaque on addressing cardiovascular risk in psoriatic arthritis. Arthritis Research & Therapy 18, 178 (2016). https://doi.org/10.1186/s13075-016-1074-2 Table 2. Carotid ultrasound findings. Variable PsA (n=69) Controls (n=69) P Any carotid plaque, n (%) 27(39.1) 17(24.6) NS Right carotid plaque, n (%) 18(26.1) 8(11.6) 0.049 Left carotid plaque, n (%) 19(27.5) 15(21.7) NS Increased cIMT, n (%) 9(13) 1(1.4) 0.017 Right cIMT, median (q25-q75) 0.58(0.46-0.76) 0.6(0.51-0.69) NS Left cIMT, median (q25-q75) 0.58(0.5-0.73) 0.61(0.54-0.78) NS Disclosure of Interests: None declared
Acromegaly is caused by excess growth hormone (GH) produced by a pituitary tumor. First-generation somatostatin receptor ligands (SRLs) are the first-line treatment. Several studies have linked E-cadherin loss and epithelial-mesenchymal transition (EMT) with resistance to SRLs. Our aim was to study EMT and its relationship with SRLs resistance in GH-producing tumors. We analyzed the expression of EMT-related genes by RT-qPCR in 57 tumors. The postsurgical response to SRLs was categorized as complete response, partial response, or nonresponse if IGF-1 was normal, had decreased more than 30% without normalization, or neither of those, respectively. Most tumors showed a hybrid and variable EMT expression profile not specifically associated with SRL response instead of a defined epithelial or mesenchymal phenotype. However, high SNAI1 expression was related to invasive and SRL-nonresponsive tumors. RORC was overexpressed in tumors treated with SRLs before surgery, and this increased expression was more prominent in those cases that normalized postsurgical IGF-1 levels under SRL treatment. In conclusion, GH-producing tumors showed a heterogeneous expression pattern of EMT-related genes that would partly explain the heterogeneous response to SRLs. SNAI1 and RORC may be useful to predict response to SRLs and help medical treatment decision making.
Lucas A, Llatjós M, Salinas I, Reverter J, Pizarro E, Sanmarti A. Fine-needle aspiration cytology of benign nodular thyroid disease. Value of re-aspiration. Eur J Endocrinol 1995;132:677–80. ISSN 0804–4643 Fine-needle aspiration cytology (FNAC) has become a widespread procedure for the study of thyroid nodules (TN). Some authors recommend the practice of repeated punctures for their follow-up. This study was done to determine the usefulness of repeated FNAC in patients with benign nodular thyroid disease. We have studied 251 fine-needle re-aspirations performed on 116 females aged 45.6 ± 14 years with benign nodular thyroid disease. The time elapsed between each consecutive FNAC was 1 year. No patients presented any changes in the size or consistency of their nodular goiters during this period; all FNACs were carried out by the same physician in the same thyroid area according to the Löwhagen technique, with a minimum of two or three aspirations of each nodule, and processed in the same way and valued by the same cytologist without any knowledge of previous cytological diagnoses. These were done using strictly classical criteria (Löwhagen). One hundred and five out of 116 patients (90.51%) with two consecutive FNACs (210) showed identical cytological diagnoses in the two specimens studied. The remaining 11 patients (9.48%) with two FNACs were diagnosed with colloid goiter and cyst alternately. Fifteen out of 19 patients (78.94%) with three FNACs showed identical cytological diagnoses in the three samples and the rest (21%) also demonstrated alternate diagnoses of colloid goiter and cyst. Our results show that the routine performance of repeated FNAC in the follow-up of females with benign nodular thyroid disease, without any clinical changes, is of limited usefulness. A Lucas, Endocrinology Service, Hospital Universitari "Germans Trias i Pujol", Ctra. de Canyet s/n, 08916 Badalona, Barcelona, Catalonia, Spain
Abstract Predicting which acromegaly patients could benefit from somatostatin receptor ligands (SRL) is a must for personalized medicine. Although many biomarkers linked to SRL response have been identified, there is no consensus criterion on how to assign this pharmacologic treatment according to biomarker levels. Our aim is to provide better predictive tools for an accurate acromegaly patient stratification regarding the ability to respond to SRL. We took advantage of a multicenter study of 71 acromegaly patients and we used advanced mathematical modelling to predict SRL response combining molecular and clinical information. Different models of patient stratification were obtained, with a much higher accuracy when the studied cohort is fragmented according to relevant clinical characteristics. Considering all the models, a patient stratification based on the extrasellar growth of the tumor, sex, age and the expression of E-cadherin, GHRL , IN1-GHRL , DRD2 , SSTR5 and PEBP1 is proposed, with accuracies that stand between 71 to 95%. In conclusion, the use of data mining could be very useful for implementation of personalized medicine in acromegaly through an interdisciplinary work between computer science, mathematics, biology and medicine. This new methodology opens a door to more precise and personalized medicine for acromegaly patients.
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