PG Department of Medicine MLN Medical College and S.R.N. Hospital Allahabad

A STUDY OF METABOLIC ASSOCIATIONS WITH PSORIASIS

PROFORMA

Submitted to King George Medical

University, Lucknow for the Degree of M.D.

(Medicine)

AUGUST 2018

BY

SHILPA MANDAL

Junior Resident 2ND year,

PG Department of Medicine,

M.L.N. Medical College,

Allahabad

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PG Department of Medicine MLN Medical College and S.R.N. Hospital Allahabad

ToThe Vice ChancellorKing George Medical UniversityLucknow.

Through Proper ChannelSubject: Request for submission of thesis Proforma for M.D.

Medicine.

Respected Sir/Madam,

I humbly request you to kindly register my subject of thesis entitled, “A STUDY OF METABOLIC ASSOCIATIONS WITH PSORIASIS” for the degree of M.D. (Medicine) examination of King George Medical University, Lucknow to be held in year 2020..

The particulars and proforma along with recommendation of chief guide and co-guides are enclosed herewith for necessary action.

Thanking you

Yours Sincerely,

SHILPA MANDAL Junior Resident 2nd year PG Department of Medicine M.L.N. Medical College, Allahabad

Forwarded and Recommended by:

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PG Department of Medicine MLN Medical College and S.R.N. Hospital Allahabad

PROF.SARITA BAJAJ

MD, DM (Endocrinology) Director, Professor& Head PG Department of Medicine M.L.N. Medical College,

Allahabad.

CHIEF GUIDE

PROF. SARITA BAJAJ(MD,DM)Director, Professor and Head

PG Dept. of MedicineM.L.N. Medical College

Allahabad

CO-GUIDES

Dr. SUDHA YADAV(MD)Head of the Department

Dept. of Dermatology and Veneral diseasesM.L.N. Medical College

Allahabad

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PG Department of Medicine MLN Medical College and S.R.N. Hospital Allahabad

Dr. RAJPAL PRAJAPATI(MD,DM)Assistant Professor

PG Dept. of MedicineM.L.N. Medical College

Allahabad

PROFORMA FOR THE THESIS

Name of the Candidate : SHILPA MANDAL

Year and Month of Graduation : March 2015

College from which graduate : NIL RATAN SIRCAR MEDICAL COLLEGE AND HOSPITAL,KOLKATA,WEST BENGAL

University from which graduated : WEST BENGAL UNIVERSITY OF HEALTH

SCIENCES

Course to which admitted : M.D. Medicine

Date of admission : 9 May 2017

Present status : Junior Resident 2nd year, PG Department of Medicine

Present College and University : M.L.N. Medical College, Allahabad,: King George Medical University,

Lucknow

Department in which subject of : Department of Medicine. thesis fall M.L.N. Medical College, Allahabad

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PG Department of Medicine MLN Medical College and S.R.N. Hospital Allahabad

Title of Thesis : A STUDY OF METABOLIC ASSOCIATIONS WITH PSORIASIS.

Place of Study : Swaroop Rani Nehru Hospital, M.L.N. Medical College, Allahabad

Duration of Study : One Year

Brief resume of the work proposed : Attached herewithto be undertaken for thesis

CONSENT FORM

Title of the project: A Study of Metabolic Associations With Psoriasis.

Investigator: Shilpa MandalJunior Resident 2ND year, PG Department of MedicineM.L.N. Medical College, Allahabad

Collaborators

Prof.Sarita Bajaj MD, DM (Endocrinology)Director, Professor and Head, PG Dept. of Medicine,

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PG Department of Medicine MLN Medical College and S.R.N. Hospital Allahabad

M.L.N. Medical College, Allahabad.

