Male-to-female excess in diabetes diagnosed in early adulthood is not specific for the immune-mediated form nor is it HLA-DQ restricted: possible relation to increased body mass index

Weets, Ilse; Autreve, Jan Van; Auwera, Bart J. Van der; Schuit, Frans; Caju, M. V. L. Du; Decochez, Katelijn; Leeuw, Ivo H. De; Keymeulen, Bart; Mathieu, Chantal; Rottiers, R.; Dorchy, Harry; Quartier, Erik; Gorus, Frans

doi:10.1007/s001250051578

Cited by 51 publications

(48 citation statements)

References 27 publications

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“…In all nine centres the estimated male to female ratio of Type 1 diabetes incidence was greater than one in the 15 to 29 age group and greater than in children. In the age group 25 to 29 years the male to female incidence rate ratio was equal to or greater than 1.5 in all centres, although this was not statistically significant in Antwerp and Leicestershire, the two centres with the smallest study populations [21,31]. However, the Belgian Diabetes Registry has shown a significant difference between incidence rates in men and women (p<0.001) in the age range 15 to 39 years [21,32].…”

Section: Discussionmentioning

confidence: 76%

“…A Belgian study failed to confirm the finding of HLA restriction with regard to the male to female excess in young adulthood, but did not completely rule out the suggestion of an interaction between an X-linked genetic factor and high-risk HLA types as a route to diabetes [31].…”

Section: Discussionmentioning

confidence: 95%

“…The reasons for the difference are not clear, but possibly related to oestrogen secretion in women or to a higher metabolic burden due to android fat distribution. Obesity and insulin resistance could precipitate post-pubertal clinical onset of a slowly progressive immune-mediated diabetes [31].…”

Section: Discussionmentioning

confidence: 99%

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The epidemiology of Type 1 diabetes mellitus is not the same in young adults as in children

et al. 2004

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Aims/hypothesis. This prospective study examined the epidemiology of Type 1 diabetes in young adults in Europe. Methods. We ascertained incident cases of Type 1 diabetes in the 15 to 29 years (both inclusive) age group throughout Europe over a period of 2 years. Diabetes registries in nine countries, in which incidence rates for Type 1 diabetes in the 0 to 14 age group were available, took part. Incidence rates were estimated per 100000 person years and standardised for sex and age. Cumulative incidences per 1000 from birth to age 30 were estimated. Heterogeneity between centres was tested with a Poisson regression model. Results. A total of 2112 diabetes cases were ascertained in 1996 and 1997, of which 61.4% were considered to be Type 1 diabetes. Completeness of ascertainment varied from 70 to 90%. Standardised incidence varied from 4.8 per 100000 person years to 13.4 per 100000 person years. The male-female ratio was estimated to be one or more, and in the 25 to 29 age group 1.5 or more in all countries. Cumulative incidences for males and females indicate that the former exceeds the latter from age 24. In the two centres with highest childhood incidence, this applied already from 14 years of age. Conclusions/interpretation. The incidence of Type 1 diabetes in adults is lower than in children and the range of incidence is also reduced, with a less than threefold variation in adults, against an eightfold variation in children. There is a male excess in incidence, especially in the age group 25 to 29 years.

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 95%

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The epidemiology of Type 1 diabetes mellitus is not the same in young adults as in children

et al. 2004

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“…Vitamin D-deficient NOD mice are lighter and smaller at 15 days of age but they reach the same weight as control mice around weaning at 30 days of age. This lower weight during the first days of life, probably due to the vitamin D deficiency of the dams, followed by a more rapid weight gain in the weeks thereafter might be another factor contributing to the diabetes presentation since also in humans, rapid growth and weight gain are implicated in Type 1 diabetes acceleration through increased metabolic demand [39,40,41].…”

