Progression to diabetes in relatives with islet autoantibodies. Is it inevitable?

Gardner, Spencer M.; Gale, E. A. M.; Williams, A. J. K.; Gillespie, Kathleen M.; Lawrence, Katherine E.; Bottazzo, Gian Franco; Bingley, P. J.

doi:10.2337/diacare.22.12.2049

Cited by 63 publications

(52 citation statements)

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“…The quest to identify one type of autoantibody as a better predictor than another has failed, because no clear order of appearance has been detected. Rather, several studies taken together suggest that the number of autoantibodies is predictive rather than the order of their appearance (16). This is particularly true for young children, since the age (17,18) as well as sex (19) affect the expression of both insulin and IA-2 autoantibodies (rev.…”

Section: Islet Cell Autoantibodies Predict Autoimmune Diabetesmentioning

confidence: 99%

“…in 4). At this point, it is not clear whether specific combinations of autoantibodies confer different degrees of risk (20) or whether the quantity of different autoantibodies present in an individual is more important than the specific combination (16). In DPT-1, it was shown that GAD65Ab positivity is the most sensitive marker for detecting multiple antibody positivity, in that 91% of individuals who were found to be GAD65Ab positive were also positive for other antibodies, compared with 82% of ICA ϩ individuals (21).…”

Section: Islet Cell Autoantibodies Predict Autoimmune Diabetesmentioning

confidence: 99%

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Autoantibodies in Diabetes

et al. 2005

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Islet cell autoantibodies are strongly associated with the development of type 1 diabetes. The appearance of autoantibodies to one or several of the autoantigens-GAD65, IA-2, or insulin-signals an autoimmune pathogenesis of ␤-cell killing. A ␤-cell attack may be best reflected by the emergence of autoantibodies dependent on the genotype risk factors, isotype, and subtype of the autoantibodies as well as their epitope specificity. It is speculated that progression to ␤-cell loss and clinical onset of type 1 diabetes is reflected in a developing pattern of epitopespecific autoantibodies. Although the appearance of autoantibodies does not follow a distinct pattern, the presence of multiple autoantibodies has the highest positive predictive value for type 1 diabetes. In the absence of reliable T-cell tests, dissection of autoantibody responses in subjects of genetic risk should prove useful in identifying triggers of islet autoimmunity by examining seroconversion and maturation of the autoantibody response that may mark time to onset of type 1 diabetes. The complexity of the disease process is exemplified by multiple clinical phenotypes, including autoimmune diabetes masquerading as type 2 diabetes in youth and adults. Autoantibodies may also provide prognostic information in clinically heterogeneous patient populations when examined longitudinally. Diabetes 54 (Suppl. 2):S52-S61, 2005

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Section: Islet Cell Autoantibodies Predict Autoimmune Diabetesmentioning

confidence: 99%

Section: Islet Cell Autoantibodies Predict Autoimmune Diabetesmentioning

confidence: 99%

Autoantibodies in Diabetes

et al. 2005

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“…In this context it is striking that first-degree relatives who have not developed islet autoantibodies by the age of 18 have a very low risk of ever developing diabetes, even though they may share 50% or more of the genetic risk and a large part of the environmental risk (by living in the same family) as their affected siblings, children or parents [6,7]. The exact risk has not been computed as this would involve following a very large number of antibody-negative persons for a very long time, but the risk is sufficiently low for antibody-negative first-degree relatives to be excluded from follow-up in the TrialNet Natural History Study [8].…”

Section: Introductionmentioning

confidence: 99%

IFN-γ and IL-10 islet-antigen-specific T cell responses in autoantibody-negative first-degree relatives of patients with type 1 diabetes

