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

Diabetes Care. 2014 Jun;37(6):1643-9. doi: 10.2337/dc13-2383. Epub 2014 Apr 10.

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Anticholesteremic Agents / therapeutic use
  • Atorvastatin
  • Autoantibodies / blood*
  • Diabetes Mellitus, Type 1 / diagnosis*
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 2 / diagnosis*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / 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
  • Metabolic Syndrome / drug therapy
  • Middle Aged
  • Phenotype
  • Prevalence
  • Prospective Studies
  • Pyrroles / therapeutic use
  • Risk Factors

Substances

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