Psoriasis is associated with increased risk of incident Diabetes Mellitus: A Danish nationwide cohort study

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Psoriasis is associated with increased risk of incident Diabetes Mellitus: A Danish nationwide cohort study Khalid U, Hansen PR, Gislason GH, Kristensen SL, Lindhardsen J, Skov L, Torp-Pedersen C, Ahlehoff O Usman Khalid, Cardiovascular Research Unit, Copenhagen University Hospital Gentofte usman.khalid@regionh.dk No conflict of interest

Background Psoriasis is a chronic inflammatory disease affecting 125 million people worldwide There is evidence of a link between psoriasis and cardiovascular (CV) disease Diabetes mellitus (DM) is a major health problem worldwide DM, CV disease, and psoriasis share inflammatory mechanisms and risk factors.

Background Past studies have shown an increase risk of DM in psoriasis, but: Results have been conflicting. Studies mostly designed as cross-sectional and casecontrol. Only a few cohort studies on selected population. Nationwide data has not been reported previously.

Objective Our aim : In the entire Danish population we evaluated the risk of incident DM Including the impact of psoriasis severity on the risk of DM

Methods Nationwide registries Danish Civil Registration Number Danish Health Care System

Methods Danish population aged 10 years from 1 st January 1997 31 st December 2009 Followed until: - Emigration, - Incident DM, - Death, - 31 st December 2009.

Danish population aged 10 years on January 1, 1997 n = 4 614 807 Excluded at baseline: Prevalent diabetes and/ or psoriasis n = 96 551 Study cohort n = 4 518 256 Reference population n = 4 465 643 Psoriasis n = 52 613 Mild psoriasis n = 45 829 Severe psoriasis n = 6784

Methods The incidence rate ratio (IRR) for Incident DM was estimated with Poisson regression models. Adjustment for confounding factors including: age, sex, calendar year, concomitant medication, comorbidity, and socioeconomic status.

The incidence rates per 1000-person years for Incident DM

The incidence rate ratios for Incident DM

The adjusted incidence rate ratios for Incident DM

Conclusion Psoriasis is associated with increased risk of DM Our results underline the importance of considering psoriatic patients as a high risk population in terms of DM and CV risk. Screening for DM and CV risk factors in patients with psoriasis is warranted

Thank you for your kind attention Questions? Usman Khalid Email: usman.khalid@regionh.dk Tel: + 45 27 83 00 81 Cardiovascular Research Unit, Gentofte Hospital, Denmark.

Reference population (n = 4 465 643) Mild psoriasis (n = 45 829) Severe psoriasis (n = 6 784) Characteristics Mean (SD) age (years) 43.9 (19.9) 45.3 (16.9) 44.7 (16.1) Men (%) 2,189,588 (49.0) 22,631 (49.4) 3,196 (47.1) Women (%) 2,276,055 (51.0) 23,198 (50.6) 3,588 (52.9) Mean (SD) follow-up time (years) 12 (2.8) 6 (3.9) 5.5 (3.5) Mean (SD) socio-economic status 3.0 (1.4) 3.2 (1.4) 3.1 (1.3) Charlson s index 0.03 (0.2) 0.02 (0.2) 0.03 (0.3) Comorbidity (%) Congestive heart failure 9,930 (0.2) 47 (0.1) 14 (0.2) Cardio-vascular disease 12,383 (0.3) 86 (0.2) 10 (0.2) Cardiac dysrhythmia 13,990 (0.3) 112 (0.2) 27 (0.4) Renal disease 2,259 (0.1) 12 (0.0) 3 (0.0) Chronic obstructive pulmonary disease 11,305 (0.3) 60 (0.1) 16 (0.2) Cancer 24,644 (0.6) 180 (0.4) 28 (0.4) Peripheral vascular disease 5,474 (0.1) 48 (0.1) 8 (0.1) Previous myocardial infarction 6,941(0.2) 64 (0.1) 12 (0.2) Treatment (%) Anti-depressant (%) 136,860 (3.1) 1,673 (3.7) 326 (4.8) Platelet inhibitor 91,202 (2.0) 887 (2.0) 100 (1.5) Prednisolone 85,358 (1.9) 947 (2.1) 298 (4.4) Beta-Blocker 133,754 (3.0) 1773 (3.9) 266 (3.9) ACEI/ARB 105,672 (2.4) 1307 (2.9) 186 (2.7) NSAID 115,161 (2.6) 1,477 (3.2) 401 (5.9) Loop diuretic 117,683 (2.6) 890 (1.9) 185 (2.7) Calcium channel blocker 138,937 (3.1) 1,610(3.5) 238 (3.5) Thiazide diuretic 139,261 (3.1) 1,542 (3.4) 239 (3.5) Vitamin K antagonist 20,112 (0.5) 182 (0.4) 33 (0.5) Cholesterol-lowering drugs 27,025 (0.6) 431 (0.9) 58 (0.9) Spironolactone 13,636 (0.3) 106 (0.2) 17 (0.3)

New onset diabetes mellitus Incidence rate ratio 95 % confidence interval P - value Overall estimates adjusted for age and sex Mild psoriasis 1.49 1.43 1.56 <0.001 Severe psoriasis 2.13 1.91 2.37 <0.001 Sex (male vs. female) 1.37 1.36 1.38 <0.001 Age (per 10 years) 1.04 1.04 1.04 <0.001 Overall estimates adjusted for age, sex, comorbidity, medication and socioeconomic status. Severe psoriasis 2.00 1.79 2.22 <0.001 Mild psoriasis 1.47 1.40 1.54 <0.001 Prednisolone 1.26 1.22 1.29 <0.001 Sex (male vs. female) 1.54 1.53 1.55 <0.001 Age (per 10 years) 1.03 1.03 1.03 <0.001 Socioeconomic status (per level increase) 0.95 0.94 0.95 <0.001 Charlson s index (per level increase) 1.16 1.14 1.18 <0.001 Anti-depressant 1.34 1.31 1.37 <0.001 Platelet inhibitor 0.99 0.97 1.01 <0.001 Beta-Blocker 1.55 1.53 1.58 <0.001 ACEI/ARB 1.74 1.71 1.78 <0.001 NSAID 1.33 1.30 1.36 <0.001 Loop Diuretic 1.64 1.61 1.68 <0.001 Calcium channel blocker 1.40 1.38 1.42 <0.001 Thiazide diuretic 1.43 1.41 1.46 <0.001 Vitamin K antagonist 1.18 1.13 1.23 <0.001 Cholesterol-lowering drugs 1.54 1.49 1.59 <0.001 Spironolactone 1.64 1.55 1.73 <0.001

Overall incidence rates (IR) with 95% confidence intervals (CI) per 1000-person years Reference population (n = 4 466 093) Mild Psoriasis (n = 45829) Severe psoriasis (n = 6784) All-cause mortality 12.57 15.46 24.40 IR (CI) [12.54 12.60] [15.01 15.92] [22.87 26.04] Incident diabetes mellitus 3.67 6.93 9.65 IR (CI) [3.65 3.69] [6.63 7.25] [8.68 10.73]

Table 2. Incidence rate ratio (IR) with 95% confidence intervals (CI) for incident DM after application of sensitivity analysis Reference population Mild Psoriasis (n = 45829) Severe psoriasis (n = 6784) Incident diabetes mellitus 1.00 1.49 2.12 IR (CI) [1.43 1.56] [1.90-2.36]