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«Muhammad Zafar Iqbal Hydrie Thesis submitted as a part of the Master of Philosophy Degree in International Community Health University of Oslo ...»

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Metabolic Syndrome and Insulin Resistance in Pakistan:

a population based study in adults 25 years and above in Karachi

Muhammad Zafar Iqbal Hydrie

Thesis submitted as a part of the

Master of Philosophy Degree in International Community Health

University of Oslo

Faculty of Medicine

Institute of General Practice and Community Medicine

Section for International Health

June 2007

1

Muhammad Zafar

Metabolic Syndrome and Insulin Resistance in Pakistan:

a population based study in adults 25 years and above in Karachi Muhammad Zafar Iqbal Hydrie

Supervisor:

Professor Akhtar Hussain

Co-supervisors:

Professor A Samad Shera Professor Abdul Basit University of Oslo Faculty of Medicine Institute of General Practice and Community Medicine Section for International Health June 2007 Thesis submitted as a part of the Master of Philosophy Degree in International Community Health 2 Muhammad Zafar Abstract Background : Sedentary lifestyle along with easy access to fast foods have resulted in a global epidemic of diabetes with a prediction that it will rise from the current estimate of 190 million to 324 million in 2025. WHO predicts that 170% increase of diabetes will be in the developing countries. Type 2 diabetes (T2DM) has become one of the major causes of premature illness and death and cardiovascular disease (CVD) will be responsible for up to 80% of these deaths. So it seems that at the moment we are faced with the twin pandemic of T2DM and CVD and the brunt of this would be borne by the developing countries. The clustering of central obesity, dyslipidaemia, hypertension, and hyperglycaemia known as metabolic syndrome has been associated with a 2-3 fold increase in T2DM and CVD. It is recognized that the features of the metabolic syndrome can be present 10 years preceding T2DM and CVD. The prevalence rates of metabolic syndrome appear varied using the WHO, EGIR, AACE, ATP III and IDF definitions. Therefore it is needed to study the suitability of metabolic syndrome definitions in this population.

Objective: To estimate the prevalence of metabolic syndrome in adults aged 25 years and above from an urban population of Karachi.

Methods: The survey was conducted from July to December 2004 by generating a computerized random sample of 500 households from houses in Lyari Town using a Geographical Imaging System (GIS). The survey activities were divided into two phases—the household interview and blood sample collection. Field work entailed visits to the selected household by a field team (medical students and health worker), introduction to the purpose of the research study, consent, interviews and physical measurements. In the 532 households visited 867 adults 25 years old consented to take part in the survey out of which 363 gave blood samples.

Results: Prevalence of Diabetes was 9.4% while 5.6% had impaired fasting glucose (Abnormal glucose tolerance 15%). Prevalence of metabolic syndrome was found to be 49% by modified ATP III, 34.8% by IDF, 16.9% by AACE, 15.2% by EGIR and 7.4% by WHO definition. Insulin resistance defined by 75th percentile of HOMA-IR was measured as 1.94.

Conclusion: Inclusion of modified waist circumference and BMI cutoffs may help to predict metabolic syndrome more precisely as incorporated in modified ATP III and IDF definition.

The rising prevalence of obesity and metabolic syndrome has received increased attention in recent years as both place individuals at risk for T2DM and CVD. Thus epidemiological and intervention trial studies which support lifestyle changes as the main modifiable risk factor in the treatment of individual components of the metabolic syndrome can then be initiated.

Key Words: Prevalence, Metabolic Syndrome, IDF Definition, Diabetes, Pakistan, WHO, Modified ATP III

–  –  –

I am sincerely grateful to all my colleagues at Baqai Institute of Diabetology and Endocrinology (BIDE) who have helped me though the years and helped in my development.

I would especially like to thank my colleagues at the research department of BIDE for all their assistance.

I would also like to acknowledge the Quota Program and the department of International Health, University of Oslo for the financial support that has enabled me to take up this programme.

My heartfelt gratitude goes to my supervisor Dr. Akhtar Hussain, Professor, Section for International Health, Department of General Practice and Community Medicine, Faculty of Medicine, University of Oslo for his patient teaching and guidance in the whole process of planning, field work and final write up of thesis. His support and understanding helped me to fulfill the task of thesis writing.

Special thanks to our teachers Prof. Gunnar Bjune and Prof. Johanne Sundby for their valuable inputs during our study. I would like to thank Vibeke Christie, Ine Andersen, Ragnhild Beyrer and other staff of the department for their kind help and cooperation during my study.

I would also like to thank my classmates here in Norway, friends and relations for their well wishes towards me.

I am indebted to my wife for her constant cooperation and support during my time of study here. I am humbled to note her single handed efforts to take care of the family in my absent.





I am grateful to the encouraging emails of my sister and inspiration during my study. My mother’s inspiration and estimable opinion helped me to look forward and words of wisdom of my father helped me during my study.

