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The SAUDI
DIABETES
What…
?
Why do we have
more Diabetes…?
Genetic,…
Nutritional,…
Cultural,…
Clues
The 1st Arab-Iranian Congress of Endocrinology and Diabetes
The?RED ZONE
What…
50% of the total Diabetic patients (~ 100 millions)
More prevalence
Less population
Genetic:
Ethnicity
Family history
Nutritional:
Diet change
Calorie intake
Cultural:
Physical activity
WHO report (2000)
Less prevalence
More population
25
Type 2 Diabetes Prevalence
20
15
10
5
0
West countries
East countries
Genetic
in Diabetes
What…
?
Type 2 Diabetes Mellitus
Genes
• Higher concordance in monozygotic than
dizygotic twins.
Environment
• Links to life-style and diet.
• Clustering in families.
• Different incidence in genetically similar
population living in different area.
• Higher prevalence in certain ethnic group.
• 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.
Joslin’s Diabetes Mellitus, 14 edition, 2005
Genetic
Risk
Diabetes
Environmental
Risk
Birmingham
Study
What…
?
A random sample of 4886 birth.
Comparison between the most valid data:
2432
956
North European babies
British Pakistani babies
Couple family relation in the two group:
0.4%
69%
North European
British Pakistani
Prevalence of congenital and genetic disorders:
4.3%
7.9%
North European
British Pakistani
80
Corrected congenital malformation
60
Disability
40
Death 1 month - 5 years
Death <1 month (lethal malformation)
20
Genetic abortion
0
North
European
British
Pakistani
Genetic Scin. 48, 446 2002
Genetic ?Factors in Type 2 Diabetes
What…
• Strong family history of diabetes add to other factors like obesity.
• Ethnicity and family history show the genetic factor in type 2 diabetes.
12
Impact of diabetogenes
on obesity induced insulin
resistance
11
Insulin sensivity
10
9
8
7
6
5
4
90
100 110 120 130 140 150 160 170 180
Ideal body weight (%)
Genetic ?Factors in Type 2 Diabetes
What…
Ethnicity Effect
Familial Effect
90.00%
General Population
50%
General Population
African Descent
Latin American Descent
Parent or Sibling
Native American Descent
Identical Twin
Pima Indians
10.60%
10.20%
12.20%
5.20%
Diabetes Care, 23, 589-594. 2000
12.00%
5.20%
Ethnicity
as a risk factor
What…
?
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.
Plevalence %%
75
70
Male
Female
52
50
45
30
28
31
25
14
8.5
10
20-29
30-39
8
0
40-49
Age group
Diabetes Care, Vol. 27, 2004
50-59
>60
Genetic study
What… Saudi
?
• Common disease.
Family 1
Family 2
Family 3
187
74
118
93/94
33/41
67/51
56
55
47
82%
48.6%
7%
Number
Male/Female
• Behave Genetically.
Age (mean)
Diabetes + IGT
• Extended families.
46
36
34
DM
IGT
• Known tribes.
11
5
Family 1
SAUDI DIABETES GENOME
Family 2
2
Family 3
What… ? One Saudi Family
• All are type 2 diabetic patients.
• Five level study.
Sex
Males
Females
Total
Total
33
41
74
Affected
20
16
36
%
60.6
39
48.6
• Intermarriage.
90’s
• Gene mixture.
• High diabetes prevalence
70’s
50’s
Affected female
Affected male
30’s
Non-affected female
Non-affected male
<30
Mean
Range
AGE (years)
.
23
15-31
SAUDI DIABETES GENOME
Age
group
Diabetes
susceptibility loci
What…
?
Chromosome 2
Chromosome 5
Chromosome 6
Chromosome 10
IDDM1
IDDM10
IDDM15
IDDM7
IDDM12
IDDM13
Chromosome 11
IDDM18
Chromosome 14
IDDM5
IDDM8
Chromosome 15
IDDM17
Chromosome 18
IDDM2
IDDM4
IDDM17
IDDM11
IDDM3
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.
Study Results
What… ?
1.
2.
Hypothesis
Result
Conclusion
Association of KCNJ11
E/E 529 (71%)
Support association
gene E23K polymorphis
E/K 190 (26%)
in susceptibility or
K/K 23 (3%)
pathogenesis.
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
gene P12A
the P12 allele (95%)
More relevant
Genetic? Role in the Prevalence
What…
Community tolerance to glucose metabolism differ in different communities and
affect the prevalence of both diabetes and IGT.
50
SAUDI ARABIA
25
KUWAIT
25
Genetic effect
Age effect
0
0
20-30
30-40
40-50
Acta Diabetol, 1999
20-30
30-40
40-50
50-60
Chronic disease in SA 1999
>60
Diabetes
Prevalence in Saudis
What…
?
Types of diabetes:
100
Distribution pattern of Diabetes Mellitus according
100
to age group
94.4
90
87.5
Type 2 start earlier than before.
80
Type 1 dominate population <18
years of age.
60
Gestational diabetes in the
reproductive age is found in
3.6% pregnant and nonpregnant subjects.
