scholarly journals The glucocorticoid receptor agonistic modulators CpdX and CpdX-D3 do not generate the debilitating effects of synthetic glucocorticoids

2019 ◽  
Vol 116 (28) ◽  
pp. 14200-14209 ◽  
Author(s):  
Guoqiang Hua ◽  
Naimah Zein ◽  
Laetitia Paulen ◽  
Pierre Chambon
Keyword(s):  
Rheumatoid Arthritis ◽  
Type 2 Diabetes ◽  
Side Effects ◽  
Fatty Liver ◽  
Skin Atrophy ◽  
Bona Fide ◽  
Anti Inflammatory ◽  
Synthetic Glucocorticoids

Seventy years after the discovery of their anti-inflammatory properties, glucocorticoids (GCs) remain the mainstay treatment for major allergic and inflammatory disorders, such as atopic dermatitis, asthma, rheumatoid arthritis, colitis, and conjunctivitis, among others. However, their long-term therapeutical administration is limited by major debilitating side effects, e.g., skin atrophy, osteoporosis, Addison-like adrenal insufficiency, fatty liver, and type 2 diabetes syndrome, as well as growth inhibition in children. These undesirable side effects are mostly related to GC-induced activation of both the direct transactivation and the direct transrepression functions of the GC receptor (GR), whereas the activation of its GC-induced indirect tethered transrepression function results in beneficial anti-inflammatory effects. We have reported in the accompanying paper that the nonsteroidal compound CpdX as well as its deuterated form CpdX-D3 selectively activate the GR indirect transrepression function and are as effective as synthetic GCs at repressing inflammations generated in several mouse models of major pathologies. We now demonstrate that these CpdX compounds are bona fide selective GC receptor agonistic modulators (SEGRAMs) as none of the known GC-induced debilitating side effects were observed in the mouse upon 3-mo CpdX treatments. We notably report that, unlike that of GCs, the administration of CpdX to ovariectomized (OVX) mice does not induce a fatty liver nor type 2 diabetes, which indicates that CpdX could be used in postmenopausal women as an efficient “harmless” GC substitute.

Long-Term Stimulation of the Ileal Hormones by Aphoeline: Effects on Metabolic Syndrome, Fatty Liver, Type 2 Diabetes and Hepatitis C

2012 ◽  
Vol 107 ◽  
pp. S114-S115
Author(s):  
Joseph Fayad ◽  
Aditi Singh ◽  
Thomas Hunt ◽  
Christine Fayad ◽  
Ashok Singh ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Hepatitis C ◽  
Fatty Liver ◽  
Stimulation Of

scholarly journals Treating nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus: a review of efficacy and safety

2017 ◽  
Vol 9 (1) ◽  
pp. 15-28 ◽  
Author(s):  
Elizabeth P. Mills ◽  
K. Paige D. Brown ◽  
Jennifer D. Smith ◽  
Phillip W. Vang ◽  
Katie Trotta
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Efficacy And Safety ◽  
Nonalcoholic Fatty Liver

Objective: To review current literature for the efficacy and safety of treatment for nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). Data sources: A PubMed literature search from January 1990 to June 2017 was conducted using the search terms nonalcoholic fatty liver disease, diabetes mellitus, type 2, therapy, treatment, treat, therapeutics, nonalcoholic fatty liver, nonalcoholic hepatosteatosis, NASH, NAFLD, metformin, and statin. Bibliographies of chosen articles were reviewed. Study selection and data extraction: Relevant articles on metformin, thiazolidinediones (TZD), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and statins for the treatment of NAFLD which included patients with T2DM were reviewed. A total of 23 relevant studies were found and included randomized controlled, observational, and open-label designs, as well as three meta-analyses. Data synthesis: Metformin combined with weight loss provides a modest improvement in steatosis and no improvement in fibrosis in patients with NAFLD and T2DM. TZDs showed positive results on fibrosis and resolution of NASH but at least half of patients studied were nonresponders. GLP-1 RAs also showed favorable results on reductions in transaminases and steatosis and improvements in insulin sensitivity and weight loss but lack efficacy data for resolution of NASH or improvement in fibrosis scores. Statins showed favorable results on reductions in transaminases but mixed results for improvement in steatosis and fibrosis scores. Conclusion: All reviewed treatment options are safe for management of NAFLD in patients with T2DM but long-term histological improvements are minimal. TZDs are efficacious for resolution of NASH and improvements in fibrosis but long-term use is required to maintain these results.