4 Muhammad Zafar

Table of Contents

ABSTRACT

ACKNOWLEDGEMENT

TABLE OF CONTENTS

LIST OF TABLES

LIST OF FIGURES

LIST OF ACRONYMS

CHAPTER 1. INTRODUCTION

1.1 BACKGROUND - DIABETES MELLITUS AND CVD

1.1.1 DIABETES MELLITUS

1.1.2 GLOBAL BURDEN OF DIABETES

1.1.3 ISCHEMIC HEART DISEASE

1.1.4 GLOBAL BURDEN OF CARDIOVASCULAR DISEASE

1.2 METABOLIC SYNDROME (DIABETES AND CVD EPIDEMIC)

1.2.1 HISTORY OF THE METABOLIC SYNDROME

1.2.2 EVOLUTION OF METABOLIC SYNDROME DEFINITION - TOWARDS A GLOBAL CONSENSUS

1.2.3 EPIDEMIOLOGY OF THE METABOLIC SYNDROME

1.2.4 METABOLIC SYNDROME IN SOUTH ASIANS

1.3 PAKISTAN – COUNTRY PROFILE

1.3.1 GEOGRAPHY:

1.3.2 PEOPLE:

1.3.3 POPULATION DEMOGRAPHY:

1.3.4 EDUCATION

1.3.5 ECONOMY

1.3.6 LIFESTYLE AND PHYSICAL ACTIVITY

1.3.7 DIABETES IN PAKISTAN

1.3.8 CVD IN PAKISTAN

1.4 STATEMENT OF PROBLEM

1.5 RESEARCH QUESTIONS AND OBJECTIVES OF THE STUDY

1.5.1 RESEARCH QUESTIONS

1.5.2 MAIN OBJECTIVE

1.5.3 SPECIFIC OBJECTIVES

1.6 JUSTIFICATION OF THE STUDY

CHAPTER 2: MATERIAL AND METHODS

2.1 SCOPE OF STUDY

2.2 RESEARCH SETTING

2.3 LYARI TOWN GEOGRAPHICAL INFORMATION SYSTEM

2.4 STUDY POPULATION

2.5 CRITERIA FOR INCLUSION AND EXCLUSION

2.6 SAMPLE SIZE

2.7 RESEARCH DESIGN

2.7.1 SURVEY PROTOCOL AND PROCEDURES

2.7.2 HOUSEHOLD CENSUS AND INTERVIEW

2.7.3 QUESTIONNAIRE

2.7.4 BLOOD SAMPLES

2.7.5 URINE SAMPLES

5 Muhammad Zafar 2.8 STATISTICAL ANALYSIS

2.9 ETHICAL CONSIDERATIONS

2.9.1 ETHICAL CLEARANCE

2.9.2 INFORMED CONSENT

CHAPTER 3: RESULTS

3.1 RESULTS

3.1.1 PART A: HOUSEHOLD SECTION OF QUESTIONNAIRE

3.1.1.1 SECTION A1

3.1.1.2 SOCIO-DEMOGRAPHIC CHARACTERISTICS

3.1.1.3 SECTION A2

3.1.1.4 SECTION A3

3.1.1.5 SECTION A4

3.1.2 PART B: INDIVIDUAL SECTION OF QUESTIONNAIRE

3.1.2.1 SECTION B1

3.1.2.2 SECTION B2

3.1.2.3 SECTION B3

3.1.2.4 SECTION B4

3.1.2.5 SECTION B5

3.1.2.6 SECTION B6

3.1.3 PART C: ANTHROPOMETRY SECTION OF QUESTIONNAIRE

3.1.4 PREVALENCE OF ABNORMAL GLUCOSE TOLERANCE

3.1.5 DISTRIBUTION OF CARDIOVASCULAR DISEASE AND ITS RISK FACTORS

3.1.6 DESCRIPTIVE ANALYSIS OF PERSONS TAKING BLOOD TESTS

3.1.7 PREVALENCE OF METABOLIC SYNDROME – DIFFERENT DEFINITIONS

3.1.8 RISK OF IFG AND CVD ACCORDING TO METABOLIC SYNDROME DEFINITIONS

3.1.9 INSULIN LEVELS

CHAPTER 4: DISCUSSION

DISCUSSION

4.1 METHODOLOGICAL CONSIDERATION

4.1.1 STUDY DESIGN

4.2 METHODOLOGICAL DISCUSSION

4.2.1 STRENGTH OF THE STUDY

4.2.2 LIMITATIONS OF THE STUDY

4.2.2.1 SELECTION BIAS

4.2.2.2 RECALL AND REPORTING BIAS

4.2.2.3 RESPONSE BIAS

4.2.2.4 EXTERNAL VALIDITY FOR GENERALIZATION

4.2.2.5 RELIABILITY

4.3 DISCUSSION ON THE FINDINGS OF THE STUDY

4.3.1 SOCIO-DEMOGRAPHY OF THE SAMPLE

4.3.2 PREVALENCE OF ABNORMAL GLUCOSE TOLERANCE

4.3.3 RISK FACTORS FOR CARDIOVASCULAR DISEASE

4.3.4 PREVALENCE OF METABOLIC SYNDROME – DIFFERENT DEFINITIONS

4.3.5 PREVALENCE OF COMPONENTS OF THE METABOLIC SYNDROME

4.3.5.1 HYPERTENSION:

4.3.5.2 OBESITY:

4.3.5.3 DYSLIPIDEMIA:

4.3.6 DEFINING INSULIN RESISTANCE ACCORDING TO HOMA-IR

4.3.6.1 HOMEOSTASIS MODEL ASSESSMENT (HOMA)

CHAPTER 5. CONCLUSIONS, RECOMMENDATIONS AND

FUTURE RESEARCH IMPLICATION

5.1 CONCLUSIONS

6 Muhammad Zafar

5.2 RECOMMENDATIONS

5.3 FURTHER RESEARCH IMPLICATION

ACKNOWLEDGEMENT:

REFERENCES

APPENDICES

INFORMED CONSENT

STRUCTURED INTERVIEW QUESTIONNAIRE (11 PAGES)

APPROVAL OF LOCAL ETHICS COMMITTEE

7 Muhammad Zafar List of Tables Table 1. Previous criteria proposed for the diagnosis of metabolic syndrome

Table 2. IDF and AHA/NHLBI

Table 3. Top Ten Countries for Number of Persons with Diabetes

Table 4. Pakistan National Diabetes Survey

Table 5. Risk Factors that are causally linked

Table 6.

Risk markers that show associations:

Table 7: Socio-demographic characteristics of the Households

Table 8: Use of Fat and Salt in Households

