PROTOCOL

STUDY TITLE: Prospective Comparative Study to Estimate the Prevalence of Periodontitis in Type 1 and Type 2 Diabetic and Non-Diabetic Patients.

Confidential

TITLE: Prospective Comparative Study to Estimate the Prevalence of Periodontitis in Type 1 and Type 2 Diabetic and Non-Diabetic Patients.

Protocol No:

PPDN001

Version no:

1.0 1st April, 2012

Date:

Student M.Sc CR: Mohammad Afzal

Guide: (Investigator)

Dr. SujeetJha, Endocrinologist Max Super Speciality Hospital, Saket

Co-Investigator:

Eshoo Kansal

Co-guide:

Dr. Sangeeta Dheer

Guide: (Jamia Hamdard)

Dr. Fahad Haroon

Biostatistician:

Ms. Kalpana Singh

Study Site:

Max Super Speciality Hospital, Saket, New Delhi.

Protocol No.PPDN001, Version No. 1.0, Dated 1st April 2012

ii

Confidential

TABLE OF CONTENTS Page 1. INTRODUCTION................................................................................................................................... 3 2. STUDY RATIONALE ................................................................................................................... .3 3. STUDY OBJECTIVES4 1.1 Primary Objective4 4. STUDY DESIGN ............................................................................................................................... ..4 5. SELECTION AND ENROLLMENT OF PARTICIPANTS .............................................................. 4 5.1 Inclusion Criteria 4 5.2 Exclusion Criteria. ...5 5.3 Study Enrollment Procedures.5 6. STUDY PROCEDURES.........................................................................................................................5 7.. STATISTICAL CONSIDERATIONS... ...6 7.1 Hypothesis ...6 7.2 Sample Size...........6 7.3 Statistical Analysis6 7.4 Outcomes. ...7 8. DATA COLLECTION...........7 8.1 Data Collection Forms7 9. PARTICIPANT RIGHTS AND CONFIDENTIALITY...................................................................... 7 10.1 Institutional Ethics Committee......................................................................7 10.2 Participant Confidentiality.............................................................................8 10. PUBLICATION OF RESEARCH FINDINGS .................................................................................. 8 11. REFERENCES.8 12. SUPPLEMENTS/APPENDICES ........................................................................................................ 8 I (A) Case Report Form Template I (B) Dental PHP Form

Protocol No.PPDN001, Version No. 1.0, Dated 1st April 2012

iii

Confidential

LIST OF ABBREVIATIONS

T1DM

Type 1 diabetes mellitus

T2DM

Type 2 diabetes mellitus

PHP

Preventive Health Programme

ICF

Informed Consent Form

CRF

Case Report Form

IEC

Institutional Ethics Committee

1
Protocol No. PPDN001, Version No. 1.0, Dated 1st April 2012

Confidential

SYNOPSIS

STUDY TITLE

Prospect Prospective comparative study to estimate the prevalence of periodontitis in Type 1 and Type 2 diabetic and non-diabetic Patients .

PRIMARY OBJECTIVE

To estimate the prevalence of periodontitis in diabetic as compared with non-diabetic patients in diabetic clinic.

