CLINICAL EFFICACY AND SAFETY OF ADEMETIONINE IN PATIENTS WITH DIABETES-ASSOCIATED OSTEOARTHRITIS: A CROSS-OVER PILOT STUDY

Osteoarthritis (OA) is one of most common rheumatic diseases, and currently there is no effective pharmacological treatment of OA. It has been suggested that lack of effective treatment is, in part, due to the disease heterogeneity which may lead to development of several OA subtypes (phenotypes). D...

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Autores principales:	I. V. Shirinsky, O. V. Sazonova, N. Yu. Kalinovskaya, V. S. Shirinsky
Formato:	article
Lenguaje:	RU
Publicado:	SPb RAACI 2016
Materias:	osteoarthritis diabetes mellitus dna methylation immune system ademetionine Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/8170aefa1b65444588771a2cbd96c8ae
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spelling	oai:doaj.org-article:8170aefa1b65444588771a2cbd96c8ae2021-11-18T08:03:45ZCLINICAL EFFICACY AND SAFETY OF ADEMETIONINE IN PATIENTS WITH DIABETES-ASSOCIATED OSTEOARTHRITIS: A CROSS-OVER PILOT STUDY1563-06252313-741X10.15789/1563-0625-2015-6-553-560https://doaj.org/article/8170aefa1b65444588771a2cbd96c8ae2016-01-01T00:00:00Zhttps://www.mimmun.ru/mimmun/article/view/962https://doaj.org/toc/1563-0625https://doaj.org/toc/2313-741XOsteoarthritis (OA) is one of most common rheumatic diseases, and currently there is no effective pharmacological treatment of OA. It has been suggested that lack of effective treatment is, in part, due to the disease heterogeneity which may lead to development of several OA subtypes (phenotypes). Diabetes-associated OA is among the proposed OA phenotypes. The key mechanism involved into inflammatory and degenerative changes in OA is a decrease in DNA methylation suggested for several cell types, that was also demonstrated in type 2 diabetes mellitus. Therefore, pharmacological increase of DNA methylation may be an effective treatment strategy which may exert pleiotropic effects in diabetes-associated OA. In a randomized crossover study, we have evaluated efficacy and safety of ademetionine, a methyl group donor, in comparison with chondroitine sulfate in patients with OA associated with type 2 diabetes mellitus. The patients were randomly assigned to sequential treatment of chondroitine sulfate/ademetionine or ademetionine/chondroitine sulfate during one month, with a washout period of 2 weeks. The primary endpoint was pain measured according to visual analogue scale (VAS). Painful symptoms, as well as function and disease signs in knee, hip and hand joints were also assessed with KOOS, WOMAC, and FIHOA scales. General performance was assessed with SF–36 scale. To evaluate systemic inflammation, we measured serum IL-6, IL-18, adiponectin, and CRP using ELISA technique. Concentrations of serum cartilage destruction biomarkers (aggrecan and antibodies to collagen type II) were assessed by ELISA. Serum lipid levels were measured with standard method; glycated hemoglobin was assessed with liquid chromatography. Ten patients (all women, age 61.7-74.2 year with BMI of 1.1-38.4 kg/m2) were included in the study. It has been demonstrated that ademetionine showed a statistically significant analgetic effect (decrease in VAS pain), improved knee function and reduced symptoms in knee joints (as measured by KOOS subscales), and did not influence the levels of systemic inflammation or cartilage destruction biomarkers. There was also no change in lipid levels and glycated hemoglobin concentrations. Ademetionine was well tolerated, no serious adverse events occurred during the treatment. In conclusion, ademetionine does not have pleiotropic pharmacological effects in diabetes-associated OA. Its potential application in cases of different comorbidities requires further studies.I. V. ShirinskyO. V. SazonovaN. Yu. KalinovskayaV. S. ShirinskySPb RAACIarticleosteoarthritisdiabetes mellitusdna methylationimmune systemademetionineImmunologic diseases. AllergyRC581-607RUMedicinskaâ Immunologiâ, Vol 17, Iss 6, Pp 553-560 (2016)
institution	DOAJ
collection	DOAJ
language	RU
topic	osteoarthritis diabetes mellitus dna methylation immune system ademetionine Immunologic diseases. Allergy RC581-607
