scholarly journals FRI0052 INFLUENCE OF RHEUMATOID ARTHRITIS ON THE CLINICAL AND BIOLOGICAL PROFILE OF TYPE-2 DIABETES MELLITUS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 601.2-602
Author(s):  
J. Avouac ◽  
M. Elhai ◽  
M. Forien ◽  
J. Sellam ◽  
F. Eymard ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Requirement ◽  
Multivariate Logistic Regression ◽  
Biological Profile ◽  
Research Support ◽  
Insulin Resistant ◽  
Research Grant

Background:Type-2 diabetes and rheumatoid arthritis (RA) are two chronic diseases characterized by tissue inflammation and insulin resistance. To date, no data have evaluated the influence of RA-induced joint and systemic inflammation on the course of type-2 diabetes.Objectives:To study the impact of RA on type-2 diabetesMethods:Observational, multicenter, cross-sectional usual-care study, including 7 rheumatology centers. This study included over a 24-month period consecutive patients with type-2 diabetes and RA, fulfilling the 2010 ACR / EULAR criteria, and diabetic controls with osteoarthritis (OA). The following data were collected: demographics, disease activity and severity indices, current treatment for RA and diabetes, history and complications of diabetes. A systematic blood test was performed, assessing inflammatory (CRP levels) and metabolic (fasting glycemia and insulin levels, HbA1c) parameters. The HOMA2%B (insulin secretion) and HOMA2%S (tissue insulin sensitivity) indices (HOMA calculator, © Diabetes Trials Unit, University of Oxford) were used to assess insulin resistance. Ra and OA patients were compared using parametric tests after adjusting for age and BMI. A multivariate logistic regression was performed ti identify factors independently associated with insulin resistance.Results:We included 122 RA patients (74% women, mean age 64+/-11 years, mean disease duration 15+/-11 11 years, 75% with positive ACPA antibodies and 64% with erosive disease) and 54 controls with OA. 64% of RA patients were treated with oral corticosteroids <10 mg/day, 65% received methotrexate and 53% received targeted biological therapies.The characteristics of type-2 diabetes in the 54 OA patients corresponded to severe insulin-resistant diabetes: age> 65 years, high BMI> 30 kg/m2, mean HbA1c 7.3%+/-11 1.3%, 30% of insulin requirement, high frequency of other cardiovascular risk factors, macroangiopathy found in almost half of patients and biological criteria of insulin resistance (elevation of HOMA2%B and decrease of HOMA2%S).RA patients with type-2 diabetes had a younger age (64+/-11 years vs. 68+/-12 years, p=0.031) and lower BMI (27.7+/-11 5.5 vs. 31.5+/-11 6.3, p<0.001). These patients also had severe diabetes (HbA1c 7.0%+/-11 1.2%, 29% of insulin requirement, 43% of macroangiopathy) with an insulin resistance profile identical to OA controls. After adjusting for age and BMI, RA patients had a significantly increased insulin secretion compared to OA patients (HOMA2%B: 83.1+/-11 65.2 vs. 49.3+/-11 25.7, p=0.023) as well as a significant reduction of insulin sensitivity (HOMA2%S: 61.1+/-11 31.6 vs. 92.9+/-11 68.1, p=0.016). This insulin resistance was associated with the inflammatory activity of RA, with a negative correlation between the HOMA2%S and the DAS28 (r=-0.28, p=0.027). The multivariate logistic regression confirmed the independent association between the HOMA2%S index and DAS28 (OR: 3.93, 95% CI 1.02-15.06), as well as high blood pressure (OR: 1.29, 95% CI 0.33-1.99 CI).Conclusion:RA patients with type-2 diabetes displayed severe, poorly controlled diabetes, highlighting the burden of comorbidities associated with RA. The clinical-biological profile of diabetic RA patients was severe insulin-resistant diabetes, with a biological profile of insulin resistance linked to the inflammatory activity of the disease. These findings may have therapeutic implications, with the potential targeting of insulin resistance through the treatment of joint and systemic inflammation.Acknowledgments:Société Française de Rhumatologie (research grant)Bristol Myers Squibb (research grant)Disclosure of Interests:Jérôme Avouac Grant/research support from: Pfizer, Bristol Myers Squibb, Consultant of: Sanofi, Bristol Myers Squibb, Abbvie, Boerhinger, Nordic Pharma, Speakers bureau: Sanofi, Bristol Myers Squibb Abbvie, MSD, Pfizer, Nordic Pharma, Muriel ELHAI: None declared, Marine Forien: None declared, Jérémie SELLAM: None declared, Florent Eymard Consultant of: Regenlab, Anna Moltó Grant/research support from: Pfizer, UCB, Consultant of: Abbvie, BMS, MSD, Novartis, Pfizer, UCB, Laure Gossec Grant/research support from: Lilly, Mylan, Pfizer, Sandoz, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, UCB, Frédéric Banal: None declared, Joel Daminano: None declared, Philippe Dieudé: None declared, Yannick Allanore Shareholder of: Sanofi, Roche, Consultant of: Actelion, Bayer, BMS, Boehringer Ingelheim, Inventiva, Sanofi

scholarly journals Dietary Intervention with Oatmeal in Patients with uncontrolled Type 2 Diabetes Mellitus – A Crossover Study

