Spain: Study on Cardioautonomic Neuropathy in Type 1 Diabetes

A recent study noted an increase in the prevalence of asymptomatic cardioautonomic neuropathy (CAN) with menopause in women with type 1 diabetes (T1D), a recent study published in Cardiovascular Diabetology has shown.

In contrast, this age-related excess CAN risk was not seen in men, implying that women and men with type 1 diabetes have opposite associations between circulating androgens and cardioautonomic function indexes.

Given the link between cardioautonomic neuropathy and CVD (cardiovascular disease), the high prevalence of asymptomatic autonomic dysfunction in women older than 50 suggests the need to evaluate screening programs for CAN in postmenopausal women to improve their cardiovascular risk stratification.

Cardioautonomic neuropathy is a frequent complication of type 1 diabetes that is associated with increased morbidity and mortality. Sex differences characterize cardiovascular outcomes in type 1 diabetes patients. In these patients, data is scarce and controversial regarding the interplay between sex and cardiovascular autonomic neuropathy.

To fill this knowledge gap, Lía Nattero-Chávez and colleagues from Spain addressed sex-related differences in the prevalence of seemingly asymptomatic CAN in T1D and their associations with sex steroids.

For this purpose, the research team conducted a cross-sectional study comprising 322 consecutively recruited T1D patients. Diagnosis of CAN was made using power spectral heart rate data and Ewing's score. Sex hormones were assessed by tandem mass spectrometry/liquid chromatography.

Study Findings

• Considering all subjects, asymptomatic CAN prevalence was not remarkably different between women and men.
• When age was considered, the cardioautonomic neuropathy's prevalence was comparable among young men and those > 50 years.
• In women > 50 years, CAN's prevalence doubled that of young women [45.8% versus 20.4%, respectively].
• The OR of having CAN was 3.3 more significant in women above 50 years than their younger counterparts.
• Compared to men, women presented more severe cardioautonomic neuropathy. These differences were even more pronounced when women were classified according to their status of menopause rather than age.
• Menopausal and peri-menopausal women had an OR 3.5 of having CAN than their reproductive-aged counterparts [CAN prevalence: 51% versus 23%, respectively].
• A binary logistic regression model displayed age > 50 as a significant determinant of CAN only in women.
• Androgens were positively linked with heart rate variability in men and negatively in women. Accordingly, CAN was linked with an increased ratio of testosterone/estradiol in women but decreased testosterone concentrations in men.

"Our findings confirm that the prevalence of seemingly asymptomatic CAN is markedly increased in female type 1 diabetes patients age 50 and older," the researchers wrote.

Older men have a similar CAN prevalence to their younger male fellows; menopause in women is accompanied by a dramatic rise in the CAN prevalence compared to reproductive-aged women, which have 3.5 times greater odds of having CAN compared to younger women patients.

They explained, "this excess CAN risk might contribute to explain the noticeable increase in the incidence of CVD (cardiovascular disease) following the menopausal transition in females with type 1 diabetes."

It is suggested that sex steroids might be involved in the CAN's etiopathogenesis, even though further studies should be designed for confirmation.

Reference

Nattero-Chávez, L., Insenser, M., Quintero Tobar, A. et al. Sex differences and sex steroids influence on the presentation and severity of cardiovascular autonomic neuropathy of patients with type 1 diabetes. Cardiovasc Diabetol 22, 32 (2023). https://doi.org/10.1186/s12933-023-01766-y