Dr. Sudha Yadav(MD) Head of the department,Department of Dermatology and Veneral diseasesM.L.N. Medical CollegeAllahabad

Dr .Rajpal Prajapati MD,DM (Cardiology)Associate ProfessorPG Dept. of MedicineM.L.N. Medical CollegeAllahabad

PART – I

Purpose of the Study:

1. To study the prevalence of metabolic diseases in psoriasis.

2. To study the correlation of metabolic diseases with psoriasis.3. To study the prevalence of macro and microvascular

complications in psoriasis.4. To study role of insulin resistance as a link between psoriasis

and metabolic diseases.

Study Procedure:100 cases and 100 controls will be evaluated by history, examination, biochemical and radiological modalities.

Risks from the study:No particular risk is perceived.

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PG Department of Medicine MLN Medical College and S.R.N. Hospital Allahabad

Benefits from the Study: 1. To know whether insulin resistance is associated with psoriasis in

the local population so as to understand the biochemical pathway behind association of psoriasis with diabetes and other metabolic diseases.

2. And also to prompt for early diagnosis and management of diabetes ,hypertension, obesity and dyslipidemic states in psoriatic patients.

Confidentiality: All the information regarding patient will not be disclosed in any circumstances.

Rights of the participants: At any time of study patients have got the right to ask questions regarding any aspect of the study.

Alternative to participation in the study: At any time if patient wishes to leave the study he/she will be allowed to do so.

PART – II

Patient/Guardian Consent

I have had the study explained to me and have read the contents of this form/had the contents of this form read to me. I have been given the opportunity to ask questions and have them answered to my satisfaction.

I am willing to be enrolled in the study.

Name of the subject: ……………………………………………………………………………

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PG Department of Medicine MLN Medical College and S.R.N. Hospital Allahabad

Signature of patient/guardian: ………………………………….…………................................

Name……………………………………………………………………………………………

Date……………………………………………………………………………………..............

Relationship with thesubject.….…………………………………………................................

Investigators statements

I, the undersigned have explained to the patient/guardian in a language she/he understands the procedures to be followed in the study and risks and benefits.

Signature of the Investigator……………………………...Date…………………

Name of the Investigator……………………………….

Signature of witness: ……………………………………...Date…………………

Name of witness: …………………………………………

INTRODUCTION

PSORIASIS

Psoriasis is one of the most common dermatologic diseases, affecting upto 2% of the world’s population.(1)It is an immune mediated disease clinically characterised by erythematous sharply demarcated papules and rounded plaques covered by silvery micaceous scale. The skin lesions of psoriasis are variably pruritic .

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PG Department of Medicine MLN Medical College and S.R.N. Hospital Allahabad

(1)Psoriasis is histologically characterized by epidermal hyperplasia, abnormal keratinocyte differentiation, proliferation of dermal blood vessels, and accumulation of inflammatory cells, particularly neutrophils and T-lymphocytes in the dermis.(2) More than skin disease, psoriasis is nowadays considered a systemic inflammatory disorder(3),It is associated with numerous metabolic disorders like obesity, dyslipidemia, Type 2DM and hypertension.(4,5)The strict clinical connection between psoriasis and metabolic diseases are well explained by analogies in their pathogenesis(chronic inflammation)viewing active factors secreted by adipose tissue (adipocytokines) and insulin resistance.(6)

METABOLIC DISEASES TYPE 2 DIABETES MELLITUS(T2DM)- Diabetes mellitus

refers to a group of common metabolic disorders that share the phenotype of hyperglycemia. T2DM is a long term metabolic disorder that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Insulin resistance and abnormal insulin secretion are central to pathogenesis of type 2 diabetes mellitus. Insulin resistance precedes an insulin secretory defect but diabetes develops only when insulin secretion becomes inadequate. Approximately 425 million adults are living with diabetes. (7) The proportion of people with type 2 diabetes is increasing in most countries.(7)Insulin resistance and abnormal insulin secretion are central to the development of type 2 DM.(8)

