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LADA and CARDS: a prospective study of clinical outcome in established adult-onset autoimmune diabetes.

Author(s): Hawa MI(1), Buchan AP(1), Ola T(1), Wun CC(2), DeMicco DA(2), Bao W(2), Betteridge DJ(3), Durrington PN(4), Fuller JH(5), Neil HA(6), Colhoun H(7), Leslie RD(1), Hitman GA(8).

Affiliation(s): Author information: (1)Centre for Diabetes, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, U.K. (2)Pfizer Inc., New York, NY. (3)Department of Diabetes, University College London, London, U.K. (4)Department of Medicine, University of Manchester, Manchester, U.K. (5)Department of Epidemiology and Public Health, University College London, London, U.K. (6)Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, U.K. (7)Medical Research Institute, University of Dundee, Dundee, U.K. (8)Centre for Diabetes, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, U.K. g.a.hitman@qmul.ac.uk.

Publication date & source: 2014, Diabetes Care. , 37(6):1643-9

OBJECTIVE: Diabetes-associated autoantibodies can be detected in adult-onset diabetes, even when initially non-insulin requiring, i.e., with latent autoimmune diabetes. We aimed to identify adult-onset autoimmune diabetes in patients with established "type 2 diabetes" participating in the Collaborative Atorvastatin Diabetes Study (CARDS) to characterize their phenotype and clinical outcome. RESEARCH DESIGN AND METHODS: We prospectively studied 2,425 European patients with presumed type 2 diabetes (mean age 62 years, diabetes duration 7.9 years) for outcomes at 3.9 years after randomization to either atorvastatin or placebo. Subjects were screened for autoantibodies to GAD (GADA), insulinoma-associated antigen-2 (IA-2A), and zinc-transporter 8 (ZnT8A). RESULTS: A total of 173 patients (7.1%) had GADA, of whom 11 (0.5%) and 5 (0.2%) were also positive for IA-2A and ZnT8A, respectively. At baseline, 44% of GADA-positive patients were not on insulin. Fewer autoantibody-positive than autoantibody-negative patients had metabolic syndrome (64 vs. 80%), and more were on insulin (56 vs. 17%) (P < 0.0001 for each) without lower HbA1c (69 mmol/mol [8.5%] vs. 62 mmol/mol [7.8%]). The frequency of microvascular and macrovascular events was similar in both cohorts, independent of atorvastatin. CONCLUSIONS: Adult-onset autoimmune diabetes was prevalent, even in patients with established diabetes presumed to have type 2 diabetes. After 11.8 years' diabetes duration, nearly half the patients with autoimmune diabetes were not on insulin treatment and almost two-thirds had metabolic syndrome. The type of diabetes, whether autoimmune diabetes or type 2 diabetes, did not impact the risk of microvascular disease.

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