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.
Weets
I
I
Diabetes Research Center, Brussels Free University, Brussels, Belgium.
Kaufman
L
L
Van der Auwera
B
B
Crenier
L
L
Rooman
R P A
RP
De Block
C
C
Casteels
K
K
Weber
E
E
Coeckelberghs
M
M
Laron
Z
Z
Pipeleers
D G
DG
Gorus
F K
FK
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