Rheumatoid arthritis, insulin resistance, and diabetes.

Recent progress in the management of rheumatoid arthritis (RA) is turning attention toward comorbidities, such as diabetes. The objectives of this review are to clarify the links between RA and diabetes and to assess potential effects of disease-modifying antirheumatic drugs (DMARDs) on diabetes. The increased insulin resistance seen in RA is closely linked to the systemic inflammation induced by certain proinflammatory cytokines such as tumor necrosis factor α (TNFα) and interleukin-6. The prevalence of type 2 diabetes is increased in patients with RA. Furthermore, certain DMARDs including hydroxychloroquine, methotrexate, TNFα antagonist, and interleukin-1β antagonists seem to improve the markers of glucose metabolism. In contrast, glucocorticoids tend to adversely affect glycemic control, particularly when taken chronically. Consequently, a crucial yet insufficiently applied rule is that cardiovascular risk factors must be sought and treated routinely, particularly as the choice of the DMARD may affect glucose metabolism.

[1]  B. Joffe,et al.  Glucocorticoids and insulin sensitivity in rheumatoid arthritis. , 2004, The Journal of rheumatology.

[2]  D. Symmons,et al.  EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis , 2009, Annals of the rheumatic diseases.

[3]  I. Lian,et al.  Risk of Diabetes in Patients with Rheumatoid Arthritis: A 12-year Retrospective Cohort Study , 2013, The Journal of Rheumatology.

[4]  M. Donath,et al.  Blockade of interleukin 1 in type 1 diabetes mellitus , 2010, Nature Reviews Endocrinology.

[5]  Yvonne Bordon.  Immunometabolism: IL-6, the resistance fighter , 2014, Nature Reviews Immunology.

[6]  M. Houssen,et al.  Insulin resistance in early untreated rheumatoid arthritis patients. , 2010, Clinical biochemistry.

[7]  G L Freeman,et al.  High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. , 2001, Arthritis and rheumatism.

[8]  M. Papa,et al.  Tumor necrosis factor alpha-induced phosphorylation of insulin receptor substrate-1 (IRS-1). Possible mechanism for suppression of insulin-stimulated tyrosine phosphorylation of IRS-1. , 1995, The Journal of biological chemistry.

[9]  T. Pincus,et al.  Prevalence of the metabolic syndrome is increased in rheumatoid arthritis and is associated with coronary atherosclerosis. , 2008, Atherosclerosis.

[10]  M. Mula.  Investigational new drugs for focal epilepsy , 2016, Expert opinion on investigational drugs.

[11]  D. Kardassis,et al.  Anti-tumor necrosis factor therapy improves insulin resistance, beta cell function and insulin signaling in active rheumatoid arthritis patients with high insulin resistance , 2012, Arthritis Research & Therapy.

[12]  Mahboob Rahman,et al.  Diabetes mellitus and insulin resistance in patients with rheumatoid arthritis: Risk reduction in a chronic inflammatory disease , 2011, Arthritis care & research.

[13]  G. Dagenais,et al.  Hyperinsulinemia as an independent risk factor for ischemic heart disease. , 1996, The New England journal of medicine.

[14]  S. Schneeweiss,et al.  Association between disease-modifying antirheumatic drugs and diabetes risk in patients with rheumatoid arthritis and psoriasis. , 2011, JAMA.

[15]  B. Dijkmans,et al.  Rheumatoid arthritis versus diabetes as a risk factor for cardiovascular disease: a cross-sectional study, the CARRÉ Investigation , 2008, Annals of the rheumatic diseases.

[16]  D. Ye,et al.  Lack of association of IL-6 polymorphism with rheumatoid arthritis/type 1 diabetes: a meta-analysis. , 2013, Joint, bone, spine : revue du rhumatisme.

[17]  Malcolm D. Smith,et al.  Screening for diabetes in patients with inflammatory rheumatological disease administered long-term prednisolone: a cross-sectional study. , 2012, Rheumatology.

[18]  J. Fries,et al.  Hydroxychloroquine and risk of diabetes in patients with rheumatoid arthritis. , 2007, JAMA.