DURATION

Duration of the study is 3 months

TYPE OF STUDY

Prospective Case-Control Study

2
Protocol No. PPDN001, Version No. 1.0, Dated 1st April 2012

Confidential
1. INTRODUCTION Diabetes is a chronic disease which affects virtually every organ in the human system .India ranked number one as the country with the highest number of diabetes patients in 1995, at 31.7 million in 2000, with a projected 57.2 million in 2025, and 79.4 million in 2030, retaining its top position. DM has acquired a pandemic status in India. Research in several countries indicates that 5 20% of any population will have severe PD and a majority of adults suffer from moderate forms of this disease. Evidence suggests that one out of two adults above the age of 35 years have PD in India, and 35% of the teeth extracted are as a consequence of PD. The diabetes is characterized by an increased susceptibility to infection, poor wound healing, and increased morbidity and mortality associated with disease progression. Altered collagen metabolism in diabetics would be expected to contribute to the progression of periodontal disease. Hyperglycemia impairs overall cell function, as insulin is required for glucose to enter cells to provide a source of energy. Diabetes is also recognized as an important risk factor for more severe and progressive periodontitis, infection or lesions resulting in the destruction of tissues and supporting bone that form the attachment around the tooth. Both diseases are thought to share a common pathogenesis that involves an enhanced inflammatory response that can be observed at the local and systemic level. Periodontal disease has been reported as the sixth complication of diabetes, along with neuropathy, nephropathy, retinopathy, and micro- and macrovascular diseases. Many studies have been published describing the bidirectional interrelationship exhibited by diabetes and periodontal disease. Studies have provided evidence that control of periodontal infection has an impact on improvement of glycemic control evidenced by a decrease in demand for insulin and decreased hemoglobin A1C levels.

2. STUDY RATIONALE Regarding the influence of diabetes on periodontium, there are two schools of thought. One school of thought has reported increased severity of periodontal disease in diabetics not related to increased local irritants. According to them angiopathy, abnormal collagen metabolism, abnormal polymorphonuclear cell (PMN) function, and altered sulcular microbial flora are found in close association with the severity of periodontitis in diabetic patients. These factors reduce the defensive capacity of tissues and may disturb the tissue response to local irritants. These diseases are thought to be associated biologically, and a number of reviews and studies have proposed mechanisms to explain the relationship, including- 1)microvascular disease, 2) changes in components of gingival crevicular fluid, 3) changes in collagen metabolism, 4) an altered host response, 5) altered subgingival flora, 6) genetic predisposition, and 7) non-enzymatic glycation. Both population based and mechanistic studies have examined the potentiating effects of periodontal infection in the presence of hyperglycemia and have demonstrated increased innate immune responses and periodontal tissue destruction related to an altered inflammatory response. Research in several countries indicates that 5 20% of any population will have severe PD and a majority of adults suffer from moderate forms of this disease.

3
Protocol No. PPDN001, Version No. 1.0, Dated 1st April 2012

Confidential
3. STUDY OBJECTIVES 3.1 Primary Objective Estimation of the prevalence periodontitis in type 1 and type 2 diabetic patients as compared with non-diabetic patients.

4. STUDY DESIGN A prospective observational study; two groups of patient to be enrolled to participate in the study; GroupA: 30 diabetic patients , GroupB: 30 patients without diabetes from routine dental health preventive programme.. The diabetic subjects will be evaluated with glycosylated hemoglobin (GHb) to determine the glucose control; clinical periodontal evaluations will be performed for all teeth in each subject and following indexes to be included: Plaque, gingival, , probing depth, attachment level, bleeding on probing, and marginal bone loss.

5. SELECTION AND ENROLLMENT OF PARTICIPANTS Adequate number of subjects will be selected. Medical histories and demographic data, including name, sex, age, body weight (kg), height (cm) and tobacco use (including number of cigarettes smoked per day) will be recorded.

5.1 CASE Inclusion Criteria: Subject aged over 18 years old. Patients having diagnosis of type 1 or type 2 diabetes as defined by American Diabetes Association (ADA 2011) criteria. Subject able to provide consent to participate in the study.

5.2 CASE Exclusion Criteria: Pregnant or Lactation women. Patient with recent dental treatment. Patients not willing to participate in the study.

4
Protocol No. PPDN001, Version No. 1.0, Dated 1st April 2012

Confidential
5.3 CONTROL Inclusion Criteria Males and females of age between 18-80. Absence of diagnosed type 1 and type 2 diabetes mellitus or any history of diabetes i.e. HbA1c level< 6.5

5.4 CONTROL Exclusion Criteria Pregnant or lactating women. Inability or unwillingness of individual or representative to give written informed consent.

