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Psoriasis, Type 2 Diabetes Mellitus, and Obesity: Weighing the Evidence

Psoriasis, Type 2 Diabetes Mellitus, and Obesity: Weighing the Evidence Psoriasis is a common, chronic inflammatory disease that is associated with an increased risk of cardiovascular, metabolic, and renal disease in a manner that varies with the severity of psoriasis and is often independent of traditional risk factors for these other diseases.1,2 The clinical significance of these associations is emphasized by premature death, particularly in patients with more severe psoriasis, in whom excess mortality is comparable to that seen in rheumatoid arthritis treated with disease-modifying medications.3 The association of psoriasis with type 2 diabetes mellitus and obesity has been extensively studied and has been the subject of numerous meta-analyses that clearly establish an association of psoriasis with both obesity and diabetes. Lønnberg and colleagues4 have provided new insights into these associations by studying monozygotic and dizygotic twins with and without psoriasis. Their main findings were that psoriasis is associated with diabetes independent of sex, age, smoking, and body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) (odds ratio, 1.53; 95% CI, 1.03 to 2.27) and that increases in BMI are associated with increasing odds of twins reporting a diagnosis of psoriasis. Similar findings were reported for hospitalized patients in whom psoriasis was diagnosed. The unique twin design of the study by Lønnberg and colleagues, in which an increasing BMI was associated with a diagnosis of psoriasis, allowed the investigators to identify a genetic correlation between psoriasis and BMI of 0.12 (95% CI, 0.08 to 0.19). A genetic correlation of similar magnitude of psoriasis and type 2 diabetes of 0.13 (95% CI, −0.06 to 0.31) was also observed, but this finding was not statistically significant (the prevalence of diabetes in this sample was quite low, yielding only 6 patients with psoriasis who also had diabetes). The magnitude of the genetic correlation is modest and similar to what has been reported for age at menarche and type 2 diabetes (−0.13).5 Nevertheless, these findings are consistent with emerging genetic evidence linking psoriasis to diabetes. For example, genetic variation in IL12B, IL23R, and IL23A has an influence not only on the risk for psoriasis but also on its severity and type 2 diabetes.6 Other researchers have suggested a role for CDKAL1 in conferring susceptibility to both psoriasis and diabetes.7 Only a few studies have examined the incidence (risk) of diabetes in patients with psoriasis while adjusting for major confounding variables (eg, BMI and hypertension), and only a subset of these were able to evaluate effects of the severity of psoriasis on the association of diabetes with psoriasis (using treatment patterns).8 The results of these studies suggest that psoriasis is associated with an increased risk of diabetes independent of major risk factors in a manner that correlates with the severity of psoriasis. Although the design used by Lønnberg et al4 does not address diabetes risk (ie, incidence) or directly evaluate a dose-response association of the severity of psoriasis to diabetes, its careful control for BMI, which most large population-based studies are unable to capture, adds to the weight of evidence suggesting psoriasis as a risk factor for diabetes. Additional population-based studies have similarly noted an increased prevalence of insulin resistance in patients with psoriasis in a manner that varies positively with increasing body surface area affected by psoriasis and independent of major risk factors such as BMI, hypertension, and dyslipidemia.9 Although inflammation is often invoked as a mechanistic link to insulin resistance, a simultaneous analysis of patients with psoriasis and rheumatoid arthritis with adjustment for major risk factors demonstrated an increased risk for diabetes only in patients with psoriatic disease.10 The risk of diabetic complications in patients with psoriasis (compared with diabetic patients without psoriasis) is rather unexplored, but emerging studies suggest that microvascular and macrovascular complications are more common in patients who have psoriasis and diabetes, that psoriasis is associated with worse hemoglobin A1c, and that increasing body surface area affected by psoriasis is associated with an increased risk for diabetic complications.11-13 These epidemiologic findings have clear implications for clinical practice. The dermatologist is on the front line in educating patients with psoriasis about their disease, treatment options, and risks of comorbidities. The US Preventive Services Task Force (updated 2015) recommends screening for an abnormal blood glucose concentration as part of the assessment for cardiovascular risk in adults aged 40 to 70 years who are overweight or obese. Moreover, the American Diabetes Association’s 2016 Standards of Medical Care recommend testing (with a fasting plasma glucose or oral glucose tolerance test or an assay for hemoglobin A1c) for diabetes in asymptomatic adults of any age who are overweight or obese and who have 1 or more additional risk factors for diabetes. Given the association of psoriasis—particularly more severe disease—and increases in BMI, most of our patients would be recommended for diabetes screening based on standard recommendations. More important, level A evidence (ie, derived from randomized clinical trials) indicates that lifestyle changes and pharmacologic interventions (ie, treatment with metformin) can decrease the risk of diabetes in patients at high risk (ie, those with an abnormal fasting glucose concentration, impaired glucose tolerance, or both). Therefore, dermatologists have the opportunity to educate patients with psoriasis