Ætiology of Juvenile-Onset Diabetes

Cudworth, A G; White, Griffin; Woodrow, J. C.; Gamble, D. R.; Lendrum, R; Bloom, Arnold

doi:10.1016/s0140-6736(77)92602-2

Cited by 63 publications

(26 citation statements)

References 11 publications

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“…However, Rolles' sample was derived from a children's hospital, while Barbosa studied juvenile-onset diabetes patients with microangiopathy and onset before 35 years of age, suggesting that the two populations may differ. Cudworth et al [20] studied a paediatric sample of Type 1 diabetic patients and noted that B8/B15 combination cases seemed prone to onset in winter, rather than autumn. The report did not compare seasonality of onset for HLA-B8-or DR3-positive versus negative patients.…”

Section: Discussionmentioning

confidence: 99%

HLA-related heterogeneity in seasonal patterns of diagnosis in Type 1 (insulin-dependent) diabetes

et al. 1984

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Summary. HLA type, time of year of diagnosis, and age at diagnosis were studied in 52 new cases of Type 1 diabetes in Seattle, Washington. Diagnosis was found to be seasonal in diabetic patients positive for DR3 (p < 0.005), with the expected marked reduction in new cases during the summer months. This seasonality was not age-related (p>0.13). Cases who were DR3-negative did not show significant seasonality of diagnosis (p> 0.5). However, when age at diagnosis was adjusted for, a seasonal effect was found in the DR3-negative group (p< 0.006), with older cases favouring a spring onset and younger cases favouring an autumn onset. Thus, DR3-positive cases showed a seasonal diagnosis pattern that did not depend on age, while DR3-negative cases showed an age-dependent seasonal pattern. These differences may reflect the predominance of different aetiological mechanisms in these two genetic groups.Key words: Seasonality, Type 1 diabetes, HLA, aetiology.The onset of Type 1 (insulin-dependent) diabetes follows a seasonal pattern, with increased incidence of new cases in the autumn and late winter, followed by a nadir during the summer [1][2][3][4][5][6]. This pattern appears to be inverted in the southern hemisphere [7] and may not be present in children who develop diabetes in their pre-school years [5,8].Certain HLA antigens are now known to be associated with an increased risk of Type 1 diabetes [9,10]. However, the primary mechanisms of B cell damage may differ in patients with different HLA phenotypes [11,12]. In this study, we have investigated whether certain HLA specificities mark subgroups of Type 1 diabetic patients with different patterns of diagnosis, taking into account a possible relationship between season and age at diagnosis. Subjects and methodsWe studied 54 unrelated cases of newly diagnosed Type 1 diabetes, with a diagnosis between March 1976 and March 1981, who volunteered for a prospective study [13]. All patients were between 5 and 20years of age at diagnosis; the median age at diagnosis was 10.5 years. Forty-eight patients were typed for HLA-DR and 31 were typed for HLA-D. The four patients typed for HLA-D, but not DR, were all HLA-D3-negative and were assumed to be DR3-negative * Present address: City Hospital, Nottingham NG5 1PD, UK also. This assumption was felt to be reasonable since among 18 D3-negative patients who were also DR typed, only one was DR3-positive. Further, no set of reclassifications for those four patients and subsequent repeat analysis would materially alter our conclusions. Serological typing for DR was performed by standard methods [14,15]. Typing for HLA-D was performed using HLA-D homozygous typing cells as previously described [16].Statistical analysis of this data presents special problems, since time of year should be treated as a circular variable (December 31 being adjacent to January 1). For testing for seasonality, versus a null hypothesis of uniformity, the non-parametric test developed by Hodges and Ajne was applied [17]. The seasonal patterns for DR3-positive ve...

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Section: Discussionmentioning

confidence: 99%

HLA-related heterogeneity in seasonal patterns of diagnosis in Type 1 (insulin-dependent) diabetes

et al. 1984

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“…Seasonality of Type 1 diabetes appears to be more predominant for males than females [9,10]. Also seasonality appears to vary with the age of onset [9,11].…”

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confidence: 99%

The Pittsburgh insulin-dependent diabetes mellitus registry: Seasonal incidence

Fishbein

Orchard

et al. 1982

Diabetologia

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Summary. A total community (Allegheny County, Pennsylvania) Type 1 (insulin-dependent) diabetes mellitus registry was examined for evidence of seasonality at onset of the disease. No significant seasonal trend was found if all cases aged < 20 years at onset (n = 901) were considered. However, a significant pattern emerged for the age groups 5 9 years and 10-14 years. Furthermore, sex differences were apparent in that males but not females demonstrated a seasonal pattern (fewer cases in the summer months).

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“…A matching seasonal incidence was also noted. This hypothesis is being developed and applied to HLA typing (Cudworth et al, 1977). Acute JOD has been described in a boy of 18 months who had a high titre of CB2 and of CBspecific IgM (Wilson et al, 1977).…”

Section: Rubella Virusmentioning

confidence: 99%

“…Minor differences, caused 18 25 respectively. Cudworth et al (1977) however perhaps by inherent instability, in relevant alleles estimated the relative risk of B8 and BW15 at 5 59. may even explain the surprising discordancy for Cudworth and Woodrow (1976) (1976) found it was present in 38% of more common in patients with JOD-54% com-those with JOD compared with 23 % in controls in pared with 31 -8% in controls. Others found it to be Parma, while Illeni et al (1977) reported from even more common.…”

Section: Parents and Ancestorsmentioning

confidence: 99%

Juvenile diabetes mellitus: possibility of prevention.

Farquhar¹

1979

Archives of Disease in Childhood

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Ætiology of Juvenile-Onset Diabetes

Cited by 63 publications

References 11 publications

HLA-related heterogeneity in seasonal patterns of diagnosis in Type 1 (insulin-dependent) diabetes

HLA-related heterogeneity in seasonal patterns of diagnosis in Type 1 (insulin-dependent) diabetes

The Pittsburgh insulin-dependent diabetes mellitus registry: Seasonal incidence

Juvenile diabetes mellitus: possibility of prevention.

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