5.5 Study Enrollment Procedures Patients with Type 1 and Type 2 diabetes visiting the diabetic clinic ,outpatient department of Max Super Speciality Hospital will be identified and enrolled in the study, if they meet all the inclusion criteria defined for the case group. Subjects from general population without type 1 and type 2 DM and fulfilling all the inclusion criteria defined for the control group will be enrolled.

6. STUDY PROCEDURES Study would be based at the diabetic centre. Subject population would comprise of males and females of the age group (18-80 years) with and without diagnosed diabetes (type 1 and type 2). Subjects to be recruited as per criteria and their demographic variables, age, sex, duration of diabetes, Body weight and height ) BMI, history of smoking and alcohol, family history of diabetes, Family history of periodontitis, drugs regime for diabetes ( oral / insulin), home oral care (frequency of tooth brushing / flossing ) will be recorded. dental examination of both the groups of patient will be done.

5
Protocol No. PPDN001, Version No. 1.0, Dated 1st April 2012

Confidential

7. STATISTICAL CONSIDERATIONS 7.1 Hypothesis: The primary effectiveness hypothesis being tested is: H0: pT= pC vs. H1: pT pC Where pT and pC are the proportion of depression in diabetes and non diabetes groups respectively, rejection of the null hypothesis at a two sided significance level of 0.05 indicates a significant difference between two arms.

7.2 Sample size: By the previous study the prevalence of periodontitis in type I and type II diabetes mellitus was 68.18% and the prevalence of periodontitis in well controlled type ii diabetes mellitus was 31.82%. We need minimum 30 subjects in each group to achieve 80% power and 5 % level of significance. Sample size required for 80% power (n 80%) and 90% (n 90%) for level of Level of significance 1% 5% 10% N (80%) 44 29 23 N (90%) 55 38 31 significance:

7.3 Statistical Analysis: Normally distributed data are presented as mean and standard deviation; non- normally distributed data are presented as medians quartiles (inter quartile range).Categorical data will be analyzed using chi-square analysis or Fishers exact test where applicable. Continuous data will be analyzed by t-test or Mann Whitney U test as appropriate. Multiple logistic regression will be used to find the risk of different predictor variables. All data collected during the study will be included in data listings. Unless specified otherwise, all statistical testing will be two-sided and will be performed using a significance (alpha) level of 0.05. All statistical analyses will be conducted with the STATA System, version 9.0 and R (2.12).

6
Protocol No. PPDN001, Version No. 1.0, Dated 1st April 2012

Confidential

7.4 Outcome Presence of periodontitis in type 1and type 2 diabetic and non-diabetic patients.

8. DATA COLLECTION 8.1 Data Collection Forms Data generated during the conduct of study will directly be entered into case report forms and will then be recorded into the computerized format. 9. PARTICIPANT RIGHTS AND CONFIDENTIALITY. 9.1 Institutional Ethics Committee (IEC)/ Institutional Review Board (IRB) Review This protocol will be reviewed by the Institutional Ethics Committee and the study subjects will not be enrolled until the Committee/Board has approved the protocol, as submitted or with modifications in subsequent version(s). This research will be carried out in accordance with the Basic Principles defined in US 21 CFR Part 320, the ICH (62FR 25692, 09 May 1997) 'Guidance for Good Clinical Practice'. ICMR ethical guidelines for biomedical research on human participants (2006), CDSCO guidance on good clinical practice for clinical research India.

9.2 Participant Confidentiality Information will not be released without written permission of the participant, except as necessary for monitoring by IEC and any regulatory authority. 10. PUBLICATION OF RESEARCH FINDINGS After the completion of this study, we intend to immediately publish the results in international and national journals. .

