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

Weets, Ilse; Kaufman, Leonard; Auwera, Bart Van Der; Crenier, Laurent; Rooman, Raoul; Block, Christophe De; Casteels, Kristina; Weber, Eric; Coeckelberghs, M.; Laron, Zvi; Pipeleers, Daniël; Gorus, Frans

doi:10.1007/s00125-004-1369-8

Cited by 33 publications

(35 citation statements)

References 41 publications

(66 reference statements)

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“…This observation is exactly the opposite of previous findings in a smaller group of patients [11]. Furthermore, at variance with a study in children [12], but in agreement with findings in nondiabetic subjects [13], C-peptide levels were higher in the high-incidence period (October to March) as compared with the low-incidence period (April to September) [7]. The lack of association between C-peptide levels around diagnosis and HLA-DQ risk status confirms our previous finding in adult-onset patients [10], but contrasts with grading of inaugural disease severity according to HLA-DQ-linked risk in Finnish children [14].…”

Section: Discussionsupporting

confidence: 63%

“…However, the observed interactions indicated that in patients with better-preserved C-peptide levels, who are overall older at diagnosis, male subjects had a lessdecreased BMI-SDS and lower insulin needs than female patients. Of note, we previously found that the male excess in type 1 diabetes is restricted to the high-incidence period [7], which now appears to be associated with betterpreserved C-peptide levels. This is in keeping with our hypothesis [5] that in immune-mediated type 1 diabetes an increased metabolic burden, e.g.…”

Section: Discussionmentioning

confidence: 86%

“…The male-to-female excess in diabetes is mainly confined to the winter season, since the incidence peak of type 1 diabetes during that period is largely restricted to male patients diagnosed after age 10 and without the HLA-DQ2/DQ8 genotype [7]. This suggests a larger contribution of season-dependent aetiological factors in precipitating the disease process in male patients.…”

Section: Introductionmentioning

confidence: 99%

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Sex- and season-dependent differences in C-peptide levels at diagnosis of immune-mediated type 1 diabetes

et al. 2006

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Aims/hypothesis: The incidence of type 1 diabetes varies according to age, sex and season of diagnosis. We investigated whether these and other clinical, biological and anthropometric parameters were correlated with residual beta cell function in newly diagnosed patients, since it is possible that the nature of external and/or genetic disease accelerators may be (partly) reflected in the inaugural disease presentation. Materials and methods: The correlates of random Cpeptide levels sampled shortly after diagnosis (median [interquartile range]: 3 [0-14] days) were studied by multivariate analysis in 1,883 islet-antibody-positive diabetic patients aged <40 years who were diagnosed between 1989 and 2000. Results: Higher C-peptide levels (above percentile 50 of patients) were associated with older age at diagnosis, female sex, diagnosis in the high-incidence season (October to March), less-decreased BMI (expressed as a standard deviation score), lower insulin requirements after stabilisation, lower prevalence of ketonuria and a less-increased glycaemia at diagnosis (all p<0.001). C-peptide levels were not correlated with calendar year at diagnosis, duration of symptoms prior to diagnosis, HLA-DQ2/DQ8 genotype or islet antibody status.Conclusions/interpretation: Sex-and seasondependent differences in residual functional beta cell mass and/or insulin resistance have been identified at diagnosis of type 1 diabetes. They may reflect differences in disease-precipitating external or lifestyle factors and should be further investigated longitudinally in prediabetes to further identify putative aetiological factors, which may provide targets for prevention.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

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Sex- and season-dependent differences in C-peptide levels at diagnosis of immune-mediated type 1 diabetes

et al. 2006

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“…As a study of children developing T1D showed, the majority of seasonality at onset was in the non-DR3/4 males, suggesting that viral infection could be an additive risk factor in those less genetically predisposed. 13 The interferon-inducible helicase IFIH1 gene encodes a cytoplasmic viral detector critical for response to picornaviruses. 14 Picornavirus infections have been associated with MS 15,16 and T1D.…”

Section: Discussionmentioning

confidence: 99%

IFIH1-GCA-KCNH7 locus: influence on multiple sclerosis risk

et al. 2008

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A recent genome-wide scan of nonsynonymous SNPs and ulterior validation in case-control and family analyses evidenced a susceptibility locus for type 1 diabetes (T1D) on chromosome 2q24.3. We aimed at testing the effect of this locus in other autoimmune diseases with complex genetic background, such as multiple sclerosis (MS). Four SNPs along the locus, rs13422767, rs2111485, rs1990760 and rs2068330, were genotyped using TaqMan MGB chemistry in 311 T1D and 412 MS patients and 535 ethnically matched healthy controls. The previously reported association of this locus was found for the first time in MS (rs2068330, G vs C: P ¼ 0.001; OR (95% CI) ¼ 0.73 (0.6-0.88)) and a trend for replication was observed in our Spanish diabetic cohort. Therefore, genes included in this locus -IFIH1 interferon induced helicase, GCA grancalcin or the potassium channel KCNH7 -are potential candidates implicated in the pathogenesis of these autoimmune diseases, although strong linkage disequilibrium in the region hampered further localization of the etiologic gene.

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“…To the Editor: I read the paper by Weets and co-workers [1] reporting seasonality of onset of Type 1 diabetes in HLA-DQ2/DQ8-negative Belgian males with interest. One of the possible environmental factors that vary with season in Europeans and are discussed by the authors of this paper as possible determinants of Type 1 diabetes is vitamin D deficiency, a factor which might explain the authors' findings as a result of interactions with genetic factors.…”

mentioning

confidence: 99%

?to: Weets I, Kaufman L, Van der Auwera B et al. (2004) 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. Diabetologia 47:614?621

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2004

Diabetologia

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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

Cited by 33 publications

References 41 publications

Sex- and season-dependent differences in C-peptide levels at diagnosis of immune-mediated type 1 diabetes

Sex- and season-dependent differences in C-peptide levels at diagnosis of immune-mediated type 1 diabetes

IFIH1-GCA-KCNH7 locus: influence on multiple sclerosis risk

?to: Weets I, Kaufman L, Van der Auwera B et al. (2004) 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. Diabetologia 47:614?621

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