Diepen J.A.V.,Endocrinology and Metabolic Diseases |
Bos J.,Endocrinology and Metabolic Diseases |
Stienstra R.,Radboud University Nijmegen |
Hodson L.,University of Oxford |
And 9 more authors.
Journal of Lipid Research | Year: 2011
Low-grade inflammation in different tissues, including activation of the nuclear factor k B pathway in liver, is involved in metabolic disorders such as type 2 diabetes and cardiovascular diseases (CVDs). In this study, we investigated the relation between chronic hepatocyte-specifi c overexpression of IkB kinase (IKK)- β and hypertriglyceridemia, an important risk factor for CVD, by evaluating whether activation of IKK- β only in the hepatocyte affects VLDL-triglyceride (TG) metabolism directly. Transgenic overexpression of constitutively active human IKK- β specifi cally in hepatocytes of hyperlipidemic APOE*3-Leiden mice clearly induced hypertriglyceridemia. Mechanistic in vivo studies revealed that the hypertriglyceridemia was caused by increased hepatic VLDL-TG production rather than a change in plasma VLDL-TG clearance. Studies in primary hepatocytes showed that IKK- β overexpression also enhances TG secretion in vitro, indicating a direct relation between IKK- β activation and TG production within the hepatocyte. Hepatic lipid analysis and hepatic gene expression analysis of pathways involved in lipid metabolism suggested that hepatocyte- specifi c IKK- β overexpression increases VLDL production not by increased steatosis or decreased FA oxidation, but most likely by carbohydrate-responsive element binding protein-mediated upregulation of Fas expression. These fi ndings implicate that specifi c activation of infl ammatory pathways exclusively within hepatocytes induces hypertriglyceridemia. Furthermore, we identify the hepatocytic IKK- β pathway as a possible target to treat hypertriglyceridemia. Copyright © 2011 by the American Society for Biochemistry and Molecular Biology, Inc.
Aamir A.H.,Endocrinology and Metabolic Diseases |
Jan S.,Khyber Institute of Ophthalmic Medical science
Journal of Postgraduate Medical Institute | Year: 2012
Objective: The objective of this study was to determine the frequency of diabetic retinopathy in a tertiary care hospital using digital retinal imaging technology. Methodology: This descriptive study was carried out in the department of Diabetes, Endocrinology and Metabolic Diseases, Hayatabad medical complex Peshawar. Patients referred from outpatient department, general practitioners and from private clinics were included and after taking their basic demographic data were referred to the department of Diabetes for Fundus Photograph using Canon CR1 non- mydriatic digital retinal camera. Photographs were analyzed first by Endocrinologist and later by an Ophthalmologist to assess the severity of retinopathy. Results: Two thousand one hundred and twenty three patients with type 2 diabetes were evaluated clinically followed by fundus photography by retinal digital imaging The frequency retinopathy and maculopathy was 32.03% and 6.31% respectively (both retinopathy and maculopathy 38.34%). Three seventy four patients (17.6% patients) received laser treatment for prevention of blindness. Conclusion: Screening for Diabetic retinopathy using digital camera is a useful technique and detects DR effectively in diabetic patients in a tertiary care setting. This technique is useful in mass screening and can detect, reduce and prevent blindness due to diabetes in our population.
Italian Association of Clinical Endocrinologists (AME) & Italian Association of Clinical Diabetologists (AMD) Position Statement: Diabetes mellitus and thyroid disorders: recommendations for clinical practice
Guastamacchia E.,University of Bari |
Triggiani V.,University of Bari |
Aglialoro A.,Diabetology |
Aiello A.,Cardarelli Hospital |
And 12 more authors.
Endocrine | Year: 2015
Thyroid disease and diabetes mellitus, the most common disorders in endocrine practice, are not infrequently associated in the same subject. An altered thyroid function may affect glucose tolerance and worsen metabolic control in patients with diabetes. Thyrotoxicosis increases the risk of hyperglycemic emergencies, while a clinically relevant hypothyroidism may have a detrimental effect on glycemic control in diabetic patients. The association of alterations in thyroid function with diabetes mellitus may adversely affect the risk of cardiovascular and microvascular complications resulting from diabetes. Moreover, the treatments used for both diabetes and thyroid disease, respectively, can impact one other. Finally, multinodular goiter, but not thyroid carcinoma, was shown to be more prevalent in type 2 diabetes mellitus. Aim of the present Position Statement is to focus on the evidence concerning the association of thyroid disease and diabetes mellitus and to provide some practical suggestions for an updated clinical management. © 2014, Springer Science+Business Media New York.