scholarly journals Spontaneous and induced secretion of the pro-inflammatory and anti-inflammatory cytokines in patients with type 2 diabetes mellitus and diabetic foot syndrome

2020 ◽  
Vol 23 (3) ◽  
pp. 210-222
Author(s):  
E. V. Shikh ◽  
N. A. Petunina ◽  
L. V. Nedosugova ◽  
K. O. Galstyan ◽  
K. I. Kolmychkova ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Foot ◽  
Diabetic Foot Syndrome ◽  
Control Group ◽  
Metabolic Drug ◽  
Anti Inflammatory

AIMS:Investigation of spontaneous and induced secretion of the pro-inflammatory cytokine tumor necrosis factor- (TNF-) and the anti-inflammatory chemokine C-C Motif Chemokine Ligand 18 (CCL18) by monocytes isolated from blood of patients with long-term type 2 diabetes mellitus (T2DM), both with or without foot ulcers and the effect of the course use of the combined metabolic drug Kokarnit as part of complex therapy on the dynamics of the severity of symptoms of DSPN and the cytokine phenotype in patients with long-term non-healing ulcers of the lower extremities MATERIALS AND METHODS:121 patients with T2DM, 79 without diabetic foot syndrome (DFS) and 42 patients with DFS were included. CD14+ monocytes were isolated from patients blood and stimulated by interferon- (IFN-) and interleukine-4 (IL-4) for induction of pro- and anti-inflammatory monocyte activation, respectively. The concentrations of TNF- and CCL18 in the culture medium were measured using ELISA on day 1 and day 6 after cell stimulation in all patients before taking the combined metabolic drug Kokarnit. Then they were randomly allocated either to the control group (57 people), to whom Kokarnit was added to standard treatment, or to the comparison group. After a 9-day course of application of Kokarnit, the dynamics of indicators was evaluated on a TSS scale. Assessment of cytokine status was carried out in 18 people with long-term non-healing ulcerative defects of the lower extremities, on the first and ninth day of treatment. RESULTS:A correlation was found between HbA1cand levels of stimulated secretion of TNF (r=0.726, p=0.027), CCL18 (r=-0.949, p=0.051) in patients with DSPN. In all patients with different duration of VDS, an increase in secretion of TNF- and CCL18 was observed (p0.05). However, stimulation of anti-inflammatory activation was not observed in patients with ulcerative defects lasting more than 6 months (p=0.033). The use of cocarnit in these patients had a decrease in stimulated secretion of TNF and an increase in CCL18. Throughout the entire observation period with the therapy, the score for the symptoms of polyneuropathy on the TSS scale in patients of the control group was statistically significantly higher. CONCLUSION:Against the background of therapy in patients of the main group, a statistically significant dynamics of indicators on the TSS scale was established. The cytokine modulating ability of Kokarnit to switch the cytokine status into the category of anti-inflammatory.

scholarly journals POS0534 THE PREVALENCE OF HYPERTENSION AND ITS POTENTIAL ASSOCIATED FACTORS IN CHINESE PATIENTS WITH RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 501.1-501
Author(s):  
Y. W. Zou ◽  
C. Chen ◽  
J. Lin ◽  
J. D. Ma ◽  
Y. Y. Zou ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Liver Disease ◽  
Kidney Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Associated Factors ◽  
Male And Female