78.9
GDM
Type 1
Type 2
40
20
17.4
3.6
0 6.25
00
0
5.6
0
10
0
0-6 years
Diabetes Type
Type 1
Type 2
Unpublished data (80,000 subjects)
7-18 years 19-45 years 46-65 years > 65 years
Age group adjusted prevalence rate
0-6
7-18
19-45
46-65
>65
0
100
87.5
6.25
17.4
78.9
5.6
94.4
10
90
Global prevalence of childhood obesity- predictor of type 2 diabetes in youth
USA
1973-1999
2.3%
Costa Rica
1982-1996
2.7%
Haiti
1978-1995
3.5%
Japan
1970-1996
2.5%
Chile
1985-1995
1.6%
China
1991-1997
1.1%
Brazil
1974-1997
3.6%
England
1984-1994
2.4%
Ghana
1988-1994
3.8%
Morocco
1987-1992
2.5%
Egypt
1978-1996
3.9%
Australia
1985-1995
4%
Lancet 2002; 360:476
Diabetes
Prevalence
What…
?
30
Which type make the
difference?
25
Prevalence of DM using different age
cut-offs
19.8
Type 2 increase steadily with
different age cut-offs
demonstrating age effect.
Type 1 demonstrate miner
change demonstrating no age
effect.
17.8
20
15.2
15
10
12.5
Type 1
Type 2
7
5
0.8
1.2
1.4
1.5
1.6
0
Over-all
Unpublished data (80,000 subjects)
> 20 years > 25 years > 30 years > 35 years
What… G
? ene at larger scale
80
Positive family history of diabetes in Diabetic and Nondiabetic subjects
Genetic factor:
Non-Diabetic Saudi
Genetic factor start earlier.
Diabetic Saudi
60
Diabetic American
Non-Diabetic American
It has more effect than other
risk factors.
40
It work independent to other
risk factor.
70
60
Percent (%) cases of subjects with established
family history of diabetes (N = 9,055)
20
19.7 years
50
40
30
20
0
38.7%
57.7%
Non-Diabetic
Diabetic
10
0
0-6
7-18
19-45
46-65
>65
Obesity
as risk factor
What…
?
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.
60
Obesity among Diabetics and Non-Diabetics
Percent (%) cases of DM according to
Body Mass Index (BMI)
50
Obesity effect
40
42.4
50
33.5
40
30
30
20
Diabetic
Non-Diabetic
10
24.2
20
10
0
0
7-18
19-45
46-65
>65
Normal
Overweight
Obese
Physical
activity as a risk factor
What…
?
Physical activity assessment:
Physical activity duration or
frequency did not demonstrate
any effect.
6
Met Score (N)
Met Score (DM)
Activity hours (N)
4
Activity frequancy (N)
Activity hours (DM)
Activity frequancy (DM)
But the Met score show clear
reduction with age without a
significant difference between
2
diabetic and none diabetic group.
This could be explained by the
narrow physical activity range.
0
7-18
19-45
46-65
>65
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.
Physical
Activity
What…
?
30
25
20
% Change in Risk
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.
15
10
5
0
-5
-10
-15
-20
-25
-30
-35
-40
-45
TV
Watching
(2h/d)
JAMA. 2003;289:1785-1791.
Sitting
At work
(2h/d)
Other
sitting
(2h/d)
Standing
At work
(2h/d)
Standing
At home
(2h/d)
Brisk
Walkin
g (1h/d)
Activity
Diabetes/Mortality
What…
?
Leisure-time physical activity and age-adjusted CHD mortality rates in
normoglycaemic men (n=6056) and men with IGT/diabetes (n=352) in the
Whitehall study
Clin. Sci. (2006) 110, 409-425
Annual income
and diet as a risk for type 2 diabetes:
What…
?
Relationship between the proportion of energy from each food source and gross
national product per capita with the population residing in urban areas
Animal Vegetable
protein protein
10000
Annual per capita national income (USD)
7300
Vegetable
fat
Animal
fat
Carbohydrate
Sweeteners
6300
4500
Fat
35%
Carbohydrate 50%
Protein
15%
2700
2200
Increase Of fat by
40 gm/day
1700
1300
1000
Type 2 Diabetes
risk increase by
3.4 fold
700
400
200
Food balance data (FAOUN), GNP data from the world bank
Fat
20%
Carbohydrate 75%
Protein
15%
Diabetes care(17) 1994
change
What…Dietary
?
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.
4000
3600
Total fat intake
123
3000
120
3000
2000
160
1900
80
1000
40
0
0
1970
1990
USA
33
1970
1990
What… ? Diet and Exercise
Incidence of type 2 diabetes at or before the six year
follow-up in the Da Qing study
Incidence per 100 person
20
18
Lean
Obese
16
14
12
10
8
6
4
2
0
Control
Diet
Exercise
The Da Qing IGT and Diabetes Study. Diabetes Care 1997; 20: 537-544.
Exercise+Diet
Prevention
What…
?
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.
FINALLY
What…
?
Is it the Globalization ?