Emerging evidence suggests that obesity and insulin resistance play a role in the development of diabetic cardiac autonomic neuropathy (CAN) characterized by reduced heart rate variability (HRV). In this context we assessed the relationship of 127 biomarkers of lipid metabolism (11 acylcarnitines, 39 free fatty acids, 12 sphingomyelins, 56 phosphatidylcholines, and 9 lysophosphatidylcholines) in plasma using mass spectrometry with HRV indices in individuals with recent-onset type 1 (T1D) or type 2 diabetes (T2D) from the baseline cohort (known diabetes duration (DD) ≤1 year) of the German Diabetes Study (T1D/T2D [mean±SD]: n=126/243; age: 34.5±12.9/53.4±11.0 years; BMI: 24.7±4.3/31.7±6.0 kg/m²; DD: 211±93/198±90 days; HbA1c: 6.8±1.4/6.5±0.9 %). Time domain and frequency domain HRV indices were derived from NN intervals recorded during a 3 h hyperinsulinemic-euglycemic clamp. After adjustment for age, sex, and BMI as well as Bonferroni correction including seven HRV parameters and the number of metabolites of the corresponding lipid class, higher levels of three free fatty acids (myristic acid: β=-0.14, p=0.049; palmitic acid: β=-0.19, p=0.007; palmitoleic acid: β=-0.15, p=0.048), eight phosphatidylcholines (e.g., phosphatidylcholine diacyl (PC aa) C32:0: β=-0.28, p<0.001; phosphatidylcholine acyl-alkyl C34:3: β=-0.20, p<0.004), and two sphingomyelins (sphingomyelin C16:0: β=-0.15, p=0.028; sphingomyelin C16:1: β=-0.18, p=0.020) were inversely associated with the standard deviation of NN intervals (SDNN) in recent-onset T2D but not T1D. PC aa C32:0 was inversely associated with both low (LF) and high frequency (HF) power spectrum in T2D (LF: β=-0.23, p=0.001; HF: β=-0.23, p=0.001).

In conclusion, the link between higher plasma levels of specific lipid metabolites and early cardiac autonomic dysfunction in recent-onset type 2 diabetes suggests that plasma lipid panels could be useful to improve the prediction of the development or progression of CAN.


G.J. Bönhof: None. A. Strom: None. K. Strassburger: None. B. Knebel: None. J. Kotzka: None. H. Al-Hasani: Consultant; Self; Bayer AG. J. Szendroedi: None. O.P. Zaharia: None. Y. Karusheva: None. M. Roden: Advisory Panel; Self; Servier. Board Member; Self; Poxel SA. Consultant; Self; Eli Lilly and Company, Gilead Sciences, Inc., ProSciento, TARGET PharmaSolutions. Research Support; Self; Boehringer Ingelheim International GmbH, Novartis Pharma K.K., Sanofi US. Speaker’s Bureau; Self; Novo Nordisk A/S. D. Ziegler: None.

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