and initiate appropriate screenings (or refer them to primary care physicians), which can result in better health outcomes through evidence-based interventions. Moreover, obesity and diabetes have important implications for the management of psoriasis. For example, patients with psoriasis who have diabetes or who are overweight are at increased risk for developing severe liver fibrosis when being treated with methotrexate sodium. The effectiveness of treatments for psoriasis, particularly non-weight–based treatment with inhibitors of tumor necrosis factor, is adversely affected by increased BMI. Weight loss can result in improved responsiveness to treatments for psoriasis and psoriatic arthritis and in improvements in psoriasis generally.14 Despite these compelling reasons to identify diabetes in patients with psoriasis, a major practice gap remains in dermatologists’ screening and counseling of patients for cardiovascular risk factors.15 The weight of evidence linking psoriasis to cardiometabolic disease continues to increase, tipping the scale toward changing clinical practice in dermatology. Back to top Article Information Corresponding Author: Joel M. Gelfand, MD, MSCE, Department of Dermatology and Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, 1108 Dulles, 3400 Spruce St, Philadelphia, PA 19104 (joel.gelfand@uphs.upenn.edu). Published Online: April 27, 2016. doi:10.1001/jamadermatol.2016.0670. Conflict of Interest Disclosures: In the previous 12 months, Dr Gelfand reported having served as a consultant for Abbvie, AstraZeneca, Celgene, Coherus, Eli Lilly, Janssen Biologics (formerly Centocor), Sanofi, Merck, Novartis, Endo, Valeant, and Pfizer; having received honoraria; having received research grant support from Abbvie, Amgen, Eli Lilly, Janssen, Novartis, Regeneron, and Pfizer (to the trustees of the University of Pennsylvania); and having received payment for continuing medical education work related to psoriasis. Dr Gelfand is a co-patent holder of resiquimod for treating cutaneous T-cell lymphoma. Funding/Support: Funding for this work was provided by grant K24-AR064310 from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases. Role of the Funder/Sponsor: The funding source had no role in the preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. References 1. Gelfand JM, Neimann AL, Shin DB, Wang X, Margolis DJ, Troxel AB. Risk of myocardial infarction in patients with psoriasis. JAMA. 2006;296(14):1735-1741.PubMedGoogle ScholarCrossref 2. Wan J, Wang S, Haynes K, Denburg MR, Shin DB, Gelfand JM. Risk of moderate to advanced kidney disease in patients with psoriasis: population based cohort study. BMJ. 2013;347:f5961.PubMedGoogle ScholarCrossref 3. Ogdie A, Haynes K, Troxel AB, et al. Risk of mortality in patients with psoriatic arthritis, rheumatoid arthritis and psoriasis: a longitudinal cohort study. Ann Rheum Dis. 2014;73(1):149-153.PubMedGoogle ScholarCrossref 4. Lønnberg AS, Skov L, Skytthe A, Kyvik KO, Pedersen OB, Thomsen SF. Association of psoriasis with the risk for type 2 diabetes mellitus and obesity [published online April 27, 2016]. JAMA Derm. doi:10.1001/jamadermatol.2015.6262.Google Scholar 5. Bulik-Sullivan B, Finucane HK, Anttila V, et al; ReproGen Consortium; Psychiatric Genomics Consortium; Genetic Consortium for Anorexia Nervosa of the Wellcome Trust Case Control Consortium 3. An atlas of genetic correlations across human diseases and traits. Nat Genet. 2015;47(11):1236-1241.PubMedGoogle ScholarCrossref 6. Eirís N, González-Lara L, Santos-Juanes J, Queiro R, Coto E, Coto-Segura P. Genetic variation at IL12B, IL23R and IL23A is associated with psoriasis severity, psoriatic arthritis and type 2 diabetes mellitus. J Dermatol Sci. 2014;75(3):167-172.PubMedGoogle ScholarCrossref 7. Wolf N, Quaranta M, Prescott NJ, et al. Psoriasis is associated with pleiotropic susceptibility loci identified in type II diabetes and Crohn disease. J Med Genet. 2008;45(2):114-116.PubMedGoogle ScholarCrossref 8. Azfar RS, Seminara NM, Shin DB, Troxel AB, Margolis DJ, Gelfand JM. Increased risk of diabetes mellitus and likelihood of receiving diabetes mellitus treatment in patients with psoriasis. Arch Dermatol. 2012;148(9):995-1000.PubMedGoogle ScholarCrossref 9. Langan SM, Seminara NM, Shin D, et al. Prevalence of metabolic syndrome in patients with psoriasis: a population-based study in the United Kingdom. J Invest Dermatol. 2012;132(3, pt 1):556-562. PubMedGoogle ScholarCrossref 10. Dubreuil M, Rho YH, Man A, et al. Diabetes incidence in psoriatic arthritis, psoriasis and rheumatoid arthritis: a UK population-based cohort study. Rheumatology (Oxford). 2014;53(2):346-352.PubMedGoogle ScholarCrossref 11. Armstrong AW, Guérin A, Sundaram M, et al. Psoriasis and risk of diabetes-associated microvascular and macrovascular complications. J Am Acad Dermatol. 2015;72(6):968-977.e2.PubMedGoogle ScholarCrossref 12. Yeung H, Takeshita J, Mehta NN, et al. Psoriasis severity and the prevalence of major medical comorbidity: a population-based study. JAMA Dermatol. 2013;149(10):1173-1179.PubMedGoogle ScholarCrossref 13. Schwandt A, Bergis D, Dapp A, et al. Psoriasis and diabetes: a multicenter study in 222,078 type 2 diabetes patients reveals high levels of depression. J Diabetes Res.2015;2015:792968. doi:10.1155/2015/792968.Google ScholarCrossref 14. Naldi L, Conti A, Cazzaniga S, et al; Psoriasis Emilia Romagna Study Group. Diet and physical exercise in psoriasis: a randomized controlled trial. Br J Dermatol. 2014;170(3):634-642.PubMedGoogle ScholarCrossref 15. Manalo IF, Gilbert KE, Wu JJ. Survey of trends and gaps in dermatologists' cardiovascular screening practices in psoriasis patients: areas still in need of improvement. J Am Acad Dermatol.2015;73(5):872-874.e4.Google ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA Dermatology American Medical Association

