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Impact of Epidemiology on Diabetes Mellitus. Echo Lecture from Thelma D. Crisostomo,MD. Epidemiology of Diabetes Mellitus Type II. Global – 2000 AD. Total Number of People with Diabetes. Year 2000 171 Million. Year 2030 366 Million.

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Impact of epidemiology on diabetes mellitus

Impact of Epidemiology on Diabetes Mellitus

Echo Lecture from

Thelma D. Crisostomo,MD




Total number of people with diabetes
Total Number of People with Diabetes

Year 2000

171 Million

Year 2030

366 Million



Certain Ethnic Groups Who Have Experienced EpidemicRapid Modernization Of LifestyleDemonstrate The Greatest Susceptibility To Type 2 DM


2000 Epidemic


Epidemiology
Epidemiology Epidemic

Studies distribution and determinants of disease

PURPOSE

  • To understand natural history, cause of the disorder and pathogenesis.

  • For appropriate diagnostic investigation and clinical management.

  • For creation of scientifically based program for prevention and health care.


The first step of epidemiologic research begins with measuring
The First Step Of Epidemiologic Research Begins With Measuring

  • Incidence

    • Number of new cases discovered for a specific time and place.

    • Used to identify epidemics.

    • Used to search for etiology

  • Prevalence

    • Total number of cases old and new occurring in a specified time and place.

    • Tool for determining public health needs.


Is there an epidemic of type 2 diabetes mellitus
Is There An Epidemic Of Type 2 Diabetes Mellitus? Measuring

Epidemic – Definition

The occurance in a community of a disease, infectious or chronic (e.g. diabetes mellitus), occurring at a greater frequency than usually expected.

Does this apply to Type 2 DM?

Yes, particularly in developing and newly industrialized nations.


Type 2 dm a public health prospective
Type 2 DM: A Public Health Prospective Measuring

  • Type 2 DM is among the top 7 cause of death in most countries.

  • Cardiovascular complications are major cause of morbidity and mortality: This results in the impact of type 2 DM being underestimated from death certificates.

  • There is an excessive frequency of coronary artery and peripheral vascular disease and strokes.


Type 2 dm a public health prospective1
Type 2 DM: A Public Health Prospective Measuring

  • Type 2 DM is the most common cause of adult blindness and a common cause of renal failure and amputation.

  • Results in disability, reduced life expectancy and enormous health cost for any society.



The true cost of treating T2DM is not the cost of oral hypoglycemics. The true cost come from treatingcomplications with non-OADs and other forms of treatment


Cost associated with type 2 diabetes
Cost Associated with Type 2 Diabetes hypoglycemics. The true


Etiologic classification of diabetes mellitus
Etiologic Classification of hypoglycemics. The true Diabetes Mellitus

  • Type 1 Diabetes (B-cell destruction, usually leading absolute insulin deficiency).

    • Immune mediated

    • Idiopathic

  • Type 2 Diabetes (may range from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with insulin resistance).


Etiologic classification of diabetes mellitus1
Etiologic Classification of hypoglycemics. The true Diabetes Mellitus

  • Other specific types

    • Genetic defects of B-cell function

    • Genetic defects in insulin action

    • Disease of the exocrine pancreas

    • Endocrinopathies

    • Drug – or – chemical – induced

    • Infections

    • Uncommon forms of immune-mediated diabetes

    • Other genetic syndromes sometimes associated with diabetes

  • Gestational diabetes mellitus (GDM)


Ratio of diagnosed undiagnosed type 2 dm
Ratio of Diagnosed / Undiagnosed hypoglycemics. The true Type 2 DM



Prevalence of dm worldwide

Year 2000 30–64 Years

2.8%

Year 2030

4.8%

Prevalence of DM Worldwide


Global diabetes prevalence by age and sex for 2000
Global Diabetes Prevalence by 30–64 Years Age and Sex for 2000


List of countries with the highest numbers of estimated cases of diabetes for 2000 and 2030
List of Countries with the Highest Numbers of Estimated Cases of Diabetes for 2000 and 2030


Estimated Number of Adults with Diabetes by Age-Group, Year, and Countries for the Developed and Developing Categories and for the World.


Estimated Number of Adults with Diabetes by Age-Group, Year, and Countries for the Developed and Developing Categories and for the World.