7
Protocol No. PPDN001, Version No. 1.0, Dated 1st April 2012

Confidential
11. REFERENCES 1. Cheng B, Lamster IB. Identification of unrecognized diabetes and pre-diabetes in a dental setting. J dent res. 2011 jul; 90(7):855-60. epub 2011 apr 29. 2. Silvestre FJ, The effect of periodontal treatment on metabolic control of type 1 diabetes mellitus. Clin oral investig. 2008 dec;12(4):337-43. Epub 2008 apr 30. 3. Syrjlam, P, Niskanen Mc, Knuuttila Ml. Role of smoking and hba1c level in periodontitis among insulin-dependent diabetic p atients. J clin periodontol. 2003 oct;30(10):871-5. 4. Barasch A, , Safford MM, Gesko D, Qvist V, Palmore O, Gilbert GH, The Dental PracticeBased Research Network Collaborative Group. A community-based feasibility study from The Dental Practice-Based Research Network Available From: http://jada.ada.org/content/143/3/262 5. Acharya AB, Satyanarayan Aparna, and Thakur SL, status of association studies linking diabetes mellitus and periodontal disease in india, copyright international journal of diabetes in developing countries. 6. Screening for type 2 diabetes [cited 2012 Mar 20] Available From http://care.diabetesjournals.org/content/26/suppl_1/s21.full 7. Santos VR, Lima JA, De Mendona AC, Braz Maximo MB, Duarte PM. Effectiveness of full-mouth and partial-mouth scaling and root planing in treating chronic periodontitis in subjects with type 2 diabetes. j periodontol. 2009 aug;80(8):1237-45. 8. Preshaw , N De Silva , GI McCracken , DJ Fernando , CF Dalton , ND Steen , PA Heasman .compromised periodontal status in an urban Sri Lankan population with type 2 diabetes. j clin periodontol. 2010 feb;37(2):165-71 9. F Tanwir , M Altamash , A Gustafsson .Effect of diabetes on periodontal status of a population with poor oral health. acta odontol scand. 2009;67(3):129-33.

13. SUPPLEMENTS/APPENDICES

8
Protocol No. PPDN001, Version No. 1.0, Dated 1st April 2012

Confidential
APPENDIX 1 (A): CASE REPORT FORM

Date (dd/mmm/yy):____________ Patient ID: _______________ Age/ DOB____________ Gender: M F Attending doctor: _________________________ Diabetes TYPE 1 TYPE 2 Personal and family history Occupation House wife | Full time | Part time | Student | Unemployed | Retired Job nature Professional | Managerial | Non manual | Manual skilled | Manual non-skilled | Others Highest education attained College | Higher school (>11 yrs) | Middle school (>6 & <11 yrs) | Primary or illiterate (<6 yrs) | Others Smoking Y | Ex | Never Number of cigarettes/day 0 | <5 | 5~20 | 20~40 | 40 ________ years Amount of alcohol Ex | Never | Occasional | Regular (____units/wk) Significant family history1 Diabetes1 Father | Mother | Sibs | UK2 Renal disease1 Y | N | UK Premature CVD 1,3 Y | N | UK Tobacco Y / N / UK Cancers Y | N | UK Details: __________________________________________________________ Diabetes related complications, illnesses and symptoms Year of Diagnosis _________________ Symptoms at presentation: _____________________________________________________ Definite Type 1 diabetes4 Y | N | UK All heart events (with year) CHD5 Y | N | UK ________ | Coronary intervention (e.g. CABG/PCI6) Y | N | UK ________ | Myocardial infarction Y | N | UK ________ | Cardiac failure Y | N | UK ________ Stroke (with year) Stroke with full recovery Y | N | UK ________ | Completed stroke Y | N | UK ________ Peripheral vascular disease (PVD) (with year) Non-traumatic below ankle amputation Y | N | UK ________ | Non-traumatic above ankle amputation Y | N | UK ________ | Treatment for PVD (Revascularization) Y | N | UK ________ Renal failure (with year) Renal transplantation Y | N | UK ________ | Dialysis Y | N | UK ________ |

9
Protocol No. PPDN001, Version No. 1.0, Dated 1st April 2012

Confidential
Type of Dialysis: Peritoneal | Hemo | Undefined Diabetes related illnesses History of Hypertension Y | N | UK BP lowering drugs Y | N | UK Start year_______