Viereck C.,Quadratum Consulting Services LLC |
Boudes P.,Endocrinology and Metabolic Diseases
Contemporary Clinical Trials | Year: 2011
We examined the impact of FDA's 2008 guidelines for addressing cardiovascular risks of new therapies for type 2 diabetes on clinical trials. We focused on the new class of incretin-modulating drugs, exenatide, sitagliptin, saxagliptin and liraglutide, which were approved in 2005-2010. We contrasted these findings with those from 2 different groups: 1. diabetes drugs approved in the same timeframe but with a non-incretin mechanism of action (colesevelam HCl and bromocriptine mesylate) and 2. diabetes drugs with NDAs delayed and not yet approved within the same time frame (vildagliptin, alogliptin, insulin inhalation powder, and exenatide long acting release). The new guidelines have had an important impact on clinical development. Review time has increased over 2-fold. The increase is seen even if a drug with the same mechanism of action has been already approved. Whereas exenatide (approved in 2005) required 10. months of regulatory review, the approval of liraglutide in 2010 required more than twice as long (21. months). In contrast, the marketing authorization of liraglutide in the EU required 14. months. Additionally, the manufacturer of vildagliptin announced in June 2008, 30. months after the NDA was filed, that a re-submission to meet FDA's demands was not planned. The drug however received marketing authorization in the EU in 2007. The number of randomized patients and patient-years in NDAs increased more than 2.5 and 4 fold, respectively since the guidelines. The significant cost increases and negative publicity because of rare adverse reactions will adversely affect future clinical research in type 2 diabetes and not address its burgeoning health care impact. © 2011 Elsevier Inc.
Giovanella L.,Oncology Institute of Southern Switzerland |
Giovanella L.,Clinical Chemistry and Laboratory Medicine |
Suriano S.,Oncology Institute of Southern Switzerland |
Keller F.,Clinical Chemistry and Laboratory Medicine |
And 2 more authors.
European Journal of Clinical Investigation | Year: 2011
Background: Hypercalcemia occurs in 10-20% of patients with hyperthyroidism, but its pathogenesis is still unclear.Aim: To evaluate changes in parathyroid hormone-related peptide (PTH-rP) concentration in hyperthyroid patients compared with healthy controls.Methods: We studied PTH-rP, parathormone (PTH) and ionized calcium levels in 153 hyperthyroid patients, and 89 control subjects. These variables were revaluated after attainment of euthyroidism with the antithyroid drug carbimazole for 6 months in a subgroup of 47 patients.Results: Pretreatment PTH-rP and ionized calcium level were significantly higher in hyperthyroid patients than in controls, whereas an opposite trend occurred for PTH. All parameters normalized after carbimazole therapy.Conclusion: Untreated hyperthyroid patients exhibited a significant elevation in serum ionized calcium and PTH-rP and a significant reduction in serum PTH levels when compared with healthy controls. Our data favoured the hypothesis of a direct involvement of PTH-rP in the pathogenesis of hypercalcemia in hyperthyroid patients. © 2010 The Authors. European Journal of Clinical Investigation © 2010 Stichting European Society for Clinical Investigation Journal Foundation.
Triggiani V.,Endocrinology and Metabolic Diseases |
Iacoviello M.,University of Bari |
Monzani F.,University of Pisa |
Puzzovivo A.,University of Bari |
And 9 more authors.
Endocrine, Metabolic and Immune Disorders - Drug Targets | Year: 2012
Background: It has been demonstrated that hypothyroidism can lead to significant hemodynamic alterations favoring the onset of chronic heart failure (CHF) as well as its progression. Furthermore, amiodarone, an iodinecontaining antiarhythmic drug frequently used in CHF patients, is often the cause of primary hypothyroidism. Aim of the Study: To define the prevalence and incidence of hypothyroidism in a group of CHF outpatients in stable clinical conditions, with particular reference to the role of amiodarone therapy. Results: Among the 422 enrolled patients (326 males, aged 65±12 years), 51 (12%) had a previous diagnosis of hypothyroidism while 21 (5%) were newly diagnosed at the enrolment. Then, the overall prevalence of hypothyroidism at the first evaluation was 17% and, as expected, it was significantly higher in females than males (33% vs 13%; p<0.001). During follow-up (median 28 months) hypothyroidism occurred in further 19 patients (incidence rate: 26/1000/year) and it was mainly attributable to amiodarone therapy. Considering all together the hypothyroid patients, either those affected by thyroid failure at the enrolment than those developing hypothyroidism during the follow-up, levothyroxine therapy was continued or started in 69% of them; however, normal serum TSH values were obtained only in 76% of treated cases (mean levothyroxine dose: 69±44 mcg/day). In any case, in the group of patients affected by hypothyroidism a significantly greater occurrence of heart failure progression was observed. Conclusions: Hypothyroidism, especially the subclinical form, frequently occurs in patients affected by CHF receiving amiodarone therapy. Given the unfavorable impact of hypothyroidism on the progression and prognosis of CHF, and the opportunity to adequately manage thyroid failure by means of levothyroxine replacement therapy without the need to withdraw amiodarone, we recommend regular testing of thyroid function in CHF patients, in particular in those submitted to amiodarone therapy, in order to early diagnose a condition of hypothyroidism and titrate substitutive treatment. © 2012 Bentham Science Publishers.
