Controlling Blood Sugar Cut Heart Disease Risk in Half, New Study Says

People who brought their blood glucose down to a normal level had a lower risk of death from heart disease or hospitalization for heart failure after 20 years.

People with prediabetes who get their blood sugar under control may cut their risk of death from heart disease or heart failure by half, according to new research.

Prediabetes, which is estimated to affect 38 percent of U.S. adults, is a condition in which blood sugar levels are elevated but don’t meet the threshold for diabetes. The research, published Friday in the journal Lancet Diabetes & Endocrinology, suggested that people with prediabetes whose glucose levels returned to normal — those who reached “remission” — had half the risk of cardiovascular death or hospitalization from heart failure two decades after reaching remission than those who did not.

“That is an incredible finding and really gives people hope that what they do today will have an effect two decades from now,” said Dr. Latha Palaniappan, the associate dean for research at Stanford Medicine, who was not involved in the study.

There has long been evidence that Type 2 diabetes increases the risk of heart attacks and heart failure. Some data have shown prediabetes is also associated with cardiovascular disease, but it’s been unclear if that is because it often progresses to diabetes, said Elizabeth Selvin, a professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health.

The findings may add urgency for patients and doctors to take prediabetes seriously to prevent future complications: Current guidelines for managing prediabetes emphasize weight loss and lifestyle habits to delay or prevent progression to Type 2 diabetes, but they don’t specifically advocate lowering blood glucose levels to a lower-than-prediabetic range.

The new research was a follow-up analysis of data from two landmark trials, including the U.S. Diabetes Prevention Program trial, which ran from 1996 to 2001. That trial compared the effects of three interventions on the development of Type 2 diabetes in people who had prediabetes: an intensive lifestyle program including diet and exercise; the use of the blood glucose lowering drug metformin; and a placebo.

The trial showed that the intensive lifestyle program reduced the development of Type 2 diabetes by 58 percent in three years compared to placebo, while metformin reduced it by 31 percent. (The federal government halted, and then reinstated, funding for the Diabetes Prevention Program this year.)

The new research looked at participants in that trial 20 years later. About 11 percent of them had dropped to normal glucose levels after one year, regardless of which intervention they got. Twenty years later, this subset had a 50 percent lower risk of death from cardiovascular disease or hospitalization for heart failure than those who had not achieved normal glucose levels, after adjusting for certain characteristics, including whether people developed full-blown diabetes.

To test that finding, the research team conducted a follow-up analysis of a similar diabetes prevention trial in China. In that trial, about 13 percent of people with elevated glucose achieved normal levels after six years; 30 years later, those people had a 51 percent lower risk of death from heart disease or hospitalization than those who had not achieved normal levels.

“It’s interesting that this short-term intervention period has these very long-term effects,” Dr. Selvin said.

Normalizing glucose levels — with or without weight loss — can help reduce fat tissue in the abdomen, reduce inflammation and increase insulin sensitivity, said Dr. Andreas Birkenfeld, the chair of the department of diabetology, endocrinology and nephrology at University Hospital Tubingen in Germany, and the senior author of the new paper.

The researchers don’t know who among the participants made and sustained lifestyle changes after the original intervention period. They tried to control for differences between those who achieved remission and those who didn’t, but some unmeasured difference could be driving different outcomes, said Dr. Jonathan Newman, the clinical research director for the Center for the Prevention of Cardiovascular Disease at N.Y.U. Langone Heart.

Overall very few people were able to achieve normal glucose levels in either the U.S. or China trial — a major practical consideration, said Judy Regensteiner, the director of the Ludeman Family Center for Women’s Health Research at the University of Colorado Anschutz Medical Campus. (Dr. Regensteiner was an investigator on the Diabetes Prevention Program trial but was not involved in the current study.)

“It’s a good proof of concept,” she said. But, she added, “If these really well done studies have low success rates in getting people to those numbers, what do we do differently?”

Experts noted that new GLP-1 drugs that help control blood sugar and reduce weight weren’t part of the picture when participants originally enrolled in the diabetes prevention trials in the 1980s and 1990s.

“Lifestyle interventions are first-line therapy,” Dr. Selvin said. “The real open question is, how do we combine these two things?”

Lowering blood glucose levels is only one component of reducing cardiovascular disease risk. People still need to maintain a healthy weight, follow a good diet and exercise.

“Prediabetes is the canary in the coal mine” and often a sign of broader metabolic dysfunction, Dr. Newman said. Targeting blood glucose levels alone “is not a slam dunk” in eliminating cardiovascular disease risk, he added, but it can be a useful marker.

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