scholarly journals Abnormal Glucose Metabolism in Rheumatoid Arthritis

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Hui Pi ◽  
Haotong Zhou ◽  
Huan Jin ◽  
Yaogui Ning ◽  
Youlian Wang
Keyword(s):  
Rheumatoid Arthritis ◽  
Insulin Resistance ◽  
Glucose Metabolism ◽  
General Population ◽  
Effective Treatment ◽  
Inflammatory Cytokines ◽  
Cell Apoptosis ◽  
Abnormal Glucose Metabolism ◽  
Inflammatory State

The incidence of abnormal glucose metabolism in patients with rheumatoid arthritis was considerably higher than the general population. The persistent systemic inflammatory state in rheumatoid arthritis might be associated with the glucose metabolism dysfunction. In this context, insulin resistance, islet β cell apoptosis, inflammatory cytokines, and other aspects which were linked with abnormal glucose metabolism in rheumatoid arthritis were reviewed. This review will be helpful in understanding the abnormal glucose metabolism mechanism in patients with rheumatoid arthritis and might be conducive to finding an effective treatment.

scholarly journals Impact of disease activity on impaired glucose metabolism in patients with rheumatoid arthritis

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Gorica G. Ristić ◽  
Vesna Subota ◽  
Dejana Stanisavljević ◽  
Danilo Vojvodić ◽  
Arsen D. Ristić ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Insulin Resistance ◽  
Glucose Metabolism ◽  
Disease Activity ◽  
Impaired Glucose Metabolism ◽  
Inflammation Markers ◽  
C Peptide ◽  
Related Risk ◽  
The Impact

Abstract Objective To explore glucose metabolism in rheumatoid arthritis (RA) and its association with insulin resistance (IR) risk factors and disease activity indicators, including matrix metalloproteinase-3 (MMP3). Methods This single-center study included 127 non-diabetic subjects: 90 RA patients and 37 matched controls. IR-related risk factors, disease activity (DAS28-ESR/CRP), concentrations of inflammation markers, MMP3, glucose, specific insulin, and C-peptide (a marker of β-cell secretion) were determined. Homeostasis Model Assessment was used to establish insulin resistance (HOMA2-IR) and sensitivity (HOMA2-%S). Associations of HOMA2 indices with IR-related risk factors, inflammation markers, and RA activity were tested using multiple regression analyses. Results RA patients had significantly increased HOMA2-IR index than controls. In the RA group, multivariate analysis revealed DAS28-ESR, DAS28-CRP, tender joint counts, patient’s global assessment, and MMP3 level as significant positive predictors for HOMA2-IR (β = 0.206, P = 0.014; β = 0.192, P = 0.009; β = 0.121, P = 0.005; β = 0.148, P = 0.007; β = 0.075, P = 0.025, respectively), and reciprocal negative for HOMA2-%S index. According to the value of the coefficient of determination (R2), DAS28-ESR ≥ 5.1 has the largest proportion of variation in both HOMA2-IR indices. DAS28-ESR ≥ 5.1 and ESR were independent predictors for increased C-peptide concentration (β = 0.090, P = 0.022; β = 0.133, P = 0.022). Despite comparability regarding all IR-related risk factors, patients with DAS28-ESR ≥ 5.1 had higher HOMA2-IR than controls [1.7 (1.2–2.5) vs. 1.2 (0.8–1.4), P = 0.000]. There was no difference between patients with DAS28-ESR < 5.1 and controls [1.3 (0.9–1.9) vs. 1.2 (0.8–1.4), P = 0.375]. Conclusions RA activity is an independent risk factor for impaired glucose metabolism. DAS28-ESR ≥ 5.1 was the main contributor to this metabolic disturbance, followed by MMP3 concentration, outweighing the impact of classic IR-related risk factors.

