More ADVANCE: Age, Duration of Diabetes Tied to Vascular Risk

Marlene Busko

September 13, 2014

Patients who are diagnosed with type 2 diabetes at an early age need good glucose control to help avoid the risk for microvascular complications, and older patients are especially at risk for macrovascular complications, such as MI and stroke, new research suggests.

The findings, from a new analysis of the ADVANCE study, looked at how patient age, age at diagnosis, and duration of disease each affect the risk for developing the 2 types of vascular complications in diabetes. They were published online September 11 in Diabetologia.

People who were diagnosed with type 2 diabetes at a younger age appeared to be more susceptible to the adverse long-term effects of hyperglycemia on the microvasculature, lead author Sophia Zoungas, PhD, of the George Institute for Global Health, University of Sydney, Australia, commented to Medscape Medical News in an email.

Having diabetes for more than 10 years was associated with an increased risk for microvascular complications (defined as new or worsening nephropathy or retinopathy).

Thus, clinicians need to "refocus [efforts] toward intensive management of hyperglycemia at diagnosis of type 2 diabetes in young patients…if the long-term risk for microvascular complications is to be minimized," she stressed. And given the increasing number of available nonpharmacological and pharmacological approaches, better glycemic control is achievable, according to the researchers.

The second part of the study showed that among patients with type 2 diabetes, being older and having diabetes for a longer time were each associated with an increased risk of having a macrovascular event (cardiovascular death, nonfatal MI, or nonfatal stroke) or dying from any cause during a median follow-up of 5 years.

Therefore, "with respect to macrovascular complications, effective prevention requires vigilance at all stages of the disease and across all age groups," Dr. Zoungas noted.

"However, as the absolute event rates are highest in the older age groups, surveillance for macrovascular disease should be intensified in older patients," she emphasized.

Older Age and Duration of Diabetes Associated With CVD Risk

An increasing number of 20- to 40-year-olds are being diagnosed with type 2 diabetes, the authors write. However, previous studies of the effects of patient age, age at diagnosis of type 2 diabetes, and duration of diabetes on macrovascular complications, death, and microvascular complications have reported inconsistent findings.

To investigate this, they examined data from the ADVANCE trial (published in the Lancet in 2007 and the New England Journal of Medicine in 2008).

From 2001 to 2003, ADVANCE enrolled 11,140 individuals in 20 countries with type 2 diabetes who were 55 and older at increased risk for CVD.

The patients were randomized to receive standard care or intensive glucose control with the sulfonylurea glicazide (Diamicron modified release, Servier). In a second part of the study, the patients were randomized to receive placebo or the combination antihypertensive perindopril/indapamide (Preterax, Servier).

At enrollment, the patients had a mean age of 65.8 years and had had diabetes for a mean of 7.9 years. Almost a quarter (21%) had been diagnosed when they were 50 or younger, and 39% had been diagnosed when they were older than 60. Close to a third (30%) had had diabetes for more than 10 years.

Older age and longer duration of diabetes were tied to an enhanced risk for CVD events or death during follow-up. After adjustment for blood pressure, glucose treatment, and baseline HbA1c levels, each 5-year increase in age was associated with a 33% increased risk for macrovascular events and a 56% increased risk for all-cause death.

In similar adjusted analyses, each 5-year increase in duration of diabetes was associated with a 13% increased risk for macrovascular events and a 15% increased risk for all-cause death.

Duration of Disease Linked to Microvascular Events

New or worsening retinopathy or nephropathy were more likely in patients who had diabetes a long time. In adjusted analyses, a 5-year increase in the duration of diabetes was associated with a 28% increased risk for microvascular complications; there was no increased risk with increasing age.

"The most likely explanation for the findings is that macrovascular events occur commonly in the general population and are strongly age dependent," the authors write.

Thus, it is not surprising that macrovascular events increased with age, with an added risk conferred by duration of diabetes.

In contrast, "microvascular events occur more commonly in populations with diabetes, and the risk of these events might thus be expected to be predominantly related to duration of diabetes," they conclude.

Zoungas was supported by a Heart Foundation of Australia Career Development award and has received lecture fees from Servier. Disclosures for the coauthors are listed in the article.

Diabetologia. Published online September 11, 2014. Article

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