Adult-Onset Autoimmune Diabetes in Europe Is Prevalent With a Broad Clinical Phenotype
Action LADA 7
- Mohammed I. Hawa, PHD1,
- Hubert Kolb, MD2,
- Nanette Schloot, MD2,
- Huriya Beyan, PHD1,
- Stravoula A. Paschou, PHD, MD1,
- Raffaella Buzzetti, MD3,
- Didac Mauricio Puente, MD4,
- Alberto De Leiva, MD4,
- Knud Yderstraede, MD5,
- Henning Beck-Neilsen, MD5,
- Jaakko Tuomilehto, MD6,
- Cinzia Sarti, MD6,
- Charles Thivolet, MD7,
- David Hadden, MD8,
- Steven Hunter, MD8,
- Guntram Schernthaner, MD9,
- Werner A. Scherbaum, MD2,
- Rhys Williams, MD10,
- Sinead Brophy, MD10,
- Paolo Pozzilli, MD1,11,
- Richard David Leslie, MD1⇓,
- on behalf of the Action LADA consortium*
- 1Blizard Institute, Queen Mary University of London, London, U.K.
- 2Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
- 3University “La Sapienza,” Rome, Italy
- 4Hospital de Sant Pau, Barcelona, Spain
- 5Odense University Hospital, Odense, Denmark
- 6National Institute for Health and Welfare, Helsinki, Finland
- 7Hospital Edouard Herriot, Lyon, France
- 8Royal Victoria Hospital, Belfast, U.K.
- 9Rudolfstiftung Hospital, Vienna, Austria
- 10Swansea University, Swansea, U.K.
- 11University Campus Bio-Medico, Rome, Italy
- Corresponding author: Richard D. Leslie, .
OBJECTIVES Specific autoantibodies characterize type 1 diabetes in childhood but are also found in adult-onset diabetes, even when initially non–insulin requiring, e.g., with latent autoimmune diabetes (LADA). We aimed to characterize adult-onset autoimmune diabetes.
RESEARCH DESIGN AND METHODS We consecutively studied 6,156 European diabetic patients attending clinics within 5 years of diagnosis (age range, 30–70 years) examined cross-sectionally clinically and for GAD antibodies (GADA) and antibodies to insulinoma-associated antigen-2 (IA-2A) and zinc-transporter 8 (ZnT8A).
RESULTS Of 6,156 patients, 541 (8.8%) had GADA and only 57 (0.9%) IA-2A or ZnT8A alone. More autoantibody-positive than autoantibody-negative patients were younger, leaner, on insulin (49.5 vs. 13.2%), and female (P < 0.0001 for each), though LADA patients (9.7% of total) did not show categorically distinct clinical features from autoantibody-negative type 2 diabetes. Similarly, more GADA patients with high (>200 WHO IU) (n = 403) compared with low (n = 138) titer were female, lean, and insulin treated (54.6 vs. 39.7%) (P < 0.02 for each). Autoantibody-positive patients usually had GADA (541 of 598; 90.5%) and had LADA more often than type 1 autoimmune diabetes (odds ratio 3.3).
CONCLUSIONS Adult-onset autoimmune diabetes emerges as a prevalent form of autoimmune diabetes. Our results indicate that adult-onset autoimmune diabetes in Europe encompasses type 1 diabetes and LADA in the same broad clinical and autoantibody-positive spectrum. At diagnosis, patients with adult-onset autoimmune diabetes are usually non–insulin requiring and clinically indistinguishable from patients with type 2 diabetes, though they tend to be younger and leaner. Only with screening for autoantibodies, especially GADA, can they be identified with certainty.
↵* A full list of members of the Action LADA consortium can be found in the appendix.
- Received May 14, 2012.
- Accepted September 18, 2012.
- © 2013 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.