2018 ◽  
Vol 127 (09) ◽  
pp. 623-629 ◽  
Author(s):  
Graciela Delgado ◽  
Marcus E. Kleber ◽  
Bernhard K Krämer ◽  
Michael Morcos ◽  
Per M. Humpert ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Crossover Study ◽  
Dietary Intervention ◽  
Control Period ◽  
Insulin Requirement ◽  
Control Treatment ◽  
Daily Insulin

Abstract Background In a pilot study, we evaluated the efficacy of two days of oatmeal on insulin resistance and glucose metabolism and found a marked decrease of insulin requirements. The most important shortcoming of that study was that the interventions were not isocaloric (diabetes adapted diet: 1500 kcal/d vs. oatmeal 1100 kcal/d). To address these drawbacks we designed the OatMeal And Insulin Resistance (OMA-IR) study. Methods The study was a randomized, open label crossover dietary intervention study with consecutive inclusion of 15 patients with uncontrolled type 2 diabetes. The intervention comprised two days of oatmeal on days 3 and 4 of a 5 days hospital stay. During the control period, patients received a diabetes mellitus adapted diet only. The primary endpoint was the daily insulin requirement and glycemic control. Results Upon oatmeal treatment, the required insulin dose could be significantly reduced on the third and fourth day as compared to the second day of inpatient stay (82.0±30.3 and 69.9±29.9IU versus 112±36.2IU;P<0.001). During control treatment, insulin requirement did not change. There were no significant differences in the changes of mean blood glucose or fasting glucose between both treatments. HbA1c was lower four weeks after the oatmeal intervention. Conclusion In this crossover study, two days of oatmeal intervention allowed a highly significant reduction of required daily insulin doses while maintaining adequate metabolic control as compared to a diabetes adapted diet only. The beneficial effects of the intervention might last for several weeks as shown by the lower HbA1c four weeks after the intervention.

Lipid-Induced Insulin Resistance Mechanisms: The Link to Inflammation and Type 2 Diabetes.

2021 ◽  
pp. 1-9
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Fatty Acid ◽  
Molecular Mechanisms ◽  
Laboratory Data ◽  
Phosphatidyl Inositol ◽  
Resistance Mechanisms ◽  
Cellular Mechanisms ◽  
Insulin Resistant

1. Abstract Insulin Resistance is the leading cause of Type 2 diabetes mellitus [T2DM] onset. It occurs as a result of disturbances in lipid metabolism and increased levels of circulating free fatty acids [FFAs]. FFAs accumulate within the insulin sensitive tissues such as muscle, liver and adipose tissues exacerbating different molecular mechanisms. Increased fatty acid flux has been documented to be strongly associated with insulin resistant states and obesity causing inflammation that eventually causes type 2-diabetes development. FFAs appear to cause this defect in glucose transport by inhibiting insulin –stimulated tyrosine phosphorylation of insulin receptor substrate-1 [IRS-1] and IRS-1 associated phosphatidyl-inositol 3-kinase activity. A number of different metabolic abnormalities may increase intramyocellular or intrahepatic fatty acid metabolites that induce insulin resistance through different cellular mechanisms. The current review point out the link between enhanced FFAs flux and activation of PKC and how it impacts on both the insulin signaling in muscle and liver as shown from our laboratory data and highlighting the involvement of the inflammatory pathways importance. This embarks the importance of measuring the inflammatory biomarkers in clinical settings.

IL-6 as a Surrogate Biomarker: The IL-6 Clinical Value for the Diagnosis of Insulin Resistance and Type 2 Diabetes.

2021 ◽  
pp. 1-13
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Diagnostic Value ◽  
Low Grade ◽  
Clinical Value ◽  
Insulin Resistant ◽  
Tnf Α ◽  
Low Grade Inflammation

1. Abstract Insulin Resistance is the leading cause of Type 2 diabetes mellitus (T2D). It occurs as a result of lipid disorders and increased levels of circulating free fatty acids (FFAs). FFAs accumulate within the insulin sensitive tissues such as muscle, liver and adipose tissues exacerbating different molecular mechanisms. Increased levels fatty acid has been documented to be strongly associated with insulin resistant states and obesity causing inflammation that eventually causes type 2-diabetes. Among the biomarkers that are accompanying low grade inflammation include IL-1β, IL-6 and TNF-α. The current review point out the importance of measuring the inflammatory biomarkers especially focusing on the conductance and measurement for IL-6 as a screening laboratory test and its diagnostic value in clinical practice.

