Diabetes
Deborah Brauser
June 20, 2013
UPDATED JUNE 25: Depressive symptoms and use of antidepressants are associated with markers linked to risk for diabetes and cardiovascular disease (CVD), new research suggests.
A large cohort study of more than 2000 postmenopausal women participating in the Women’s Health Initiative (WHI) showed that those who had elevated symptoms of depression and who used antidepressant medications were significantly more likely to have higher levels of C-reactive protein (CRP) — a biomarker for inflammation, which increases the risk for type 2 diabetes and CVD — compared with their healthy peers.
The women with elevated symptom scores or who used antidepressants were also more likely to have a higher body mass index (BMI) and a larger waist circumference.
Interestingly, lead author Yunsheng Ma, MD, PhD, told Medscape Medical News that waist circumference actually showed a stronger association than BMI and that it may be the critical marker.
“Weight gain in the abdominal region is a huge risk factor and a very important predictor of CVD,” said Dr. Ma, who is an epidemiologist and an associate professor in the Division of Preventive and Behavioral Medicine at the University of Massachusetts Medical School in Worcester.
In addition, a separate cohort showed that those who had increased depressive symptoms were more likely to have increased levels of insulin and increased measures of insulin resistance.
Although Dr. Ma noted that the overall analysis was epidemiologic, so causation could not be determined, “it may be prudent to monitor to prevent progression to full-blown disease.”
“Identifying these markers in women is important for diabetes and cardiovascular disease prevention,” he added.
The study was published online June 13 in the American Journal of Public Health.
Women’s Health Initiative
In 2011, these investigators published study results in Diabetes Care showing that depressive symptoms and antidepressant use by women were both associated with an increased risk for diabetes. And in 2004, results published in JAMA Internal Medicine showed that depression was linked to increased CVD risk.
However, Dr. Ma noted that few studies have examined whether waist circumference, BMI, or glucose dysregulation/inflammation is associated with depression, use of antidepressants, or both.
The original WHI program recruited 161,808 postmenopausal women between the ages of 50 and 79 years from 1993 to 1998 and then collected follow-up information at regular intervals.”There really aren’t any studies that looked schematically at [the question,] ‘What is the mechanism for all of this?’ So I think this study is important. Some of these people have weight gain, but there’s a period before it becomes full-blown disease, such as diabetes or CVD. So there’s an interval where something could potentially be done to prevent this,” he said.
“This is the largest prospective study ever conducted for women, and they made sure during recruitment to have a truly representative sample, including black, Hispanic, and Asian women,” reported Dr. Ma.
“Most of these types of studies are for men. But the [WHI] has really opened up other areas of research.”
Significant Risk
For the current analysis, the investigators evaluated data on 71,809 of the WHI participants who completed baseline and year-3 assessments (mean age, 63.5 years).
In addition, they evaluated 2242 of the women who participated in a WHI observational study (WHI-OS) and 1950 participants from a WHI clinical trial (WHI-CT), all of whom were followed until 2005 (average years of follow-ups, 7.6 years).
All of these women were asked about medication use and risk factors for CVD and diabetes. Measurements of BMI and waist circumference were also taken, and fasting blood samples were collected. The blood samples were analyzed with up to 20 assays, including assays for insulin and glucose levels. CRP was also measured in the WHI-OS cohort.
In addition, the 6-item Center for Epidemiological Studies Depression Scale (CESDS) was used to assess depressive symptoms in all participants.
Results from the group of 71,809 women showed that those with elevated depressive symptom scores on the CESDS, defined as a score of more than 5 points, had significantly higher BMI and waist circumference at baseline and at the 3-year follow-up than those without symptoms. Use of antidepressants was also associated with higher BMI and waist circumference at both time points.
Among the WHI-CT cohort, higher symptom scores were significantly associated with both insulin resistance (P = .01) and increased insulin levels (P = .01).
Finally, among the WHI-OS cohort, higher CRP levels were associated with antidepressant use (P = .04) and with elevated symptom scores (P = .02).
BMI Monitoring Is “Prudent”
“Given that diabetes and cardiovascular disease can be effectively prevented or delayed in high-risk individuals with lifestyle, medication, or pharmacological interventions, our findings indicate the prudence of monitoring BMI, waist circumference, and established biomarkers for diabetes and cardiovascular risk,” said coinvestigator Simin Liu, MD, in a release.
Dr. Liu is from the Department of Epidemiology and the Division of Endocrinology at Brown University in Providence, Rhode Island.
Dr. Ma added that future studies should examine whether patients without depression who are prescribed antidepressants for anxiety, sleep problems, or other conditions are also at risk, and whether the risk decreases for any of these patients when prescribed cognitive therapy instead.
“Studies have shown that behavior therapy is underutilized. So are people thinking that treating with medication is a quick fix? In that sense, they need to think about possible consequences and at least consider trying other things,” he said.
He reported that the original WHI study is still ongoing and that the investigators hope to continue following the participants at least through 2015. They are also currently evaluating the association between mortality and depressive symptoms/antidepressant use.
“Findings Are Stunning”
“I think this is a great study that is unique in terms of the concept behind it, the design, and the execution,” Angelos Halaris, MD, PhD, professor in the Department of Psychiatry and Behavioral Neurosciences at Loyola University Stritch School of Medicine in Maywood, Illinois, told Medscape Medical News.
He noted that clinicians should routinely monitor BMI, which he said is very easy to calculate, as well cholesterol, high- and low-density lipoproteins, triglycerides, and thyroid function.”The sample that they studied is huge, the questions they addressed are highly pertinent and timely, and the findings are absolutely stunning,” added Dr. Halaris, who was not involved with this research.
“What’s new and innovative is the CRP. And I believe that also should be measured routinely along with all of the other blood tests that we do, at least in those patients that we suspect of being depressed.”
As reported at the time by Medscape Medical News, Dr. Halaris recently made a presentation at the European Congress of the International Neuropsychiatric Association in Greece that called for development of a new “psychocardiology” subspecialty — noting that this would forge closer working relationships between psychiatrists and cardiologists.
But he added that these particular measurements should be done by almost all clinicians.
“I believe that all of us who do work in this field need to assess the presence of and degree of inflammation in the body. If we determine that there’s presence of this in the bloodstream, we can assume relatively safely that it will diminish the availability of serotonin in the brain, and we can expect mood changes,” he said.
“I would like to see the day in my lifetime where the measurement of these compounds become routine and affordable, and where physicians in all specialties become familiar with these changes, how to interpret them, and what course of action to take in terms of treating these patients,” concluded Dr. Halaris.
The study was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases and from the National Heart, Lung, and Blood Institute (NHLBI). The WHI program was funded by the NHLBI, the National Institutes of Health, and the US Department of Health and Human Services. The study authors and Dr. Halaris have reported no relevant financial relationships.
Am J Public Health. Published online June 13, 2013. Abstract