Lipid regulating drugs Y | N | UK Start year_______ Anti-diabetic treatment Lifestyle changes only | OAD7 | Insulin | Both Diabetes related symptoms Calf pain on walking | Impotence | Abnormal sensation in lower limbs | Coughing | Shortness of breath | Edema | Chest pain ____________________________________________________________________________ _____ ____________________________________________________________________________ _____ Diabetes education | Follow-up | Self care Regular follow-up At least once in last 12 months Y|N Type of follow-up (can tick more than 1) Hospital based clinic | Community based clinic |Herbalist | Self medication | No follow up | Others Type of clinic Private | Public | Subsidized Education by dietitian Y | N | UK Education by podiatrist Y | N | UK Education by DM nurses Y | N | UK Frequency of hypoglycemia in last 3 months None | < once monthly | At least once monthly | At least once weekly | At least daily Nature of hypoglycemic attack Mild | Moderate | Severe8 Number of severe hypo attacks requiring medical attention in last 3 months ________ Self monitoring of glucose control Blood | Urine | Both | None Self monitoring in last 3 months None | < once monthly | At least once monthly | At least once weekly | At least daily Physical activity in last 3 months9 No regular activity | < 3 times/week |3-4 times/week | 5 times/week | > 5 times/week Adherence to balanced diet in last 3 months Y | N | Occasional | Never Cancers and other medical conditions Major operations (with year): Other illnesses (with year): Types of cancer (with year): Lung ________ | Breast ________ | Gynecological ________ | Hepato-biliary _______ | Prostate ________ | Colo-rectal ______ | Upper GI ________ | NPC10________ | Others ________ Active treatment Y | N Known hepatitis B carrier Y | N | UK

10
Protocol No. PPDN001, Version No. 1.0, Dated 1st April 2012

Confidential
Physical examination Obesity Height m Weight kg Waist cm Hip cm BMI WHR BP R arm ___/___mmHg L arm ____/___mmHg Pulse beats/min: Urine multistix test RBC -ve | trace | +ve | ++ | 3+ Ketone -ve | trace | +ve | ++ | 3+ Protein -ve | trace | +ve | ++ | 3+ Eye examination Visual acuity11 If>20/200 History of glaucoma History of cataract surgery History of laser treatment History of retinal surgery Fundus photo taken Retina seen by doctor Cataract seen by doctor R eye 20 / C F | H M |LP|NLP12 Y | N | UK Y | N | UK Y|N|UK Y|N|UK Y | N | UK Y|N|UK Y|N|UK L eye 20/ CF|HM|LP|NLP Y | N | UK Y | N | UK Y | N | UK Y | N | UK Y | N | UK Y | N | UK Y | N | UK

Diabetic Retinopathy (DMR) Clinic in the community: Laser scars (seen by doctor) Y | N | UK Y | N | UK DMR (seen by doctor) Y | N | UK Y | N | UK OR Hospital / Specialist clinic, Specify details (OPTIONAL): Maculopathy Y | N | UK Y | N | UK Non-proliferative Y | N | UK Y | N | UK Pre-proliferative Y | N | UK Y | N | UK Proliferative Y | N | UK Y | N | UK Advanced eye disease Y | N | UK Y | N | UK Foot exam R foot L foot PVD (doctor diagnosed) Y | N | UK Y | N | UK Sensory neuropathy (doctor dx) Y | N | UK Y | N | UK Specify details of foot examination (OPTIONAL) Touch 13 Y|N|UK Y | N | UK Vibration14 _____/ 8 _____/ 8 Pulse (Drs palpation) Y | N | UK Y | N | UK Abnormal wave (Doppler) Y | N | UK Y | N | UK Ankle systolic BP (Doppler) ____mmHg ___mmHg Ankle:brachial ratio (ABR) Acute foot ulcer or gangrene Y | N | U K Y | N | UK Foot deformities (can tick more than one): Charcot arthropathy | Claw toes | Digital contractures |Hammer toes | None