Marquesini

Connor

et al. 2010

Diabetologia

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Aims/hypothesis Islet antibody-negative first-degree relatives of type 1 diabetes patients have a very low risk of developing diabetes. We studied the balance between IFN-γ (proinflammatory) and IL-10 (regulatory) T cell responses in these participants. Methods Peripheral blood T cells from adult (18-50 years old, n=40) DRB1*0401-positive first-degree relatives negative for GAD and tyrosine phosphatase-like insulinoma antigen 2 (IA-2) antibodies were tested for IFN-γ and IL-10 responses in a sensitive cytokine enzyme-linked immunospot assay against a panel of seven peptide epitopes derived from IA-2 and proinsulin. Comparison was made with HLAmatched newly diagnosed type 1 diabetic patients (n=42) and healthy controls (n=39). Results First-degree relatives and newly diagnosed type 1 diabetic patients displayed a similar frequency of IFN-γ responses to the peptide panel and both were significantly greater than in healthy controls (relatives 9.6%, patients 11.8%, controls 4.0%, p=0.003). First-degree relatives and newly diagnosed type 1 diabetic patients also showed similar frequencies of IL-10 responses, which were significantly lower than in healthy controls (relatives 7.1%, patients 9.0%, controls 15.8%, p=0.003). However, individual IL-10 responses of first-degree relatives were similar in size to those in healthy controls and larger than those in newly diagnosed type 1 diabetic patients (relatives median 29 spot-forming cells/1×10 6 peripheral blood mononuclear cells, controls 33, patients 11, p=0.02). Conclusions/interpretation Taken together, these results suggest that antibody-negative first-degree relatives have a balance of proinflammatory and regulatory T cells, which is intermediate between that of newly diagnosed type 1 diabetic patients and healthy controls. This suggests that even a moderate regulatory response may be sufficient to prevent the development of clinical type 1 diabetes in genetically predisposed individuals.

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“…In fact, family members who expressed these three auto antibodies have a 75% of five-year risk of diabetes compared with a 25% of five-year risk in relatives who expressed one of them (33). These auto antibodies may be present for years before the diagnosis of diabetes and the risk for diabetes does not decline over time (34)(35)(36)(37). Among the genes mentioned above, CTLA-4 genes may play an important role in synergy with HLA for the development of both T1DM and auto immune thyroids (38,39).…”

Section: Contextmentioning

confidence: 99%

Type 1 Diabetes Mellitus Associated With Autoimmune Thyroid Disorders in Iranian Children: A Review

Zamanfar¹,

Aarabi²,

Sadeghian³

2015

J Pediatr Rev

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Context: Type one diabetes mellitus (T1DM) is an autoimmune disorder that is yet the most common type of diabetes in children and adolescents. Several genetic risk factors have been associated with T1DM, auto immune thyroiditis and other autoimmune disorder. Among autoimmune disorders, autoimmune thyroid disease (ATD) is the most frequent disorder associated with T1DM. Its prevalence varies depending on age, sex and ethnic origin of the subjects and is considerably higher than the general population and increases with duration of T1DM. The aim of this study was to review the prevalence of ATD in Iranian children with T1DM compared with other countries. Evidence Acquisition: We conducted a review on all papers published on the association between autoimmune thyroiditis and T1DM, which was available on Google Scholar, Scientific Information Database (SID), Magiran and Iran Medex databases up to June 2014. Both Persian and English articles were checked. The searched terms were: diabetes mellitus, autoimmune thyroiditis, prevalence, frequency, Iranian children and adolescents. All papers which were done on patients with age under 20 years old and have used Anti-TPO and Anti-TG to evaluate patients were included. Results: Six papers met all the criteria. A total of 736 participants were included in this review. After review of all the papers, the prevalence of Anti-TPO was reported between 8% and 30% and Anti-TG was reported 6.06% to 23.6% in diabetic children in Iran. Conclusions: Autoimmune thyroid disorders are the most prevalent immunological diseases in patients with type 1 diabetes. All these studies have shown a higher prevalence of the disorder in patients with T1DM compared to the Iranian healthy population. Anti-TPO reported between 8% and 30% and Anti-TG reported 6.06% to 23.6% in diabetic children in Iran that was similar to the studies in other countries.

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Progression to diabetes in relatives with islet autoantibodies. Is it inevitable?

Cited by 63 publications

References 0 publications

Autoantibodies in Diabetes

Autoantibodies in Diabetes

IFN-γ and IL-10 islet-antigen-specific T cell responses in autoantibody-negative first-degree relatives of patients with type 1 diabetes

Type 1 Diabetes Mellitus Associated With Autoimmune Thyroid Disorders in Iranian Children: A Review

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