Diabetic heart risk: NMR offers molecular explanation

Diabetes, hearts and fats

 

A small, but potentially very important, study that utilises NMR spectroscopy and other techniques has been used to reveal a possible mechanism that explains why patients with diabetes have a greater risk of developing heart disease.

Researchers in the Division of Endocrinology and Metabolism at the MedUni Vienna working with colleagues at the Magnetic Resonance Centre of Excellence Vienna and the Institute of Biomedical Engineering-National Research Council, Padova, Italy, have found shown that high blood sugar in combination with high levels of insulin - rather than an influx of fats into heart cells - is the underlying cause of fat deposits forming within heart cells. Tests in diabetes patients often reveal an increase of fatty deposits in the cells of the heart muscle, but researchers were not clear as to why this might be, until now. The discovery could be used to develop novel treatments for diabetes that are also beneficial to hearth health, particularly in the early stages of the disease's development in an individual.

In the study, published in the journal Diabetes, the researchers recruited 18 healthy women and men. The volunteers were each given glucose (from grape sugar) intravenously and the fat levels in cardiac muscle cells were determined using spectroscopy and imaging techniques. The team says that deposits rose within six hours. The injection of grape sugar, in combination with the release of insulin triggered by the glucose, resulted in what team leader Michael Krebs describes as "an overexertion of the heart's metabolism". This proves, he adds, that fatty deposits - cardiac steatosis - can occur without the direct influx of fats.

Beating heart

"This method makes it possible to observe the beating heart, not only as it works, but non-invasively and without ionizing radiation as it metabolizes energy," team member Martin Krssak explains.

Type 2 diabetes is on the increase in Western society and seems to grow in parallel with rates of overweight and obesity. It is associated with cardiovascular problems and an increased risk of high blood pressure, stroke and heart disease. Unfortunately, diagnosis is usually serendipitous and often occurs about five years after initial onset in most patients. The result is that preventative therapies that can avoid the massively increased risk of heart disease are late in being administered for many patients and the majority succumb to heart diseases.

"Our data show that the foundation for damage can be laid early on, especially in patients with high blood sugar and hyperinsulinaemia - an elevated insulin level - during pre-diabetes and early diabetes." The team hopes that this study can build on studies of elevated blood sugar (hyperglycaemia) and hyperinsulinaemia and allow drug development to be targeted at patients earlier. Of course, this would perhaps rely on the instigation of regular screening of patients even before they have obvious symptoms.

"Based on our findings, we conclude that combined hyperglycaemia and hyperinsulinaemia induce short-term myocardial lipid accumulation and alterations in myocardial function in normal subjects, indicating that these alterations might be directly responsible for cardiac steatosis in metabolic diseases," the team concludes in their paper.

Glucose solution

"We are currently studying the effects of glucose-lowering therapies including insulin on myocardial (lipid) metabolism, morphology and function in patients with type 2 diabetes," Krebs told SpectroscopyNOW. "In line with the published study preliminary data suggests that rapid lowering of blood glucose concentrations might (transiently) foster myocardial lipid accumulation. At present it is unclear whether this effect has meaningful implications for the outcome of diabetic patients and whether alternative treatment strategies designed to avoid myocardial steatosis are beneficial."