Prevalence of dm philippines 1982 1983
Prevalence of DM (Philippines) and Countries for the Developed and Developing Categories and for the World.1982 - 1983


Prevalence of igt philippines 1982 1983
Prevalence of IGT (Philippines) and Countries for the Developed and Developing Categories and for the World.1982 - 1983


What is the prevalence of diabetes mellitus in the philippines
What is the Prevalence of Diabetes Mellitus in the Philippines?

  • 2 out of 100

  • 4 out of 100

  • 6 out of 100

  • 8 out of 100

  • 10 out of 100

2.8 M

Filipinos

5th National Nutrition Survey

FNRI, DOST Oct 1999

N = 70, 000 99 areas


Diabetes genetics environment
Diabetes Philippines?Genetics Environment


Aetiology of niddm the interaction of genetic susceptibility and environment factors
Aetiology of NIDDM: The Interaction of Genetic Susceptibility and Environment Factors

Heredity

Genetic

Susceptibility

Obesity

Physical inactivity

Nutritional Factors

Aging

Intrauterine Factors

Hyperinsulinemia

Insulin Resistance

Beta-cell Failure

Type 2 DM


Collision hunter gatherer genes vs 20 th century lifestyle type 2 dm
Collision Susceptibility and Environment Factors Hunter Gatherer Genes VS 20th Century LifestyleType 2 DM


Thrifty gene hypothesis
Thrifty Gene Hypothesis Susceptibility and Environment Factors

Past populations subjected to cycles of feast/famine

Genes were adopted to store energy efficiently

Rapid Modernization

Famine rare. Abundant food stored efficiently

Results in Obesity, hyperinsulinemia and diabetes


Thrifty genotype hyperinsulinemia
‘Thrifty Genotype’ Susceptibility and Environment Factors (Hyperinsulinemia)

Modern society

Hunter-gatherer society

Feast + famine

Feast

  • Maximum metabolic efficiency

  • Hepatic gluconeogenesis

  • Hepatic lipogenesis

  • Selective insulin resistance in muscle

  • Insulin resistance

  • diet energy dense, high saturated fat

  • Physical inactivity

  • Obesity

  •  B-cell exhaustion

Survival

Glucose intolerance

Dyslipidemia

Hypertension

A proposal for the operation of the “thrifty genotype” in the pathogenesis of non-insulin dependent diabetes and other associated cardiovascular disease risk factors in populations who have changed their life-style from hunter gatherer to modern.


Age-Standardized prevalence of diabetes in adults in “urban” pacific populations (25-74 years)


Prevalence of diabetes by ethnic groups in Mauritius (25-74 years). Age-standardized by direct method to total Mauritius population – 1986.


Prevalence of NIDDM in Chinese (30 – 64 years) in China, Singapore and Mauritius. Age-standardized by the direct method to Segi’s world population.


Stages in the development of type 2 dm
Stages in the Development of Singapore and Mauritius. Age-standardized by the direct method to Segi’s world population. Type 2 DM

Genetic susceptibility

Hyperinsulinemia and/or insulin resistance

Impaired glucose tolerance

Non-insulin dependent diabetes


Development of type 2 diabetes

Normal Singapore and Mauritius. Age-standardized by the direct method to Segi’s world population.

IGT

Type 2 Diabetes

Development of Type 2 Diabetes


Development of type 2 diabetes1

Type 2 Singapore and Mauritius. Age-standardized by the direct method to Segi’s world population.

Diabetes

IGT

Impaired Glucose

Metabolism

Normal Glucose

Metabolism

Development of Type 2 Diabetes

Macrovascular disease is closely linked to Insulin Resistance

Groop Etiology of non-insulin-dependent diabetes mellitus.

Hormone Res. 1997; 22:131-156


Studies that confirm the strong genetic basis of type 2 dm
Studies that Confirm the Strong Genetic Basis of Type 2 DM Singapore and Mauritius. Age-standardized by the direct method to Segi’s world population.

  • Twin studies

  • Familial aggregation

  • High prevalence population

  • Genetic Admixture studies

  • Prevalence in different ethnic groups in same environment

  • MODY/Nauruans/Pimas – autosomal dominant inheritance


Genetic factor
Genetic Factor Singapore and Mauritius. Age-standardized by the direct method to Segi’s world population.

