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. 2021 Feb;64(2):458-468.
doi: 10.1007/s00125-020-05310-5. Epub 2020 Oct 21.

Association of cardiac autonomic dysfunction with higher levels of plasma lipid metabolites in recent-onset type 2 diabetes

Dan Ziegler  1   2   3 , Alexander Strom  4   5 , Klaus Straßburger  5   6 , Birgit Knebel  5   7 , Gidon J Bönhof  4   8 , Jörg Kotzka  5   7 , Julia Szendroedi  4   8   5 , Michael Roden  4   8   5 ; German Diabetes Study group
Affiliations

Association of cardiac autonomic dysfunction with higher levels of plasma lipid metabolites in recent-onset type 2 diabetes

Dan Ziegler et al. Diabetologia. 2021 Feb.

Abstract

Aims/hypothesis: Emerging evidence suggests that in addition to hyperglycaemia, dyslipidaemia could represent a contributing pathogenetic factor to diabetic neuropathy, while obesity and insulin resistance play a role in the development of diabetic cardiac autonomic neuropathy (CAN) characterised by reduced heart rate variability (HRV), particularly in type 2 diabetes. We hypothesised that distinct lipid metabolites are associated with diminished HRV in recent-onset type 2 diabetes rather than type 1 diabetes.

Methods: We analysed 127 plasma lipid metabolites (11 acylcarnitines, 39 NEFA, 12 sphingomyelins (SMs), 56 phosphatidylcholines and nine lysophosphatidylcholines) using MS in participants from the German Diabetes Study baseline cohort recently diagnosed with type 1 (n = 100) and type 2 diabetes (n = 206). Four time-domain HRV indices (number of normal-to-normal (NN) intervals >50 ms divided by the number of all NN intervals [pNN50]; root mean square of successive differences [RMSSD]; SD of NN intervals [SDNN]; and SD of differences between adjacent NN intervals) and three frequency-domain HRV indices (very-low-frequency [VLF], low-frequency [LF] and high-frequency [HF] power spectrum) were computed from NN intervals recorded during a 3 h hyperinsulinaemic-euglycaemic clamp at baseline and in subsets of participants with type 1 (n = 60) and type 2 diabetes (n = 95) after 5 years.

Results: In participants with type 2 diabetes, after Bonferroni correction and rigorous adjustment, SDNN was inversely associated with higher levels of diacyl-phosphatidylcholine (PCaa) C32:0, PCaa C34:1, acyl-alkyl-phosphatidylcholine (PCae) C36:0, SM C16:0 and SM C16:1. SD of differences between NN intervals was inversely associated with PCaa C32:0, PCaa C34:1, PCaa C34:2, PCae C36:0 and SM C16:1, and RMSSD with PCae C36:0. For VLF power, inverse associations were found with PCaa C30:0, PCaa C32:0, PCaa C32:1, PCaa C34:2 and SM C16:1, and for LF power inverse associations were found with PCaa C32:0 and SM C16:1 (r = -0.242 to r = -0.349; p ≤ 0.0005 for all correlations). In contrast, no associations of lipid metabolites with measures of cardiac autonomic function were noted in participants recently diagnosed with type 1 diabetes. After 5 years, HRV declined due to ageing rather than diabetes, whereby prediction analyses for lipid metabolites were hampered.

Conclusions/interpretation: Higher plasma levels of specific lipid metabolites are closely linked to cardiac autonomic dysfunction in recent-onset type 2 diabetes but not type 1 diabetes, suggesting a role for perturbed lipid metabolism in the early development of CAN in type 2 diabetes. Graphical abstract.

Keywords: Cardiac autonomic dysfunction; Heart rate variability; Lipid metabolites; Recent-onset type 2 diabetes.

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Graphical abstract
Fig. 1
Fig. 1
(a–d) Representative examples for inverse correlations of lipid metabolites with SDNN in participants recently diagnosed with type 2 diabetes
See this image and copyright information in PMC

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References

    1. Spallone V, Ziegler D, Freeman R, et al. Cardiovascular autonomic neuropathy in diabetes: clinical impact, assessment, diagnosis, and management. Diabetes Metab Res Rev. 2011;27:639–653. doi: 10.1002/dmrr.1239. - DOI - PubMed
    1. Herder C, Roden M, Ziegler D. Novel insights into sensorimotor and cardiovascular autonomic neuropathy from recent-onset diabetes and population-based cohorts. Trends Endocrinol Metab. 2019;30:286–298. doi: 10.1016/j.tem.2019.02.007. - DOI - PubMed
    1. Eid S, Sas KM, Abcouwer SF, et al. New insights into the mechanisms of diabetic complications: role of lipids and lipid metabolism. Diabetologia. 2019;62:1539–1549. doi: 10.1007/s00125-019-4959-1. - DOI - PMC - PubMed
    1. Callaghan BC, Gallagher G, Fridman V, Feldman EL. Diabetic neuropathy: what does the future hold? Diabetologia. 2020;63:891–897. doi: 10.1007/s00125-020-05085-9. - DOI - PMC - PubMed
    1. Davis TM, Yeap BB, Davis WA, Bruce DG. Lipid-lowering therapy and peripheral sensory neuropathy in type 2 diabetes: the Fremantle Diabetes Study. Diabetologia. 2008;51:562–566. doi: 10.1007/s00125-007-0919-2. - DOI - PubMed

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