Background:Cardiovascular disease (CVD) is the leading cause of mortality in patients with rheumatoid arthritis (RA), and hypertension is a modifiable risk-factor for CVD. In addition, comorbidities may shorten the life span of RA patients, which appears to be the consequence of an increased prevalence of CVD. RA patients with comorbidities might not be given the equal treatment in daily practice compared with patients without comorbidities.Objectives:To investigate the prevalence of hypertension and its associated factors in Chinese RA patients.Methods:Consecutive patients with RA were recruited from August 2015 to September 2019 at Department of Rheumatology, Sun Yat-sen Memorial Hospital. Demographic and clinical characteristics were collected including indicators of disease activity, functional assessment and radiographic assessment and CV-related comorbidities.Results:There were 674 RA patients recruited with 82.3% female and mean age 49.9±13.0 years. The prevalence rate of hypertension in RA patients was 32.9%, followed by dyslipidemia (9.9%), type 2 diabetes (8.8%), hyperuricemia (8.5%), fatty liver disease (8.0%), CVD (6.2%) and chronic kidney disease (3.3%). The prevalence of hypertension was 38.7% and 31.7% in male and female RA patients respectively (P = 0.144). Further age stratification showed no hypertension in RA patients at 16-19 years, 2.0% at 20-29 years and 8.1% at 30-39 years. The prevalence of hypertension greatly increased after 40 years old with 24.5%, 38.6%, 54.9%, and 63.6% in RA patients of 40-49, 50-59, 60-69, ≥ 70 years old respectively, and there was no significant difference between male and female RA patients of different age (Figure 1). Compared with those without hypertension, RA patients with hypertension had advanced age (57.3 ± 9.3 years vs. 46.3 ± 13.0 years), long-standing disease duration (median 60 months vs. 48 months), higher disease activity indicators [including PtGA (median 4 vs. 3), PrGA (median 3 vs. 3) and ESR (median 33 mm/h vs. 27 mm/h)], higher functional indicator [HAQ-DI (median 0.25 vs. 0.13)], worse joint destruction [JE subscore (median 10 vs. 6)] and higher proportions of comorbidities [including type 2 diabetes (14.9% vs. 5.8%), hyperuricemia (13.1% vs. 6.1%), chronic kidney disease (6.3% vs. 1.8%), dyslipidemia (15.8% vs. 7.1%), CVD (10.4% vs. 4.2%) and fatty liver disease (13.5% vs. 5.3%), all P < 0.005]. Multivariate logistic regression analysis showed that comorbidities including hyperuricemia (OR = 1.977, 95% CI: 1.002-3.900), dyslipidemia (OR = 1.903, 95% CI: 1.102-3.288) and fatty liver disease (OR = 2.335, 95% CI: 1.278-4.265) were associated factors of hypertension after adjustment for age and genderFigure 1.The prevalence of hypertension in different age and sex groups of RA patients.Conclusion:Hypertension is the most common CV-related comorbidity in Chinese RA patients which is associated with hyperuricemia, dyslipidemia and fatty liver disease. Detection and management of hypertension and other CV-related comorbidities in RA patients should be emphasized.Fund program:National Natural Science Foundation of China (81801605, 81801606, 81971527); Guangdong Natural Science Foundation (2018A030313541, 2018A030313690, 2019A1515011928); Guangzhou Science and Technology Program (201904010088); Guangdong Basic and Applied Basic Research Foundation (2020A1515110061); Guangdong Medical Scientific Research Foundation (A2018062)Disclosure of Interests:None declared

Abstract #238: Improved Short Term and Long Term Outcomes of Early Insulin Initiation in Type 2 Diabetes Over 10 Years

2017 ◽  
Vol 23 ◽  
pp. 50
Author(s):  
Jothydev Kesavadev ◽  
Shashank Joshi ◽  
Banshi Saboo ◽  
Hemant Thacker ◽  
Arun Shankar ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Initiation ◽  
Long Term Outcomes ◽  
Short Term
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