What… ?The SAUDI DIABETES

Why do we have more Diabetes…?Genetic,…

Nutritional,… Cultural,…

Clues

The 1st Arab-Iranian Congress of Endocrinology and Diabetes

What… ? The RED ZONE

WHO report (2000)

More prevalenceLess population

Less prevalenceMore population

Genetic:EthnicityFamily history

Nutritional:Diet changeCalorie intake

Cultural:Physical activity

50% of the total Diabetic patients (~ 100 millions)

0

5

10

15

20

25

West countries East countries

Type 2 Diabetes Prevalence

What… ?Genetic in Diabetes

Type 2 Diabetes MellitusType 2 Diabetes Mellitus

GenesGenes EnvironmentEnvironment

• Higher concordance in monozygotic than dizygotic twins.

• Clustering in families.

• Higher prevalence in certain ethnic group.

• Higher concordance in monozygotic than dizygotic twins.

• Clustering in families.

• Higher prevalence in certain ethnic group.

• Links to life-style and diet.

• Different incidence in genetically similar population living in different area.

• Type 2 diabetes secondary to other conditions.

• Links to life-style and diet.

• Different incidence in genetically similar population living in different area.

• Type 2 diabetes secondary to other conditions.

• Genetic risk: will be the result of the following factor/s:

Ethnicity: Arab, black, Hispanic,…….

Tribe: Pima Indians

Familial factor: Different studies.

Twin: Identical & non-identical.

• Environmental Risk: The result of change in life style.

Genetic Risk

Enviro- nmental

RiskDiabetes

Joslin’s Diabetes Mellitus, 14 edition, 2005

What… ? Birmingham Study

0

20

40

60

80

NorthEuropean

BritishPakistani

Corrected congenital malformation

Disability

Death 1 month - 5 years

Death <1 month (lethal malformation)

Genetic abortion

A random sample of 4886 birth.

Comparison between the most valid data: 2432 North European babies

956 British Pakistani babies

Couple family relation in the two group: 0.4% North European

69% British Pakistani

Prevalence of congenital and genetic disorders: 4.3% North European 7.9% British Pakistani

Genetic Scin. 48, 446 2002

What… ? Genetic Factors in Type 2 Diabetes

• Strong family history of diabetes add to other factors like obesity.• Ethnicity and family history show the genetic factor in type 2 diabetes.

4

5

6

7

8

9

10

11

12

90 100 110 120 130 140 150 160 170 180

Ideal body weight (%)

Insu

lin s

ensiv

ity ControlsOffspring of type 2

diabetes subjects

Impact of diabetogenes on obesity induced insulin

resistance

What… ? Genetic Factors in Type 2 Diabetes

Ethnicity EffectFamilial Effect

5.20%

10.60% 10.20%12.20%

50%General Population

African Descent

Latin American Descent

Native American Descent

Pima Indians

5.20%12.00%

90.00%

General Population

Parent or Sibling

Identical Twin

Diabetes Care, 23, 589-594. 2000

What… ? Ethnicity as a risk factor

Arab Americans study

Metabolic syndrome study:

The Adult Treatment Panel (APT III):

Increase in prevalence with time.Prevalence is the same for both men and women but higher in women aged 50 years. 8

30 31

45

8.5 10

28

52

70

14

0

25

50

75

20-29 30-39 40-49 50-59 >60

MaleFemale

Age group

Plev

alen

ce %

%

Diabetes Care, Vol. 27, 2004

What… ? Saudi Genetic study

• Common disease.

• Behave Genetically.

• Extended families.

• Known tribes.

Family 1 Family 2 Family 3

187 74 118Number

93/94 33/41 67/51Male/Female

56 55 47Age (mean)

82% 48.6% 7%Diabetes + IGT

46

34

5

36

11

2

Family 1 Family 2 Family 3

DM IGT

SAUDI DIABETES GENOME

What… ? One Saudi Family

90’s

70’s

50’s

30’s

<30

Agegroup

• All are type 2 diabetic patients.

• Five level study.

• Intermarriage.

• Gene mixture.

