High frequency of persisting or increasing islet-specific autoantibody levels after diagnosis of type 1 diabetes presenting before 40 years of age. The Belgian Diabetes Registry (original) (raw)
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Diabetic Medicine, 2011
Aim Maturity-onset diabetes of the young is a monogenic form of familial, young-onset diabetes. It is rare (1% diabetes) and may be misdiagnosed as Type 1 diabetes and inappropriately treated with insulin. Type 1 diabetes is characterized by the presence of islet autoantibodies, including glutamate decarboxylase (GAD) and islet antigen-2 (IA-2) antibodies. The prevalence of islet autoantibodies is unknown in maturity-onset diabetes of the young and may have the potential to differentiate this form of diabetes from Type 1 diabetes. The aim of this study was to determine the prevalence of GAD and IA-2 antibodies in patients with maturity-onset diabetes of the young and Type 1 diabetes. Methods We measured plasma GAD and IA-2 antibodies in 508 patients with the most common forms of maturity-onset diabetes of the young (GCK: n = 227; HNF1A: n = 229; HNF4A: n = 52) and 98 patients with newly diagnosed Type 1 diabetes (diagnosed < 6 months). Autoantibodies were considered positive if ‡ 99th centile of 500 adult control subjects.
Diabetologia, 1987
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.
Diabetologia, 1994
An 11-year prospective study was carried out in 180 non-diabetic patients with organ-specific autoimmune diseases to evaluate islet cell antibodies in predicting Type i (insulin-dependent) diabetes mellitus. Islet cell antibodies were characterised according to titres, persistence, complement-fixing ability, and pattern. During follow-up, 14 of 46 patients with islet cell antibodies persistently greater than 5 Juvenile Diabetes Foundation Units (JDF-U) (30.4 %), none of 23 with islet cell antibodies between 2.5 and 5 JDF-U or fluctuating, and 3 of 109 without islet cell antibodies (2.7 %), developed diabetes. The cumulative risk of developing diabetes was 70 %, 0 %, and 4 %, resp ectively. All the patients who developed diabetes were females. Eight progressed to insulin-dependence acutely, four showed a transient period of non-insulin-dependence, while two were still insulin-free. No difference was found in titres of islet cell antibodies for the risk of diabetes. Comple-ment-fixing islet cell antibodies enhanced the cumulative risk for the disease in patient s with conventional islet cell antibodies at low-middle ( > 2.5-40 JDF-U), but not at high ( > 80 JDF-U) titres. Forty-two patients with islet cell antibodies were investigated for the whole or the selective pattern. In the presence of the whole pattern the cumulative risk for diab et es rose to 100 %, while with the selective pattern it declined to 34 %. The whole pattern was found in 83 % of patients who developed Type 1 diabetes acutely. In patients with organ-specific autoimmune diseases, the whole islet cell antibody pattern greatly enhances the prediction for diabetes. [Diabetologia (1994) 37: 95-103]
Metabolism, 1998
The age at diagnosis of insulin-dependent diabetes mellitus (type I DM) varies between childhood and adulthood. The aim of this study was to define the immunologic and metabolic characteristics of the disease according to the age at which it is diagnosed. We evaluated the residual 13-cell function (basal and stimulated C-peptide) and frequency of two major islet cell-related autoantibodies, glutamic acid decarboxylase (GAD) and tyrosine phosphatase-like molecule (IA-2ic), at the onset of type I DM. A population-based study was performed with 235 consecutive cases of recent-onset (<4 weeks) type I DM (ages 5 to 45 years) diagnosed in the Lazio region of central Italy. Five age groups were considered: patients diagnosed between ages 5 and 7 years (n = 10), 7 and 10 years (n = 38), 10 and 17 years (n = 94), 17 and 20 years (n = 17), and 20 and 45 years (n = 76). Patients diagnosed before puberty had significantly reduced C-peptide secretion compared with patients diagnosed at a later age (P < .02). Glycosylated hemoglobin (HbAlc) did not differ at diagnosis between the different age groups. Patients diagnosed at puberty or after required significantly less insulin compared with younger patients (P < .04). GAD antibodies were found in 65% and IA-2ic antibodies in 59% of patients. GAD antibodies tended to be more frequent in patients diagnosed after age 17 compared with younger patients (P = .05), while IA-2ic antibodies were not age-related. These data suggest that (1) the extent of 13-cell damage differs between patients diagnosed before and after puberty, the process being more destructive in children less than 7 years of age, when C-peptide levels are the lowest; and (2) residual 13-cell function at diagnosis is not influenced by the presence or absence of islet cell-related antibodies. These findings have implications for trials in type I DM diagnosis aimed at protecting 13 cells from end-stage destruction and in attempts to prevent the disease in susceptible individuals.
Autoimmunity Reviews, 2009
Type 1 diabetes mellitus (T1DM) has been shown to be a disease characterized by immunemediated destruction of the insulin-producing islet beta-cells (β-cells) in the pancreas. Intensive studies, in both patients and animal models are trying to elucidate the specific antigenic targets that are responsible for islet cell autoimmunity. So far, the most important molecules that have been recognized are the native insulin, the 65-kDa form of glutamic acid decarboxylase (GAD 65) and the insulinoma-antigen 2 (IA-2). Identification of those specific autoantibodies that are involved in the primary immunological events of the autoimmune disease process will allow the development of novel diagnostic procedures for early detection and initiation of potential therapy prior to irreversible loss of β-cells. Within the framework of polyglandular disorders, T1DM may coexist with other organ specific autoimmune diseases such as autoimmune thyroid disease (ATD), autoimmune gastritis (AG), celiac disease (CD) and Addison's disease (AD), which are associated with the production of organ-specific autoantibodies. So, as a subset of patients with those autoantibodies will develop clinical disease, screening T1DM patients could prognosticate morbidity relative to unrecognised clinical entities. The close follow-up of patients with organ-specific autoantibodies could lead to seasonable identification of those requiring therapy.