FREQUENCY OF METABOLIC SYNDROME IN PSORIASIS AND ITS INFLUENCE ON CERTAIN BIOCHEMICAL PARAMETERS

1. Fifth Half Yearly Progress Presentation : Yenepoya University PhD – July 2012 batch Ms ChetanaShenoy Junior Research Fellow Dept of DermatologyYenepoyaMedical College YenepoyaUniversity Deralakatte,Mangalore -18Guide: Dr ManjunathShenoyProfessor and Head Dept of Dermatology Yenepoya Medical College YenepoyaUniversity Deralakatte, Mangalore -18 FREQUENCY OF METABOLIC SYNDROME IN PSORIASIS AND ITS INFLUENCE ON CERTAIN BIOCHEMICAL PARAMETERS Co-Guide: DrManjulaShantaram Coordinator - PG Dept of Biochemistry Mangalore University PG Centre, ChikkaAluvara Kodagu District - 571232

2. DECEMBER 2015 - MAY 2016 CONTENTS • Introduction & literature review • Aim & Objectives • Work done so far • Results • Plan of work for the next 6 months • References

3. COMMENTS OF THE PREVIOUS PRESENTATION

4. INTRODUCTION

5. PSORIASIS • Chronic inflammatory, immune-mediated skin disease • 2-3% population worldwide (Gisondiet al.,2010) • Exact etiology of psoriasis - unknown • Autoimmune basis with a strong genetic component

6. PSORIASIS • Genetic predisposition in conjunction - environmental trigger - disease expression (Gisondiet al., 2007) • Contemporary medical literature is accumulating to support the assertion that psoriasis - multisystem disease

7. PSORIASIS AND CO-MORBIDITIES • Association - serious co-morbidities (Gottlieb et al., 2008) • Diabetes Mellitus (DM), obesity, dyslipidemia, Metabolic Syndrome (MetS) and nonalcoholic fatty liver disease • Link - not completely elucidated • Underlying chronic inflammatory nature of psoriasis (Zayed , 2010) • Pro-inflammatory factors - central to the pathogenesis of psoriasis

8. PSORIASIS AND CO-MORBIDITIES • Exploring correlations between psoriasis and other disease states is increasingly essential • Biomarkers of psoriatic inflammation must be uncovered • Link between psoriasis and co-morbidities like MetS

9. PSORIASIS AND CO-MORBIDITIES • Unveil newer dimensions in the pathogenesis of psoriasis • Predictors of future risk of morbidity and mortality must be identified • High-risk psoriasis populations can be identified and more aggressively managed

10. LITERATURE REVIEW

11. PSORIASIS AND METABOLIC SYNDROME • Psoriasis has been associated with MetS • Higher prevalence of MetS in psoriasis compared to controls (Gisondiet al., 2007; Love et al., 2011; Zindanciet al., 2012; Madanagobalaneet al., 2012) • Psoriatic patients have an increased risk for the individual components of MetS

12. ADIPOKINES AND METABOLIC SYNDROME • Leptin and adiponectin- adipokines – adipocytes • Link between obesity, insulin resistance and endothelial dysfunction • Hyperleptinemia and hypo adiponectinaemia - associated with MetS • Predicts the risk of developing MetS (Gallettiaet al., 2007; Premchandraet al., 2012)

13. ADIPOKINES AND PSORIASIS • Lower adiponectin levels and higher leptin levels in psoriasis patients (Kauret al., 2011) • Studies - possible relationship between leptin levels in both serum and tissues, and the severity of psoriasis vulgaris(Zayed, 2010)

14. URIC ACID • Serum uric acid levels-Strong and independent predictor of incident MetS (Shi-Dou Lin et al., 2006) • Increases significantly as the number of metabolic components increase • Predicts the development of MetS per se (Sui et al., 2008 ) • Levels exacerbate by increases in the severity and duration of psoriasis (Kwon et al., 2011; Ghiasiet al., 2012)

15. CRP AND METABOLIC SYNDROME • Sensitive marker of subclinical inflammation. • Elevated C-Reactive Protein (CRP) - related to insulin resistance and presence of the MetS • CRP may play a major role in the pathogenesis of CVD (Devarajet al., 2009) • Increasing severity of MetS is associated with increasing CRP (Rutteret al.,2004)

16. CRP AND PSORIASIS • CRP levels have been associated with psoriasis • 20 folds increase in patients with psoriasis • Useful marker of psoriasis severity and worsening (Ishaetal., 2011)

17. AIM • To evaluate the prevalence of MetS in patients with psoriasis in this region. This study also aims at estimating the levels of leptin, adiponectin, CRP and uric acid in patients with psoriasis and controls to evaluate their role in the development of MetS in them

18. OBJECTIVES • To determine the prevalence of MetS in psoriasis patients • To determine the levels of leptin, adiponectin, CRP and uric acid in psoriasis patients and controls • To compare these biochemical markers among the patients with various groups of psoriasis based on the severity

19. OBJECTIVES • To compare the levels of these biochemical markers in psoriasis patients with and without MetS • To compare the levels of these biochemical markers with their respective control groups • To develop a correlation of these biochemical parameters with respect to MetS among study population

20. HYPOTHESIS • Prevalence of MetS will be significantly different in the psoriasis group compared to the control group • Levels of leptin, adiponectin, CRP and uric acid will differ significantly in the psoriasis group compared to the control group • Levels of leptin, adiponectin, CRP and uric acid will differ significantly in the four groups

21. WORK DONE SO FAR

22. SAMPLING AND HISTORY • 200 patients with psoriasis and 200 participants without psoriasis (control) • An informed consent was taken • Detailed history • Clinical examination - general, systemic and dermatological examination

