Nearly 10% of patients with adult-onset diabetes were found to have diabetes-associated autoantibodies in a large European cross-sectional study.
Many of those with autoimmune diabetes did not require insulin at diagnosis and, although they tended to be younger and leaner, overall did not show categorically distinct clinical differences from autoantibody-negative patients with type 2 diabetes.
”Only with screening for autoantibodies, especially [glutamic acid decarboxylase autoantibodies (GADA)], can they be identified with certainty,” Mohammed I. Hawa, PhD, from the Blizard Institute, Queen Mary University of London, United Kingdom, and colleagues write.
Their findings were published online December 17 in Diabetes Care.
The 6156 study patients were aged 30 to 70 years (mean, 54.4 years) with less than 5 years (mean, 2.2 years) since diabetes diagnosis. Most (84.6%) were white, and 58.5% were men. The patients were recruited between 2004 and 2007 from 9 European countries at primary care, community, or hospital centers participating in the Action Latent Auto-Immune Diabetes in Adults (LADA) study.
At least a single type of diabetes-associated autoantibody was found in 9.7% of the total group. These included GADA in 8.8%, insulinoma-associated antigen-2 autoantibodies in 2.3%, and zinc-transporter 8 autoantibodies in 1.8%.
Of the 598 patients with autoantibodies, nearly a quarter (24.1%) had more than a single different autoantibody type and 90.5% were positive for GADA.
”These observations show that adult-onset autoimmune diabetes is not rare,” the authors note.
”Clinically, knowledge that adult-onset diabetic patients have GADA should alert physicians to the increased likelihood of more rapid progression to insulin therapy,” they add.
Compared with patients with autoantibody-negative diabetes, those with autoantibodies were significantly younger (49.6 vs 54.9 years; P < .001) and had significantly lower body mass indexes (27.2 vs 30.9 kg/m 2; P < .001). They also had lower systolic blood pressure and triglyceride levels and higher levels of high-density lipoprotein cholesterol (all P < .001), but low-density lipoprotein cholesterol values were not different between the 2 groups.
At the time of the study, 49.5% of autoantibody-positive patients were using insulin compared with 13.2% of the autoantibody-negative patients ( P < .001).
Of the 279 autoantibody-positive patients receiving insulin, precise information on time to insulin therapy was available for 203 patients. Of those 203 patients, 56.2% were designated as having type 1 diabetes, defined by autoantibody positivity and by having started on insulin at the time of diagnosis.
Another 32.0% were classified as having LADA, defined as being autoantibody-positive but not using insulin for at least 6 months after diagnosis. A third group, accounting for the other 11.8%, fell in between: they were autoantibody-positive and started insulin more than 1 month but less than 6 months after diagnosis.
Compared with the LADA group, those with classic type 1 diabetes were younger and had lower age of onset, body mass index, waist circumference, and waist to hip ratio ( P < .001 for all).
In the entire study population, the prevalence of LADA was more than 3 times greater than that of classic autoimmune type 1 diabetes (377 vs 114 patients), with an odds ratio of 3.3.
Additional analyses showed that although patients with higher titers of GADA more closely resembled patients with type 1 diabetes (younger, leaner, receiving insulin, etc) than did those with lower GADA levels, ”each form of autoimmune diabetes could be found across the range of GADA titers,” Dr. Hawa and colleagues note.
Reminder for Clinicians
Professor Paul Zimmet, AO, MD, PhD, director emeritus of the Baker IDI Heart and Diabetes Institute and professor at Monash University, Melbourne, Australia, and the University of Pittsburgh, Pennsylvania, told Medscape Medical News that this work replicates, in part, findings that he and his group published 20 years ago and that others have demonstrated since.
”This paper is a very large study which actually just confirms much of the information on LADA that has been published during the last 2 decades by others. On the positive side, it provides an important further alert to clinicians, including primary care doctors, of awareness that LADA is a prevalent condition, particularly in European populations,” said Dr. Zimmet, who cochairs the International Diabetes Federation Task Force on Epidemiology and Prevention.
Clinically, he said, although antibody testing for all patients with adult-onset diabetes is not cost-effective, it makes sense to test for GADA in newly diagnosed adults who are not obese, particularly those of European origin, as well as those who are obese and present as having type 2 diabetes but who fail to respond to conventional therapy.
”Awareness of the possibility is key,” Dr. Zimmet told Medscape Medical News.
This study was partially funded by the 5th Framework Programme of the European Union. This study was also funded by DeveloGen. One of the authors was supported by a grant from Instituto Carlos III, Madrid, Spain. The authors have disclosed no relevant financial relationships. Dr. Zimmet is on the on the advisory boards for Novartis and Novo Nordisk.
Diabetes Care. Published online December 17, 2012
www.medscape.com
ABSTRACT
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*
+ Author Affiliations
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
Abstract
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 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.
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