Celastrol Exerts Cardioprotective Effect in Rheumatoid Arthritis by Inhibiting TLR2/HMGB1 Signaling Pathway-Mediated Autophagy

2021 ◽  
pp. 1-10
Author(s):  
Xiaohong Lu ◽  
Sha Gong ◽  
Xiaojun Wang ◽  
Nan Hu ◽  
Dan Pu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Cytokines ◽  
Rat Model ◽  
Cell Apoptosis ◽  
Signal Pathway ◽  
Index Score ◽  
Cardioprotective Effect ◽  
Rat Cardiomyocytes ◽  
Swelling Degree ◽  
Collagen Iii

<b><i>Objective:</i></b> Rheumatoid arthritis (RA) is a kind of chronic inflammatory disease characterized by the release of inflammatory cytokines and cardiomyocyte apoptosis, which lead to increased riskfor heart diseases. This study aims to explore the possible effect and mechanism of Celastrol on RA induced cardiac impairments in rats. <b><i>Methods:</i></b> Collagen induced RA wistar rat models (CIA) were established for the measurement on secondary foot swelling degree, polyarthritis index score, spleen and thymus index. Pathological morphology was observed using H&amp;E staining. Heart fibrosis was measured after Sirius red staining, while cell apoptosis was determined by TUNEL staining. For in vitro experiments, rat cardiomyocytes were isolated to determine the inflammatory cytokine secretion and cell apoptosis using ELISA and flow cytometry, respectively. Protein expressions of related index and autophagy were detected by Western blot and immunofluorescence. <b><i>Results:</i></b> CIA rat model was successfully established and characterized by severe secondary foot swelling degree, and increased polyarthritis index score and spleen and thymus index. Synovial hyperplasia, disordered cardiomyocytes, cell infiltration and fibrosis were also observed in CIA rat model. Compared with CIA model, Celastrol treatment could suppress the release of inflammatory cytokines, including TNF-α, IL-6, IL-1β, as well as inhibiting the expressions of Bax, cleaved caspase3, collagen I, collagen III and α-SMA. In addition to that, Celastrol treatment can attenuate cell apoptosis and fibrosis of cardiomyocytes and elevate Bcl-2 expression. RA induced cell autophagy can be suppressed by Celastrol through inhibiting the activation of TLR2/HMGB1 signal pathway. <b><i>Conclusion:</i></b> Celastrol can regulate TLR2/HMGB1 signal pathway to suppress autophagy and therefore exert cardioprotective effect in RA.

scholarly journals Prevalence of Abnormal Glucose Metabolism and Insulin Resistance Among Subtypes of Ischemic Stroke in Japanese Patients

Stroke ◽  
2009 ◽  
Vol 40 (4) ◽  
pp. 1289-1295 ◽  
Author(s):  
Takao Urabe ◽  
Hirotaka Watada ◽  
Yasuyuki Okuma ◽  
Ryota Tanaka ◽  
Yuji Ueno ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Ischemic Stroke ◽  
Glucose Metabolism ◽  
Japanese Patients ◽  
Abnormal Glucose Metabolism

Abstract TP416: Effects Of Pioglitazone In Patients With Abnormal Glucose Metabolism After Stroke The J-SPIRIT Study

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Ryota Tanaka ◽  
Kazuo Yamashiro ◽  
Yasutaka Tanaka ◽  
Nobukazu Miyamoto ◽  
Yuji Ueno ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Ischemic Stroke ◽  
Glucose Metabolism ◽  
Recurrent Stroke ◽  
Controlled Trial ◽  
Control Group ◽  
Placebo Control ◽  
Newly Diagnosed ◽  
Abnormal Glucose Metabolism ◽  
Multicenter Randomized Controlled Trial

Background and aims: The stroke patients with abnormal glucose metabolism are increasing in Japan. The J-SPIRIT study (Juntendo the Stroke Prevention study in Insulin Resistance and Impaired glucose Tolerance) was planned to investigate the effect of pioglitazone on the reduction of recurrent stroke in the patients with abnormal glucose metabolism and insulin resistance after ischemic stroke. Methods: The study is a multicenter, randomized controlled trial performed in the four hospitals in Tokyo or neighboring cities in Japan. We enrolled the patients who ; (1) were 35 to 85 years old ; (2) had symptomatic ischemic stroke; (3) had no history of diabetes and no evidence of diabetes by initial blood test. Among those patients, a standard OGTT with 75g of glucose was performed at least 2 weeks after admission. We enrolled the patients of newly diagnosed diabetes and IGT by OGTT, and randomized these patients to receive either pioglitazone or matching placebo. Results: Total 134 patients were enrolled. 58 patients were received pioglitazone, 61 were placebo control. Mean HbA1c were not different among both groups (5.6±0.38 pioglitazone vs 5.5±0.38 control) and mean observation period were 25±19.9 months in piolgitazone group and 30±16 months in control group. The data showed a trend of benefit with pioglitazone for the primary end point of recurrence of ischemic stroke compared to placebo control. (event rate=3.4% pioglitazone vs 11.6% control) Conclusions: Our data indicated pioglitazone might be able reduce the risk of recurrent stroke in the patients of ischemic stroke with newly diagnosed abnormal glucose metabolism and insulin resistance.