Type 2 DM – 100% Concordance in Identical Twins

Type 1 DM – 30-50% in Concordance in Identical Twins


Impaired glucose tolerance worsening to diabetes in siblings
Impaired Glucose Tolerance Worsening to Diabetes in Siblings

Overall Occurrence Rate

Diabetes 12%

Impaired Glucose Tolerance 12%


Igt worsening to diabetes
IGT Worsening to Diabetes

Filipino Siblings

50% Conversion in 8 years

Conversion rate: 9.3 per 100 cases/year


Igt conversion rate
IGT Conversion Rate

PIMA Indians

9.3 cases per 1000/year

Filipino Siblings


Impaired glucose tolerance igt natural history

10 yr

Follow up

Impaired Glucose Tolerance (IGT)Natural History

Subjects with IGT


Major behavioral environmental and social risk factors for type 2 dm
Major Behavioral, Environmental and Social Risk Factors for Type 2 DM

These may vary within and between populations and include:

  • Age

  • Nutritional factors

  • Obesity (central)

  • Physical inactivity

  • Degree of modernization

  • Intra-uterine environment

  • ? Stress, ? others


Fat Type 2 DM

40+%

Fat

15 to 20%

Fat

10 to 15%

Sugar 5%

Sugar

20%

Starch

50 to 70%

Starch

60 to 75%

Starch

23 to 30%

Protein

12%

Protein

15 to 20%

Protein

10 to 15%

Changes in Component of the Diet that Have Been Seen in the Change From Hunter Gatherer to the Modern “Western” Diet


High fat high simple sugar low complex carbohydrate diet
High Fat, High Simple Sugar Type 2 DM Low Complex Carbohydrate Diet

in westernized Societies are contributing to the excess Obesity and NIDDM


Environmental determinant of type 2 dm
Environmental Determinant of Type 2 DM Type 2 DM

Obesity

If there were no obesity, the prevalence of diabetes would be greatly reduced


Central distribution of body fats as risk factor for niddm
Central Distribution of Body Fats as Risk Factor for NIDDM Type 2 DM

Implicated in:

  • Europids (Sweden)

  • Mexican Americans

  • Native Americans

  • Micronesians (Nauruans)

  • Asian Indians (Hindu and Muslim)

  • Creoles

  • Chinese

  • Japanese Americans


Insulin resistance in obesity
Insulin Resistance in Obesity Type 2 DM

Plasma glucose response

(mg/dl)

Plasma glucose response

(U/dl)

Minutes

Normal weight (mean 66.1kg)

Moderately obese (mean 91.1kg)

Reaven et al.: Diabetes 32, 600,1 983


Environmental determinant of type 2 dm1
Environmental Determinant of Type 2 DM Type 2 DM

Intrauterine Factor

Low Birth Weight-Risk Factor for NIDDM

Impaired Development of Endocrine Pancreas


Physical inactivity risk factor for diabetes
Physical Inactivity Type 2 DM Risk Factor for Diabetes

Possible Explanation Insulin Resistance


  • New NIDDM

  • inactive

  • active

  • BMI Tertile

  • BMI Tertile

  • Prevalence of abnormal glucose tolerance by body mass index and physical activity (Mauritius) 1997


Higher prevalence in urban than rural environment
Higher Prevalence in Urban Than Rural Environment Type 2 DM

Explanation:

  • Change in lifestyle

  • Physical Activity

  • More Refined Diet

  • Greater Occurrance of Obesity


Major behavioral environmental and social risk factors for type 2 dm1
Major Behavioral, Environmental and Social Risk Factors for Type 2 DM

These may vary within and between populations and include:

  • Age

  • Nutritional factors

  • Obesity (central)

  • Physical inactivity

  • Degree of modernization

  • Intra-uterine environment

  • ? Stress; ? Others


Preventing type 2 dm
Preventing Type 2 DM Type 2 DM

Evidence that it is possible

  • Primate studies of Type 2 DM

  • Prevention of coronary artery disease

  • Reversion to traditional life-style

  • Rural-urban studies of risk factors

  • Influence of physical activity Type 2 DM prevalence and incidence


Marked Improvement in Fasting Metabolic Parameters in Ten Australian Aborigines with 7 Week Reversion to Traditional Lifestyle


Interventional strategies
Interventional Strategies Australian Aborigines with 7 Week Reversion to Traditional Lifestyle

  • Weight Reduction

  • Dietary composition

  • Exercise

  • Pharmacologic therapy


People at high risk of developing type 2 dm
People at High Risk of Developing Australian Aborigines with 7 Week Reversion to Traditional Lifestyle Type 2 DM

  • Impaired glucose tolerance (IGT).