Psoriasis, Type 2 Diabetes Mellitus, and Obesity: Weighing the Evidence

JAMA Dermatology , Volume 152 (7) – Jul 1, 2016

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Publisher
American Medical Association
Copyright
Copyright © 2016 American Medical Association. All Rights Reserved.
ISSN
2168-6068
eISSN
2168-6084
DOI
10.1001/jamadermatol.2016.0670
pmid
27120484
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Abstract

Psoriasis is a common, chronic inflammatory disease that is associated with an increased risk of cardiovascular, metabolic, and renal disease in a manner that varies with the severity of psoriasis and is often independent of traditional risk factors for these other diseases.1,2 The clinical significance of these associations is emphasized by premature death, particularly in patients with more severe psoriasis, in whom excess mortality is comparable to that seen in rheumatoid arthritis treated with disease-modifying medications.3 The association of psoriasis with type 2 diabetes mellitus and obesity has been extensively studied and has been the subject of numerous meta-analyses that clearly establish an association of psoriasis with both obesity and diabetes. Lønnberg and colleagues4 have provided new insights into these associations by studying monozygotic and dizygotic twins with and without psoriasis. Their main findings were that psoriasis is associated with diabetes independent of sex, age, smoking, and body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) (odds ratio, 1.53; 95% CI, 1.03 to 2.27) and that increases in BMI are associated with increasing odds of twins reporting a diagnosis of psoriasis. Similar findings were reported for hospitalized patients in whom psoriasis was diagnosed. The unique twin design of the study by Lønnberg and colleagues, in which an increasing BMI was associated with a diagnosis of psoriasis, allowed the investigators to identify a genetic correlation between psoriasis and BMI of 0.12 (95% CI, 0.08 to 0.19). A genetic correlation of similar magnitude of psoriasis and type 2 diabetes of 0.13 (95% CI, −0.06 to 0.31) was also observed, but this finding was not statistically significant (the prevalence of diabetes in this sample was quite low, yielding only 6 patients with psoriasis who also had diabetes). The magnitude of the genetic correlation is modest and similar to what has been reported for age at menarche and type 2 diabetes (−0.13).5 Nevertheless, these findings are consistent with emerging genetic evidence linking psoriasis to diabetes. For example, genetic variation in IL12B, IL23R, and IL23A has an influence not only on the risk for psoriasis but also on its severity and type 2 diabetes.6 Other researchers have suggested a role for CDKAL1 in conferring susceptibility to both psoriasis and diabetes.7 Only a few studies have examined the incidence (risk) of diabetes in patients with psoriasis while adjusting for major confounding variables (eg, BMI and hypertension), and only a subset of these were able to evaluate effects of the severity of psoriasis on the association of diabetes with psoriasis (using treatment patterns).8 The results of these studies suggest that psoriasis is associated with an increased risk of diabetes independent of major risk factors in a manner that correlates with the severity of psoriasis. Although the design used by Lønnberg et al4 does not address diabetes risk (ie, incidence) or directly evaluate a dose-response association of the severity of psoriasis to diabetes, its careful control for BMI, which most large population-based studies are unable to capture, adds to the weight of evidence suggesting psoriasis as a risk factor for diabetes. Additional population-based studies have similarly noted an increased prevalence of insulin resistance in patients with psoriasis in a manner that varies positively with increasing body surface area affected by psoriasis and independent of major risk factors such as BMI, hypertension, and dyslipidemia.9 