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Gender affects heart’s response to diabetes therapy
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The effect of diabetes therapy on myocardial metabolism and diastolic function differs between men and women, according to recent study data.
Researchers performed PET, ECG and whole-body tracer studies in 78 patients with diabetes before and 3 months after they were randomly assigned to metformin alone (n=33), metformin with rosiglitazone (Avandia, GlaxoSmithKline; n=26) or metformin with omega-3-acid ethyl esters (Lovaza, GlaxoSmithKline; n=30). Patients completed therapy in 27 cases in the metformin group, 23 in the rosiglitazone group and 28 in the omega-3-acid ethyl esters group.
At baseline, men and women, regardless of group, differed significantly according to whole-body glucose appearance rate, glucose clearance, fatty acid appearance rate, myocardial blood flow, myocardial oxygen consumption and myocardial fatty acid uptake and metabolism, all of which were higher among women.
In the metformin group, patients experienced a significant weight decrease (P=.02) and trended toward decreased systolic BP (P=.07), but did not experience changes in myocardial metabolism. Men experienced a decrease in whole-body fatty acid clearance, and a subsequent significant increase in myocardial fatty acid utilization and oxidation (P=.02). Women did not experience a change in myocardial glucose metabolism, plasma glucose level or myocardial metabolism, whereas men trended toward lower myocardial glucose uptake and utilization.
The rosiglitazone group experienced significant decreases in plasma fatty acid levels (P=.02) and trended toward decreased fatty acid utilization (P=.07), along with increases to fat-free mass, left ventricular mass and HDL and decreases to plasma glucose, insulin and HbA1c levels and diastolic BP. Researchers noted that most of these changes occurred among women, as fatty acid and whole-body glucose clearance increased significantly, whereas men experienced no change to plasma glucose or insulin levels.
No patients in the omega-3-acid ethyl esters group, regardless of sex, experienced metabolic changes after treatment. Diastolic function improved in this group (P=.02), but this change was specific to men (P=.02), as no change was observed among women.
The researchers noted that the effects of the three treatments did not differ greatly between the groups, and they attributed this observation to the differing effect on the sexes. Analysis of treatment effects according to sex yielded several differences between the groups, including different effect on BMI (P=.0007), plasma free fatty acids (P=.04) and total cholesterol (P=.05) among men, and on plasma glucose (P=.01) and plasma insulin (P<.05) levels among women.
“We saw dramatic sex differences in how the heart responds to the different therapies,” researcher Robert J. Gropler, MD, professor of radiology at Washington University School of Medicine, said in a press release. “Our study suggests that we need to better define which therapies are optimal for women with diabetes and which ones are optimal for men. … This may mean we have to do more complex imaging of the heart to better understand which therapies are best for which patients.”
Disclosure: Gropler reports receiving a grant from GlaxoSmithKline to perform a different study.
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