Adiponectin, Free Fatty Acids, and Cardiovascular Outcomes in Patients With Type 2 Diabetes and Acute Coronary Syndrome

Diabetes Care. 2018 Aug;41(8):1792-1800. doi: 10.2337/dc18-0158. Epub 2018 Jun 14.


Objective: In observational cohorts, adiponectin is inversely associated and free fatty acids (FFAs) are directly associated with incident coronary heart disease (CHD). Adiponectin tends to be reduced and FFAs elevated in type 2 diabetes. We investigated relationships of adiponectin and FFA and major adverse cardiovascular events (MACEs) and death in patients with acute coronary syndrome (ACS) and type 2 diabetes using data from the AleCardio (Effect of Aleglitazar on Cardiovascular Outcomes After Acute Coronary Syndrome in Patients With Type 2 Diabetes Mellitus) trial, which compared the PPAR-α/γ agonist aleglitazar with placebo.

Research design and methods: Using Cox regression adjusted for demographic, laboratory, and treatment variables, we determined associations of baseline adiponectin and FFAs, or the change in adiponectin and FFAs from baseline, with MACEs (cardiovascular death, myocardial infarction, or stroke) and death.

Results: A twofold higher baseline adiponectin (n = 6,998) was directly associated with risk of MACEs (hazard ratio [HR] 1.17 [95% CI 1.08-1.27]) and death (HR 1.53 [95% CI 1.35-1.73]). A doubling of adiponectin from baseline to month 3 (n = 6,325) was also associated with risk of death (HR 1.20 [95% CI 1.03-1.41]). Baseline FFAs (n = 7,038), but not change in FFAs from baseline (n = 6,365), were directly associated with greater risk of MACEs and death. There were no interactions with study treatment.

Conclusions: In contrast to prior observational data for incident CHD, adiponectin is prospectively associated with MACEs and death in patients with type 2 diabetes and ACS, and an increase in adiponectin from baseline is directly related to death. These findings raise the possibility that adiponectin has different effects in patients with type 2 diabetes and ACS than in populations without prevalent cardiovascular disease. Consistent with prior data, FFAs are directly associated with adverse outcomes.

Trial registration: NCT01042769.

Publication types

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

MeSH terms

  • Acute Coronary Syndrome / complications
  • Acute Coronary Syndrome / drug therapy*
  • Acute Coronary Syndrome / epidemiology
  • Adiponectin / blood*
  • Aged
  • Coronary Disease / complications
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetic Angiopathies / blood
  • Diabetic Angiopathies / drug therapy*
  • Diabetic Angiopathies / epidemiology
  • Fatty Acids, Nonesterified / blood*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / complications
  • Myocardial Infarction / epidemiology
  • Oxazoles / therapeutic use*
  • Retrospective Studies
  • Stroke / complications
  • Stroke / epidemiology
  • Thiophenes / therapeutic use*
  • Treatment Outcome


  • ADIPOQ protein, human
  • Adiponectin
  • Fatty Acids, Nonesterified
  • Oxazoles
  • Thiophenes
  • aleglitazar

Associated data