[19]  K. Liao,et al.  Specific association of type 1 diabetes mellitus with anti-cyclic citrullinated peptide-positive rheumatoid arthritis. , 2009, Arthritis and rheumatism.

[20]  Maureen A. Smith,et al.  Monitoring diabetes in patients with and without rheumatoid arthritis: a Medicare study , 2012, Arthritis Research & Therapy.

[21]  B. Spiegelman,et al.  Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. , 1993, Science.

[22]  Ming-Chi Lu,et al.  Risk of Rheumatoid Arthritis in Patients with Type 2 Diabetes: A Nationwide Population-Based Case-Control Study , 2014, PloS one.

[23]  S. Schneeweiss,et al.  Risk of diabetes among patients with rheumatoid arthritis, psoriatic arthritis and psoriasis , 2010, Annals of the rheumatic diseases.

[24]  J. Manson,et al.  C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. , 2001, JAMA.

[25]  JoAnn E. Manson,et al.  Cardiovascular Morbidity and Mortality in Women Diagnosed With Rheumatoid Arthritis , 2003, Circulation.

[26]  N. Paquot,et al.  Anti-inflammatory agents to treat or prevent type 2 diabetes, metabolic syndrome and cardiovascular disease , 2015, Expert opinion on investigational drugs.

[27]  M. Budoff,et al.  Insulin Resistance in Rheumatoid Arthritis: Disease‐Related Indicators and Associations With the Presence and Progression of Subclinical Atherosclerosis , 2015, Arthritis & rheumatology.

[28]  Pierre-Antoine Gourraud,et al.  Traditional cardiovascular risk factors in rheumatoid arthritis: a meta-analysis. , 2011, Joint, bone, spine : revue du rhumatisme.

[29]  D. Solomon,et al.  Changes in glycosylated hemoglobin after initiation of hydroxychloroquine or methotrexate treatment in diabetes patients with rheumatic diseases. , 2010, Arthritis and rheumatism.

[30]  I. Bruce,et al.  Seropositivity is associated with insulin resistance in patients with early inflammatory polyarthritis: results from the Norfolk Arthritis Register (NOAR): an observational study , 2011, Arthritis research & therapy.

[31]  M. Hochberg,et al.  OP0161 Use of TNF Inhibitors is Associated with a Reduced Risk of Diabetes in RA Patients , 2013 .

[32]  P. Dieudé,et al.  Testing for linkage and association with rheumatoid arthritis a ptpn22 promoter polymorphism reported to be associated and linked with type 1 diabetes in the Caucasian population , 2008, Annals of the rheumatic diseases.

[33]  S. Mathieu,et al.  Cardiovascular risk in rheumatoid arthritis. , 2014, Joint, bone, spine : revue du rhumatisme.

[34]  Edward Flynn,et al.  Overlapping genetic susceptibility variants between three autoimmune disorders: rheumatoid arthritis, type 1 diabetes and coeliac disease , 2010, Arthritis research & therapy.

[35]  B. Spiegelman,et al.  IRS-1-Mediated Inhibition of Insulin Receptor Tyrosine Kinase Activity in TNF-α- and Obesity-Induced Insulin Resistance , 1996, Science.

[36]  T. Pincus,et al.  Inflammation-associated insulin resistance: differential effects in rheumatoid arthritis and systemic lupus erythematosus define potential mechanisms. , 2008, Arthritis and rheumatism.

[37]  Lawrence Joseph,et al.  The metabolic syndrome and cardiovascular risk a systematic review and meta-analysis. , 2010, Journal of the American College of Cardiology.

[38]  B. Joffe,et al.  Insulin resistance and impaired beta cell function in rheumatoid arthritis. , 2006, Arthritis and rheumatism.

[39]  P. Pouwels,et al.  Low-dose glucocorticoid treatment affects multiple aspects of intermediary metabolism in healthy humans: a randomised controlled trial , 2011, Diabetologia.

[40]  T. Merriman,et al.  Only one independent genetic association with rheumatoid arthritis within the KIAA1109-TENR-IL2-IL21 locus in Caucasian sample sets: confirmation of association of rs6822844 with rheumatoid arthritis at a genome-wide level of significance , 2010, Arthritis research & therapy.