11
Protocol No. PPDN001, Version No. 1.0, Dated 1st April 2012

Confidential
Skin abnormalities (can tick more than one): Callus | Dry skin | Fungal infection | Healed ulcers |Nail dystrophy | Paronychia | None Laboratory results Renal function test Plasma sodium Plasma potassium Plasma uric acid Plasma calcium Urine albumin Urine creatinine Haematology Haematocrit Platelet Liver function test ALP ALT Metabolic control Total cholesterol Fasting PG

Plasma urea Plasma phosphate Urine ACR

Plasma creatinine

Haemoglobin White cell count

Albumin

Bilirubin

GGT

HDL-C Random PG

Triglyceride

LDL-C

HbA1c

Special investigations Novel risk markers & others (with Units) C peptide hsCRP TSH Fasting insulin serum B12 folate HOMA-IR HOMA- Abnormal CXR Y|N Details: R carotid mm mm Y|N Y|N

Abnormal cardiac imaging Y | N Type of cardiac imaging CT | MRI | Angiogram | Others Details:

Carotid IMT (date: _________) Mean mm Maximal mm Plaque Abnormal Y|N

L carotid

Y|N

Abnormal ECG Y|N ECG abnormalities LVH15| AF16 | ST changes | Old MI changes | Abnormal stress test Y | N Type of stress test Treadmill | Echo | Isotope scan Details: Other investigations:

Others: Ultrasound scan (date: ______) Details: Kidney abnormalities Y | N Fatty liver Y | N Details

Quality of Life (tick one for each section) Reasons for suboptimal risk factor control : 1. Mobility (can tick more than one) I have no problems in walking about Change in diet | Change in activity |

12
Protocol No. PPDN001, Version No. 1.0, Dated 1st April 2012

Confidential
I have some problems in walking about lifestyle | I am confined to bed 2. Self-Care I have no problems with self-care Change in weight | Change in Change in Rx | Change in stress level | Change In medication compliance | Others

I have some problems washing or dressing myself I am unable to wash or dress myself 3. Usual Activities (e.g. work, study, housework, family or leisure activities) I have no problems with performing my usual activities I have some problems performing my usual activities I am unable to perform my usual activities 4. Pain/Discomfort I have no pain or discomfort I have moderate pain or discomfort I have extreme pain or discomfort 5. Anxiety/Depression I am not anxious or depressed I am moderately anxious or depressed I am extremely anxious or depressed We would like you to indicate on this scale how good or bad your own health is today, in your opinion (best=100, worst=0). Scale: 0.100 Drug allergy (details):

Medications History Generic Dosage Freq Duration of New Repeat name Prescription Rx Anti-diabetic and anti-obesity drugs Y/N Y/N Y/N Y/N Y/N Y/N Y/N Y/N Y/N Y/N Drugs for BP, angina and heart failure Y/N Y/N Y/N Y/N Y/N Y/N Y/N Y/N

Start Date

Discontinuation Date

13
Protocol No. PPDN001, Version No. 1.0, Dated 1st April 2012

Confidential
blockers, anti-arrthymics, inotropes Y/N Y/N Anti-thrombotic and lipid regulating drugs Y/N Y/N GI Drugs and analgesics Y/N Y/N Other endocrine drugs Y/N Y/N Y/N Y/N Drugs for erectile dysfunction, central nervous & respiratory system Y/N Y/N Drugs being discontinued in this visit: Ad-hoc drugs given in this visit: Y/N Y/N Y/N Y/N Y/N Y/N

^Action items Recommended date of next contact: Agreed date of next contact: Other referrals: DM nurse Dietitian Podiatrist Dentist Other specialists Others: Y|N Y|N Y|N Y|N Y|N

Other investigations Blood test Y|N Urine test Y|N Special investigations Y | N Details:

14
Protocol No. PPDN001, Version No. 1.0, Dated 1st April 2012

Confidential

APPENDIX 1 (B): DENTAL PHP FORM

Patient ID: Age: Sex: Date: Medical Condition: 1.Have you undergone under any dental treatment earlier? 2.Have you ever been hospitilised for any other ailment? 3.Do you consume tobacco on any form ,smoking or chewable? Yes No

