Twenty-five years later, UM group has learned a lot about preventing diabetes

More than two decades ago, the University of Miami’s Diabetes Prevention Program began recruiting people to take part in what would become a landmark nationwide study for the prevention of Type 2 diabetes in people at high risk for developing the disease.

Miami was one of 25 sites across the United States that enrolled 3,819 participants in the clinical trial to see if medication or changes in lifestyle such as weight loss and more exercise could delay the onset of Type 2 diabetes or its complications in prediabetic people with impaired glucose tolerance.

Beginning in 1996, the program recruited 144 local participants to join the national study. After careful screening, it randomized them into four groups: those who got a placebo, those in an intensive lifestyle group, and those who took Metformin, a drug commonly used for those who have already developed diabetes, or the new drug Troglitazone.

With help from a lifestyle coach and group exercise classes, those in the intensive lifestyle group were asked to aim for and maintain a 7 percent weight loss (14 pounds for someone who weighs 200) and to increase their weekly exercise activity by 150 minutes. For many, walking was the exercise of choice.

Troglitazone was dropped from the study in June 1998 and is no longer available after a patient at another center taking part in the DPP study developed serious liver damage and died despite a liver transplant.

But the two other options, taking Metformin as a preventative and making lifestyle changes showed such promise and initial findings were so overwhelming that researchers announced them in August 2001 — a year ahead of schedule. The research was published in the New England Journal of Medicine in 2002.

Dramatic results from changing diet, exercising

DPP researchers found that intensive lifestyle changes reduced the rate of developing Type 2 diabetes by 58 percent over an average of three years, and Metformin, which was distributed to participants under an investigational drug license for treatment of prediabetes, reduced the rate of diabetes development by 31 percent.

“The results were so dramatic; we were so impressed with the results of the Metformin and lifestyle groups,” said Dr. Ronald B. Goldberg, the principal investigator for the Miami branch of the study and a UM professor of medicine, biochemistry and molecular biology.

But the diabetes study, which was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, didn’t stop there.

Learning about complications of diabetes

Since the initial study, researchers have successfully applied for a series of five-year grants for the Diabetes Prevention Program Outcomes Study (DPPOS) and have continued to follow many of the same participants to learn more about the longer-term effects of diabetes and prediabetes on the body and mind.

“This has been our baby for the past 25 years,” said Goldberg, who is also co-director of the UM Diabetes Research Institute Clinical Laboratory. Goldberg emphasizes that the Miami research has been “a team effort. There is no way I could have gotten this done myself.”

The Miami team includes co-coordinators Jeanette Calles, who is also the lifestyle coach, and Juliet Sanguily, who have been with the study since the beginning, and Bertha Veciana, a research assistant who has worked with participants for the past 13 years.

Nationwide, about 84 percent of all surviving study participants joined the extended DPPOS programs. There are 87 active participants in the Miami group.

Many are in their 80s; the youngest are now in their late 50s. One is a centenarian. Some original patients have passed away, others have retired, switched jobs, married or remarried, and watched children grow up but one thing remains constant: The study goes on.

Even some who retired and moved away continue to take part via phone surveys and fly in from as far away as Texas, Kentucky, North Carolina and Georgia or drive in from retirement homes around the state for their annual visits.

“It’s a very special group,” said Veciana. “The participants have been very committed to the study.”

In the name of science, countless vials of their blood have been drawn; breathing, heart rates, blood pressure, circulation and body measurements have been monitored; the soles of their feet pricked to check nerve sensitivity.

They’ve undergone electrocardiograms, an ultrasound of their carotid arteries, and bone density, oral glucose tolerance and urine tests, and had multiple photographs of their retinas taken. Tests to check their physical conditioning and memory and other cognitive abilities also have been given.

Type 2 diabetes, the most common form of diabetes, occurs when the body doesn’t produce sufficient insulin and too much glucose builds up in the bloodstream. Over time this excess glucose can damage blood vessels, kidneys, eyes and nerves. It is the main cause of kidney failure, limb amputation and new onset blindness in adults and a major cause of heart disease and stroke.

Now the continuation study is focused on the longer-term effects of the lifestyle and medication interventions on the development of Type 2 diabetes and diabetic complications.

Such complications can take years off a person’s life as well as impair their quality of life, said Calles. Every year 170,000 Americans die of diabetes or its complications and the risk of developing Type 2 diabetes increases with age.

Because the participants in the studies are an aging population, about 60 percent of them have now developed Type 2 diabetes despite the lifestyle and medication interventions, said Goldberg.

Lifestyle changes prove very beneficial

However, the first 10-year follow-up study showed that participants who made lifestyle changes were still one-third less likely to develop Type 2 diabetes than individuals who had taken a placebo. The rate of development of diabetes in participants taking Metformin was reduced by 18 percent.

For those who did develop diabetes, the lifestyle interventions delayed the onset of diabetes by four years and taking Metformin delayed the onset by two years.