• High diabetes prevalence

AGE (years) .Mean 23Range 15-31

Sex Males Females Total

Total 33 41 74

Affected 20 16 36

% 60.6 39 48.6

Affected femaleAffected male

Non-affected femaleNon-affected male

SAUDI DIABETES GENOME

What… ? Diabetes susceptibility loci

Chromosome 2 Chromosome 5 Chromosome 6 Chromosome 10

IDDM10

IDDM17

IDDM1

IDDM15

IDDM5IDDM8

IDDM18IDDM7IDDM12IDDM13

Chromosome 11 Chromosome 14 Chromosome 15 Chromosome 18

IDDM17

IDDM3IDDM11

IDDM2

IDDM4

18 regions of the genome have been linked with influencing type 2 diabetes risk

What… ? DNA analysis

• Central genetic lab.

• DNA samples stored in tissue bank.

• DNA analyzed with the same team.

What… ? Study Results

Hypothesis ResultConclusion

1. Association of KCNJ11 E/E 529 (71%) Support association

gene E23K polymorphis E/K 190 (26%) in susceptibility or

K/K 23 (3%) pathogenesis.

2. Association of CAPN10 111/111 haplotype Compared with that

gene haplotypes combination observed seen in other population

and other combinations

3. Association of PPARG very high incidence of More relevant

gene P12A the P12 allele (95%)

What… ?Genetic Role in the Prevalence

Community tolerance to glucose metabolism differ in different communities and affect the prevalence of both diabetes and IGT.

Acta Diabetol, 1999 Chronic disease in SA 1999

0

25

20-30 30-40 40-50

KUWAIT

0

25

50

20-30 30-40 40-50 50-60 >60

SAUDI ARABIA

Age effect

Genetic effect

What… ? Diabetes Prevalence in Saudis

Types of diabetes:

Type 2 start earlier than before.

Type 1 dominate population <18 years of age.

Gestational diabetes in the reproductive age is found in 3.6% pregnant and non-pregnant subjects.

Distribution pattern of Diabetes Mellitus according to age group

0 0 0 03.6

87.5

17.410

6.25

78.9

90

100

5.60

94.4

0

20

40

60

80

100

0-6 years 7-18 years 19-45 years 46-65 years > 65 years

GDMType 1Type 2

Diabetes Type Age group adjusted prevalence rate0-6 7-18 19-45 46-65 >65

Type 1 0 87.5 17.4 5.6 10Type 2 100 6.25 78.9 94.4 90

Unpublished data (80,000 subjects)

Brazil1974-1997

3.6%

Brazil1974-1997

3.6%

Chile1985-1995

1.6%

Chile1985-1995

1.6%

Haiti1978-1995

3.5%

Haiti1978-1995

3.5%

Costa Rica1982-1996

2.7%

Costa Rica1982-1996

2.7%

USA1973-1999

2.3%

USA1973-1999

2.3%

Ghana1988-1994

3.8%

Ghana1988-1994

3.8%

England1984-1994

2.4%

England1984-1994

2.4%

Australia1985-1995

4%

Australia1985-1995

4%

China1991-1997

1.1%

China1991-1997

1.1%

Japan1970-1996

2.5%

Japan1970-1996

2.5%

Morocco1987-1992

2.5%

Morocco1987-1992

2.5%

Egypt1978-1996

3.9%

Egypt1978-1996

3.9%

Global prevalence of childhood obesity- predictor of type 2 diabetes in youthGlobal prevalence of childhood obesity- predictor of type 2 diabetes in youth

Lancet 2002; 360:476

What… ? Diabetes Prevalence

Which type make the difference?

Type 2 increase steadily with different age cut-offs demonstrating age effect.

Type 1 demonstrate miner change demonstrating no age effect.

Prevalence of DM using different age cut-offs

0.8 1.2 1.4 1.5 1.6

7

12.5

15.2

17.819.8

0

5

10

15

20

25

30

Over-all > 20 years > 25 years > 30 years > 35 years

Type 1

Type 2

Unpublished data (80,000 subjects)

What… ? Gene at larger scale

Genetic factor:

Genetic factor start earlier.

It has more effect than other risk factors.

It work independent to other risk factor.

