Increased CVD Risk Seen Up to 30 Years Before Type 2 Diabetes Diagnosis

An increased risk of cardiovascular disease may be present as early as 30 years before a type 2 diabetes diagnosis is made, Danish registry data show.

Over that span, the rate of MI or ischemic stroke was more than twice as high in those who would eventually be diagnosed with diabetes than in nondiabetic controls (11.2% vs 4.7%), researchers led by Christine Gyldenkerne, MD (Aarhus University Hospital, Denmark), report.

This indicates that the elevated risk of CVD seen in patients with type 2 diabetes may not be related entirely to the diabetes itself, they say.

“There may be some underlying risk factors, such as obesity, hypertension, and dyslipidemia, that are associated both with the development of later type 2 diabetes and also cardiovascular disease,” Gyldenkerne told TCTMD, noting that hospital-diagnosed obesity and hypertension were more common in those who would go on to receive a diabetes diagnosis in this study.

In their paper, published online ahead of the December 3, 2024, issue of the Journal of the American College of Cardiology, the investigators note that 537 million adults around the world were estimated to have diabetes in 2021, with that figure projected to balloon to 783 million by 2045.

I was quite surprised to find this even 30 years back in time, where the median age of these patients was 32 years. Christine Gyldenkerne

In that context, the current findings “indicate that comprehensive preventive strategies may be initiated much earlier than today” and “highlight that primary prevention is vital throughout the life course,” Gyldenkerne said. “We already know that, but our findings underscore that more can be done.”

Indeed, Laurence Sperling, MD (Emory University, Atlanta, GA), commented to TCTMD, “this is an essential study for people to recognize challenges before us and ahead of us related to cardiovascular risk that plays out over many decades.”

Looking Back in Time

Though prior studies have demonstrated that CVD risk is higher at least several years preceding a diabetes diagnosis, it had been unknown how far back that risk could be detected.

To explore this question, Gyldenkerne and her colleagues turned to Danish national health registries to examine CVD occurrence in the 30 years before and 5 years after a type 2 diabetes diagnosis. The study included 127,092 patients who were diagnosed between 2010 and 2015 and 381,023 peers from the general population, matched by age and sex, who were not diagnosed with diabetes; median age was 62, and 54% were men.

At the index date (the time of diabetes diagnosis or matched time in the control group), patients with diabetes had a higher comorbidity burden and had greater use of various cardiovascular medications, including statins and antihypertensives. Patterns were similar as far back as 15 years before the index date, with low rates of morbidities 20 and 30 years prior.

The occurrence of CVD—MI or ischemic stroke—was higher in people who would eventually be diagnosed with type 2 diabetes than in the controls for the entire 30-year period leading up to the index date, with ORs ranging from 2.18 (95% CI 1.91-2.48) in the earliest time period to 2.96 (95% CI 2.85-3.08) in the most recent 5 years.

“I was quite surprised to find this even 30 years back in time, where the median age of these patients was 32 years,” Gyldenkerne said. “I expected to find it for many years, but not necessarily 30 years back in time.”

The incidence of CVD remained higher in diabetic patients in the 5-year period following the index date (4.6% vs 2.5%; HR 2.20; 95% CI 2.12-2.27).

These findings were consistent in both men and women, across various age groups, and for MI and ischemic stroke as individual endpoints.

Urgent Need to Address the Diabetes Epidemic

These results put a spotlight on the need for primary prevention throughout life, Gyldenkerne et al say, noting that the recently developed PREVENT equations from the American Heart Association, which provide estimates of 10- and 30-year risks of CVD, can be used to guide shared decision-making conversations about lifestyle behaviors and drug therapy with people as young as 30.

Still, randomized data to guide primary prevention in young adults are lacking, Gyldenkerne pointed out. She added, however, that the ongoing PRECAD trial, which is looking at aggressive CV risk factor control in otherwise healthy young adults, may help fill that knowledge gap.

Sperling, who wrote an editorial accompanying the Danish study, underscored to TCTMD how imperative it is to address the epidemic of type 2 diabetes, which “is one of the most important challenges for humans today and in the future.”

By the time a lot of these patients get to cardiologists or endocrinologists, subspecialists, the clock has been ticking for many decades. Laurence Sperling

Data show that the global community is not doing a good job so far, he said. “This paper points out the urgency of the situation. And unfortunately, there’s a lot of complacency related to chronic diseases because they’ve become so common that many have become accepting that this is going to be the course of individuals and communities and populations.”

The “ticking clock” prior to the diagnosis of diabetes, as illustrated in the current study, is “a cause for concern, but also a window of opportunity,” Sperling argued. He suggested that advances in technology and drug therapies, as well as lower barriers to accessing care through universal healthcare (as in Denmark), are not enough to tackle the problem of type 2 diabetes.

He pointed to investment in public health initiatives, a focus on health promotion and disease prevention in schools, efforts to improve maternal health, changes in the food environment, and environmental engineering to encourage people to be more active as needed elements of a broader strategy to start making gains in this area.

“I do think clinicians should be much more aware of this risk across time, and that dials all the way back to pediatricians and children, family practitioner physicians, because by the time a lot of these patients get to cardiologists or endocrinologists, subspecialists, the clock has been ticking for many decades,” Sperling said.

Although CVD risk can be modified at older ages, he added, “I do think in the big scheme of things, this paper needs to bring us back to the importance of prevention, health promotion, and investment in public health and public policy.”