What is the clinical evidence from this study?

Study design: Cross-Sectional. Population: Diabetes mellitus (n=928). Intervention: Elevated blood HbA1c vs. Lower blood HbA1c / Nondiabetic population. Primary outcome: High-frequency heart rate variability (HF-HRV) in participants with diabetes mellitus (Sb -0.118, 95% CI -0.208, -0.027, p=0.012).

What does this research mean for the field?

Elevated blood HbA1c levels are significantly associated with adverse differences in heart rate variability in individuals with diabetes, but not in those without diabetes. Novelty: ClaimNovelty.CONFIRMATORY. Consensus alignment: ConsensusAlignment.SUPPORTS_CONSENSUS.

August 23, 2022Open Access

Blood hemoglobin A1c might predict adverse differences in heart rate variability in a diabetic population: Evidence from the Midlife in the United States (MIDUS) study

YHYing HuangNorth Dakota State University HCHong ChenHarbin Medical University DHDongxia HuNanchang University

Key Result

Elevated blood HbA1c levels were significantly associated with adverse differences in high-frequency heart rate variability (Sb -0.118) in the diabetic population, but not in the nondiabetic population.

Study Design

Type

Cross-Sectional (n=928)

Multicenter

Yes

Structured PICO

Are elevated blood HbA1c levels associated with adverse differences in heart rate variability in adults with and without diabetes mellitus?

Population

928 adult individuals with and without diabetes mellitus (DM) from the Midlife in the United States (MIDUS) study

Intervention

Blood hemoglobin A1c (HbA1c) levels

Outcome

Heart rate variability (HRV), specifically high-frequency (HF-HRV) and low-frequency (LF-HRV)surrogate

Elevated blood HbA1c levels are associated with adverse differences in heart rate variability in diabetic patients, suggesting long-term hyperglycemia contributes to autonomic nerve injury.

Main Result

Effect estimate: Sb -0.118 (95% CI -0.208, -0.027)

p-value: p=0.012

Limitations

Cross-sectional design cannot establish causality between elevated HbA1c and adverse differences in HRV.
Potential selection bias as participants needed to be relatively healthy to attend the clinical research centers.
Specific type of diabetes, duration of the disease, and medications were unclear.
History of cardiovascular diseases relied on self-reported questionnaire data.
327 individuals with missing data were excluded from the analysis.
LF-HRV is considered a poor indicator of sympathetic nervous system activity.
The lack of association in the non-DM group could be due to the constricted range of HbA1c in this group.

Abstract

Background: Cardiac autonomic neuropathy in population with diabetes mellitus (DM) is frequent and linked with high risk of cardiovascular mortality. However, studies on whether blood hemoglobin A1c (HbA1c) levels are related to adverse differences in heart rate variability (HRV) in individuals with DM are scarce. Aim: We aimed to investigate the association of blood HbA1c levels with adverse differences in HRV, which is an indicator of cardiac autonomic control, in adult individuals with and without DM. Methods: Data were collected from the Midlife in the United States (MIDUS) study, and 928 individuals were analyzed for the relationship between blood HbA1c levels and HRV through a cross-sectional analysis. Results: Participants with DM had significantly higher HRV than those without DM. The smooth curve suggested inverse relationships between blood HbA1c levels and HF- and LF-HRV seen in participants with DM but not in those without DM after controlling for all covariates (age, sex, BMI, smoking, number of drinking years and exercise). Furthermore, linear regression analysis demonstrated that elevated blood HbA1c levels did contribute to adverse differences in HF-HRV (Sβ= -0.118; 95% CI -0.208, -0.027; P=0.012) and LF-HRV (Sβ= -0.097; 95% CI -0.177, -0.017; P=0.019) after controlling for these covariates in participants with DM, while in participants without DM, blood HbA1c was not significantly related to adverse differences in HF-HRV (Sβ=0.095; 95% CI -0.059, 0.248; P=0.228) or LF-HRV (Sβ=0.043; 95% CI -0.103, 0.189; P=0.565). DM has a significant modifying effect on associations between blood HbA1c and adverse differences in HF-HRV (P for interaction=0.019) and LF-HRV (P for interaction=0.029). Conclusions: We reported strong evidence that elevated blood levels of HbA1c were associated with adverse differences in HRV in the diabetic population but not in the nondiabetic population. This finding supported that long-term hyperglycemia is related to autonomic nerve injury in the diabetic population. Blood HbA1c might be a good indicator of cardiac autonomic neuropathy.

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