ON EXAMINATION TEETH: Decayed: Few: Multiple: Stains: Calculus: Root Stumps: Any other: GINGIVA: Normal: Yes/No Bleeding on Probing: Surface Texture: Colour: Suppuration: Size: Shape: PERIODONTAL POCKETS: Yes/no Depth:

15
Protocol No. PPDN001, Version No. 1.0, Dated 1st April 2012

Confidential

ORAL MUCOSA: Buccal: Palatal: Floor of mouth:

TONGUE: Normal/Fissured

OTHER FINDINGS: Xerostomia: Burning sensation: Bad taste: PROVISIONAL DIAGONOSIS

16
Protocol No. PPDN001, Version No. 1.0, Dated 1st April 2012

Confidential APPENDIX 2 Site Consent Version 1.0 English Number_________ Site Consent Version 1 April 2012 Subject ID:

INFORMED CONSENT TO PARTICIPATE IN A STUDY

TITLE: Prospective Comparative Study to Estimate the Prevalence of Periodontitis

in Type 1 and Type 2 Diabetic and Non-Diabetic Patients.

PROTOCOL NUMBER: PPDN001 PROTOCOL DATE: 1st April 2012 INVESTIGATOR: Dr. Sujeet Jha MAX Super Speciality Hospital 2, Press Enclave Road New Delhi 110017 TELEPHONE: 9910609000

INTRODUCTION
This study is designed and initiated by Dr.Sujeet Jha, alongwith a post-graduate Clinical Research student. This is a prospective case-control study which will be conducted at the outpatient department of Max Super Speciality hospital. It will include two groups of subjects, one comprising of patients with diagnosed type 1 or type 2 diabetes and another group will be a control group of subjects without diabetes. Before you agree to join this research study, it is important that you read and understand the following information about the study. This document describes your right to withdraw from the study at any time. Please read this consent form carefully and ask as many questions as you like before deciding whether you want to take part in this study.

PURPOSE OF STUDY AND BACKGROUND

The purpose of this study is to estimate the prevalence of periodontitis in type 1 and type 2 diabetic patients as compared to those without diabetes in a diabetic clinic and to extend our understanding of the relationship of periodontitis to diabetes.
Diabetes is a chronic disease which affects virtually every organ in the human system. The World Health Organization projected that 300 million people will suffer from diabetes by 2025. India has the largest number of diabetic population in the world and it is expected that there will be 69.9 million diabetic populations in India by 2025.

17
Protocol No. PPDN001, Version No. 1.0, Dated 1st April 2012

Confidential Site Consent Version 1.0 English Number_________ Site Consent Version 1 April 2012 Subject ID

Periodontitis is a set of inflammatory diseases affecting the periodontium, i.e., the tissues that surround and support the teeth. Periodontitis involves progressive loss of the alveolar bone around the teeth, and if left untreated, can lead to the loosening and subsequent loss of teeth. Periodontitis is caused by microorganisms that adhere to and grow on the tooth's surfaces, along with an overly aggressive immune response against these microorganisms. A diagnosis of periodontitis is established by inspecting the soft gum tissues around the teeth with a probe (i.e. a clinical exam) and by evaluating the patient's xray films (i.e. a radiographic exam), to determine the amount of bone loss around the teeth.

STUDY OUTLINE
A total of 60 patients will participate in this study, out of which30 will be having type 1 type 2 Diabetes and other 30 will be those without Type 1 and type 2 diabetes. All those patients visiting the OPD at Max Hospital with type 1 and type 2 diabetes mellitus and fulfilling the defined inclusion criteria for the Case group of the study will be eligible to participate in this study (Group 1), and those from general population without diabetes mellitus and fulfilling defined criteria for Control group will be eligible for participation (Group 2). The study has only one part, the initial contact requesting your participation and collecting the required information. Your dental examination will be done.

