Value of Insulin Autoantibodies as Serum Markers for Insulin-Dependent Diabetes Mellitus

Wilkin, Terence J.; Armitage, Mary; Casey, Cecily; Pyke, David A.; Hoskins, Paul; Rodier, M.; Díaz, José‐Luis; Leslie, R. D. G.

doi:10.1016/s0140-6736(85)92086-0

Cited by 135 publications

(78 citation statements)

References 14 publications

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“…Furthermore, ICA levels may fluctuate or be only transiently high [46], and they correlate poorly with Beta-cell function [43]. IAA, even though detectable in some patients before onset are strongly correlated with age but poorly associated with Beta-cell dysfunction or future Type 1 diabetes in ICA-negative individuals [43,44]. 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].…”

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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“…Islet cell autoantibodies (ICA), especially those which fix complement (CF-ICA), are considered to be serological markers of this silent autoimmune aggression against the islets of Langerhans in first degree relatives of Type 1 diabetic patients [4], in autoimmune patients [5] and in identical twins discordant for Type I diabetes [6]. Insulin autoantibodies (IAA) have also been described and detected in newly diagnosed Type I diabetic patients before treatment [7], in identical twins [8] and in first degree relatives of Type i diabetic patients [9,10], but their predictive value in these subjects is still under discussion.…”

Section: Discussionmentioning

confidence: 99%

Islet cell and insulin autoantibodies in organ-specific autoimmune patients. Their behaviour and predictive value for the development of Type 1 (insulin-dependent) diabetes mellitus. A 10-year follow-up study

Betterle¹,

Presotto²,

Pedini³

et al. 1987

Diabetologia

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Summary.To evaluate the behaviour and predictive value of islet cell and insulin autoantibodies in patients with organspecific autoimmune diseases, we followed 21 non-diabetic subjects for a mean period of 84 4-27 months. Ten patients were persistently seropositive for complement-fixing islet cell antibodies and high titres of immunoglobulin G islet cell antibodies (>--1 : 8). The prevalence of persistent insulin autoantibodies in this group was 67%. Seven patients (70%) developed Type I (insulin-dependent) diabetes mellitus after a latency period of 2-60 months. The predictive value of complement-fixing islet cell antibodies was 65%, and in the presence of both complement-fixing islet cell and insulin autoantibodies the predictive value rose to 76%. Eleven patients were seronegative for complement-fixing islet cell antibodies and had low immunoglobulin G islet cell antibodies titres (< 1 : 8) that were either persistent or transient, or that fluctuated during follow-up. The prevalence of persistent insulin autoantibodies in this group was 45%; only one subject developed Type 1 diabetes. The predictive value of persistent islet cell antibodies (complement-fixing positive/negative) was 54%, and it rose to 70% when both islet cell and insulin autoantibodies were present. Individuals with only insulin autoantibodies or immunoglobulin G islet cell antibodies did not develop diabetes mellitus. A high frequency of HLA-DR3 and/or DR4 was found in patients who developed diabetes mellitus. Thus, the presence of both islet cell and insulin autoantibodies in patients with organ-specific autoimmune disease appears to confer the highest risk of progression toward Type 1 diabetes.

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“…Other investigations of non-diabetic MZ co-twins of diabetic twins have shown even higher frequencies of autoantibodies. For example, of 11 non-diabetic MZ co-twins of diabetic twins, 100 % (11/11) had IAA in at least one of two blood samples taken at different times [35]. Similarly, another study found that of 12 MZ co-twins of diabetic twins who had remained non-diabetic for 8±39 years, 66 % (8/12) nevertheless had persistent autoantibodies or evidence of beta-cell damage or both [36].…”

Section: Evidence For a Genetic Basis: Family And Twin Studies Of Typmentioning

confidence: 97%

Genetic linkage and association studies of Type I diabetes: challenges and rewards

Field

2002

Diabetologia

104

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Type I diabetes (formerly called insulin-dependent diabetes mellitus) results from the autoimmune destruction of the insulin-producing beta cells of the pancreas. It is now known that Type I diabetes is a genetically complex disease, i. e. a disease caused by multiple genes interacting with non-genetic (environmental and stochastic) factors. Family studies have clearly shown a genetic basis but inheritance of the disease does not follow a simple mendelian single-locus pattern. Population and family studies also suggest that most (perhaps all) affected individuals are genetically predisposed to Type I diabetes, particularly through HLA region genes. However, non-genetic factors appear to be required to precipitate the disease in these genetically susceptible persons because in monozygote (MZ) twin pairs in which one twin has Type I diabetes the MZ twin concordance rate is less than 100 %. It is not clear whether there are any purely genetic cases of Type I Diabetologia (2002) AbstractFamily and twin studies have shown clearly that Type I (insulin-dependent) diabetes mellitus has a genetic basis. However, only within the past decade has it been possible to systematically attempt to identify the genes that increase susceptibility to this disorder using linkage and association analysis of genetic markers distributed across the genome. More than 20 putative diabetes-predisposing genes have been localised in addition to HLA region susceptibility genes detected more than 25 years ago. Unfortunately, the effects of most diabetes-predisposing genes are weak, with the exception of HLA region susceptibility genes (which contribute about half of the genetic risk). The overall effects of diabetes-predisposing genes could be weak because the susceptibility gene occurs in only a small proportion of diabetic patients or the susceptibility gene (although it might be common) produces only a modest increase in risk, probably by acting in concert with other such genes to cause disease. The weak effects of these genes have made them difficult to locate, difficult to confirm in independent studies and difficult to isolate by genetic procedures. This paper summarizes the major challenges that have faced geneticists in mapping Type I diabetes genes, and reviews the progress achieved to date. The rewards of the genetic studies will be twofold: increased understanding of the causes of Type I diabetes, facilitating creation of preventative therapies, and enabling clinicians in the future to use genetic information to predict which children are predisposed to diabetes in order to target them for preventative therapies. [Diabetologia (2002) 45: 21±35]

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Value of Insulin Autoantibodies as Serum Markers for Insulin-Dependent Diabetes Mellitus

Cited by 135 publications

References 14 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

Islet cell and insulin autoantibodies in organ-specific autoimmune patients. Their behaviour and predictive value for the development of Type 1 (insulin-dependent) diabetes mellitus. A 10-year follow-up study

Genetic linkage and association studies of Type I diabetes: challenges and rewards

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