Although inflammation is often invoked as a mechanistic link to insulin resistance, a simultaneous analysis of patients with psoriasis and rheumatoid arthritis with adjustment for major risk factors demonstrated an increased risk for diabetes only in patients with psoriatic disease.10 The risk of diabetic complications in patients with psoriasis (compared with diabetic patients without psoriasis) is rather unexplored, but emerging studies suggest that microvascular and macrovascular complications are more common in patients who have psoriasis and diabetes, that psoriasis is associated with worse hemoglobin A1c, and that increasing body surface area affected by psoriasis is associated with an increased risk for diabetic complications.11-13 These epidemiologic findings have clear implications for clinical practice. The dermatologist is on the front line in educating patients with psoriasis about their disease, treatment options, and risks of comorbidities. The US Preventive Services Task Force (updated 2015) recommends screening for an abnormal blood glucose concentration as part of the assessment for cardiovascular risk in adults aged 40 to 70 years who are overweight or obese. Moreover, the American Diabetes Association’s 2016 Standards of Medical Care recommend testing (with a fasting plasma glucose or oral glucose tolerance test or an assay for hemoglobin A1c) for diabetes in asymptomatic adults of any age who are overweight or obese and who have 1 or more additional risk factors for diabetes. Given the association of psoriasis—particularly more severe disease—and increases in BMI, most of our patients would be recommended for diabetes screening based on standard recommendations. More important, level A evidence (ie, derived from randomized clinical trials) indicates that lifestyle changes and pharmacologic interventions (ie, treatment with metformin) can decrease the risk of diabetes in patients at high risk (ie, those with an abnormal fasting glucose concentration, impaired glucose tolerance, or both). Therefore, dermatologists have the opportunity to educate patients with psoriasis and initiate appropriate screenings (or refer them to primary care physicians), which can result in better health outcomes through evidence-based interventions. Moreover, obesity and diabetes have important implications for the management of psoriasis. For example, patients with psoriasis who have diabetes or who are overweight are at increased risk for developing severe liver fibrosis when being treated with methotrexate sodium. The effectiveness of treatments for psoriasis, particularly non-weight–based treatment with inhibitors of tumor necrosis factor, is adversely affected by increased BMI. Weight loss can result in improved responsiveness to treatments for psoriasis and psoriatic arthritis and in improvements in psoriasis generally.14 Despite these compelling reasons to identify diabetes in patients with psoriasis, a major practice gap remains in dermatologists’ screening and counseling of patients for cardiovascular risk factors.15 The weight of evidence linking psoriasis to cardiometabolic disease continues to increase, tipping the scale toward changing clinical practice in dermatology. Back to top Article Information Corresponding Author: Joel M. Gelfand, MD, MSCE, Department of Dermatology and Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, 1108 Dulles, 3400 Spruce St, Philadelphia, PA 19104 (joel.gelfand@uphs.upenn.edu). Published Online: April 27, 2016. doi:10.1001/jamadermatol.2016.0670. Conflict of Interest Disclosures: In the previous 12 months, Dr Gelfand reported having served as a consultant for Abbvie, AstraZeneca, Celgene, Coherus, Eli Lilly, Janssen Biologics (formerly Centocor), Sanofi, Merck, Novartis, Endo, Valeant, and Pfizer; having received honoraria; having received research grant support from Abbvie, Amgen, Eli Lilly, Janssen, Novartis, Regeneron, and Pfizer (to the trustees of the University of Pennsylvania); and having