Association of Lower Cardiovagal Tone and Baroreflex Sensitivity With Higher Liver Fat Content Early in Type 2 Diabetes

J Clin Endocrinol Metab. 2018 Mar 1;103(3):1130-1138. doi: 10.1210/jc.2017-02294.


Context: Cardiovascular autonomic neuropathy (CAN) diagnosed by diminished heart rate variability (HRV) is prevalent and carries an increased risk of mortality in patients with diabetes and chronic liver diseases.

Objective: To determine whether lower HRV is associated with increased liver fat content in recent-onset diabetes.

Design: Cross-sectional study.

Setting: German Diabetes Study (GDS), Düsseldorf, Germany.

Participants: Individuals with type 1 diabetes (n = 97) or type 2 diabetes (n = 109) with known diabetes duration ≤1 year and two age- and sex-matched glucose-tolerant control groups from the GDS baseline cohort.

Main outcome measures: Four time and frequency domain HRV indices each were measured over 3 hours during a hyperinsulinemic-euglycemic clamp, whereas spontaneous cross-correlation baroreflex sensitivity (xBRS) was computed over 5 minutes. Hepatic fat content was determined by 1H magnetic resonance spectroscopy, and values >5.56% were defined as hepatic steatosis.

Results: Hepatic steatosis was observed in 52% and 5% of patients with type 2 and type 1 diabetes, respectively. After adjustment for sex, age, body mass index, smoking, diabetes duration, hemoglobin A1c, M-value, and triglycerides, all four vagus-mediated time domain HRV indices, three of four frequency domain indices, and xBRS were inversely associated with liver fat content in participants with type 2 diabetes (all P < 0.05) but not in the group with type 1 diabetes.

Conclusions: Both lower cardiovagal tone and baroreflex sensitivity are strongly associated with prevalent hepatic steatosis in patients with recent-onset type 2 as opposed to type 1 diabetes, suggesting a role for hepatic steatosis in the early development of parasympathetic CAN in type 2 diabetes.

Trial registration: NCT01055093.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autonomic Nervous System / physiopathology*
  • Autonomic Nervous System Diseases / etiology
  • Baroreflex / physiology*
  • Case-Control Studies
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 1 / physiopathology
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Fatty Liver / etiology*
  • Female
  • Glucose Clamp Technique
  • Heart Rate / physiology*
  • Humans
  • Liver / pathology
  • Magnetic Resonance Spectroscopy
  • Male

Associated data