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November 1, 2022JCI InsightOpen Access

Cardiac autonomic neuropathy was independently associated with a 23% increased risk of a first severe hypoglycemic event (HR 1.23) among adults with type 2 diabetes.

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Why the study?

Data on the link between cardiac autonomic neuropathy and severe hypoglycemia in type 2 diabetes were limited.

Does cardiac autonomic neuropathy increase the risk of severe hypoglycemia in adults with type 2 diabetes?

Population

7,421 adults with type 2 diabetes from the ACCORD study

Comparison

Participants with CAN vs without CAN

Design

Observational cohort study

Follow-up

4.7 years

Key result

Cardiac autonomic neuropathy was independently associated with a 23% increased risk of a first severe hypoglycemic event (HR 1.23) among adults with type 2 diabetes.

Authors

AKArnaud D. KazéMYMatthew F. YuyunRARexford S. Ahima

Discussion

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Overview

CAN may flag higher severe hypoglycemia risk in T2D, especially on standard glycemic control; leaves open whether CAN-targeted interventions reduce events.

Study Design

Type

Observational (n=7,421)

Multicenter

Yes

Structured PICO

Does cardiac autonomic neuropathy increase the risk of severe hypoglycemia in adults with type 2 diabetes?

P
Population
7,421 adults aged 40 to 79 years with type 2 diabetes and cardiovascular risk factors, followed for a median of 4.7 years.
E
Exposure
Presence of cardiac autonomic neuropathy (CAN), defined by ECG-derived heart rate variability measures (SDNN < 8.2 ms and rMSSD < 8.0 ms)
C
Comparator
Absence of cardiac autonomic neuropathy (no CAN)
O
Outcome
First episode of severe hypoglycemia (symptomatic low glycemia <50 mg/dL or symptoms resolving with treatment and requiring medical assistance) and recurrent episodes of severe hypoglycemiahard clinical

Main Result

Hazard Ratio: 1.23 (95% CI 1.01–1.5)

Absolute Event Rate: 21.9% vs 15.4%

p-value: p=0.038

Cardiac autonomic neuropathy is independently associated with a higher risk of first and recurrent severe hypoglycemia in adults with type 2 diabetes.

Limitations

  • CAN was defined using ECG-derived time-domain indices rather than gold standard dynamic cardiovascular autonomic reflex tests.
  • Continuous glucose monitoring was not used, potentially missing hypoglycemic episodes during sleep or in the setting of hypoglycemia unawareness.
  • Lack of data on the specific dose of insulin used.
  • Generalizability is limited by the intrinsic characteristics of participants included in the ACCORD study.
  • Observational design leaves the possibility of unmeasured, residual confounding.
  • CAN was defined using ECG-derived time-domain indices rather than dynamic cardiovascular autonomic reflex tests, potentially underestimating the association

Cite This Study

Kazé et al. (2022) conducted an observational in Type 2 diabetes (n=7,421). Cardiac autonomic neuropathy (CAN) vs. No cardiac autonomic neuropathy was evaluated on First episode of severe hypoglycemia (HR 1.23, 95% CI 1.01-1.50, p=0.038). Cardiac autonomic neuropathy was independently associated with a 23% increased risk of a first severe hypoglycemic event (HR 1.23) among adults with type 2 diabetes.

synapsesocial.com/papers/6a773f5b576efb0ddaf732c2https://doi.org/10.1172/jci.insight.156334
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