Autoimmunity and familial risk of type 1 diabetes

Hämäläinen, Anu‐Maaria; Knip, Mikael

doi:10.1007/s11892-002-0025-2

Cited by 39 publications

(28 citation statements)

References 49 publications

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“…(Adapted from von Herrath et al 2007;with permission. ) remains that 85% of new T1D cases reside in individuals with no known family history for the disease (Hämäläinen and Knip 2002). Another interesting observation is that differences in risk are also dependent on which parent has diabetes-children of T1D mothers have only a 2% risk of developing T1D, whereas children of T1D fathers have a 7% risk (Redondo et al 2001).…”

Section: Geneticsmentioning

confidence: 99%

The Pathogenesis and Natural History of Type 1 Diabetes

Atkinson

2012

Cold Spring Harbor Perspectives in Medicine

250

176

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Section: Geneticsmentioning

confidence: 99%

The Pathogenesis and Natural History of Type 1 Diabetes

Atkinson

2012

Cold Spring Harbor Perspectives in Medicine

250

176

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“…The increased cumulative risk in offspring of type 1 diabetic fathers (4 -9%) compared with offspring of type 1 diabetic mothers (ϳ2-3%) has been frequently observed and published (9,(17)(18)(19). However, the reason for this parental sex difference is still not known, although several hypotheses have been proposed (e.g., genomic imprinting and immunologic tolerance in utero) (20 -22).…”

Section: Discussionmentioning

confidence: 99%

Secondary Attack Rate of Type 1 Diabetes in Colorado Families

Steck¹,

Barriga²,

Emery³

et al. 2005

Diabetes Care

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OBJECTIVE -Families of children diagnosed with type 1 diabetes require counseling concerning type 1 diabetes risk in nondiabetic siblings and parents. No U.S. population-specific life-table risk estimates are currently available for parents, and those for siblings (2-6% by age 20 years) are based on family studies completed before 1987.RESEARCH DESIGN AND METHODS -We analyzed family histories of 1,586 patients in Colorado with type 1 diabetes (83% non-Hispanic white, 10% Hispanic, and 7% other) diagnosed before 16 years of age and interviewed during 1999 -2002. Families of probands with type 2, undetermined, or secondary diabetes (n ϭ 53) or those with incomplete data (n ϭ 137) were excluded. The median age at onset of the proband was 7.1 years and the median diabetes duration 3.5 years. Cumulative risk estimates were calculated using survival analysis for 2,081 full siblings and 3,016 biological parents.RESULTS -In siblings, the overall risk of type 1 diabetes by age 20 years was 4.4%, but it was significantly (P Ͻ 0.0001) higher in siblings of probands diagnosed under age 7 years than in those diagnosed later. In parents, the overall risk by age 40 years was 2.6% and higher in fathers (3.6%) than in mothers (1.7%) of probands (P Ͻ 0.001). Similar to siblings, the risk was also higher (P ϭ 0.006) in parents of probands diagnosed Ͻ7 years of age than in those diagnosed later.CONCLUSIONS -Current risks of type 1 diabetes in Colorado siblings and parents of type 1 diabetic probands are higher than in the 1982 Pittsburgh study but similar to contemporary European rates. Recurrence risk of type 1 diabetes is significantly higher in first-degree relatives of probands diagnosed at a young age. Diabetes Care 28:296 -300, 2005O f the U.S. general population, 0.3% develop type 1 diabetes by the age of 20 years (1). The risk among siblings of type 1 diabetic patients is 10 -20% higher, up to 3-6% by age 20 years (2-4) and increases further to 10% by age 60 years (5). The cumulative risk to parents of type 1 diabetic patients is less elevated than among siblings and has been reported to be between 3 and 5% by the age 40 years to lifetime (2,4,6,7).Previously published cumulative risk estimates among first-degree relatives (FDRs) vary widely by age, ethnicity, and period of time and also likely vary due to differences in methods of ascertainment.Currently available risk estimates for the U.S. population are mainly based on family studies completed before 1987 (2,3) and may be outdated, since the incidence of type 1 diabetes has been increasing worldwide by 3-5% annually (8).In Europe, children with an early age of onset seem to have more siblings and parents affected by type 1 diabetes (9). In a recent U.K. study, survival analysis stratified according to the age at diagnosis of the proband gave much higher risk estimates in siblings of probands diagnosed before age 5 years (cumulative risk by age 20 years 11.7% compared with 3.6% for ages 5-9 years and 2.3% for ages 10 -14 years) (4); the same difference by the proband's a...

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“…Differences in risk are also developed in the parents of children. Children who have their mother suffering from T1D have 2% risk of developing T1D, but children whose fathers have diabetes have a greater risk [12]. No single gene is predicted to develop diabetes, but more than two dozen susceptibility loci have been associated with susceptibility to T1D.…”

Section: Etiologymentioning

confidence: 99%

Immunotherapy in Autoimmune Diabetes

Haque¹,

Sandhu²,

Ravi³

et al. 2017

Immunopathogenesis and Immune-Based Therapy for Selected Autoimmune Disorders

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Autoimmune diabetes is a chronic autoimmune disease caused by the loss or selective destruction of the insulin-producing cells, called pancreatic beta cells. Damage to beta cells results in an absence or insufficient production of insulin produced by the body.Most cases of autoimmune diabetes have an autoimmune basis, and the immune system mistakenly attacks and destroys beta cells. The immune system plays a critical role in controlling the development of autoimmune diabetes. Over the past years there have been significant progress and an accumulation of scientific evidence for the concept of immunotherapy. Immunotherapy for the prevention and treatment of autoimmune diabetes has become the main focus of the research community. Three regimens of immunotherapy have been investigated: (1) Antigen-specific vaccines: Insulin-related molecules have attracted great interest in vaccine development, including the whole recombinant human GAD65 (rhGAD65) and the DiaPep277 peptide of HSP60. (2) Systemic immunomodulators: A large number of non-antigen-specific immunomodulators have been studied, including monoclonal anti-CD3 antibody, anti-CTLA-4 Ig, TNF-a, IFN-a, IL-1R antagonist, regulatory T cells, and dendritic cells. (3) Combination treatments: Combination therapies have the ability to enhance efficacy and will become the standard of care for autoimmune diabetes. Development of safe and efficient prevention of autoimmune diabetes is a general public health object in modern countries now. Although large numbers of preventive modalities including immunotherapy have been accomplished in animal models of autoimmune diabetes, prevention of human autoimmune diabetes remains indefinable. Genetic and environmental factors that control the relapsing-remitting course of β-cell destruction, terminating in complete insulin addiction are being determined. In the long run, initial prevention of islet autoimmunity will likely be the optimal approach to the prevention of autoimmune diabetes. However, environmental causes of islet autoimmunity need to be well stated. Modest predictive assessment of the existing genetic screening tools also means that the number of children requiring intervention will stay great, concerning the number of autoimmune diabetes cases prohibited. Nevertheless, combination treatments are more likely to be used for autoimmune diabetes. Primary systemic immunosuppression followed by antigen-specific induction of tolerance or islet regeneration is a sound approach.

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Autoimmunity and familial risk of type 1 diabetes

Cited by 39 publications

References 49 publications

The Pathogenesis and Natural History of Type 1 Diabetes

The Pathogenesis and Natural History of Type 1 Diabetes

Secondary Attack Rate of Type 1 Diabetes in Colorado Families

Immunotherapy in Autoimmune Diabetes

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