Abstract 636: Accelerated Atherosclerosis in the Context of Rheumatoid Arthritis

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Alexandra Bäcklund Bäcklund ◽  
Martina Johansson ◽  
Massimiliano Ria ◽  
Daniel F Ketelhulth ◽  
Panagiota Tsikrika ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune System ◽  
General Population ◽  
Atherosclerotic Lesion ◽  
Clinical State ◽  
Lipid Levels ◽  
Cvd Risk ◽  
Lesion Development ◽  
Increased Risk ◽  
Inflammatory State

Atherosclerotic lesion development and acceleration of lesion size, leading to a cardiovascular event can be affected by many factors, where both the immune system and lipid levels have been implicated. It is well recognized that patients with chronic inflammatory diseases, such as rheumatoid arthritis (RA) have an increased risk for cardiovascular disease (CVD) compared with the general population. It has also been suggested that CVD presented in RA patients is of an altered, more aggressive, phenotype compared to subjects without RA. Therefore, the investigation of atherosclerosis lesion development during chronic inflammation may lead to novel pathways that are not only relevant to the general population but also able to target this high CVD risk patient group. Thus, there is a need to gain a deeper understanding of how the exacerbated inflammatory state of arthritis affects the atherosclerosis process when both syndromes are presented in the same individual. Such studies are hampered in humans by the influence of different factors, such as the environment and large genetic heterogeneity of the population. We have developed a novel murine model where the human relevant genes of CVD (LDLr, thus increased LDL levels) and RA (MHCII, thus susceptible to collagen-induced arthritis) have been crossed into the common C57Bl6/J strain, enabling both arthritis and atherosclerosis being presented simultaneously in a clinically relevant fashion. This model mirrors the clinical state where the systemic inflammation of arthritis enhances atherosclerosis progression, where mice presenting arthritis have a significant increase in atherosclerotic lesion progression compared with their non-arthritic littermates. Interestingly, there was an inverse correlation with cholesterol levels, but a positive correlation with macrophages, and macrophage associated cytokines but not T cells. This model thus demonstrates that the lipid levels are vital in initiation of lesion development but it is the enhanced innate immune system that is driving the lesion acceleration in a chronic inflammatory state. This novel combined model is now able to be used to investigate altered clinical treatment strategies or novel treatments of atherosclerosis in the context of arthritis

O-163 Hyperandrogenaemia in early adulthood is an independent risk factor for abnormal glucose metabolism in later life

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
K Tuorila ◽  
M M Ollila ◽  
M R Järvelin ◽  
J Tapanainen ◽  
S Franks ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Metabolism ◽  
Fasting Glucose ◽  
Early Adulthood ◽  
Positive Association ◽  
Population Based ◽  
Androgen Excess ◽  
Abnormal Glucose Metabolism ◽  
Increased Risk