  • Certain ethic groups such as Pacific Islanders, Australians Aborigines, migrant Asian Indians, American Indians, Black and Hispanics who show high diabetes prevalence.

  • Positive family history of Type 2 DM in first degree relatives (parents, siblings or children).

  • Obesity especially in women with a past history of gestational diabetes or large babies.


People at high risk of developing type 2 dm1
People at High Risk of Developing Australian Aborigines with 7 Week Reversion to Traditional Lifestyle Type 2 DM

  • Age greater than 50 years in Europids and lower ages (30 to 40 years) in high prevalence groups.

  • History of previous abnormality of glucose tolerance, particularly in pregnancy.

  • Hypertension, macrovascular disease or dyslipidemia.


Epidemiology of type i dm
Epidemiology of Type I DM Australian Aborigines with 7 Week Reversion to Traditional Lifestyle


Type 1 genetics environment
Type 1 Australian Aborigines with 7 Week Reversion to Traditional Lifestyle Genetics Environment


Aetiology of type 1 dm
Aetiology of Type 1 DM Australian Aborigines with 7 Week Reversion to Traditional Lifestyle

Viruses

Genetic susceptibility

(HLA – DQ)

? Chemicals

? Nutrition

Autoimmune Process

Beta-cell destruction

Insulin-dependent diabetes mellitus

(Type 1 DM)

Modified from Schoffling, K.: Diabetologic in Klinik und Praxis, Thieme, 37-41 1984


Features of type 1 dm
Features of Type 1 DM Australian Aborigines with 7 Week Reversion to Traditional Lifestyle

  • Occurs at any age

    • Proneness to ketoacidosis

    • Low insulin and C peptide levels

  • Specific associations with the HLA complex

    • Islet cell antibodies

    • High frequency of insulin auto antibodies


Comparison of characteristics of type 1 dm and type 2 dm
Comparison of Characteristics of Australian Aborigines with 7 Week Reversion to Traditional Lifestyle Type 1 DM and Type 2 DM


Standardized Incidence Rates Australian Aborigines with 7 Week Reversion to Traditional Lifestyle

Age 0 – 14 years

Denmark

Finland

Sardinia

Sicily

Incidence of Childhood Onset Type 1 DM (1998 - 1990) European Study


Incidence Rate of Type 1 DM in Children less than 15 yrs old Australian Aborigines with 7 Week Reversion to Traditional Lifestyle

Incidence Rate / 100,000


Geographic and ethnic variation
Geographic and Ethnic Variation Australian Aborigines with 7 Week Reversion to Traditional Lifestyle

Markeded Variations are Reflections of Difference in:

  • Environment

  • Genetic Susceptibility


Environmental factors
Environmental Factors Australian Aborigines with 7 Week Reversion to Traditional Lifestyle

  • Nature of these factors are still obscure

  • Possible cause

    • Viral infections

      • Rubella

      • Coxsackle B

      • Mumps

    • Chemicals

      • Rodernticides

      • Alloxan

      • Streptozocin

    • Changes in breast feeding habits


Early cow’s milk exposure may be an important determinant of subsequent Type 1 Diabetes and may increase the risk – 1.5 times


Cow s milk consumption and type 1 dm incidence
Cow’s Milk Consumption and of subsequent Type 1 Diabetes and may increase the risk – 1.5 timesType 1 DM Incidence


Type 1 dm
Type 1 DM of subsequent Type 1 Diabetes and may increase the risk – 1.5 times

  • Genetic Factors

    Concordance rate

    Monozygotic twins : 25 – 30%

    Dizygotic twins : 5 – 10%

    Siblings : 5%

    Offspring : 2 – 3 % (if mother is diabetic)

    5 – 6 % (if father is diabetic)


