38
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      GAD Antibody Positivity Predicts Type 2 Diabetes in an Adult Population

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          OBJECTIVE

          To evaluate the significance of GAD antibodies (GADAs) and family history for type 1 diabetes (FH T1) or type 2 diabetes (FH T2) in nondiabetic subjects.

          RESEARCH DESIGN AND METHODS

          GADAs were analyzed in 4,976 nondiabetic relatives of type 2 diabetic patients or control subjects from Finland. Altogether, 289 (5.9%) were GADA +—a total of 253 GADA + and 2,511 GADA subjects participated in repeated oral glucose tolerance tests during a median time of 8.1 years. The risk of progression to diabetes was assessed using Cox regression analysis.

          RESULTS

          Subjects within the highest quartile of GADA + (GADA + high) had more often first-degree FH T1 (29.2 vs. 7.9%, P < 0.00001) and GADA + type 2 diabetic (21.3 vs. 13.7%, P = 0.002) or nondiabetic (26.4 vs. 13.3%, P = 0.010) relatives than GADA subjects. During the follow-up, the GADA + subjects developed diabetes significantly more often than the GADA subjects (36/253 [14.2%] vs. 134/2,511 [5.3%], P < 0.00001). GADA + high conferred a 4.9-fold increased risk of diabetes (95% CI 2.8–8.5) compared with GADA —seroconversion to positive during the follow-up was associated with 6.5-fold (2.8–15.2) and first-degree FH T1 with 2.2-fold (1.2–4.1) risk of diabetes. Only three subjects developed type 1 diabetes, and others had a non–insulin-dependent phenotype 1 year after diagnosis. GADA + and GADA subjects did not clinically differ at baseline, but they were leaner and less insulin resistant after the diagnosis of diabetes.

          CONCLUSIONS

          GADA positivity clusters in families with type 1 diabetes or latent autoimmune diabetes in adults. GADA positivity predicts diabetes independently of family history of diabetes, and this risk was further increased with high GADA concentrations.

          Related collections

          Most cited references30

          • Record: found
          • Abstract: found
          • Article: not found

          Incidence of childhood type 1 diabetes worldwide. Diabetes Mondiale (DiaMond) Project Group.

          To investigate and monitor the patterns in incidence of childhood type 1 diabetes worldwide. The incidence of type 1 diabetes (per 100,000 per year) from 1990 to 1994 was determined in children 350-fold variation in the incidence among the 100 populations worldwide. The global pattern of variation in incidence was evaluated by arbitrarily grouping the populations with a very low ( or =20/100,000 per year) incidence. Of the European populations, 18 of 39 had an intermediate incidence, and the remainder had a high or very high incidence. A very high incidence (> or =20/ 100,000 per year) was found in Sardinia, Finland, Sweden, Norway Portugal, the U.K., Canada, and New Zealand. The lowest incidence (<1/100,000 per year) was found in the populations from China and South America. In most populations, the incidence increased with age and was the highest among children 10-14 years of age. The range of global variation in the incidence of childhood type 1 diabetes is even larger than previously described. The earlier reported polar-equatorial gradient in the incidence does not seem to be as strong as previously assumed, but the variation seems to follow ethnic and racial distribution in the world population.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Antibodies to glutamic acid decarboxylase reveal latent autoimmune diabetes mellitus in adults with a non-insulin-dependent onset of disease.

            The classification of adults with diabetes mellitus can be invalidated by patients who initially present as NIDDM but who later become frankly insulin dependent. In some of these, the pathogenesis could be similar to that in IDDM, namely autoimmune destruction of the pancreatic beta-cells. We studied 102 patients > 35 yr of age at diabetes onset who had initially been nonketotic and non-insulin-dependent for > or = 6 mo. They were classified according to glucagon-stimulated C-peptide levels into an insulin-deficient group (n = 33) and a non-insulin-deficient group (n = 69). We measured antibodies to GAD, islet cell cytoplasm, thyroid antigens, and gastric parietal cells in both groups. Anti-GAD was significantly higher in the insulin deficient group, 76% (25 of 33), than in the non-insulin deficient group, 12% (8 of 69), and this difference was substantially greater than that shown for ICAs. Thus, in a proportion of adults who present with NIDDM, a slowly evolving autoimmune insulitis can be revealed by testing for anti-GAD. This could have important connotations not only for early intervention, but also for the correct classification of diabetes.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              High titer of autoantibodies to GAD identifies a specific phenotype of adult-onset autoimmune diabetes.

              The aim of the present study was to define heterogeneity of adult-onset autoimmune diabetes based on characterization of GAD antibodies (GADAs). Patients enrolled in a nationwide survey, the Non Insulin Requiring Autoimmune Diabetes (NIRAD) Study, have been screened for GADAs and IA-2 antibodies (IA-2As) and further characterized for GADA titer, antibodies to thyroid peroxidase (TPO), and HLA DRB1-DQB1 polymorphisms. Of 4,250 consecutive type 2 diabetic patients, 4.5% had either GADAs and/or IA-2As. Patients with autoimmune diabetes showed a clinical phenotype significantly different from that of type 2 diabetes, including higher fasting glucose and A1C, lower BMI and uric acid, lower prevalence of metabolic syndrome and its components, and higher frequency of TPO antibodies. More interestingly, analysis of GADA titers showed a bimodal distribution that identified two subgroups of patients with high (>32 GADA arbitrary units) and low (< or =32 GADA arbitrary units) GADA titers. Compared with those with low GADA titers, patients with high GADA titers had more prominent traits of insulin deficiency and a profile of more severe autoimmunity resulting in higher A1C, lower BMI, a lower prevalence of metabolic syndrome and its components (P < 0.02 for all), a higher prevalence of IA-2As, TPO antibodies (P < 0.003 for both), and DRB1*03-DQB1*0201 (50 vs. 26.8%, P = 0.001), and a decreasing frequency of DQB1*0602 and DRB1*0403 (from type 2 to low and to high GADA titer autoimmune diabetes; P < 0.001 for trend for both comparisons). GADA titers identify two subgroups of patients with adult-onset autoimmune diabetes having distinct clinical, autoimmune, and genetic features.
                Bookmark

                Author and article information

                Journal
                Diabetes
                diabetes
                diabetes
                Diabetes
                Diabetes
                American Diabetes Association
                0012-1797
                1939-327X
                February 2010
                28 October 2009
                : 59
                : 2
                : 416-422
                Affiliations
                [1] 1Department of Medicine, Helsinki University Central Hospital, and Research Program of Molecular Medicine, University of Helsinki, Helsinki, Finland;
                [2] 2Folkhalsan Research Centre, Helsinki, Finland;
                [3] 3Folkhälsan Östanlid and Malmska Municipal Health Care Center and Hospital, Jakobstad, Finland;
                [4] 4Department of Clinical Sciences, Diabetes and Endocrinology, Clinical Research Center, Malmö University Hospital, Lund University, Malmö, Sweden;
                [5] 5StatFinn Oy, Espoo, Finland, and the Department of Statistics, University of Turku, Turku, Finland.
                Author notes
                Corresponding author: Tiinamaija Tuomi, tiinamaija.tuomi@ 123456hus.fi .
                Article
                0747
                10.2337/db09-0747
                2809967
                19864397
                e87ec1c0-e9f0-46e0-880e-9d72f98b7130
                © 2010 by the American Diabetes Association.

                Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

                History
                : 18 May 2009
                : 14 October 2009
                Categories
                Original Article
                Immunology and Transplantation

                Endocrinology & Diabetes
                Endocrinology & Diabetes

                Comments

                Comment on this article