Abstract Study question What is the role of androgen excess as a contributing factor to insulin resistance and abnormal glucose metabolism (AGM) in women? Summary answer There was a positive association between early adulthood hyperandrogenaemia with AGM. Serum SHBG levels could help identifying women at risk for disordered glucose metabolism. What is known already It is commonly recognised that insulin resistance induces compensatory hyperinsulinaemia which promotes ovarian androgen secretion. Studies in rodents have also suggested that testosterone causes prolonged activation of androgen receptor in pancreatic islet β-cells, inducing insulin hypersecretion and eventually secondary β-cell failure, thus predisposing to type 2 diabetes (T2D). However, the exact physiology behind the association between androgens, insulin resistance and T2D in women is not well understood. Many previously published studies are limited by cross-sectional study design, unrepresentative clinic populations, as well as variying steroid hormone measurement methods and definitions of androgen excess. Study design, size, duration A prospective longitudinal population-based cohort (n = 5,889) to investigate whether serum levels of testosterone (T, measured using LC-MS/MS) and free androgen index (FAI) at ages 31 and 46 associated with AGM at age 46 years. After exclusion of pregnant women, users of hormonal intrauterine device, contraceptive pills, hormone therapy, minipills and statins, there were 4,421 women at age 31 and 4,457 women at age 46. At age 46 a two-hour OGTT was performed in 2,780 women. Participants/materials, setting, methods Serum fasting glucose and insulin, insulin resistance (HOMA–IR) and pancreatic β-cell function (HOMA–B) assessments were performed at ages 31 and 46. Elevated T levels (age 31: &gt;2.3nmol/l; age 46: &gt;1.7nmol/l) were defined according to the 97.5% percentile. T2D diagnoses were gathered from postal questionnaire at age 46, and verified and completed from the hospital discharge and national medication reimbursement registers. Impaired fasting glucose, impaired glucose tolerance or T2D were categorised as AGM. Main results and the role of chance At age 31, hyperandrogenic (HA) women displayed increased insulin resistance estimated by HOMA-IR (1.35±0.96 vs. 1.03±0.44, P = 0.05), increased insulin secretion estimated by HOMA-B (115.05±34.67 vs. 99.25±25.47, P = 0.006), and higher fasting insulin level (10.48±7.54 mU/l vs. 7.93±3.42 mU/l, P = 0.034) compared with normoandrogenic (NA) women, after BMI adjustment. At age 46, HA women had comparable HOMA-B levels (98.04±60.03 vs. 96.27±65.89, P = 0.93) but their fasting glucose (5.57±1.06 mmol/l vs. 5.37±0.77 mmol/, P = 0.07) and glycated haemoglobin levels (37.47±7.83 mmol/mol vs. 36.18±4.99 mmol/mol, P = 0.07) tended to be higher. Women in the highest T quartile (Q4 odds ratio [OR]=1.77, 95%CI: [1.14–2.76]) and in the two highest FAI quartiles at age 31 (Q4: OR = 3.61 [2.16–6.03] and Q3: OR = 2.11 [1.24–3.59]) had increased risk for AGM at age 46, independently of BMI, when compared with women in the lowest quartile. Similarly, women in the two highest FAI quartiles at age 46 had increased risk for AGM (Q4: OR = 2.91 [1.82–4.64]) when compared with women in the lowest quartile, after BMI adjustment. The three highest sex hormone-binding globulin (SHBG) quartiles inversely associated with AGM, both at ages 31 and 46, independently of BMI (at age 31: Q4: OR = 0.38 [0.24–0.62], at age 46: Q4: OR = 0.27 [0.17–0.44]). Limitations, reasons for caution We used only serum T as a marker of HA, even though other androgens, such as androstenedione and adrenal androgens have a place in the evaluation of androgenicity in women. Further studies of other large populations are needed to confirm our results. Wider implications of the findings This is the first longitudinal, general population based study to confirm a positive association between early adulthood hyperandrogenaemia with AGM in middle adulthood independently of confounding factors. Our results further suggest that SHBG levels could help to identify women at risk for AGM. Trial registration number NA

scholarly journals Disturbance in glucose metabolism in patients with lichen planus

2016 ◽  
Vol 9 (4) ◽  
pp. 177
Author(s):  
A. S. M. Zakaria ◽  
Md. Kamal Hossain ◽  
Mohammed Saiful Islam Bhuiyan ◽  
Abida Sultana ◽  
Mahmudur Rahman ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Blood Glucose ◽  
Glucose Metabolism ◽  
Lichen Planus ◽  
Resistance Index ◽  
Abnormal Glucose Metabolism ◽  
Insulin Resistance Index ◽  
The Mean ◽  
Level 2

<p>The aim of this study was to see the association of lichen planus (n=80) with glucose metabolism disturbance. Classic variety of lichen planus was the most common (76.3%), followed by ashy dermatosis, hypertrophic, oral, actinic and nail lichen planus. The blood glucose level 2 hours after glucose drink was abnormal in 20 cases. HbA<sub>1</sub>c was abnormal in 7 cases. The mean homeostasis model of assessment formulation- insulin resistance index (HOMA-IR) was 2.1 ± 1.6 and it was higher (&gt;4.8) in 12.5% patients. Diabetes mellitus was found in 30 patients. Impaired glucose tolerance was found in 15 cases and high HOMA-IR was found in 10 cases. Total number of cases of abnormal glucose metabolism was found in 55 (68.8%) cases of lichen planus. In conclusion, patients with lichen planus  have higher risk of abnormal glucose metabolism specially diabetes mellitus.</p>

scholarly journals Metformin protects against insulin resistance induced by high uric acid in cardiomyocytes via AMPK signaling pathways in vitro and in vivo

