CORRESPONDENCE: LETTER TO THE EDITOR
Reply
Dominick J. Angiolillo, MD, PhD, FACC, FESC*,
Esther Bernardo, BSc,
Marco A. Costa, MD, PhD, FACC,
Manel Sabaté, MD, PhD,
Theodore A. Bass, MD, FACC,
Carlos Macaya, MD, PhD and
Antonio Fernandez-Ortiz, MD, PhD
* Division of Cardiology, University of Florida, Shands Jacksonville, 655 West 8th Street, Jacksonville, Florida 32209 (Email: dominick.angiolillo{at}jax.ufl.edu).
We appreciate the comments raised by Drs. Scheen and Legrand. In their letter, they reveal a status of "apprehension" toward the potential impact of our study (1) on how clinicians may approach glucose-control management, in particular, avoiding switching to insulin in patients not well controlled on oral glucose-lowering medication. Recognizing the importance of the concerns raised regarding the potential unintended effects of our investigation (1) this was neither the intent nor the correct interpretation of our findings.
Insulin-treated diabetes mellitus (ITDM) patients are at a more advanced stage of their metabolic disorder, which implies biological differences with patients with non-ITDM. In type 2 diabetes mellitus (T2DM), insulin resistance is a pivotal component of the metabolic disorder, which increases over time. We agree with Drs. Scheen and Legrand that progression of the disease may include a deficiency in insulin secretion, and consequently may lead patients to require exogenous insulin therapy (2). However, this does not invalidate our findings. In fact, it is well established that patients with a longer history of T2DM—thus at an advanced stage of insulin resistance—are more prone to have less optimal glycemic control on oral medication and to require exogenous insulin therapy. Scheen et al. disagree with our interpretation regarding the prevalence of female subjects in the ITDM group. Although evaluation of this aspect was not within our study objectives, we provide recent and robust literature to explain our study findings.
Drs. Scheen and Legrand also raise concerns regarding the impact of hemoglobin A1c (HbA1c) levels on platelet reactivity. We would like to rectify that in our study, the coefficient of variation of HbA1c levels in our T2DM study population was 
16%, and not 6%, which is still narrow overall (3), especially when compared to the broad variability of platelet-function measures. Although we recognize that glucose control plays a pivotal role on platelet reactivity, no correlation between the two variables was observed in our study. This finding supports the hypothesis that there may be more explicit biological differences between ITDM and non-ITDM. Although our results (1) differ from the findings of Watala et al. (4), profound differences exist between the 2 studies. These differences include number of patients, type of antiplatelet treatment, degree of glycemic control, and platelet-function assays used.
Our study is the largest platelet-function analysis performed in T2DM on sustained dual antiplatelet therapy (1). Most studies assessing platelet function in T2DM do not describe differences between ITDM and non-ITDM or they fail to find any difference due to limited patient sample sizes (5). This can result in failure to appreciate the biological factors contributing to the less favorable prognosis in ITDM and may also explain why many clinicians incorrectly consider insulin treatment per se a "surrogate" of increased atherothrombotic risk. Our study demonstrates that biological differences exist between the subgroups of patients with T2DM. Indeed, we agree with Drs. Scheen and Legrand that the biological effects of insulin remain controversial (6). However, ITDM represents among the highest risk of patients for recurrence of atherothrombotic events.
"Do not throw the baby out with the bathwater"? Indeed, as cardiologists, we also concur that insulin therapy is necessary and often irreplaceable to optimally treat hyperglycemia in T2DM. Nevertheless, this should not hinder our efforts to proactively investigate alternative factors that contribute to the enhanced atherothrombotic risk and that affect T2DM, and it is important that we continue to explore more aggressive and/or customized antithrombotic treatment regimens in these high-risk patients (7).
 |
References
|
|---|
- Angiolillo DJ, Bernardo E, Ramirez C, et al. Insulin therapy is associated with platelet dysfunction in patients with type 2 diabetes mellitus on dual oral antiplatelet treatment J Am Coll Cardiol 2006;48:298-304.[Abstract/Free Full Text]
- Kahn SE. The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes Diabetologia 2003;46:3-19.[CrossRef][ISI][Medline]
- Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, et al. High clopidogrel loading dose during coronary stenting: effects on drug response and interindividual variability Eur Heart J 2004;25:1903-1910.[Abstract/Free Full Text]
- Watala C, Golanski J, Pluta J, et al. Reduced sensitivity of platelets from type 2 diabetic patients to acetylsalicylic acid (aspirin)—its relation to metabolic control Thromb Res 2004;113:101-113.[CrossRef][ISI][Medline]
- Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, et al. Platelet function profiles in patients with type 2 diabetes and coronary artery disease on combined aspirin and clopidogrel treatment Diabetes 2005;54:2430-2435.[Abstract/Free Full Text]
- Muis MJ, Bots ML, Grobbee DE, Stolk RP. Insulin treatment and cardiovascular disease; friend or foe? A point of view Diabet Med 2005;22:118-126.[CrossRef][ISI][Medline]
- Alfonso F, Angiolillo DJ. Platelet function assessment to predict outcomes after coronary interventions: hype or hope? J Am Coll Cardiol 2006;48:1751-1754.[Free Full Text]
Top
References