Transplant study shows toxic effects of diabetes on the heart
medwireNews: Follow-up of patients after heart transplant reveals rapid cardiomyocyte lipid accumulation, a probable forerunner of diabetic cardiomyopathy, in those with pre-existing type 2 diabetes.
However, the research, published in the Journal of the American College of Cardiology by Raffaele Marfella (University of Campania “Luigi Vanvitelli,” Naples, Italy) and team, also suggests that metformin could hinder this process.
The author of a linked editorial, Charles Alexander (Alexander Associates LLC, Gwynedd Valley, Pennsylvania, USA), stresses that patients in this study were not randomly assigned to receive metformin. But he says that if the findings are confirmed in randomized trials, “re-evaluation of metformin use in heart failure will be required because the most recent guidelines do not encourage use of metformin” in this population.
And Alexander notes that metformin should also be tested against and in combination with sodium-glucose cotransporter 2 inhibitors, given their proven benefits for heart failure outcomes.
Marfella and team also cite “accumulating data” indicating an effect of metformin on lipid metabolism, and say this supports a role for metformin in slowing the progression of prediabetes to diabetes, as well as in heart failure.
The researchers studied 158 heart transplant recipients, who all had endomyocardial biopsies taken for routine monitoring. During the first 4 weeks after transplant, none of the biopsies showed myocardial lipid accumulation, but those taken between 5 and 12 weeks after transplant revealed lipid accumulation in samples from 28.6% of the 41 patients with type 2 diabetes who were not taking metformin versus none of the samples from the 82 patients without diabetes.
In biopsies taken between 13 and 48 weeks after transplant, the prevalence of lipid accumulation rose to 87.8% in people with diabetes, whereas this remained absent in transplant recipients who did not have diabetes.
Moreover, insulin resistance evaluated both before and during immunosuppressive therapy correlated with lipid accumulation in transplanted hearts in the whole cohort.
Thirty-five transplant recipients were taking metformin, and lipid accumulation in the hearts of these patients “was both delayed and reduced,” relative to those not taking metformin. Of those taking metformin, 5.7% and 20.0% had lipid accumulation at 5–12 and 13–48 weeks, respectively, and at the latter timepoint around 2.5% of cells in positive biopsies had lipid accumulation, compared with around 5% of cells in biopsies from people with diabetes who were not taking metformin.
Clinical outcomes reflected these changes, the team reports. Cardiac function was similar in the three groups just after transplant, but by 1 year ejection fraction and tricuspid annular plane systolic excursion had both improved in patients without diabetes and in those using metformin versus a decrease in those with diabetes.
In addition, the ratio of transmitral early filling velocity to mitral annular early diastolic velocity reduced less in patients with than without diabetes, irrespective of metformin use.
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