Patients who received high-intensity statin therapy had a 23% elevated risk for developing type 2 diabetes (T2D) compared to those on low-intensity statins, the results of a large study showed. In addition, this risk increased progressively with higher BMI.
On the plus side, compared to the least fit patients, cardiorespiratory fitness was protective, either “obliterating” the risk associated with high-intensity statins or reducing it enough to be protective, lead study investigator Peter Kokkinos, PhD, director for exercise and aging at Rutgers University in New Brunswick, New Jersey, told Medscape Medical News.
The study was published online in Mayo Clinic Proceedings.
The overall risk–benefit calculation still favors statins, said Kokkinos, who is also a professor in the Department of Kinesiology and Health at Rutgers University.
“What is very clear is that statins do prevent major cardiac events, so there is no argument for stopping statins to lower the risk of diabetes,” he explained. Mortality in individuals taking high-intensity statins was 11% lower compared to those taking low-intensity statins, which is “consistent with other research showing statins do work.”
The question remains: how best to lower or reverse the T2D risk? Kokkinos and his colleagues set out to look at the impact of cardiorespiratory fitness on this risk.
More Than a Decade of Follow-Up
Kokkinos and colleagues studied 311,269 US veterans with dyslipidemia from the Exercise Testing and Health Outcomes Study (ETHOS) dataset. All were prescribed statin therapy for at least 6 months and had no diabetes at baseline. Mean age was 61 years and approximately 5% were women. After a mean of 10.9 years of follow-up, about 18% developed T2D.
A BMI of 18-24.9 was considered normal weight. Overweight was defined as 25 to less than 29.9; obesity class I was 30-34.9, and obesity classes II and III were combined as a BMI of 35 or greater.
Key Findings: BMI
Compared to normal-weight patients prescribed low-intensity statins (the reference group), the adjusted risk of developing T2D increased by 44% with each 5 units additional BMI (HR, 1.44; 95% CI, 1.43-1.46; P < .001). The normal weight/low-intensity statin group had a 28% higher risk than the reference group (HR, 1.28; 95% CI, 1.21-1.35; P < .001); participants with overweight taking low-intensity statins had a 63% higher risk (HR, 1.63; 95% CI, 1.56-1.72; P < .001); and those with overweight taking high-intensity statin therapy were two times more likely (HR, 2.08; 95% CI, 1.98-2.18; P < .001) to develop T2D.
Veterans with obesity class I prescribed low-intensity statins were 2.56 times more likely and those taking high-intensity therapy were 3.17 times more likely than the reference group to develop T2D. People with class II and III obesity were 3.52 times more likely if prescribed low-intensity statins and 4.44 times more likely if prescribed a high-intensity regimen (P < .001 for all comparisons).
“What is obvious is that if you are on high-intensity statins, the risk is a little bit higher, no matter what your BMI is,” Kokkinos said.
Rita Kalyani, MD, MHS, chief scientific and medical officer at the American Diabetes Association, noted, “Obesity is a major risk factor for developing type 2 diabetes, primarily because excess body fat causes the body’s cells to become less responsive to insulin, leading to insulin resistance. As a result, blood glucose levels rise and can lead to the development of diabetes.”
Key Findings: Cardiorespiratory Fitness
Researchers assigned veterans to one of five fitness cohorts based on peak metabolic equivalents (METs) as determined by standard exercise treadmill tests: least-fit, low-fit, moderate-fit, fit, and high-fit.
Using the least-fit group as a reference, the adjusted risk of developing T2D was 18% lower for the low-fit group. That adjusted risk improved to 27% lower for the moderate fit group, 40% lower for the fit group, and soared to 57% lower for the high-fit group, regardless of statin intensity.
The moderate-fit group achieved an 8.4 MET or more peak treadmill test result, and this was associated with a 30% decreased risk of developing T2D independent of statin intensity or BMI. This level of fitness is achievable for most middle-aged and older adults who meet the recommendation for 150 minutes of moderate-to-intense physical activity per week, such as brisk walking most days, the researchers noted.
“The current study provides persuasive evidence that moderate improvements in cardiorespiratory fitness and reducing body weight may mitigate the ‘collateral damage’ of the diabetogenic effects of statin therapy, ultimately leading to more favorable health outcomes,” they write.
Kokkinos recommended a gradual approach to initiating exercise, with the caveat to consult a physician before starting a new exercise regimen. Start with a brisk walk for 10 minutes per day, most days of the week, he suggested. Add 1 to 3 minutes to each exercise session after week 2 and add a day to your routine after week 4 and another day after week 8. This will result in 150 minutes or more of exercise per week within 10 to 12 weeks, he said.
Combining Statins and Exercise
“Interestingly, recent research has suggested that higher levels of cardiorespiratory fitness can confer cardiovascular benefits that are roughly comparable to those seen with moderate statin therapy in certain populations,” Diaa Hakim, MBBS, PhD, director of the Cardiac Vascular & Intravascular Imaging Core Lab at Brigham and Women’s Hospital in Boston, told Medscape Medical News.
Observational studies also show that patients with high fitness have lower rates of cardiovascular events, even in the presence of risk factors like diabetes, added Hakim, who is also a research associate in the hospital’s Department of Medicine.
The benefits are seen through improved insulin sensitivity, lipid profiles, endothelial function and blood pressure. “In some analyses, high fitness can offset the risk associated with T2D to a degree similar to moderate-intensity statin therapy, though combining both interventions is still superior for most patients,” he said.
The study was independently supported. Kokkinos, Kalyani, and Harim report no relevant financial relationships.