Hla system in type 1 diabetes mellitus
HLA System in Type 1 Diabetes Mellitus of subsequent Type 1 Diabetes and may increase the risk – 1.5 times

  • Genes Conferring Susceptibility

    Class II Allele : HLA – DR, -DQ, -DP LOGI

    European : DR3, DR4 (5-8x risk)

    : DR3/DR4 (20 – 40x risk)

    : HLA – DR3 DQW2

    : HLA – DR4 DQW8

    : DOA1*0501, DQB1*0302

    Genes Conferring Protection

    : HLA-DR2

    : HLA DQB1*0602


Hla system
HLA System of subsequent Type 1 Diabetes and may increase the risk – 1.5 times



Type 1 dm immunological factors
Type 1 DM – Immunological Factors Virus Infection

  • Not yet well defined

  • Initiating autoantigens identified through studies on:

    • Islet Cell Cytoplasmic Antibodies

    • Insulin Autoantibodies

    • Anti-GAD

    • Antibodies to Pancreatic B Cell Surface Protein p69

  • Immune phenomena decline rapidly

    • Shown by rapid disappearance ICA (Type 1A) 85 – 90% (Viral Etiology)

  • Immune phenomenon may persist

    • (Type 1B) 10 – 15% characteristics of primary autoimmune endocrine disorder.


Insulin Cell Virus Infection

Cytotoxic Thymphocyte cell

Natural

killer cell

Killer cell

The Known an Unknown Immunological Phenomena Possibly Involved in the Recognition and Subsequent Damage of Pancreatic Beta Cells

Complement

?

  • ?

  • virus or modified (tumour) antigens

  • HLA-A, -B, -C histocompatibility antigens


Onset of type 1 dm
Onset of Type 1 DM Virus Infection

  • Protracted Prodromal Period

  • Over hyperglycemia occurs many years after islet cell antibodies and insulin autoantibodies are detected.


Seasonal distribution of onset of type i diabetes

50 Virus Infection

40

30

Number of Patients Chile

Number of Patients UK

20

10

J A S O N D J F M E M J

Seasonal Distribution of Onset of Type I Diabetes

Combined data from studies carried out in the UK and Chile (38, 41). Approximately 1500 cases have been analyzed (age of onset: UK: 0-15 year; Chile 0-30 years). Major peeks are seen in autumn and winter and this pattern have been confirmed in a number of countries in the northern hemisphere.


Pattern of age onset of type 1 diabetes

Relative Frequency % Virus Infection

Total

Males

Females

Pattern of Age Onset of Type 1 Diabetes

Age (Years)

Combined data from studies out in Denmark, Chile, USA and Canada. The relative frequency of Type 1 diabetes up to age 28 years is shown. Diabetes can occur in the first months of life and its frequency increase abruptly at about 9 months of age, rising to a major peak at puberty. This peak is earlier in girls than boys.


Causes of death in type 1 dm age 30 years
Causes of Death in Type 1 DM Virus Infection(Age < 30 years)


The natural history of insulin dependent diabetes mellitus

Onset of diabetes Virus Infection

Environmental factors

Complications

e.g. viral infection

cow’milk

nutrition

Disability

Genetic Susceptibility

DEATH

ICA +

IAA +

Anti-GAD +

e.g. certain HLA

types

Hyperglycemia insulin dependency

Retinopathy

Nephropathy

Atherosclerosis

Neuropathy

Blindness

Renal failure

Coronary heart disease

Amputation

The Natural History of Insulin-dependent diabetes mellitus*

* HLA, Human Leukocyte Antigen: ICA, Islet-Cell Cytoplasmic Antibodies;

IAA, Insulin Autoantibodies; anti-GAD, antibodies to glutamate Decarboxylase


Can type 1 dm be prevented
Can Type 1 DM be Prevented? Virus Infection

Insulin Prophylaxis

Nicotinamide

Cow’s milk Exclusion

Dual Parameter Model

Loss of FPIR

> 20JDFu

IAA

ICA +

FH +

Baseline Risk

IAA etc.

ICA +

Genetics Markers

FH -

The decision tree representation of prediction Type 1 DM with intervention trials planned in 1994


Insulin therapy for end stage prediabetes state
Insulin Therapy for End Stage Prediabetes State Virus Infection

Rationale:

  • Improve  cell function to delay onset of Diabetes.