scholarly journals Insulin Resistance in Osteoarthritis: Similar Mechanisms to Type 2 Diabetes Mellitus

2020 ◽  
Vol 2020 ◽  
pp. 1-16 ◽  
Author(s):  
Elena V Tchetina ◽  
Galina A Markova ◽  
Eugeniya P Sharapova
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
The Body ◽  
Whole Body ◽  
Insulin Resistant ◽  
Resistant State ◽  
Insulin Resistant State

Osteoarthritis (OA) and type 2 diabetes mellitus (T2D) are two of the most widespread chronic diseases. OA and T2D have common epidemiologic traits, are considered heterogenic multifactorial pathologies that develop through the interaction of genetic and environmental factors, and have common risk factors. In addition, both of these diseases often manifest in a single patient. Despite differences in clinical manifestations, both diseases are characterized by disturbances in cellular metabolism and by an insulin-resistant state primarily associated with the production and utilization of energy. However, currently, the primary cause of OA development and progression is not clear. In addition, although OA is manifested as a joint disease, evidence has accumulated that it affects the whole body. As pathological insulin resistance is viewed as a driving force of T2D development, now, we present evidence that the molecular and cellular metabolic disturbances associated with OA are linked to an insulin-resistant state similar to T2D. Moreover, the alterations in cellular energy requirements associated with insulin resistance could affect many metabolic changes in the body that eventually result in pathology and could serve as a unified mechanism that also functions in many metabolic diseases. However, these issues have not been comprehensively described. Therefore, here, we discuss the basic molecular mechanisms underlying the pathological processes associated with the development of insulin resistance; the major inducers, regulators, and metabolic consequences of insulin resistance; and instruments for controlling insulin resistance as a new approach to therapy.

scholarly journals Metabolic signature of obesity-associated insulin resistance and type 2 diabetes

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Haya Al-Sulaiti ◽  
Ilhame Diboun ◽  
Maha V. Agha ◽  
Fatima F. S. Mohamed ◽  
Stephen Atkin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Serum Samples ◽  
Metabolic Markers ◽  
Insulin Resistant ◽  
Increased Risk ◽  
Novel Biomarkers ◽  
Prospective Cohorts

Abstract Background Obesity is associated with an increased risk of insulin resistance and type 2 diabetes mellitus (T2DM). However, some obese individuals maintain their insulin sensitivity and exhibit a lower risk of associated comorbidities. The underlying metabolic pathways differentiating obese insulin sensitive (OIS) and obese insulin resistant (OIR) individuals remain unclear. Methods In this study, 107 subjects underwent untargeted metabolomics of serum samples using the Metabolon platform. Thirty-two subjects were lean controls whilst 75 subjects were obese including 20 OIS, 41 OIR, and 14 T2DM individuals. Results Our results showed that phospholipid metabolites including choline, glycerophosphoethanolamine and glycerophosphorylcholine were significantly altered from OIS when compared with OIR and T2DM individuals. Furthermore, our data confirmed changes in metabolic markers of liver disease, vascular disease and T2DM, such as 3-hydroxymyristate, dimethylarginine and 1,5-anhydroglucitol, respectively. Conclusion This pilot data has identified phospholipid metabolites as potential novel biomarkers of obesity-associated insulin sensitivity and confirmed the association of known metabolites with increased risk of obesity-associated insulin resistance, with possible diagnostic and therapeutic applications. Further studies are warranted to confirm these associations in prospective cohorts and to investigate their functionality.

A novel small molecule A2A adenosine receptor agonist, indirubin-3′-monoxime, alleviates lipid-induced inflammation and insulin resistance in 3T3-L1 adipocytes

2019 ◽  
Vol 476 (16) ◽  
pp. 2371-2391 ◽  
Author(s):  
Saynaz A. Choudhary ◽  
Nikita Bora ◽  
Dipanjan Banerjee ◽  
Leena Arora ◽  
Anindhya Sundar Das ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Adenosine Receptor ◽  
In Vitro Study ◽  
A2a Adenosine Receptor ◽  
Insulin Resistant ◽  
Adenosine Receptor Agonist ◽  
Inflammatory State

