Diabetic autonomic neuropathy does not hinder improvement in hypoglycemia awareness: HypoCOMPaSS Trial Sub-Study

The study found that impaired awareness of hypoglycemia (IAH) can be improved in patients with type 1 diabetes mellitus (T1DM) and a long disease duration, with and without cardiac autonomic dysfunction.

These findings, published in Diabetic Medicine, suggest cardiac autonomic neuropathy (CAN) is not a prime driver for modulating IAH reversibility.

Hypoglycemia, characterized by dangerously low blood sugar levels, poses a significant challenge for individuals living with diabetes, often leading to debilitating symptoms and, in severe cases, loss of consciousness or death. Impaired hypoglycemia awareness, a common complication in diabetes, further complicates management efforts by blunting the body's ability to perceive and respond to low blood sugar levels, increasing the risk of adverse outcomes.

IAH increases severe hypoglycemia risk in patients with T1DM. IAH can be reversed through meticulous avoidance of hypoglycemia. Diabetic autonomic neuropathy (DAN) has been proposed as an underlying mechanism contributing to IAH; however, data has been consistent. Ahmed Iqbal, University of Sheffield, Sheffield, UK, and colleagues aimed to examine the effects of CAN on IAH reversibility in T1DM.

The study included participants with type 1 diabetes and IAH (Gold score ≥4) recruited to the HypoCOMPaSS (24-week 2 × 2 factorial randomized controlled) trial. All underwent screening for cardiac autonomic function testing at baseline and received comparable support and education for improving hypoglycemia awareness and avoiding hypoglycemia.

Definite CAN was defined as the presence of ≥2 abnormal cardiac reflex tests. Participants were divided according to their CAN status, and Gold score changes were compared.

The study included eighty-three participants (62.7% women) with a mean age of 48 years and a mean HbA1c of 66 mmol/mol. The mean duration of T1DM was 29 years.

The study led to the following findings:

• The prevalence of CAN was low, with 6% of participants having definite autonomic neuropathy and 13% classified with possible/early neuropathy.
• Regardless of their autonomic function status, all participants showed a mean improvement in Gold score of ≥1 (mean improvement −1.2).

The study revealed that the prevalence of cardiac autonomic neuropathy was low overall. CAN presence did not impede hypoglycemia awareness improvement as participants with or without CAN improved their hypoglycemia awareness.

"There is a need for more research with larger numbers to elucidate pathophysiological defects culminating in IAH by addressing the challenge of clinical heterogeneity," the researchers wrote.

Reference:

Arshad, M. F., Walkinshaw, E., Solomon, A. L., Bernjak, A., Rombach, I., Little, S. A., M. Shaw, J. A., Heller, S. R., & Iqbal, A. Diabetic autonomic neuropathy does not impede improvement in hypoglycaemia awareness in adults: Sub-study results from the HypoCOMPaSS trial. Diabetic Medicine, e15340. https://doi.org/10.1111/dme.15340