OBESITY-Obesity is a state of excess adipose tissue mass.(9)Although not a direct measure of adipocity, it is most commonly measured by Body Mass Index(BMI).(9)Although the adipocyte has generally been regarded as a storage depot for fat, it is also an endocrine cell that releases numerous molecules in a regulated fashion.(10)These include cytokines such as tumour necrosis factor α(TNF-α),and interleukin(IL)-6,energy balance regulating hormone leptin, adiponectin etc.(10)

HYPERTENSION-According to 2017 ACC/AHA guideline hypertension is defined as systolic blood pressure >=130 mm of Hg and diastolic blood pressure >=80 mm of Hg.(11) In addition

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PG Department of Medicine MLN Medical College and S.R.N. Hospital Allahabad

to its metabolic effects,insulin induces vasorelaxation by stimulating the production of nitric oxide(NO) in the endothelium(12).It also regulates sodium homeostasis by enhancing sodium reabsorbtion in the kidney(13,14).Insulin has complex vascular actions that either appear as vascular protective or deletorious.

DYSLIPIDEMIA-Disorders of lipoprotein metabolism are collectively referred to as ‘dyslipidemias’(15) Dyslipidemia is characterised by increased plasma levels of cholesterol or triglycerides(TG) or both, variably accompanied by reduced level of High density lipoprotein(HDL).(15)Obesity and insulin resistance are frequently accompanied by dyslipidemia and are characterised by elevated plasma level of TG, low HDL-C and variable level of Low Density Lipoprotein (LDL-C ) and increased level of Very Low Density Lipoprotein (VLDL).(15)

Lipids Cut off values(mg/dl)

Total cholesterol >=200

LDL-C >=130

HDL-C <=40(Men);<=50(Women)

TG >=150

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PG Department of Medicine MLN Medical College and S.R.N. Hospital Allahabad

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PG Department of Medicine MLN Medical College and S.R.N. Hospital Allahabad

REVIEW OF LITERATURE

Many studies have been performed to evaluate the correlation between Psoriasis and different metabolic diseases. A case control study was conducted in Teerthanker Mahaveer Medical College, Moradabad, Uttar Pradesh ,India by Jain S.K et a on the topic “Metabolic syndrome in patients with chronic plaque psoriatic disease”, and used the students t-test, Mann Whitney U test and chi-square test to calculate the statistical significance and they concluded that metabolic syndrome in psoriasis was associated with higher age .Among the cases,64% had metabolic syndrome as compared to 48% of controls(p value-0.158).The mean for serum triglycerides(TG) level for psoriasis patients(159.42mg/dl) was higher than controls (144.25mg/dl).46% of cases had elevated TG>=150mg/dl as compared to 40% of controls.(16)

Another study was done by Mohammad Ebrahimzade et al on “Prevalence of Insulin resistance in patients with psoriasis” in Shahid Sadoughi University of Medical Sciences, Yazd, Iran, on 110 patients with psoriasis and equal no. of healthy people. The study design was case control and used chi-square test as statystical analysis and found out that the mean fasting plasma glucose was 106mg/dl in patient group and 103.93mg/dl in the control group, insulin resistance was found in 46.4% of patients(p-value:0.665)and 39.1% of controls(p-value:0.276). According to this study there was no association between insulin resistance and psoriasis.(17)

Jing-Ji et al, made a meta-analysis from 12 case control studies with a total of 3831 psoriatic patients to study the “Association between psoriasis and metabolic syndrome” in Tianjin First Centre Hospital, Tianjin, China. The results showed that metabolic syndrome was more prevalent in psoriatic patients than in controls. The odds ratio(OR) was 2.07[95% Confidence interval(CI)].It also demonstrated that higher prevalence of obesity and hypertension was found in psoriasis patients, the OR being 1.64 and 2.24 respectively. (18)

Another study was conducted by Doddaengaiah R. Shivanand et al,on “Insulin Resistsance and Dyslipidemia in Psoriasis Patients” which was a case control study. They studied on 52 psoriasis patients and 50 healthy control in Shridevi Institute of Medical Sciences and Research Hospital, Tumkur, Karnataka, India. They concluded that fasting insulin levels and insulin resistance measured by HOMA-IR method were significantly (p<0.05)higher in mild and severe psoriasis cases when compared to healthy controls. Total cholesterol, triacyl glycerol, LDL-cholesterol levels were significantly higher in mild and severe psoriasis

