A lifestyle intervention program of increased physical activity, healthy eating, and a goal weight loss of 7% or more, or taking the drug metformin were effective long-term in delaying or preventing type 2 diabetes in adults with prediabetes. However, neither approach reduced the risk of cardiovascular disease for study participants over the 21 years of the study, according to findings from the Multicenter Diabetes Prevention Program Outcomes Study (DPPOS), published today in the peer-reviewed flagship journal of the American Heart Association. Circulation.
Type 2 diabetes (T2D) is the most common form of diabetes, affecting more than 34 million people in the US, representing almost 11% of the US population. Cardiovascular disease (CVD) It is the leading cause of death and disability among people with T2D. Type 2 diabetes occurs when the body can’t efficiently use the insulin it makes and the pancreas can’t make enough insulin. Adults with type 2 diabetes are twice as likely to die from cardiovascular diseases, including heart attacks, strokes, or heart failure, compared to adults without type 2 diabetes. People with T2D often have other risk factors of cardiovascular diseases, such as being overweight or obese, high blood pressure or high cholesterol.
The DPPOS evaluated 21 years of follow-up (through 2019) for the 3,234 adults who participated in the original 3-year Diabetes Prevention Program (DPP) trial. This DPPOS analysis focused on whether the drug metformin or lifestyle intervention could reduce the risk of cardiovascular disease or the rate of major cardiac events, such as heart attack, stroke, or death from cardiovascular disease.
“The risk of cardiovascular disease in people with prediabetes increases, and the risk of CVD increases further over time after type 2 diabetes develops and progresses,” said Ronald B. Goldberg, MD, chair of the writing group of DPPOS and professor of medicine. , biochemistry and molecular biology in the division of diabetes, endocrinology and metabolism, and senior faculty member and co-director of the Clinical Laboratory of the Diabetes Research Institute at the University of Miami Miller School of Medicine in Miami, Florida. “We focused on evaluating the impact of lifestyle or metformin interventions for the prevention of type 2 diabetes in people with prediabetes to reduce cardiovascular disease.”
The DPP was a landmark randomized trial of 27 centers in the US between 1996 and 2001 to assess how to prevent or delay the onset of T2D in people with prediabetes. Study participants were evaluated and accepted into the DPP based on these criteria: initially, a glucose reading of 140-199 mg/dL at 2 hours on an oral glucose tolerance test; fasting glucose levels of 95-125 mg/dL; and body mass index of 24 kg/m2 or higher.
A racially diverse group of 3,234 adults was studied in the original DPP for almost three years. The participants had an average age of 51 years, and almost 70% of the participants were women. People in the intensive lifestyle intervention group (nutritional improvement and physical activity aimed at achieving 7% weight loss) reduced the incidence of developing T2DM by 58%, and participants taking doses of metformin twice times a day had a 31% reduced incidence for T2D, compared to people in the placebo group who received standard care, which included information about effective treatment and management of T2D at diagnosis.
The DPPOS began in 2002 and was open to all participants in the original DPP trial. DPPOS enrolled nearly 90% of the original study participants for up to 25 years of follow-up to assess the long-term impact of interventions on the development of T2D and its complications. Due to the success of the lifestyle intervention, all study participants were offered to participate in the lifestyle intervention through a group format during a one-year bridging period. The group that took metformin in the original DPP trial were able to continue taking the drug during the DPPOS, and they knew they were taking metformin, not placebo. (The metformin and placebo groups were blinded in the original DPP, so participants did not know whether they were taking metformin or placebo during that time period.)
“From the beginning of the Diabetes Prevention Program, we were primarily interested in whether diabetes prevention would lead to a reduction in the development of complications caused by type 2 diabetes: cardiovascular disease, kidney disease, retinopathy and neuropathy.” Goldberg said. “Controlling blood glucose levels is important and we encourage interventions to prevent long-term complications of type 2 diabetes.”