[41]  G. Frühbeck,et al.  Adipokines in the treatment of diabetes mellitus and obesity , 2009, Expert opinion on pharmacotherapy.

[42]  Allan Vaag,et al.  Interleukin-1-receptor antagonist in type 2 diabetes mellitus. , 2007, The New England journal of medicine.

[43]  H. John,et al.  Methotrexate therapy associates with reduced prevalence of the metabolic syndrome in rheumatoid arthritis patients over the age of 60- more than just an anti-inflammatory effect? A cross sectional study , 2009, Arthritis research & therapy.

[44]  M. Bala,et al.  Cardiovascular disease and risk factors in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. , 2006, The Journal of rheumatology.

[45]  I. Georgiou,et al.  Validation of the TAGAP rs212389 polymorphism in rheumatoid arthritis susceptibility. , 2013, Joint, bone, spine : revue du rhumatisme.

[46]  M. Mittleman,et al.  Prevalent rheumatoid arthritis and diabetes among NHANES III participants aged 60 and older. , 2007, The Journal of rheumatology.

[47]  M. Laudes,et al.  Effects of Inhibition of Interleukin-6 Signalling on Insulin Sensitivity and Lipoprotein (A) Levels in Human Subjects with Rheumatoid Diseases , 2010, PloS one.

[48]  D. O'leary,et al.  Relative contribution of cardiovascular risk factors and rheumatoid arthritis clinical manifestations to atherosclerosis. , 2005, Arthritis and rheumatism.

[49]  M. Netea,et al.  The role of TNF-alpha in chronic inflammatory conditions, intermediary metabolism, and cardiovascular risk. , 2007, Journal of lipid research.

[50]  S. Pearce,et al.  An association between the CTLA4 exon 1 polymorphism and early rheumatoid arthritis with autoimmune endocrinopathies. , 2002, Rheumatology.

[51]  I. McInnes,et al.  Explaining how "high-grade" systemic inflammation accelerates vascular risk in rheumatoid arthritis. , 2003, Circulation.

[52]  A. Ogdie,et al.  Diabetes incidence in psoriatic arthritis, psoriasis and rheumatoid arthritis: a UK population-based cohort study. , 2014, Rheumatology.

[53]  Harvey F Lodish,et al.  Insulin resistance in adipose tissue: direct and indirect effects of tumor necrosis factor-alpha. , 2003, Cytokine & growth factor reviews.

[54]  T. Hirano,et al.  Improvement of HbA1c during treatment with humanised anti-interleukin 6 receptor antibody, tocilizumab , 2010, Annals of the rheumatic diseases.

[55]  W. Lems,et al.  Glucose tolerance, insulin sensitivity and β-cell function in patients with rheumatoid arthritis treated with or without low-to-medium dose glucocorticoids , 2011, Annals of the rheumatic diseases.

[56]  B. Dijkmans,et al.  Metabolic effects of high-dose prednisolone treatment in early rheumatoid arthritis: balance between diabetogenic effects and inflammation reduction. , 2012, Arthritis and rheumatism.

[57]  B. Lu,et al.  Effect of Hydroxychloroquine on Insulin Sensitivity and Lipid Parameters in Rheumatoid Arthritis Patients Without Diabetes Mellitus: A Randomized, Blinded Crossover Trial , 2014, Arthritis care & research.

[58]  M. Wasko,et al.  Diabetes mellitus risk in rheumatoid arthritis: Reduced incidence with anti–tumor necrosis factor α therapy , 2012, Arthritis care & research.

[59]  T. Therneau,et al.  How much of the increased incidence of heart failure in rheumatoid arthritis is attributable to traditional cardiovascular risk factors and ischemic heart disease? , 2005, Arthritis and rheumatism.

[60]  R. Haynes,et al.  The effectiveness of hydroxychloroquine in patients with type 2 diabetes mellitus who are refractory to sulfonylureas--a randomized trial. , 2002, Diabetes research and clinical practice.