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


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.
Centre for Diabetes, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, U.K.
Mohammed Iqbal
MI
Hawa
Centre for Diabetes, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, U.K.
Ana Paula
AP
Buchan
Centre for Diabetes, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, U.K.
Thomas
T
Ola
Pfizer Inc., New York, NY.
Chuan Chuan
CC
Wun
Pfizer Inc., New York, NY.
David A
DA
DeMicco
Pfizer Inc., New York, NY.
Weihang
W
Bao
Department of Diabetes, University College London, London, U.K.
D John
DJ
Betteridge
Department of Medicine, University of Manchester, Manchester, U.K.
Paul N
PN
Durrington
Department of Epidemiology and Public Health, University College London, London, U.K.
John H
JH
Fuller
Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, U.K.
H Andrew W
HA
Neil
Medical Research Institute, University of Dundee, Dundee, U.K.
Helen
H
Colhoun
Centre for Diabetes, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, U.K.
Richard David
RD
Leslie
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.
Graham A
GA
Hitman
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D000069059:Atorvastatin; D001323:Autoantibodies / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D005858:Germany / Q000453:epidemiology; D018149:Glucose Intolerance; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006538:Heptanoic Acids / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D024821:Metabolic Syndrome / Q000175:diagnosis / Q000188:drug therapy; D008875:Middle Aged; D010641:Phenotype; D015995:Prevalence; D011446:Prospective Studies; D011758:Pyrroles / Q000627:therapeutic use; D012307:Risk Factors
D000924:Anticholesteremic Agents; D001323:Autoantibodies; D006538:Heptanoic Acids; D007004:Hypoglycemic Agents; D007328:Insulin; D011758:Pyrroles; D000069059:Atorvastatin; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1