0

20

40

60

80

0-6 7-18 19-45 46-65 >65

Non-Diabetic Saudi

Diabetic Saudi

Diabetic American

Non-Diabetic American

Positive family history of diabetes in Diabetic and Non-diabetic subjects

19.7 years19.7 years

Percent (%) cases of subjects with established family history of diabetes (N = 9,055)

57.7%38.7%

0

10

20

30

40

50

60

70

Non-Diabetic Diabetic

What… ? Obesity as risk factor

0

10

20

30

40

50

60

7-18 19-45 46-65 >65

Diabetic

Non-Diabetic

Obesity among Diabetics and Non-Diabetics

Percent (%) cases of DM according to Body Mass Index (BMI)

24.2

33.5

42.4

0

10

20

30

40

50

Normal Overweight Obese

Obesity as a risk factor:

It has a major effect earlier in life (before 50 years of age)Older population (>65 years of age) obesity did not demonstrate any effect.

Obesity effectObesity effect

What… ? Physical activity as a risk factor

0

2

4

6

7-18 19-45 46-65 >65

Met Score (N)

Met Score (DM)

Activity hours (N)

Activity frequancy (N)

Activity hours (DM)

Activity frequancy (DM)

Physical activity assessment:

Physical activity duration or frequency did not demonstrate any effect.

But the Met score show clear reduction with age without a significant difference between diabetic and none diabetic group.

This could be explained by the narrow physical activity range.

The magnitude of risk contributed by obesity is much greater than that imparted by lack of physical activity.The magnitude of risk contributed by obesity is much greater than that imparted by lack of physical activity.

Diabetes Care. 2007 Jan;30(1):53-8.

What… ? Physical Activity

-45

-40

-35

-30

-25

-20

-15

-10

-5

0

5

10

15

20

25

30

TV Watching

(2h/d)

Sitting At work (2h/d)

Other sitting (2h/d)

Standing At work (2h/d)

Standing At home

(2h/d)

Brisk Walking (1h/d)

% C

han

ge

in

Ris

k

Percentage Changes in Risk of Developing type 2 Diabetes Among Non-diabetic Women Associated With Television (TV) Watching, Other Sedentary Behaviors, and Walking. Adjusted for age, smoking, alcohol consumption, family history of diabetes, and dietary covariates. All sedentary behavior variables are included simultaneously in the model. Other sitting includes reading, mealtime, and at desk. Error bars indicate 95% confidence intervals.

JAMA. 2003;289:1785-1791.

What… ? Activity Diabetes/Mortality Leisure-time physical activity and age-adjusted CHD mortality rates in Leisure-time physical activity and age-adjusted CHD mortality rates in

normoglycaemic men (n=6056) and men with IGT/diabetes (n=352) in the normoglycaemic men (n=6056) and men with IGT/diabetes (n=352) in the Whitehall study Whitehall study

Clin. Sci. (2006) 110, 409-425

Vegetable protein

Vegetable fat

Animal fat

Carbohydrate

Animal protein

10000

7300

6300

4500

2700

2200

1700

1300

1000

700

400

200

An

nu

al

pe

r c

ap

ita

na

tio

na

l in

co

me

(US

D)

Sweeteners

What… ?Annual income and diet as a risk for type 2 diabetes:

Relationship between the proportion of energy from each food source and gross national product per capita with the population residing in urban areas

Fat 20%Carbohydrate 75%Protein 15%

Fat 35%Carbohydrate 50%Protein 15%

Increase Of fat by

40 gm/day

Type 2 Diabetes risk increase by

3.4 fold

Increase Of fat by

40 gm/day

Type 2 Diabetes risk increase by

3.4 fold

Diabetes care(17) 1994Food balance data (FAOUN), GNP data from the world bank

What… ? Dietary change

Diet change in SAUDI ARABIA:

There has been an increase in the total calorie in-take from 1900 to 3000 cal.

This increase is associated with low fiber diet.

1900

3000

3600

0

1000

2000

3000

4000

1970 1990 USA

33

123

0

40

80

120

160

1970 1990

Total fat intake

What… ? Diet and Exercise

0

2

4

6

8

10

12

14

16

18

20

Control Diet Exercise Exercise+Diet

Lean

Obese

Inc

ide

nc

e p

er

10

0 p

ers

on

Incidence of type 2 diabetes at or before the six year follow-up in the Da Qing study

The Da Qing IGT and Diabetes Study. Diabetes Care 1997; 20: 537-544 .

What… ? Prevention

Cumulative incidence of type 2 diabetes with: placebo, metformin and lifestyle intervention

Diabetes is a reversible pathological condition that can be done with:

Exercise

Diet

Drugs

N Engl J Med 2002; 346: 393-403.

What… ?FINALLY

Is it the Globalization ?