Table 9: Monthly and Annual Income

Table 10: Mode of Treatment

Table 11: Personal Demography of Individuals

Table 12: Family Medical History

Table 13: Parental Age at Death

Table 14: Tobacco Consumption

Table 15: Food items used on daily, weekly or monthly basis

Table 16: Chest pain on physical exertion

Table 17: Average duration of Physical Activity

Table 18: Weekly and daily chores of households

Table 19: Mean Anthropometry Measurements

Table 20: Categorical variables of Anthropometry

Table 21: Means of anthropometric and biochemical parameters of subjects

Table 22: Cut-off values for biochemical variables

Table 23: Risk Factors of CVD

Table 24: Age and Gender distribution of variables in subjects of blood tests

Table 25: Age & gender specific prevalence of metabolic syndrome by different definitions68 Table 26: Prevalence of components of the metabolic syndrome

Table 27: Risk of IFG

Table 28: Risk of CVD

Table 29: Total Mean Values of Insulin Levels and HOMA-IR

8 Muhammad Zafar List of Figures Figure 1: Metabolic Syndrome - Clustering of CVD Risk Factors

Figure 2: Features of Metabolic Syndrome / Insulin Resistance in South Asians....... 25 Figure 3 : Geographic Location of Pakistan

Figure 4: Lyari Town

Figure 5: Randomly Selected 500 Households

Figure 6: Household Survey – No of Eligible Persons

Figure 7: Age and Gender distribution of Sample (n=3608)

Figure 8: Ethnicity in Households (n=3608)

Figure 9: Division of the population on the basis of language (n=3608)

Figure 10: age distribution for place of birth

Figure 11: Type of Residence

Figure 12: Household Items

Figure 13: Cause of Death

Figure 14: Use of Additional Salt

Figure 15: Physical Activity

Figure 16: Prevalence of Diabetes and IFG

Figure 17: Age Distribution of Prevalence of glucose tolerance

Figure 18: Error Bar of Glucose Tolerance with Age

Figure 19: Mean Values of HOMA-IR according to Age

Figure 20: Percentiles of Insulin and HOMA-IR

–  –  –

Changes in work patterns from heavy labour to sedentary, the increase in computerization and mechanization, and improved transport are just a few of the changes that have made an impact on human health (1). These sedentary changes along with easy access to fast foods and empty calories have resulted in escalating rates of both obesity and type 2 diabetes globally (2,3). Paradoxically, part of the problem relates to the achievements in public health during the 20th century, with people living longer owing to elimination of many of the communicable diseases (4).

Non-communicable diseases (NCD) such as diabetes and cardiovascular disease (CVD) have now become the main public health challenge for the 21st century, as a result of their impact on personal and national health system and the premature morbidity and mortality associated with the NCDs (1,5).

1.1.1 Diabetes Mellitus

Diabetes mellitus is a metabolic disorder with both genetic and lifestyle etiologies that results in abnormal glucose control. It is a chronic disease caused by inherited and/or acquired deficiency in production of insulin by the pancreas, or by the ineffectiveness of the insulin produced. An acquired deficiency may be triggered by life style factors.

However a deficiency of insulin results in increased concentrations of glucose in the blood, which in turn damages many of the body's systems. Genetics has an influential role on the epidemiology of the disease.

1.1.2 Global Burden of Diabetes

The global figure of people with diabetes is set to rise from the current estimate of 190 million to 324 million in 2025 (6,7). WHO predicts 170% increase in the number of people with diabetes for the developing countries (6).The greatest increase is projected in India (195%) (6).



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