Abstract Saturated free fatty acid-induced adipocyte inflammation plays a pivotal role in implementing insulin resistance and type 2 diabetes. Recent reports suggest A2A adenosine receptor (A2AAR) could be an attractive choice to counteract adipocyte inflammation and insulin resistance. Thus, an effective A2AAR agonist devoid of any toxicity is highly appealing. Here, we report that indirubin-3′-monoxime (I3M), a derivative of the bisindole alkaloid indirubin, efficiently binds and activates A2AAR which leads to the attenuation of lipid-induced adipocyte inflammation and insulin resistance. Using a combination of in silico virtual screening of potential anti-diabetic candidates and in vitro study on insulin-resistant model of 3T3-L1 adipocytes, we determined I3M through A2AAR activation markedly prevents lipid-induced impairment of the insulin signaling pathway in adipocytes without any toxic effects. While I3M restrains lipid-induced adipocyte inflammation by inhibiting NF-κB dependent pro-inflammatory cytokines expression, it also augments cAMP-mediated CREB activation and anti-inflammatory state in adipocytes. However, these attributes were compromised when cells were pretreated with the A2AAR antagonist, SCH 58261 or siRNA mediated knockdown of A2AAR. I3M, therefore, could be a valuable option to intervene adipocyte inflammation and thus showing promise for the management of insulin resistance and type 2 diabetes.

A gene expression signature for insulin resistance

2011 ◽  
Vol 43 (3) ◽  
pp. 110-120 ◽  
Author(s):  
Nicky Konstantopoulos ◽  
Victoria C. Foletta ◽  
David H. Segal ◽  
Katherine A. Shields ◽  
Andrew Sanigorski ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Large Scale ◽  
Gene Expression Signature ◽  
Channel Blockers ◽  
Expression Signature ◽  
Insulin Resistant ◽  
Novel Strategy

Insulin resistance is a heterogeneous disorder caused by a range of genetic and environmental factors, and we hypothesize that its etiology varies considerably between individuals. This heterogeneity provides significant challenges to the development of effective therapeutic regimes for long-term management of type 2 diabetes. We describe a novel strategy, using large-scale gene expression profiling, to develop a gene expression signature (GES) that reflects the overall state of insulin resistance in cells and patients. The GES was developed from 3T3-L1 adipocytes that were made “insulin resistant” by treatment with tumor necrosis factor-α (TNF-α) and then reversed with aspirin and troglitazone (“resensitized”). The GES consisted of five genes whose expression levels best discriminated between the insulin-resistant and insulin-resensitized states. We then used this GES to screen a compound library for agents that affected the GES genes in 3T3-L1 adipocytes in a way that most closely resembled the changes seen when insulin resistance was successfully reversed with aspirin and troglitazone. This screen identified both known and new insulin-sensitizing compounds including nonsteroidal anti-inflammatory agents, β-adrenergic antagonists, β-lactams, and sodium channel blockers. We tested the biological relevance of this GES in participants in the San Antonio Family Heart Study ( n = 1,240) and showed that patients with the lowest GES scores were more insulin resistant (according to HOMA_IR and fasting plasma insulin levels; P < 0.001). These findings show that GES technology can be used for both the discovery of insulin-sensitizing compounds and the characterization of patients into subtypes of insulin resistance according to GES scores, opening the possibility of developing a personalized medicine approach to type 2 diabetes.

scholarly journals Five stages of progressive β-cell dysfunction in the laboratory Nile rat model of type 2 diabetes

2016 ◽  
Vol 229 (3) ◽  
pp. 343-356 ◽  
Author(s):  
Kaiyuan Yang ◽  
Jonathan Gotzmann ◽  
Sharee Kuny ◽  
Hui Huang ◽  
Yves Sauvé ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Pancreatic Islet ◽  
Cell Mass ◽  
Β Cell ◽  
High Fiber ◽  
Insulin Resistant ◽  
Cell Dysfunction

We compared the evolution of insulin resistance, hyperglycemia, and pancreatic β-cell dysfunction in the Nile rat (Arvicanthis niloticus), a diurnal rodent model of spontaneous type 2 diabetes (T2D), when maintained on regular laboratory chow versus a high-fiber diet. Chow-fed Nile rats already displayed symptoms characteristic of insulin resistance at 2 months (increased fat/lean mass ratio and hyperinsulinemia). Hyperglycemia was first detected at 6 months, with increased incidence at 12 months. By this age, pancreatic islet structure was disrupted (increased α-cell area), insulin secretion was impaired (reduced insulin secretion and content) in isolated islets, insulin processing was compromised (accumulation of proinsulin and C-peptide inside islets), and endoplasmic reticulum (ER) chaperone protein ERp44 was upregulated in insulin-producing β-cells. By contrast, high-fiber-fed Nile rats had normoglycemia with compensatory increase in β-cell mass resulting in maintained pancreatic function. Fasting glucose levels were predicted by the α/β-cell ratios. Our results show that Nile rats fed chow recapitulate the five stages of progression of T2D as occurs in human disease, including insulin-resistant hyperglycemia and pancreatic islet β-cell dysfunction associated with ER stress. Modification of diet alone permits long-term β-cell compensation and prevents T2D.

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