23. CLINICAL EXAMINATION • Anthropometric & clinical data • Age, gender, weight, height, diet, body mass index (BMI), waist circumference, blood pressure, age of onset, smoking and alcoholism • Duration of psoriasis, type and severity of psoriasis – recorded • Body mass index (BMI) • Calculated as weight in kilograms/height2 in meters

24. CLINICAL EXAMINATION • Severity • Psoriasis Area Severity Index • Waist circumference • Placing the measuring tape snugly around the abdomen at the level of the iliac crest • Blood pressure - as the average of two measurements

25. INCLUSION CRITERIA • All cases of psoriasis above 18 years of age who are willing to participate in the study and have voluntarily signed the informed consent form

26. EXCLUSION CRITERIA • Acute febrile illness, active systemic diseases/events such as arthritis, hepatic disease, renal disease, malignancies, pregnancy etc • Individuals with prior history of taking medications for DM, hypertension and dyslipidemia • Subjects on systemic therapy or phototherapy for past one month

27. ANALYSIS • Fasting venous blood samples were taken from the patients and controls • Fasting Lipid profile and plasma glucose were measured in patients and controls by enzymatic methods • All subjects included in the study were screened for MetS

28. METABOLIC SYNDROME DIAGNOSIS • South Asian modified version of National Cholesterol Education Programme - Adult Treatment Panel III criteria (SAM-NCEP ATP III criteria) (Enaset al., 2007)

29. SAM-NCEP ATP III CRITERIA Presence of three or more out of five criteria • Waist circumference (definition of abdominal obesity was modified using Asia Pacific WHO guidelines as waist circumference ) ≥ 90 cm for males and ≥ 80 cm for female • Triglycerides ≥ 150 mg/dl • Blood pressure ≥ 130/85 mmHg • Fasting plasma glucose ≥ 100 mg/dl • HDL cholesterol ( <40 mg/dl for males and < 50 mg/dl for females)

30. ANALYSIS • Uric acid was measured by enzymatic method • CRP was measured by immunoturbidometric method • Serum leptin and adiponectin were by Enzyme - Linked Immunosorbent Assay

31. STATISTICAL ANALYSIS • Percentage distribution, mean and standard deviation for the understanding of the distribution of the samples • Student’s unpaired ‘t’ test for comparison between the groups • Fishers exact/chi square for comparison between the groups • Comparison between multiple groups were done by one- way anova

32. RESULTS

33. STUDY GROUPS Control Psoriasis WithMetS WithoutMetS Duration Severity MetS < 2 yrs > 2 yrs Mild to Moderate ( < 12) Severe ( > 12) with without

34. DEMOGRAPHIC DATA • 200 patients with psoriasis and 200 participants without psoriasis (control) • Both groups - matched for age and sex • Out of the 400 subjects, 102 were females and 298 were males • The age of subjects included in the study varied from 18-73 years

35. Table 1 : Characteristics of patients with psoriasis and controls Analysis by student’s unpaired t test

36. Table 2 : Grouping according to severity based on PASI *Psoriasis Area Severity Index

37. Table 3 : Grouping according to duration of the disease Cases divided based on the duration of the disease

38. Table 4 : Analysis of components of Metabolic Syndrome in cases versus controls *High density Lipoprotein; ** p value < 0.05 is considered statistically significant; chi-square test is used to compare between the cases and controls *

39. Table 5: Prevalence of Metabolic Syndrome in Psoriasis Analysis by chi-square test; * p value < 0.05 is considered statistically significant

40. Table 6: Comparison of mean values of Metabolic Syndrome components between cases and controls *High Density Lipoprotein; Student’s unpaired t test is used to compare between the cases and controls; ** p value < 0.05 is considered statistically significant. Values are expressed as mean ± SD *

41. Table 7: Relation between disease severity and Metabolic Syndrome *Psoriasis Area Severity Index, chi-square test was used to compare between groups

42. Table 8: Relation between disease duration and Metabolic Syndrome Statistical analysis used to compare between the cases and controls was chi-square test ; ** p value < 0.05 is considered statistically significant

43. Table 9: Comparison of uric acid values between controls and psoriasis patients group Student’s unpaired t test is used to compare between the cases and controls; **p value < 0.05 is considered significant

44. . . Table 10 : Comparison of uric acid values between mild to moderate psoriasis and severe psoriasis groups *Psoriasis Area Severity Index ; Student’s unpaired t test is used to compare between the cases and controls

45. . . Table 11 : Comparison of uric acid values between psoriasis patients having short duration and long duration of disease Student’s unpaired t test is used to compare between the cases and controls ** p value < 0.05 is considered statistically significant

46. Fig. 1: Comparison of Uric Acid values between groups Serum uric acid levels were highest in psoriasis patients with MetS and lowest in controls without MetS

47. Table 12: Comparison of Uric acid values between groups Group 1 compared with group 2 ,*Metabolic syndrome, ** p value < 0.05 is considered significant; comparison between groups were done by anova

48. . . Table 13 : Comparison of adiponectin and leptin values between control and psoriasis patient group Student’s unpaired t test is used to compare between the cases and controls ** p value < 0.05 is considered statistically significant

49. Table 14: Comparison of adiponectin and leptin values between mild to moderate psoriasis and severe psoriasis groups Student’s unpaired t test is used to compare between the cases and controls *Psoriasis Area Severity Index

50. Table 15: Comparison of adiponectin and leptin values between psoriasis patients having short duration and long duration of disease Student’s unpaired t test is used to compare between the cases and controls; ** p value < 0.05 is considered statistically significant