spellingShingle	osteoarthritis diabetes mellitus dna methylation immune system ademetionine Immunologic diseases. Allergy RC581-607 I. V. Shirinsky O. V. Sazonova N. Yu. Kalinovskaya V. S. Shirinsky CLINICAL EFFICACY AND SAFETY OF ADEMETIONINE IN PATIENTS WITH DIABETES-ASSOCIATED OSTEOARTHRITIS: A CROSS-OVER PILOT STUDY
description	Osteoarthritis (OA) is one of most common rheumatic diseases, and currently there is no effective pharmacological treatment of OA. It has been suggested that lack of effective treatment is, in part, due to the disease heterogeneity which may lead to development of several OA subtypes (phenotypes). Diabetes-associated OA is among the proposed OA phenotypes. The key mechanism involved into inflammatory and degenerative changes in OA is a decrease in DNA methylation suggested for several cell types, that was also demonstrated in type 2 diabetes mellitus. Therefore, pharmacological increase of DNA methylation may be an effective treatment strategy which may exert pleiotropic effects in diabetes-associated OA. In a randomized crossover study, we have evaluated efficacy and safety of ademetionine, a methyl group donor, in comparison with chondroitine sulfate in patients with OA associated with type 2 diabetes mellitus. The patients were randomly assigned to sequential treatment of chondroitine sulfate/ademetionine or ademetionine/chondroitine sulfate during one month, with a washout period of 2 weeks. The primary endpoint was pain measured according to visual analogue scale (VAS). Painful symptoms, as well as function and disease signs in knee, hip and hand joints were also assessed with KOOS, WOMAC, and FIHOA scales. General performance was assessed with SF–36 scale. To evaluate systemic inflammation, we measured serum IL-6, IL-18, adiponectin, and CRP using ELISA technique. Concentrations of serum cartilage destruction biomarkers (aggrecan and antibodies to collagen type II) were assessed by ELISA. Serum lipid levels were measured with standard method; glycated hemoglobin was assessed with liquid chromatography. Ten patients (all women, age 61.7-74.2 year with BMI of 1.1-38.4 kg/m2) were included in the study. It has been demonstrated that ademetionine showed a statistically significant analgetic effect (decrease in VAS pain), improved knee function and reduced symptoms in knee joints (as measured by KOOS subscales), and did not influence the levels of systemic inflammation or cartilage destruction biomarkers. There was also no change in lipid levels and glycated hemoglobin concentrations. Ademetionine was well tolerated, no serious adverse events occurred during the treatment. In conclusion, ademetionine does not have pleiotropic pharmacological effects in diabetes-associated OA. Its potential application in cases of different comorbidities requires further studies.
format	article
author	I. V. Shirinsky O. V. Sazonova N. Yu. Kalinovskaya V. S. Shirinsky
author_facet	I. V. Shirinsky O. V. Sazonova N. Yu. Kalinovskaya V. S. Shirinsky
author_sort	I. V. Shirinsky
title	CLINICAL EFFICACY AND SAFETY OF ADEMETIONINE IN PATIENTS WITH DIABETES-ASSOCIATED OSTEOARTHRITIS: A CROSS-OVER PILOT STUDY
title_short	CLINICAL EFFICACY AND SAFETY OF ADEMETIONINE IN PATIENTS WITH DIABETES-ASSOCIATED OSTEOARTHRITIS: A CROSS-OVER PILOT STUDY
title_full	CLINICAL EFFICACY AND SAFETY OF ADEMETIONINE IN PATIENTS WITH DIABETES-ASSOCIATED OSTEOARTHRITIS: A CROSS-OVER PILOT STUDY
title_fullStr	CLINICAL EFFICACY AND SAFETY OF ADEMETIONINE IN PATIENTS WITH DIABETES-ASSOCIATED OSTEOARTHRITIS: A CROSS-OVER PILOT STUDY
title_full_unstemmed	CLINICAL EFFICACY AND SAFETY OF ADEMETIONINE IN PATIENTS WITH DIABETES-ASSOCIATED OSTEOARTHRITIS: A CROSS-OVER PILOT STUDY
title_sort	clinical efficacy and safety of ademetionine in patients with diabetes-associated osteoarthritis: a cross-over pilot study
publisher	SPb RAACI
publishDate	2016
url	https://doaj.org/article/8170aefa1b65444588771a2cbd96c8ae
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CLINICAL EFFICACY AND SAFETY OF ADEMETIONINE IN PATIENTS WITH DIABETES-ASSOCIATED OSTEOARTHRITIS: A CROSS-OVER PILOT STUDY

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