Seasonality in clinical onset of type 1 diabetes in belgian patients above the age of 10 is restricted to HLA-DQ2/DQ8-negative males, which explains the male to female excess in incidence.
OBJECTIVE
Type 1 diabetes arises from an interplay between environmental and genetic factors. The reported seasonality at diagnosis supports the hypothesis that currently unknown external triggers play a role in the onset of the disease. We investigated whether a seasonal pattern is observed at diagnosis in Belgian Type 1 diabetic patients, and if so whether seasonality varies according to age, sex and genetic risk, all known to affect the incidence of Type 1 diabetes.


METHODS
The seasonal pattern at clinical diagnosis was assessed in 2176 islet antibody-positive diabetic patients aged 0 to 39 years diagnosed between 1989 and 2000. Additional stratification was performed for age, sex and HLA-DQ genotype.


RESULTS
Overall, a significant seasonal pattern at clinical diagnosis of diabetes was observed (p<0.001). More subjects were diagnosed in the period of November to February (n=829) than during the period of June to September (n=619) characterised by higher averages of maximal daily temperature and daily hours of sunshine. However, the seasonal pattern was restricted to patients diagnosed above the age of 10 (0-9 years: p=0.398; 10-19 years: p<0.001; 20-29 years: p=0.003; 30-39 years: p=0.015). Since older age at diagnosis is associated with a male to female excess and a lower prevalence of the genetic accelerator HLA-DQ2/DQ8, we further stratified the patients aged 10 to 39 years (n=1675) according to HLA-DQ genotype and sex, and we found that the seasonal pattern was largely restricted to male subjects lacking DQ2/DQ8 (n=748; p<0.00 vs all others: n=927; p=0.031).


CONCLUSIONS
In a subgroup of male patients diagnosed over the age of 10, the later stages of the subclinical disease process may be more driven by sex- and season-dependent external factors than in younger, female and genetically more susceptible subjects. These factors may explain the male to female excess in diabetes diagnosed in early adulthood.
Diabetes Research Center, Brussels Free University, Brussels, Belgium.
I
I
Weets
L
L
Kaufman
B
B
Van der Auwera
L
L
Crenier
R P A
RP
Rooman
C
C
De Block
K
K
Casteels
E
E
Weber
M
M
Coeckelberghs
Z
Z
Laron
D G
DG
Pipeleers
F K
FK
Gorus
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001323:Autoantibodies / Q000032:analysis; D001530:Belgium / Q000453:epidemiology; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000503:physiopathology*; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D006801:Humans; D008297:Male; D011446:Prospective Studies; D012042:Registries; D012621:Seasons; D012727:Sex Characteristics
D001323:Autoantibodies; D005819:Genetic Markers; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; C109756:HLA-DQ8 antigen