2021 ◽  
Author(s):  
Zhenyu Jiao ◽  
Yingqun Chen ◽  
Yang Xie ◽  
Yanbing Li ◽  
Zhi Li
Keyword(s):  
Insulin Resistance ◽  
Uric Acid ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Mouse Model ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Abnormal Glucose Metabolism ◽  
Insulin Tolerance

Abstract BackgroundHigh uric acid (HUA) is associated with insulin resistance and abnormal glucose metabolism in cardiomyocytes. Metformin is a recognized agonist of AMP-activated protein kinase (AMPK) and an antidiabetic drug widely used for type 2 diabetes. It can play a cardioprotective role in many pathways. We investigated whether metformin protects against HUA-induced insulin resistance and abnormal glucose metabolism in cardiomyocytes.MethodsWe exposed primary cardiomyocytes to HUA, and cellular glucose uptake was quantified by measuring the uptake of 2-NBDG, a fluorescent glucose analog, after insulin excitation.ResultsTreatment with metformin (10 µmol/L) protected against HUA-inhibited glucose uptake induced by insulin in primary cardiomyocytes, as shown by fluorescence microscopy and flow cytometry analysis. HUA directly inhibited the phosphorylation of Akt and the translocation of glucose transporter type 4 (GLUT4) induced by insulin, which was blocked by metformin. Metformin promoted phosphorylation of AMPK, renewed HUA-inhibited glucose uptake induced by insulin and protected against insulin resistance in cardiomyocytes. As a result of these effects, in a mouse model of acute hyperuricemia, metformin improved insulin tolerance and glucose tolerance, accompanied by increased AMPK phosphorylation, Akt phosphorylation and translocation of GLUT4 in myocardial tissues. As expected, AICAR, another AMPK activator, had equivalent effects to metformin, demonstrating the important role of AMPK activation in protecting against insulin resistance induced by HUA in cardiomyocytes. Metformin protects against insulin resistance induced by HUA in cardiomyocytes and improves insulin tolerance and glucose tolerance in an acute hyperuricemic mouse model, along with the activation of AMPK.ConclusionsConsequently, metformin may be an important potential new treatment strategy for hyperuricemia-related cardiovascular disease.

scholarly journals Metformin protects against insulin resistance induced by high uric acid in cardiomyocytes via AMPK signaling pathways in vitro and in vivo

2021 ◽  
Author(s):  
Zhenyu Jiao ◽  
Yingqun Chen ◽  
Yang Xie ◽  
Yanbing Li ◽  
Zhi Li
Keyword(s):  
Insulin Resistance ◽  
Uric Acid ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Mouse Model ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Abnormal Glucose Metabolism ◽  
Insulin Tolerance ◽  
High Uric Acid

AbstractHigh uric acid (HUA) is associated with insulin resistance and abnormal glucose metabolism in cardiomyocytes. Metformin is a recognized agonist of AMP-activated protein kinase (AMPK) and an antidiabetic drug widely used for type 2 diabetes. It can play a cardioprotective role in many pathways. We investigated whether metformin protects against HUA-induced insulin resistance and abnormal glucose metabolism in cardiomyocytes. We exposed primary cardiomyocytes to HUA, and cellular glucose uptake was quantified by measuring the uptake of 2-NBDG, a fluorescent glucose analog, after insulin excitation. Treatment with metformin (10 μmol/L) protected against HUA-inhibited glucose uptake induced by insulin in primary cardiomyocytes, as shown by fluorescence microscopy and flow cytometry analysis. HUA directly inhibited the phosphorylation of Akt and the translocation of glucose transporter type 4 (GLUT4) induced by insulin, which was blocked by metformin. Metformin promoted phosphorylation of AMPK, renewed HUA-inhibited glucose uptake induced by insulin and protected against insulin resistance in cardiomyocytes. As a result of these effects, in a mouse model of acute hyperuricemia, metformin improved insulin tolerance and glucose tolerance, accompanied by increased AMPK phosphorylation, Akt phosphorylation and translocation of GLUT4 in myocardial tissues. As expected, AICAR, another AMPK activator, had equivalent effects to metformin, demonstrating the important role of AMPK activation in protecting against insulin resistance induced by HUA in cardiomyocytes. Metformin protects against insulin resistance induced by HUA in cardiomyocytes and improves insulin tolerance and glucose tolerance in an acute hyperuricemic mouse model, along with the activation of AMPK. Consequently, metformin may be an important potential new treatment strategy for hyperuricemia-related cardiovascular disease.

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