Section: Discussionmentioning

confidence: 99%

Vitamin D deficiency in early life accelerates Type 1 diabetes in non-obese diabetic mice

et al. 2004

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Aims/hypothesis. 1,25-dihydroxyvitamin D 3 , the active form of vitamin D, prevents Type 1 diabetes in non-obese diabetic (NOD) mice. Epidemiological data show a threefold increase in human Type 1 diabetes when vitamin D deficiency was present in the first months of life. To evaluate whether a similar dietary deficiency affects diabetes incidence in NOD mice, we generated NOD mice with vitamin D deficiency in early life. Methods. Breeding pairs of NOD mice, as well as their offspring (test mice), were kept in surroundings devoid of ultraviolet light and were fed a vitamin Ddepleted diet for 100 days. Mice were followed for 250 days. Results. At 250 days, 35% (12/35) male and 66% (22/33) female vitamin D-deficient mice were diabetic compared to 15% (6/40, p=0.05) and 45% (13/29, p<0.01) of the control mice. At 100 days no difference in insulitis was seen, but more vitamin D-deficient mice were glucose intolerant. Higher IL1 expression was detected in islets of vitamin D-deficient mice and their peritoneal macrophages had an aberrant cytokine profile (low IL1 and IL6, high IL15). Thymus and lymph nodes of vitamin D-deficient mice contained less CD4 + CD62L + cells. Conclusion/interpretation. Vitamin D status increases the expression of Type 1 diabetes in NOD mice. Our data in NOD mice, as well as human epidemiological data, point to the importance of preventing vitamin D deficiency in early childhood. Controlling this dietary factor could be an easy and safe way to reduce the incidence of Type 1 diabetes in subjects who are genetically at risk. [Diabetologia (2004)

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“…A recent Belgian study however, found that this male bias is age-dependent, is not present in diagnosed patients younger than 15 years of age, and is independent of the presence of anti-islet autoantibodies or HLA type, suggesting that insulin resistance can play a role. [7].…”

Section: Introductionmentioning

confidence: 99%

Genetic control of autoimmunity in Type I diabetes and associated disorders

2002

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Type I (insulin-dependent) diabetes mellitus is a heterogeneous disease with major subdivisions termed Type 1A (immune-mediated) and Type 1B. Immunemediated diabetes is also heterogeneous with ªmono-genicº, oligogenic, and polygenic forms present in humans and in animal models. Single-gene mutations of two transcription factors have been recently identified in rare syndromes of autoimmunity with type 1A diabetes: autoimmune polyendocrine syndrome type 1 (APS-1) and X-linked polyendocrinopathy, immune dysfunction and diarrhoea (XPID). For more common forms of diabetes, susceptibility loci within the major histocompatibility complex and at the insulin locus have been identified. Both DQ* and DR* alleles provide susceptibility and certain alleles dominant protection. In the Diabetes Autoimmunity Study of the Young approximately 50 % of the siblings studied with the highest-risk HLA genotype develop anti-islet autoantibodies by age 3. Insulin could be a crucial autoantigen related to genetic susceptibility. The crystal structure of the high-risk allele, HLA-DQ8, complexed with an insulin peptide has just been reported. Insulin production by macrophage-dendritic cells within the thymus and lymphoid organs could underlie insulin gene polymorphisms influencing the risk of diabetes. Genome-wide scans for linkage in animal models and in humans have not conclusively identified other susceptibility genes though many loci have been implicated. We favour the hypothesis that HLA is a major determinant of susceptibility in animal models and in most families, and that the search for diabetogenes should concentrate on unique families to decrease heterogeneity and favour the eventual discovery of genes influencing risk. [Diabetologia (2002) 45:605±622]

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Male-to-female excess in diabetes diagnosed in early adulthood is not specific for the immune-mediated form nor is it HLA-DQ restricted: possible relation to increased body mass index

Cited by 51 publications

References 27 publications

The epidemiology of Type 1 diabetes mellitus is not the same in young adults as in children

The epidemiology of Type 1 diabetes mellitus is not the same in young adults as in children

Vitamin D deficiency in early life accelerates Type 1 diabetes in non-obese diabetic mice

Genetic control of autoimmunity in Type I diabetes and associated disorders

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