STUDY PROCEDURES
Enrollment If you are willing to participate in the study, please read and sign this consent form and provide your contact details.

18
Protocol No. PPDN001, Version No. 1.0, Dated 1st April 2012

Confidential Site Consent Version 1.0 English Site Consent Version 1 April 2012 Subject ID Number_________

Providing contact information is required to ensure complete follow-up of all patients (if required) and to make sure that the data collected are precise. Once you have read and signed the informed consent, please return the form to the co-ordinating person at the site. All the clinical information required will be obtained from your medical reports. The study does not require you to take any experimental medications.

PATIENT RESPONSIBILITIES
While you do not bear any responsibility towards the study, it is important for you to be completely truthful with us regarding your health history.

RISKS and BENEFITS

This study put your health at minimal risk. While you may not directly benefit from this study, your participation may yield information that could benefit other diabetic patients around the world suffering from periodontitis.

CONFIDENTIALITY
Your medical records will be treated as confidentially as possible under local, state and federal laws. All personal information obtained, including your name, address, date of birth, medical history, and clinical data in relation to the study will be used for the purposes of research and medical education. Such information will be kept confidential and only authorized personnel will have access to it. Data collected from study participants therefore, will never identify study participants by name but by a code number. The personal information will be kept at the investigators office of the hospital conducting the study. Results of the study may be published, but your identity will never be revealed. You can access your data upon written request sent to, Dr. Sujeet Jha Max Super Speciality Hospital 2, Press Enclave Road New Delhi- 110017 Ph- 9910609000

19
Protocol No. PPDN001, Version No. 1.0, Dated 1st April 2012

Confidential Site Consent Version 1.0 English Number_________ Site Consent Version 1 April 2012 Subject ID

IRB CONTACT
For more information about your rights as a research participant, Contact: EC Contact Person: Prof.Arun K. Aggarwal Chairperson Name of the EC Telephone: : Max Healthcare Ethics Committee 011-23231478

COSTS
There will be no charge to you for your participation in this study.

VOLUNTARY PARTICIPATION AND EARLY WITHDRAWAL

Taking part in this research study is voluntary. You may refuse to take part or you may withdraw from the study at any time for any reason without penalty and without any effect on your future medical care. The study staff is required, by law, to respect your wishes to not continue participation in this study.

20
Protocol No. PPDN001, Version No. 1.0, Dated 1st April 2012

Confidential Site Consent Version 1.0 English Number_________ Site Consent Version 1 April 2012 Subject ID

CONSENT TO PARTICIPATE
I understand that I remain free to withdraw from this study at any time and this will not prejudice or change my future care. I have read and understand the purpose of this study, the procedures that will be used, the risks and benefits associated with my involvement in the study and the confidential nature of the information that will be collected and disclosed during the study. I have had the opportunity to ask my questions regarding the various aspects of this study and my questions have been answered to my satisfaction. I, the undersigned, agree to participate in this study and authorize the collection and disclosure of my personal information as outlined in this consent form. I understand that I will be given a copy of the signed information sheet and consent form.

________________________ Subjects Signature

_______________ Date

________________________ Subjects Printed Name Subjects residential address ____________________________________________________________________________ ____________________________________________________________________________ Subjects telephone number:________________ Alternate telephone number: ______________

21
Protocol No. PPDN001, Version No. 1.0, Dated 1st April 2012

Confidential Site Consent Version 1.0 English Number_________ Site Consent Version 1 April 2012 Subject ID

STUDY PERSONNEL STATEMENT

The person signing this consent form has had the study fully and carefully explained and has been given an opportunity to ask any questions regarding the nature, risks and benefits of the subjects participation in this research study.

___________________________________ Signature of Person Obtaining Consent

________________ Date

___________________________________ Printed Name of Person Obtaining Consent

_________________ Date

_______________________________ Signature of Site Investigator

_________________ Date

_______________________________ Printed Name of Site Investigator

22
Protocol No. PPDN001, Version No. 1.0, Dated 1st April 2012