The longer people had diabetes, the greater their rate of incident heart failure, suggests a recently published review of prospectively collected observational data from nearly 24,000 people with diabetes in the UK Biobank.
The findings “add to the growing body of evidence suggesting that duration of diabetes is an important and independent determinant of heart failure among patients with diabetes,” comments Justin B. Echouffo-Tcheugui, MD, PhD, in an accompanying editorial.
Collectively, the new UK Biobank results and prior findings, “provide additional persuasive evidence that the link between duration of diabetes and heart failure is real,” although the physiological mechanisms behind the relationship remain incompletely understood, writes Echouffo-Tcheugui, an endocrinologist at Johns Hopkins Medicine in Baltimore, Maryland.
“The duration of diabetes may reflect cumulative effects of various adverse processes in the setting of diabetes” that result in “intrinsic myocardial lesions,” he suggests. These adverse processes might include not only hyperglycemia, but also glucotoxicity, lipotoxicity, hyperinsulinemia, advanced glycosylation end products, oxidative stress, mitochondrial dysfunction, cardiac autonomic neuropathy, and coronary microvascular dysfunction. Long-duration diabetes may also contribute to declining kidney function that can further worsen heart failure risk.
The upshot is that clinicians may need to consider more systematically duration of diabetes when assessing people with diabetes for heart failure.
Existing risk-assessment tools for predicting heart failure in people with diabetes “have not always accounted for diabetes duration,” Echouffo-Tcheugui notes.
Intensify Heart Failure Detection With Longer Diabetes Duration
“Active heart failure detection should perhaps be intensified with increased diabetes duration,” Echouffo-Tcheugui suggests in his editorial. He notes that a 2022 consensus report by the American Diabetes Association recommends clinicians measure natriuretic peptide or high-sensitivity cardiac troponin in all people with diabetes “on at least a yearly basis to identify the earliest heart failure stages and implement strategies to prevent transition to symptomatic heart failure.”
The UK Biobank study was run by investigators primarily based in China and included data from 23,754 people with type 1 or type 2 diabetes and no heart failure at baseline. The prospectively collected data allowed for a median follow-up of 11.7 years, during which time 2081 people developed incident heart failure.
In an analysis that divided participants into four categories of diabetes duration (< 5 years, 5-9 years, 10-14 years, and ≥ 15 years) and adjusted for potential confounders, heart failure incidence showed a significant 32% increased incidence among those with diabetes for ≥ 15 years compared with those with diabetes for < 5 years. People with a diabetes duration of 5-14 years showed a trend toward having more incident heart failure compared with those with diabetes for < 5 years, but the difference was not significant.
An adjust analysis also showed poor glycemic control at baseline (A1c ≥ 8.0%) significantly linked with a 46% increased incidence of heart failure compared with those with baseline A1c < 7.0%.
When the authors analyzed the effect of both these variables, they saw a roughly additive effect.
Patients with diabetes for at least 15 years and a baseline A1c ≤ 8.0% had a 98% increased incidence of heart failure compared with those who had diabetes for less than 5 years and a baseline A1c < 7.0%, after adjustment. This association was independent of age, sex, and race.
These findings “highlight the paramount role of the duration of diabetes and its interaction with glycemic control in the development of heart failure,” the authors conclude. “Long duration of diabetes and poor glycemic control may result in structural and functional changes in the myocardium, which is likely to underlie the pathogenesis of heart failure among individuals with diabetes,” they add.
In his editorial, Echouffo-Tcheugui lauds the report for its “robust” analyses that included a large sample and accounted for key confounders, such as glycemic control. However, he also cites eight “shortcomings” of the study, including its sole reliance on A1c levels to identify diabetes, a likely underestimation of diabetes duration, the lumping together of people with type 1 and type 2 diabetes, and lack of a subanalysis of incident heart failure in those with preserved or reduced left ventricular ejection fraction.
Among prior reports of evidence also suggesting an effect of diabetes duration on incident heart failure, Echouffo-Tcheugui cites a study he led, published in 2021, that analyzed prospective, longitudinal, observational data from 9734 adults enrolled in the Atherosclerosis Risk in Communities study. The results showed that, compared to those without diabetes, the incidence of heart failure rose with longer diabetes duration, with the highest risk among those with diabetes for at least 15 years, who had a 2.8-fold increase in heart failure versus the reference group. Each 5-year increase in diabetes duration was associated with a significant 17% relative increase in heart failure incidence.
The study received no commercial funding. The authors and editorialist have reported no relevant financial relationships.
J Clin Endocrinol Metab. Published online November 16, 2022. Abstract, Editorial
Mitchel L. Zoler is a reporter for Medscape and MDedge based in the Philadelphia area. @mitchelzoler
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