Impact of epidemiology on diabetes mellitus
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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

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


Developing Countries Most Affected In This Global Diabetes Epidemic


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


2000


Epidemiology

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

  • 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?

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 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 Prospective

  • 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.


Cause of Death in Type 2 DM


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


Etiologic Classification of 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 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


Prevalence of NIDDM in Selected Populations in the Age Range 30–64 Years


Year 2000

2.8%

Year 2030

4.8%

Prevalence of DM Worldwide


Global Diabetes Prevalence by Age and Sex for 2000


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 IGT (Philippines)1982 - 1983


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


DiabetesGenetics Environment


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


CollisionHunter Gatherer Genes VS 20th Century LifestyleType 2 DM


Thrifty Gene Hypothesis

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)

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

Genetic susceptibility

Hyperinsulinemia and/or insulin resistance

Impaired glucose tolerance

Non-insulin dependent diabetes


Normal

IGT

Type 2 Diabetes

Development of Type 2 Diabetes


Type 2

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

  • 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

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

Overall Occurrence Rate

Diabetes12%

Impaired Glucose Tolerance12%


IGT Worsening to Diabetes

Filipino Siblings

50% Conversion in 8 years

Conversion rate: 9.3 per 100 cases/year


IGT Conversion Rate

PIMA Indians

9.3 cases per 1000/year

Filipino Siblings


10 yr

Follow up

Impaired Glucose Tolerance (IGT)Natural History

Subjects with IGT


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

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

in westernized Societies are contributing to the excess Obesity and NIDDM


Environmental Determinant of 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

Implicated in:

  • Europids (Sweden)

  • Mexican Americans

  • Native Americans

  • Micronesians (Nauruans)

  • Asian Indians (Hindu and Muslim)

  • Creoles

  • Chinese

  • Japanese Americans


Insulin Resistance in Obesity

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 DM

Intrauterine Factor

Low Birth Weight-Risk Factor for NIDDM

Impaired Development of Endocrine Pancreas


Physical Inactivity Risk Factor for Diabetes

Possible Explanation Insulin Resistance


  • IGT

  • 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

Explanation:

  • Change in lifestyle

  • Physical Activity

  • More Refined Diet

  • Greater Occurrance of Obesity


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

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

  • Weight Reduction

  • Dietary composition

  • Exercise

  • Pharmacologic therapy


People at High Risk of Developing 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 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


Type 1Genetics Environment


Aetiology of Type 1 DM

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

  • 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


Standardized Incidence Rates

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

Incidence Rate / 100,000


Geographic and Ethnic Variation

Markeded Variations are Reflections of Difference in:

  • Environment

  • Genetic Susceptibility


Environmental Factors

  • 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


Type 1 DM

  • 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

  • Genes Conferring Susceptibility

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

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

    : DR3/DR4 (20 – 40x risk)

    : HLA – DR3DQW2

    : HLA – DR4 DQW8

    : DOA1*0501, DQB1*0302

    Genes Conferring Protection

    : HLA-DR2

    : HLA DQB1*0602


HLA System


Reports of Diabetes Mellitus and ICA Associated with Known Virus Infection


Type 1 DM – Immunological Factors

  • 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

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

  • Protracted Prodromal Period

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


50

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.


Relative Frequency %

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)


Onset of diabetes

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?

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

Rationale:

  • Improve  cell function to delay onset of Diabetes.

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


Thank you!


Clinical classes

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 Intolerance*

  • Other categories

    • Impaired glucose tolerance (IGT)

    • Gestational Diabetes Mellitus (GDM)

      * WHO Study Group on Diabetes Mellitus - 1995


NIDDM – A Public Health Perspective

  • 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

  • Modernization of Lifestyle in situ

  • Rural-Urban comparisons

  • Migration studies

  • Several ethnic groups living in same location


Thrifty Genotype

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

  • Non-insulin-dependent diabetes mellitus

  • Central obesity

  • Dyslipidemia

  • Hyperinsulinemia

  • Hypertension


Hyperinsulinemia / insulin resistance

Insulinemia deficiency

NIDDM – A Spectrum Ranging from Hyperinsulinemia to Hypoinsulinemia


Preventing NIDDM

  • 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

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


NIDDM

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?

  • 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

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


Dietary Factors DeterminingIGT 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:

  • Population growth

  • AGING

  • URBANIZATION

  • Increasing prevalence of obesity and physical inactivity


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