A Prospective Study of the Development of Diabetes in Relatives of Patients with Insulin-Dependent Diabetes

Wj, Riley; Nk, Maclaren; Krischer, Jeffrey P.; Rp, Spillar; Jh, Silverstein; Da, Schatz; Schwartz, Sherwyn; Malone, John I.; Shah, Shirish C.; Vadheim, Constance M.

doi:10.1056/nejm199010253231704

Cited by 283 publications

(208 citation statements)

References 30 publications

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“…Individuals with not only high titre ICA but also IAA and/or a decrease in first-phase insulin response have been reported to be at higher risk for Type 1 diabetes [14,45,46]. A large study on ICA in first-degree relatives showed that ICA-positive relatives in multiplex families are at a higher risk for developing Type 1 diabetes than relatives of simplex families [47]. Our finding that 64K antibodies correlate with progressively impaired Beta-cell function and high risk for Type 1 diabetes suggests that 64K antibodies may be a more specific marker 731 for autoimmune processes leading to Type 1 diabetes than ICA and/or IAA.…”

Section: Resultsmentioning

confidence: 99%

Risk for developing Type 1 (insulin-dependent) diabetes mellitus and the presence of islet 64K antibodies

et al. 1991

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Summary. First-degree relatives of Type i (insulin-dependent) diabetic patients are at increased risk for developing clinical diabetes. The presence of islet cell or insulin autoantibodies further identifies relatives at greater risk, but not all immunologic-marker-positive relatives progress to disease. Beta-cell dysfunction, however, seems to be more prevalent than clinical Type 1 diabetes, since stable subclinical pancreatic Beta-cell dysfunction may occur. Antibodies against a Mr 64,000 (64K) islet Beta-cell protein, identified as glutamic acid decarboxylase, have been reported both at and several years prior to the clinical onset of Type i diabetes. We measured 64K antibodies in first-degree relatives with varying degrees of Beta-cell dysfunction and risk for subsequent Type i diabetes to determine whether 64K antibodies improve the predictive power of islet cell antibodies and/or insulin autoantibodies. In the Seattle Family Study first-degree relatives of Type 1 diabetic patients are followed prospectively using detailed Beta-cell function tests, insulin sensitivity, quantitative evaluation of islet cell antibodies and fluid phase assay insulin autoantibodies. 64K antibodies were measured using dog islets. Relatives were selected, based on Beta-cell function to represent individuals at high (n = 6) and low (n = 30) risk for subsequent Type 1 diabetes. The 30 low-risk individuals followed-up for 78 months, had stable Beta-cell function, and six (20%) were negative for all autoantibodies, ten (33%) were positive for insulin autoantibodies, 16 (53%) were islet cell antibody positive While six (20%) were positive for 64K antibodies. In contrast, of the six subjects with progressively declining Beta-cell function who are therefore at high risk, two of whom have already developed Type i diabetes, two (33%) were positive for insulin autoantibodies, four (67%) were islet cell antibody positive, while all six (100%) were positive for 64K antibodies. We conclude that antibodies to the Mr 64,000 islet protein correlate with progressive Beta-cell dysfunction more closely than either islet cell antibodies or insulin autoantibodies, but can sometimes be present in individuals whose Beta-cell function remains stable over several years.

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Section: Resultsmentioning

confidence: 99%

Risk for developing Type 1 (insulin-dependent) diabetes mellitus and the presence of islet 64K antibodies

et al. 1991

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“…Such non-genetic factors may either initiate autoimmunity or accelerate/ precipitate beta cell destruction [7]. Follow-up studies of first-degree relatives of type-1 diabetic patients have shown that autoimmunity often precedes clinical disease by many years [8][9][10]. Not all individuals that carry autoantibodies towards the beta cells ultimately develop clinical diabetes, and the signs of autoimmunity may disappear [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Can we slow the rising incidence of childhood-onset autoimmune diabetes? The overload hypothesis

2005

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“…In 719 such individuals in the Bart's-Windsor/Bart's-Oxford Study, 2 of 679 ICA negative subjects have developed Type 1 diabetes compared with 16 of 40 ICA positive subjects [9]. Data from Gainesville agree -with 70% of people with ICA levels in excess of 20 JDF units developing Type 1 diabetes, 35% within 5 years of detection [10]. A few false positives may account for the 10-30% of ICA positive subjects who do not progress to Type 1 diabetes.…”

Section: $62mentioning

confidence: 86%

Scientific and ethical consequences of disease prediction

1992

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A Prospective Study of the Development of Diabetes in Relatives of Patients with Insulin-Dependent Diabetes

Abstract: Nondiabetic relatives of probands with IDDM who are in the first two decades of life, are members of multiplex pedigrees, and have increased titers of islet-cell antibodies are the most likely to contract IDDM themselves.

Cited by 283 publications

References 30 publications

Risk for developing Type 1 (insulin-dependent) diabetes mellitus and the presence of islet 64K antibodies

Risk for developing Type 1 (insulin-dependent) diabetes mellitus and the presence of islet 64K antibodies

Can we slow the rising incidence of childhood-onset autoimmune diabetes? The overload hypothesis

Scientific and ethical consequences of disease prediction

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