Patients receiving an increased loop-diuretic dose rate of heart failure drugs may have a greater risk of developing diabetes.

Researchers in Denmark reviewed the cases of 99,362 heart failure patients in the Danish National Patient Registry who had not previously been diabetic between 1997 through 2010. They were followed until Dec. 31, 2010, development of diabetes as shown by filling a prescription for hypoglycemic agents or death.

Patients were categorized into five groups based on their loop-diuretic dose. Thirty one percent of patients used no loop diuretics (group one). Group two used between 0 to 40 mg/day (25 percent), group three used about 40 to 80 mg/day (17 percent). Group four, 12 percent of patients, used around 80 to 159 mg/day. Fifteen percent of patients (group five) used more than 160 mg/day.

“Among those in the group receiving the highest dosage, the 10-year cumulative risk of developing diabetes exceeded 25%,” wrote first author Malene N. Demant, MD, of Copenhagen University’s Department of Cardiology, and her colleagues.

While a large number of the patients eventually died, 8 percent of the Danish heart failure patients developed diabetes about three years following discharge. “Our data add important insights to the understanding of the mechanisms underlying this poor prognosis, because it might be that the sickest patients are those who develop diabetes. Thus, diabetes may, in part, be a marker of heart failure severity in addition to being a causal risk factor for mortality in heart failure cohorts.”

While this study didn’t explain the mechanism for the development of diabetes in heart failure patients, they did discuss several possibilities that the Danish National Patient Registry did not provide enough information to test.

“Patients with heart failure have decreased cardiac output and thereby diminished oxygen, glucose and insulin distribution to peripheral muscular tissue,” they wrote. “Impaired blood flow further increases levels of adrenaline (epinephrine) and noradrenaline (norepinephrine). This neurohumoral compensating mechanism has been suggested to increase insulin resistance and hepatic gluconeogenesis as well as decrease the release of insulin from the pancreatic beta cells.”

They added that loop diuretics may contribute to impaired glucose tolerance, although it is not a well-established side effect.

This study builds on the research team’s previous work on diabetes, loop diuretics and heart failure, broadening the study population to encompass the entire Danish population discharged following treatment for heart failure.

The study was published May 22 in Diabetologia.