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PG Department of Medicine MLN Medical College and S.R.N. Hospital Allahabad

cases in comparision to controls. HDL-cholesterol levels were significantly lower in both mild and severe cases as compared to controls.(19)

According to another study conducted by April W.Armstrong et al, on “Psoriasis and risk of diabetes associated microvascular and macrovascular complications” in department of Dermatology, University of Colorado, Boston studied,Study was conducted on 6164 diabetic patients with psoriasis and matched them to 6164 diabetic patients without psoriasis and concluded that patients with psoriasis were significantly more likely to develop microvascular and macrovascular complications. Greater psoriasis severity did not increase the risk of diabetic complications.(20)

Sinead M.Langan et al studied on 4065 psoriasis patients and 4065 controls on the topic, “Metabolic syndrome in patients with psoriasis” in University of Pennsylvania, Philadelphia, Pennsylvania, USA . They concluded that Psoriasis is associated with obesity, hypertryglyceridemia and hyperglycemia. These associations increase in a ‘dose response manner’,from mild(OR 1.22,95% CI 1.11-1.35)to severe psoriasis(OR 1.98,95%CI 1.62-2.43).(21)

AIMS AND OBJECTIVES

To study prevalence of metabolic diseases in patients of psoriasis. To study prevalence of insulin resistance using HOMA-IR index in

patients of psoriasis.

IMPLICATIONS OF THE STUDY

To prompt for early diagnosis and management of diabetes, hypertension, obesity and dyslipidemic states in psoriatic patients.

METHODOLOGY

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PG Department of Medicine MLN Medical College and S.R.N. Hospital Allahabad

ETHICS: Institutional ethics committee permission will be procured prior to the start of the study.

STUDY DESIGN: Case Control Study

CASE SELECTION: Patients (both male and female)attending medicine and dermatology department in SRN Hospital ,Allahabad will be the source of data.

CONTROL SELECTION: Equal number of age and sex matched individuals having no history and clinical signs of psoriasis, not falling under criteria of metabolic syndrome.

INCLUSION CRITERIA:Patients aged more than 18years having definite clinical confirmation of psoriasis.

EXCLUSION CRITERIA: Psoriatic patients having received systemic treatment(especially

cyclosporine) for more than 1 month. Patients having any other skin lesion except psoriasis. Pregnant patients.

STUDY PROCEDURE:

After obtaining written informed consent, patient qualifying inclusion criteria will be assessed as follows:

1. Detailed epidemiological information along with history regarding age, gender,address will be collected..All participants will undergo routine investigation.

2. Waist circumference of all the patients will be measured..3. Following an overnight fast, 2 ml of venous blood will be collected

in plain (red topped) vacutainer from anterior cubital vein under aseptic condition in all subjects. Laboratory tests including fasting plasma insulin, fasting blood glucose, lipid profile,liver function test, kidney function test etc will be performed. A 2 hour post prandial plasma glucose will also be measured.

4. Fundus examination, Electrocardiography(ECG) and 2D Echocardiography will be performed.

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PG Department of Medicine MLN Medical College and S.R.N. Hospital Allahabad

STATISTICAL ANALYSIS:

The data will be analyzed using appropriate statistical tests within different groups.

REFERENCES 1)Harrison’s principles of internal medicine19th edition,pg-503.