The third phase of the study has looked at the longer-term effects of the interventions on the development of eye, foot, nerve, and kidney disease and whether sugar levels affect physical and cognitive function and bone density. It’s also specifically looked at the long-term effects of the Metformin intervention on cancer and cardiovascular disease.

Preliminary findings of the DPP Outcomes Study found no significant difference among the three research groups in the prevalence of eye, nerve, and kidney complications. “It may take even longer to see if those complications develop,” said Goldberg.

The interventions also didn’t appear to make a difference in cognitive functioning. “They didn’t but it could be that 25 years isn’t enough time for cognitive complications to show up,” he said.

The data for the third phase of the study is still being analyzed and the results will be published within the next six months, said Goldberg.

He said it’s still too early to tell if initially delaying the onset of diabetes will translate into long-lasting effects.

Funding for the third phase of the DPP Outcomes Study ends in January 2022 and the program will take the first few months of the new year to close out.

But at the invitation of the National Institute on Aging, DPPOS researchers are applying for another grant that would study cognitive and physical functioning as a person ages and if any differences are associated with changes in blood sugar.

“Because many of our participants are now in their 70s, we’ve become more and more interested in what happens with complications in older patients,” said Goldberg.

“We have all kinds of data that we’ve been collecting for the past 25 years,” said Calles.

By next summer researchers should hear if their grant application is successful.

Meanwhile, the studies have continued to pay dividends for those at risk of developing Type 2 diabetes.

As a result of the initial DPP study, Congress authorized the National Diabetes Prevention Program, a partnership of public and private organizations that work to prevent or delay the onset of Type 2 diabetes.

Through messaging, events and educational materials, the National Diabetes Education Program, which is funded by the National Institute of Diabetes and Digestive and Kidney Diseases, is helping communities to develop programs based on DPP research.

The NDEP isn’t just working with healthcare centers or businesses. Some of the certified programs are being developed with senior centers, places of worship and other community organizations.

Millions of people with prediabetes

Currently there are about 88 million adults in the United States with prediabetes, but it’s “still a minority of people who are identified as prediabetics,” Goldberg said.

Early intervention is important, he said. “Each 1 percent reduction in weight means a 16 percent lower chance of developing diabetes,” Goldberg said.

Physicians often tell their prediabetic patients to lose weight, “but most people don’t get into any type of program, and they often need that push to lose weight and exercise,” said Goldberg. “If they do get into a prediabetes monitoring program, their physicians can identify any worsening much earlier.”

As part of the National Diabetes Education Program, the University of Miami has developed a phone app called UPrevent to help patients understand how they can better control or delay the onset of diabetes. It’s expected to go live soon, said Goldberg.

In 2018, the Center for Medicare and Medicaid Services began covering some lifestyle-change programs for Medicare recipients.

Participants in the study say they also continue to reap benefits from taking part in the research.

Program changed his life

“The knowledge and health benefits shared with me throughout the years are immeasurable,” said Bennie Perdue, who was in the lifestyle modification group. “The information associated with healthy eating and its relationship to exercise changed my daily routine. I walk and work out at a fitness center on an average of three days a week,” said Perdue, who lives in Pembroke Pines. He’s also diligent about his diet.

The 74-year-old lost the recommended weight, has kept it off and hasn’t developed diabetes. Perdue said his overall health benefited from the monitoring he received during the program as well as the constant encouragement to see his primary physician if any issues were raised during the testing.

Iliana Gonzalez was working as an administrative assistant in the Diabetes Research Institute building in 1996 when she heard the study was enrolling participants. She had gestational diabetes when she was pregnant with the last of her four children, but it went away after she gave birth. Her mother also had diabetes although she was undiagnosed for years.

Gonzalez was randomized into the lifestyle group and managed to take off 7 percent of her weight initially but said her weight has yo-yoed up and down in the intervening years. She developed diabetes in 2004, and currently takes Metformin and insulin at night if her blood sugar readings are high.

“I’m controlled,” said Gonzalez, 70, who lives in Kendall. “This program really teaches you a lot. I’m really thankful for the beautiful crew we have at DPPOS. They’ve always taken care of me. To me, they are family.”

Mimi Whitefield has been a participant in the DPP and DPPOS programs since 1996.

What is prediabetes?

Among the risk factors for prediabetes are a family history of Type 2 diabetes, overweight, over age 40, high blood pressure and gestational diabetes during pregnancy. Prediabetes is more prevalent in Hispanics, Blacks, Asians, and Native Americans.

It is determined by a blood test and there are three ways to diagnose it:

Fasting blood glucose:At least 126 mg/dL

Two-hour blood glucose:140-199 mg/dL

HbA1c: Between 5.7 percent and 6.4 percent is considered prediabetes

©2021 Miami Herald. Visit miamiherald.com. Distributed by Tribune Content Agency, LLC.