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

Abstract

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.

• Authors: Mohammed Iqbal Hawa, Ana Paula Buchan, Thomas Ola, Chuan Chuan Wun, David A DeMicco, Weihang Bao, D John Betteridge, Paul N Durrington, John H Fuller, H Andrew W Neil, Helen Colhoun, Richard David Leslie, Graham A Hitman
• Journal: Diabetes care (Diabetes Care) Vol. 37 Issue 6 Pg. 1643-9 (Jun 2014) ISSN: 1935-5548 [Electronic] United States
• PMID: 24722498 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 by the American Diabetes Association.

Chemical References

• Anticholesteremic Agents
• Autoantibodies
• Heptanoic Acids
• Hypoglycemic Agents
• Insulin
• Pyrroles
• Atorvastatin
• Glutamate Decarboxylase
• glutamate decarboxylase 1

Topics

• Adult
• Age of Onset
• Aged
• Anticholesteremic Agents (therapeutic use)
• Atorvastatin
• Autoantibodies (blood)
• Diabetes Mellitus, Type 1 (diagnosis, drug therapy, immunology)
• Diabetes Mellitus, Type 2 (diagnosis, drug therapy, immunology)
• Double-Blind Method
• Female
• Germany (epidemiology)
• Glucose Intolerance
• Glutamate Decarboxylase (immunology)
• Heptanoic Acids (therapeutic use)
• Humans
• Hypoglycemic Agents (therapeutic use)
• Insulin (therapeutic use)
• Male
• Metabolic Syndrome (diagnosis, drug therapy)
• Middle Aged
• Phenotype
• Prevalence
• Prospective Studies
• Pyrroles (therapeutic use)
• Risk Factors