2)Griffiths CE,Barker JN.Pathogenesis and clinical features of psoriasis.Lancet 2007;370:263-71 3)Reich K.The concept of psoriasis as a systemic inflammation: implications for disease management.J Eur Acad Dermatol Venerol2012;26(Suppl 2):3-11.4)M.Farschian,A.Zamanian,M.Farschian,A.Rmonsef,and H.Mahjub,”Serum lipid level in Iranian patients with psoriasis,”

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PG Department of Medicine MLN Medical College and S.R.N. Hospital Allahabad

Journal of the European Academy of Dermatology and Venerology,vol.21,no.6,pp.802-805,2007.5)Buerger C,Richter B,Woth K,Salgo R,Malisiewicz b,et al.(2012)Interleukin-1B interferences with epidermal homeostasis through induction of insulin resistance:implications for psoriasis pathogenesis.J invest Dermatol 132:2206-2214.6) Buerger C,Richter B,Woth K,Salgo R,Malisiewicz b,et al.(2012)Interleukin-1B interferences with epidermal homeostasis through induction of insulin resistance:implications for psoriasis pathogenesis.J invest Dermatol 132:2206-2214 7)IDF,2017.8)Harrison’s principles of Internal medicine,19th edition,pg-2974. 9)Harrison’s principles of Internal medicine,19th edition,pg-622.10)Harrison’s principles of Internal medicine,19th edition,pg-62411)JAMA.2017;318:2083-2084

12)Scherrer U,Randin D,Vollenweider L,Nicod P:Nitriic oxide release accounts for insulin’s vascular effects in humans.J Clin Invest 1994,94:2511-2515.

13)Manhiani MM,Cormican MT,Brands MW:Chronic sodium retaining action of insulin in diabetic dogs.Am J Physiol 2011,300:F957-F965.

14)Horita S<Seki G,Yamada H,Suzuki M,Koike K,Fujita T:Insulin resistance,obesity,hypertension,and renal sodium transport. Int J Hypertens 2011,2011:391-762.

15)Harrisons’s principles of Internal medicine,19th edition,pg-3218.

16)Jain S.K et al, Metabolic syndrome in patients with chronic plaque psoriatic disease, International Journal of Research in Medical Sciences,2018,vol 6,issue 2,pg-688-692.

17)MOHAMMAD EBRAHIMZADEH et al,PREVALENCE OF INSULIN RESISTANCE IN PATIENTS WITH PSORIASIS,IRANIAN JOURNAL OF DIABETES AND OBESITY,2016,VOLUME 7,NUMBER 4,PG-172-176.

18)Jing-Ji et al, Association between psoriasis and metabolic syndrome,Int J Chin Exp Med,2016;9(9):PG-17933-17939 .

19) Doddaengaiah R.Shivanand et al,JInsulin Resistsance and Dyslipidemia in Psoriasis Patients in a Tertiary Care Hospital,South India,KIMSU,Vol 5,No 1,,2016,Pg-14-19.

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20) April W.Armstrong et al, Psoriasis and risk of diabetes associated microvascular and macrovascular complications,American Academy of Dermatology ,inc.2015;72:pg-968-977.

21 Sinead M.Langan et al , Metabolic syndrome in patients with psoriasis:A population based study in the United Kingdom,Journal of Investigative Dermatology(2012),Volume 132,pg-556-561.

WORKING PROFORMA

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PG Department of Medicine MLN Medical College and S.R.N. Hospital Allahabad

NAME:………………………………………………………………………………………

AGE/SEX:……………………………………………………………………………………..

ADDRESS:…………………………………………………………………….........................

OCCUPATION:……………………………………………………………………………….

DATE OF ADMISSION:……………………………………………………………………..

PRESENTING COMPLAINTS:……………………………………………………………..

PAST HISTORY:………………………………………………………………………………

GENERAL EXAMINATION:………………………………………………………………..

SYSTEMIC EXAMINATION:

CNS- CVS-

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PG Department of Medicine MLN Medical College and S.R.N. Hospital Allahabad

RESP- P/A-

INVESTIGATIONS

FPG/PPG: Fasting Lipid Profile: HOMA-IR Assay: Fasting plasma glucose(mmol/L)x Fasting plama

insulin(U/ml)/22.5 

A1C : LFT: KFT: Urine for microalbumin: Fundus: ECG: 2D Echo:

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