The DPPOS evaluated cardiovascular disease outcomes to determine the effects of lifestyle and metformin interventions on participants’ risk of nonfatal heart attack, stroke, or death due to a cardiovascular event, comparing the results of each intervention group with the placebo group. . The researchers reported results based on a median follow-up of 21 years, which included the average follow-up period of three years from the original DPP trial. The authors performed a futility analysis of cardiovascular outcomes, resulting in study termination before completion of the planned 25-year follow-up.
Throughout the study, participants were evaluated annually with electrocardiogram tests; measures of your risk factors for cardiovascular disease, including smoking, cholesterol levels, and blood pressure levels; and body mass index measurements. The percentage of all participants taking medications to lower blood pressure and cholesterol increased over the duration of the study and was slightly lower among participants in the lifestyle group compared to the other two groups.
After an average follow-up of 21 years, the researchers found no significant difference in the incidence of heart attack, stroke, or cardiovascular death among the three intervention groups. Specifically, the analysis found:
There was a continuous reduction or delay in the development of T2D for up to 15 years. The number of nonfatal heart attacks in each group was similar: 35 heart attacks occurred in the lifestyle intervention group; 46 in the metformin group; and 43 in the placebo group. Similarities were also found in the number of non-fatal strokes: 39 stroke incidents in the lifestyle intervention group; 16 in the metformin alone group; and 28 in the placebo group. The number of deaths due to cardiovascular events was low: 37 deaths among lifestyle intervention participants; 39 in the metformin group; and 27 in the participants who took the placebo during the original DPP trial.
“The fact that neither a lifestyle intervention program nor metformin led to a decrease in cardiovascular disease among people with prediabetes may mean that these interventions have limited or no efficacy in preventing cardiovascular disease, despite the fact that they are very effective in preventing or delaying the development of type 2 diabetes,” Goldberg said. “It is important to note that most study participants also received treatment with cholesterol and blood pressure medications, which are known to reduce CVD risk. Therefore, the low rate of development of cardiovascular disease found in general it may be due to these drugs, which would make “It is difficult to identify a beneficial effect of lifestyle or intervention with metformin. Future research is needed to identify higher risk subgroups to develop a more targeted approach to cardiovascular disease prevention in people with prediabetes and type 2 diabetes.”
There were several limitations in the study. The researchers selected a subgroup of people who met the criteria for prediabetes; however, these results cannot be generalized to all people with prediabetes. Furthermore, the intensity of the lifestyle intervention was reduced after the initial DPP phase and, over the 21-year study period, there was a gradual reduction in medication adherence by participants in the treatment group. metformin. There was also off-study use of metformin in patients diagnosed with type 2 diabetes, which may have diluted differences between study groups. The high level of blood pressure and cholesterol medications prescribed by the participants’ primary care team, as well as the lower use of blood pressure medications in the lifestyle group, may have influenced the results. There may also be an underestimation of cardiovascular events, as some participants did not complete 21 years of follow-up.
“These long-term findings confirm that the link between type 2 diabetes and cardiovascular disease is complex and requires more research to better understand,” said American Heart Association medical director for prevention Eduardo Sanchez, MD, MPH, FAHA, FAAFP, and clinical lead for Know Diabetes by Heart, a collaborative initiative between the American Heart Association and the American Diabetes Association that addresses the link between diabetes and cardiovascular disease. “However, these important results also tell us that lifestyle intervention is remarkably effective in delaying or preventing type 2 diabetes, which itself reduces the risk of cardiovascular disease. The CDC estimates that nearly 1 in Every 3 adults in the US have prediabetes, therefore preventing or delaying type 2 diabetes is a public health imperative to help prolong and improve the lives of millions of people.”
The study was funded through grants from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. Several other divisions of the National Institutes of Health provided additional funding: the National Institute of Child Health and Human Development, the National Institute on Aging, the National Eye Institute, the National Heart, Lung, and Blood Institute, the National Cancer Institute, and the National Institute on Minority Health and Health Disparities; as well as the Office of Research on Women’s Health of the US Department of Health and Human Services; the US Centers for Disease Control and Prevention; and the American Diabetes Association.
Source: www.sciencedaily.com