Clinical Research
Diabetes and Cardiovascular Disease
Insulin Therapy Is Associated With Platelet Dysfunction in Patients With Type 2 Diabetes Mellitus on Dual Oral Antiplatelet Treatment

https://doi.org/10.1016/j.jacc.2006.03.038Get rights and content
Under an Elsevier user license
open archive

Objectives

This study sought to assess the influence of type 2 diabetes mellitus (T2DM) and the impact of hypoglycemic treatment (insulin vs. noninsulin) on platelet function profiles in patients treated with dual oral antiplatelet therapy.

Background

Insulin inhibits platelet aggregation by suppressing the P2Y12pathway. However, T2DM patients have a loss of responsiveness to insulin that leads to upregulation of the P2Y12pathway, increased platelet reactivity, and reduced responsiveness to antiplatelet agents. Patients with insulin-treated diabetes mellitus (ITDM) have a more advanced disease status and higher atherothrombotic risk compared with non-ITDM (NITDM). However, the impact of insulin therapy on platelet dysfunction in patients treated with P2Y12antagonists is unknown.

Methods

A total of 201 T2DM and 65 nondiabetic patients with coronary artery disease in a steady phase of aspirin and clopidogrel treatment were studied. Platelet aggregation was assessed using agonists specific (6 and 20 μM adenosine diphosphate [ADP]) and nonspecific (6 μg/ml collagen and 20 μM epinephrine) for the P2Y12pathway. High shear-induced platelet reactivity was assessed by means of the PFA-100 system (Dade-Behring International, Miami, Florida).

Results

The T2DM patients had platelet aggregation and shear-induced platelet function significantly increased compared with nondiabetic patients using all assays. Platelet aggregation was increased in ITDM (n = 68) compared with NITDM (n = 133) patients after P2Y12-specific stimuli. Insulin treatment was the strongest predictor of ADP-induced aggregation. Platelet function profiles were similar between ITDM and NITDM using assays nonspecific to the P2Y12pathway. Platelet dysfunction was independent of glycemic control and inflammatory status.

Conclusions

The P2Y12-dependent and -independent pathways of platelet reactivity are altered in T2DM compared with nondiabetic patients, and ITDM have greater ADP-induced platelet aggregation compared with NITDM.

Abbreviations and Acronyms

ADP
adenosine diphosphate
CADP
collagen/ADP
CEPI
collagen/epinephrine
CT
closure time
HbA1C
hemoglobin A1C
ITDM
insulin-treated diabetes mellitus
NITDM
noninsulin-treated diabetes mellitus
PPP
platelet-poor plasma
PRP
platelet-rich plasma
T2DM
type 2 diabetes mellitus

Cited by (0)

1

Dr. Angiolillo is on the Speakers’ Bureau and is consultant for Sanofi-Aventis and Bristol Myers Squibb. He declares to have had full access to all study data and has the final responsibility for deciding to submit this manuscript for publication in the Journal of the American College of Cardiology.