Professional Documents
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diabetes pathogenesis
Ake Lernmark
From
Joerg Ermann &
C. Garrison Fathman
Nature Immunology
2, 759 - 761 (2001)
Insulitis
Residual -cell function in new
onset Type 1 diabetes
Age C-peptide level within normal range
(years) At diagnosis One year Two years
rhw 5/99
Type 1 diabetes genes
v HLA DQ2, DQ8, or both, represents almost 90% of all
type 1 diabetes patients younger than 20 years of age.
v The risk of DQ2/8 heterozygotes decreases with
increasing age.
v The protection of DQ6.2 is attenuated by increasing age
and is lost at about 35 years of age.
v Class I - INS VNTR -short tandem repeats - increase the
risk by about 2-5 %.
rhw12/98
GENETIC EFFECTS ON AGE-DEPENDENT ONSET AND
ISLET CELL ANTIBODIES IN TYPE 1 DIABETES.
0.8
0.6
0.4 0 DQ2
0.2
0 DQ2
0 10 20 30 0 10 20 30
Age at clinical onset (years)
A B
0 DQ8, Females 0 DQ8, Males
0.8
1 DQ2
0.6
0.4 0 DQ2
1 DQ2
0.2
0 DQ2
0 10 20 30 0 10 20 30
Age at clinical onset (years)
A B
0 DQ8, Females 0 DQ8, Males
2 DQ2
0.8
2 DQ2
1 DQ2
0.6
0.4 0 DQ2
1 DQ2
0.2
0 DQ2
0 10 20 30 0 10 20 30
Age at clinical onset (years)
RISK FOR TYPE 1 DIABETES AS FUNCTION
OF AGE, GENDER, HLA AND GAD65A.
THE ODDS TO DEVELOP TYPE 1 DIABETES:
0.6
0.4
0.2
0.0
0 10 20 30 0 10 20 30
Age at clinical onset (years)
A B
0 DQ8, Females 0 DQ8, Males
0.8 0 DQ2 0 DQ2
1 1
0.6
0.4
0.2
0.0
0 10 20 30 0 10 20 30
Age at clinical onset (years)
A B
0 DQ8, Females 0 DQ8, Males
0.8 0 DQ2 0 DQ2
1 1
0.6
2 2
0.4
0.2
0.0
0 10 20 30 0 10 20 30
Age at clinical onset (years)
RISK FOR TYPE 1 DIABETES AS FUNCTION
OF AGE, GENDER, HLA, AND IA-2Ab.
THE ODDS FOR TYPE 1 DIABETES WITH IA-2Ab
AT 5 YEARS OF AGE IS 11 TIMES THAT AT
34 YEARS OF AGE.
80
OF ISLET CELL 60
ANTIBODIES 40
PREDICT
20
0
0 2 4 6 8 10
Years of follow-up
673 67 3
591 59 1
686 68 6
652 65 2
708 70 8
613 61 3
826 82 6
898 89 8
853 85 3
1306 1 30 6
0 .0 2 .5 5 .0 7 .5 10 .0 1 2 .5
0,0 2,5IL -2 con5,0 7,5 10,0
cen tra tio n (U /m l)
12,5 0,0
0.00
0,25
0.2 5
0,5
0 .5 0
0,75
0 .7 5
G A D 6 5 a n tib o d y in d e x
1,0
1 .00
1,25
1.2 5