Rossi E.D.,Catholic University of the Sacred Heart |
Bizzarro T.,Catholic University of the Sacred Heart |
Fadda G.,Catholic University of the Sacred Heart |
Pontecorvi A.,Catholic University of the Sacred Heart |
And 2 more authors.
Cytopathology | Year: 2016
Objective: In fine needle aspiration cytology (FNAC), the category of benign thyroid lesions (BTL), which constitutes 65-70% of all thyroid FNAC, and can be correctly diagnosed by morphology alone, is an important entity. A diagnosis of BTL denotes a lesion managed with follow-up unless found in conjunction with compressive symptoms. Although this diagnosis can be quite simple, there are cases in which the scant cellular or colloid component may pose diagnostic issues. Herein, we describe the experiences of evaluating BTL at two large academic institutions. We evaluated the clinical importance of a correct diagnosis of BTL to define the exact inherent risk of a false-negative result (FNR). Methods: From January 2008 through to June 2013, 506 (3.6%) out of 15 850 patients with BTL underwent surgery. All nodules were sampled under sonographic guidance (US) and processed either with liquid-based cytology (LBC), Diff-Quik® smears or alcohol-Papanicolaou staining methods. Results: The histological follow-up of 506 BTL series included 493 benign and 13 malignant lesions. The latter group included four follicular carcinomas (FC), two classic variants of papillary thyroid carcinoma (PTC), one macrofollicular PTC and six follicular variants of PTC (FVPC). The malignancy rate for the BTL category was 2.5%. Conclusions: When diagnosed by expert cytopathologists, BTL represents a robust diagnosis and might reduce the number of FNR. Additional diagnostic experience and a large case series could enable cytopathologists to recognise all the morphological entities of BTL. An important additional aid is the extensive sampling of the lesions to reduce issues related to a low cellularity. © 2016 John Wiley & Sons Ltd.
PubMed | Catholic University of the Sacred Heart, Pathology and Laboratory Medicine and Endocrinology and Metabolic Diseases
Type: Journal Article | Journal: Cytopathology : official journal of the British Society for Clinical Cytology | Year: 2016
In fine needle aspiration cytology (FNAC), the category of benign thyroid lesions (BTL), which constitutes 65-70% of all thyroid FNAC, and can be correctly diagnosed by morphology alone, is an important entity. A diagnosis of BTL denotes a lesion managed with follow-up unless found in conjunction with compressive symptoms. Although this diagnosis can be quite simple, there are cases in which the scant cellular or colloid component may pose diagnostic issues. Herein, we describe the experiences of evaluating BTL at two large academic institutions. We evaluated the clinical importance of a correct diagnosis of BTL to define the exact inherent risk of a false-negative result (FNR).From January 2008 through to June 2013, 506 (3.6%) out of 15 850 patients with BTL underwent surgery. All nodules were sampled under sonographic guidance (US) and processed either with liquid-based cytology (LBC), Diff-Quik smears or alcohol-Papanicolaou staining methods.The histological follow-up of 506 BTL series included 493 benign and 13 malignant lesions. The latter group included four follicular carcinomas (FC), two classic variants of papillary thyroid carcinoma (PTC), one macrofollicular PTC and six follicular variants of PTC (FVPC). The malignancy rate for the BTL category was 2.5%.When diagnosed by expert cytopathologists, BTL represents a robust diagnosis and might reduce the number of FNR. Additional diagnostic experience and a large case series could enable cytopathologists to recognise all the morphological entities of BTL. An important additional aid is the extensive sampling of the lesions to reduce issues related to a low cellularity.