  • Initiating active insulin substitution rapidly may save as many  cells as possible.


Thank you
Thank you! Virus Infection


Classification of diabetes mellitus and other categories of glucose intolerance

Clinical classes Virus Infection

Diabetes mellitus

Insulin-dependent (IDDM)

Non-insulin dependent (NIDDM)

Non-obese

Obese

Malnutrition related (MRDM)

Other types

Pancreatic

Endocrine

Drug-induced, etc.

Classification of Diabetes Mellitus and Other Categories of Glucose Intolerance*


Classification of diabetes mellitus and other categories of glucose intolerance1
Classification of Diabetes Mellitus and Other Categories of Glucose Intolerance*

  • Other categories

    • Impaired glucose tolerance (IGT)

    • Gestational Diabetes Mellitus (GDM)

      * WHO Study Group on Diabetes Mellitus - 1995


Niddm a public health perspective
NIDDM – A Public Health Perspective Glucose Intolerance*

  • NIDDM is amongst the top 7 causes of death most countries.

  • Cardiovascular complications are a major cause of morbidity and mortality. This results in the impact if NIDDM being underestimated from death certificates.

  • There is an excessive frequency of coronary artery and peripheral vascular disease and strokes.

  • NIDDM is the most common cause of adult blindness and a common cause of renal failure and amputations.

    • Results in disability, reduced life expectancy and enormous health cost for any society


Studies of diabetes epidemiology
Studies of Diabetes Epidemiology Glucose Intolerance*

  • Modernization of Lifestyle in situ

  • Rural-Urban comparisons

  • Migration studies

  • Several ethnic groups living in same location


Thrifty genotype
Thrifty Genotype Glucose Intolerance*

How does a genetic disorder, such as Diabetes, with adverse impact on fertility and mortality, survive with such a high prevalence within population?


The new world syndrome
The New World Syndrome Glucose Intolerance*

  • Non-insulin-dependent diabetes mellitus

  • Central obesity

  • Dyslipidemia

  • Hyperinsulinemia

  • Hypertension


Niddm a spectrum ranging from hyperinsulinemia to hypoinsulinemia

Hyperinsulinemia / insulin resistance Glucose Intolerance*

Insulinemia deficiency

NIDDM – A Spectrum Ranging from Hyperinsulinemia to Hypoinsulinemia


Preventing niddm
Preventing NIDDM Glucose Intolerance*

  • Evidence that it is possible:

    • Primate studies of NIDDM

    • Prevention of coronary artery disease

    • Reversion to traditional life-style

    • Rural-urban studies of risk factors

    • Influence of physical activity on NIDDM prevalence and incidence


Primary prevention
Primary Prevention Glucose Intolerance*

The promotion of health by personal and community-wide efforts, e.g. improving nutritional status, physical fitness etc.


Niddm
NIDDM Glucose Intolerance*

Hyperinsulinemia

Insulin resistance

Dyslipidemia

Central obesity

hypertension

NIDDM is the “tip of the iceberg” of a cluster cardiovascular disease risk factors.


Why is diabetes mellitus important
Why is Diabetes Mellitus Important? Glucose Intolerance*

  • Many people have the disease.

  • Those who have the disease are at greater risk of dying.

  • Those who have the disease puts a burden on health care cost because of the complications that develop.


Prevalence if diabetes of diabetes by usual physical activity level (males > 20 years; age-standardized).


Prevalence of niddm adults 25 years and over in the usa
Prevalence of NIDDM Adults 25 years and Over in the USA activity level (males

Harris MI, et al: Diabetes 36, 523-534, 1978


Dietary factors determining igt and niddm
Dietary Factors Determining activity level (males IGT and NIDDM

  • High fat intake contributes to risk of glucose intolerance.

    • Fish, potatoes, vegetables, legumes may have protective effects.

    • Vitamin C and Antioxidants may have protective effects.

      Finnish and Dutch Study

      Diabetes Care August 1995


Total number of people with diabetes is increasing due to
Total Number of People With Diabetes is Increasing Due to: activity level (males

  • Population growth

  • AGING

  • URBANIZATION

  • Increasing prevalence of obesity and physical inactivity