received payment for continuing medical education work related to psoriasis. Dr Gelfand is a co-patent holder of resiquimod for treating cutaneous T-cell lymphoma. Funding/Support: Funding for this work was provided by grant K24-AR064310 from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases. Role of the Funder/Sponsor: The funding source had no role in the preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. References 1. Gelfand JM, Neimann AL, Shin DB, Wang X, Margolis DJ, Troxel AB. Risk of myocardial infarction in patients with psoriasis. JAMA. 2006;296(14):1735-1741.PubMedGoogle ScholarCrossref 2. Wan J, Wang S, Haynes K, Denburg MR, Shin DB, Gelfand JM. Risk of moderate to advanced kidney disease in patients with psoriasis: population based cohort study. BMJ. 2013;347:f5961.PubMedGoogle ScholarCrossref 3. Ogdie A, Haynes K, Troxel AB, et al. Risk of mortality in patients with psoriatic arthritis, rheumatoid arthritis and psoriasis: a longitudinal cohort study. Ann Rheum Dis. 2014;73(1):149-153.PubMedGoogle ScholarCrossref 4. Lønnberg AS, Skov L, Skytthe A, Kyvik KO, Pedersen OB, Thomsen SF. Association of psoriasis with the risk for type 2 diabetes mellitus and obesity [published online April 27, 2016]. JAMA Derm. doi:10.1001/jamadermatol.2015.6262.Google Scholar 5. Bulik-Sullivan B, Finucane HK, Anttila V, et al; ReproGen Consortium; Psychiatric Genomics Consortium; Genetic Consortium for Anorexia Nervosa of the Wellcome Trust Case Control Consortium 3. An atlas of genetic correlations across human diseases and traits. Nat Genet. 2015;47(11):1236-1241.PubMedGoogle ScholarCrossref 6. Eirís N, González-Lara L, Santos-Juanes J, Queiro R, Coto E, Coto-Segura P. Genetic variation at IL12B, IL23R and IL23A is associated with psoriasis severity, psoriatic arthritis and type 2 diabetes mellitus. J Dermatol Sci. 2014;75(3):167-172.PubMedGoogle ScholarCrossref 7. Wolf N, Quaranta M, Prescott NJ, et al. Psoriasis is associated with pleiotropic susceptibility loci identified in type II diabetes and Crohn disease. J Med Genet. 2008;45(2):114-116.PubMedGoogle ScholarCrossref 8. Azfar RS, Seminara NM, Shin DB, Troxel AB, Margolis DJ, Gelfand JM. Increased risk of diabetes mellitus and likelihood of receiving diabetes mellitus treatment in patients with psoriasis. Arch Dermatol. 2012;148(9):995-1000.PubMedGoogle ScholarCrossref 9. Langan SM, Seminara NM, Shin D, et al. Prevalence of metabolic syndrome in patients with psoriasis: a population-based study in the United Kingdom. J Invest Dermatol. 2012;132(3, pt 1):556-562. PubMedGoogle ScholarCrossref 10. Dubreuil M, Rho YH, Man A, et al. Diabetes incidence in psoriatic arthritis, psoriasis and rheumatoid arthritis: a UK population-based cohort study. Rheumatology (Oxford). 2014;53(2):346-352.PubMedGoogle ScholarCrossref 11. Armstrong AW, Guérin A, Sundaram M, et al. Psoriasis and risk of diabetes-associated microvascular and macrovascular complications. J Am Acad Dermatol. 2015;72(6):968-977.e2.PubMedGoogle ScholarCrossref 12. Yeung H, Takeshita J, Mehta NN, et al. Psoriasis severity and the prevalence of major medical comorbidity: a population-based study. JAMA Dermatol. 2013;149(10):1173-1179.PubMedGoogle ScholarCrossref 13. Schwandt A, Bergis D, Dapp A, et al. Psoriasis and diabetes: a multicenter study in 222,078 type 2 diabetes patients reveals high levels of depression. J Diabetes Res.2015;2015:792968. doi:10.1155/2015/792968.Google ScholarCrossref 14. Naldi L, Conti A, Cazzaniga S, et al; Psoriasis Emilia Romagna Study Group. Diet and physical exercise in psoriasis: a randomized controlled trial. Br J Dermatol. 2014;170(3):634-642.PubMedGoogle ScholarCrossref 15. Manalo IF, Gilbert KE, Wu JJ. Survey of trends and gaps in dermatologists' cardiovascular screening practices in psoriasis patients: areas still in need of improvement. J Am Acad Dermatol.2015;73(5):872-874.e4.Google ScholarCrossref

Journal

JAMA DermatologyAmerican Medical Association

Published: Jul 1, 2016

References