Collagen turnover is associated with cardiovascular autonomic and peripheral neuropathy in type 1 diabetes: novel pathophysiological mechanism?

Cardiovascular Diabetology

Research

Morten A. Karsdal¹  Daniel G. K. Rasmussen¹  Federica Genovese¹  Signe Holm Nielsen²  Christian S. Hansen³  Tine W. Hansen³  Simone Theilade⁴  Peter Rossing⁴ 

[1] Nordic Bioscience, Herlev, Denmark;Nordic Bioscience, Herlev, Denmark;Technical University of Denmark, Lyngby, Denmark;Steno Diabetes Center Copenhagen, Niels Steensens Vej 2-4, 2820, Gentofte, Denmark;Steno Diabetes Center Copenhagen, Niels Steensens Vej 2-4, 2820, Gentofte, Denmark;Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark;

关键词: Cardiovascular autonomic neuropathy;    Collagen;    Diabetes;    Inflammation;    Peripheral neuropathy;    Cardiovascular disease;   

DOI  :  10.1186/s12933-023-01891-8

 received in 2023-02-24, accepted in 2023-06-17,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundDiabetic cardiovascular autonomic neuropathy (CAN) and distal symmetrical polyneuropathy (DSPN) are severe diabetic complications. Collagen type VI (COL6) and III (COL3) have been associated with nerve function. We investigated if markers of COL6 formation (PRO-C6) and COL3 degradation (C3M) were associated with neuropathy in people with type 1 diabetes (T1D).MethodsIn a cross-sectional study including 300 people with T1D, serum and urine PRO-C6 and C3M were obtained. CAN was assessed by cardiovascular reflex tests: heart rate response to deep breathing (E/I ratio), to standing (30/15 ratio) and to the Valsalva maneuver (VM). Two or three pathological CARTs constituted CAN. DSPN was assessed by biothesiometry.Symmetrical vibration sensation threshold above 25 V constituted DSPN.ResultsParticipants were (mean (SD)) 55.7 (9.3) years, 51% were males, diabetes duration was 40.0 (8.9) years, HbA1c was 63 (11 mmol/mol, (median (IQR)) serum PRO-C6 was 7.8 (6.2;11.0) ng/ml and C3M 8.3 (7.1;10.0) ng/ml. CAN and DSPN were diagnosed in 34% and 43% of participants, respectively. In models adjusted for relevant confounders a doubling of serum PRO-C6, was significantly associated with odds ratio > 2 for CAN and > 1 for DSPN, respectively. Significance was retained after additional adjustments for eGFR only for CAN. Higher serum C3M was associated with presence of CAN, but not after adjustment for eGFR. C3M was not associated with DSPN. Urine PRO-C6 analyses indicated similar associations.ConclusionsResults show previously undescribed associations between markers of collagen turnover and risk of CAN and to a lesser degree DSPN in T1D.

【 授权许可】

CC BY   
© The Author(s) 2023

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