Rapid Lipid Buildup Seen In Hearts Of Transplant Patients With Diabetes

Metformin may help reduce cardiomyocyte lipid accumulation and subsequent diabetic cardiomyopathy (DMCM), new findings suggest.

Diabetic patients had progressive cardiomyocyte lipid accumulation within 3 months of receiving a heart from a non-diabetic donor, while fat accumulation was reduced in those on metformin, Dr. Raffaele Marfella of the University of Campania "Luigi Vanvitelli" in Naples and colleagues found.

"This may constitute a novel target for therapy of DMCM," they conclude in the Journal of the American College of Cardiology.

Most hypotheses on the pathogenesis of DMCM are based on animal studies, Dr. Marfella and his team note. In the DMCM-AHEAD (Diabetes and Lipid Accumulation and Heart Transplant) study, they are following 158 heart-transplant recipients, 76 of whom have diabetes mellitus (DM). Thirty-five of the DM patients were on metformin.

The researchers took 474 endomyocardial biopsies (EMB) from transplanted patients, which they classified as basal (1 to 4 weeks after transplant), intermediate (5 to 12 weeks) and final (13 to 48 weeks).

There was no lipid accumulation in cardiomyocytes in any basal EMBs. But 28.6% of the intermediate samples from the patients with DM had lipid accumulation, vs none of the non-DM patients. Two of the patients with DM on metformin (5.7%) had intermediate EMBs showing lipid accumulation.

At final follow-up, 87.8% of the DM patients had fat accumulation in their heart tissue, including 20% of those who were taking metformin, while none of the non-DM patients did.

At baseline and at follow-up, the DM patients on metformin had lower plasma glucose and systemic insulin resistance. While DM patients had worse ventricular function compared to those without DM, cardiac functioning was less impaired for those on metformin.

The DM group also had higher levels of triacylglycerol and ceramide, which correlated with HOMA-IR, and increased lipotoxic factors, which were also reduced in those on metformin.

Overall, the DM patients on metformin were significantly less likely to have lipid accumulation (hazard ratio. 6.6) than those who were not on metformin.

"This finding supports further investigations into the effects of diabetic milieu on pathogenetic mechanisms of the main causes of HF. However, further studies on a larger population will be needed to support these observations," Dr. Marfella and colleagues conclude.

"If the results of Marfella et al. are confirmed by appropriately designed studies, re-evaluation of metformin use in heart failure will be required because the most recent guidelines do not encourage use of metformin," Dr. Charles M. Alexander of Alexander Associates LLC in Gwynedd Valley, PA, writes in an editorial accompanying the study.

"Studies of SGLT-2 inhibitors combined with metformin compared with SGLT-2 inhibitors alone will need to be considered if the findings of Marfella et al. of metformin benefit are subsequently confirmed," he concludes.

—Reuters Staff

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