Look AHEAD for CVD Risk in Patients With Type 2 Diabetes and Depression

Gregory A. Nichols, PhD


June 25, 2013

Four-Year Analysis of Cardiovascular Disease Risk Factors, Depression Symptoms, and Antidepressant Medicine Use in the Look AHEAD (Action for Health in Diabetes) Clinical Trial of Weight Loss in Diabetes

Rubin RR, Peyrot M, Gaussoin SA, et al; Look AHEAD Research Group
Diabetes Care. 2013;36:1088-1094

Study Summary

Look AHEAD is a randomized clinical trial of 5145 overweight or obese individuals with type 2 diabetes that was designed to assess the long-term effects of comprehensive behavioral weight loss intervention on cardiovascular and other health outcomes. Participants were randomly assigned to intensive lifestyle intervention or diabetes support and education. The primary objective of this report was to assess the association between elevated depression (measured with the Beck Depression Inventory [BDI] or reported use of antidepressant medication) and subsequent cardiovascular disease (CVD) risk factor-positive status.

Nine elements of 5 CVD risk factors were each dichotomized into risk-positive or risk-negative. Risk factor-positive status was defined as:

Current smoking;

Body mass index ≥ 30 kg/m2;

A1c > 7.0% or use of insulin;

Systolic blood pressure > 130 mm Hg;

Diastolic blood pressure > 80 mm Hg;

Low-density lipoprotein (LDL) cholesterol ≥ 100 mg/dL;

High-density lipoprotein (HDL) cholesterol ≤ 40 mg/dL;

Total cholesterol ≥ 200 mg/dL; and

Triglycerides ≥ 150 mg/dL.

The use of any antihypertensive or lipid-lowering agent was considered an "at risk" indicator for the above.

The study assessed the association between positive status for each CVD risk factor and elevated BDI scores and use of antidepressants in the prior year. The researchers controlled for CVD risk factor status in the prior year, demographic variables, history of CVD, and duration of diabetes.

In the diabetes support and education arm, elevated BDI in the prior year was associated with subsequent elevated A1c levels and insulin use, but the odds of elevated total cholesterol were decreased. In the lifestyle intervention arm, the association between elevated BDI and the odds of low HDL cholesterol and elevated total cholesterol reached statistical significance.

In the support and education cohort, antidepressant use in the prior year was associated with more prevalent low HDL cholesterol, elevated total cholesterol, and current smoking. In the lifestyle intervention cohort, antidepressant use in the prior year was associated with more prevalent elevated A1c or insulin use, low HDL cholesterol, elevated total cholesterol, elevated systolic blood pressure, and body mass index ≥ 30 kg/m2.


The relationships among diabetes, depression, CVD, and the treatments for each of these conditions are extremely confounded and highly complex. We have long known that the prevalence of depression is elevated in patients with diabetes.[1] Although this relationship is probably bidirectional,[2] depression is more likely to precede diabetes, and depressive symptoms seem to increase diabetes risk.[3,4] It is further complicated by the fact that antidepressant medications seem to increase diabetes risk (independent of symptoms),[5,6] thereby suggesting that they may also exacerbate existing diabetes. The known elevated risk for CVD in patients with diabetes becomes even greater when depression is present.[7]

Given all of these interconnections, it was somewhat reassuring to see that the associations between depressive symptoms and subsequent CVD risk factor status were modest and mostly nonexistent in patients with diabetes. As the investigators noted, there was little evidence of a temporal relationship.

Somewhat more troubling were the associations between antidepressant use and CVD risk factors; although modest, these were more frequent. Further study is needed, but in the meantime, patients with diabetes who are treated with antidepressants may need to be monitored even more carefully for CVD risk.