Troponin T Parallels Structural Nerve Damage in Type 2 Diabetes: A Cross-sectional Study Using Magnetic Resonance Neurography

Abstract

COMPLICATIONS that different patterns of nerve damage can be attributed to different risk factors (e.g., hyperglycemia and dyslipidemia), and that diffusion tensor imaging (DTI) allows for a very accurate assessment of the structural integrity of affected nerves (13-15). This study combined hsTNT and proBNP assays with results derived from automated nerve fiber segmentation after 3T DTI MRN, as well as clinical, electrophysiological, and serological testing, to investigate whether hsTNT and proBNP may serve as potential markers for nerve damage in DN. RESEARCH DESIGN AND METHODS Study Design and Participants The local ethics committee approved this study (Heidelberg Study on Diabetes and Complications [HEIST-DiC], local ethics number S-383/2016, ClinicalTrials.gov identifier NCT03022721), and all study participants gave informed, written consent. There were 51 patients (17 women, 34 men; mean age 66.7 6 9.7 years; age range 41-86 years) with T2D (23 without DN, 28 with DN) and 10 control subjects (7 women, 3 men; mean age 55.9 6 12.6 years; age range 31-69 years) who took part in this study between June 2015 and February 2019. Overall exclusion criteria were age ,18, pregnancy, any history of lumbar surgery or disc protrusion, any contraindications for MRI, any other risk factors for neuropathy, such as alcoholism, hypovitaminosis, malignant or infectious diseases, any previous or ongoing exposure to neurotoxic agents, monoclonal gammopathy, and any chronic neurological diseases such as Parkinson disease, multiple sclerosis, or restless leg syndrome. Additional exclusion criteria for control subjects were any signs of neuropathy in their medical history or in the clinical and electrophysiological examinations listed below.

Diabetic Polyneuropathy Is Associated With Pathomorphological Changes in Human Dorsal Root Ganglia: A Study Using 3T MR Neurography

“…One must consider, however, that all images used in this study were acquired at the same scanner and that DRG signal intensity was normalized to adjacent muscle tissue, which should make the results reproducible. In future studies, quantitative T2 imaging of DRG and the assessment of other quantitative MRN imaging parameters such as proton density and fractional anisotropy, that have been shown to be accurate markers of structural peripheral nerve integrity for different neuropathies, should be investigated ( Godel et al, 2016 ; Kollmer et al, 2018 ; Jende et al, 2019b , 2020 ; Sollmann et al, 2019 ; Sato et al, 2020 ).…”

Diffusion Tensor Imaging of the Sciatic Nerve as a Surrogate Marker for Nerve Functionality of the Upper and Lower Limb in Patients With Diabetes and Prediabetes

“…DN is generally acknowledged to be a late complication of diabetes that starts at the level of the feet and then progresses further upwards until, at later stages, the upper limbs become involved as well, starting at the level of the hands (Nawroth et al, 2018). In contrast to the progression of clinical symptoms, recent studies applying high-resolution magnetic resonance neurography (MRN) at three Tesla (3T) have come to show that nerve lesions predominate proximally at the level of the sciatic nerve and that the sciatic nerve's fractional anisotropy (FA), a dimensionless quantity for directed diffusion in nerve tissue, is a highly sensitive parameter for structural nerve damage in patients with diabetic neuropathy in previous clinical studies (Vaeggemose et al, 2017b;Jende et al, 2019Jende et al, , 2020a. Despite the assumption that length-dependent nerve damage in DN starts at the level of the feet and progresses to further proximally with an involvement of the upper limbs at later stages, recent studies revealed that sensory and motor functions of the upper limb are frequently affected already at early stages of DN but often remain undiagnosed until a certain degree of functional impairment becomes apparent, indicating that the progression of nerve fiber damage at the level of the hands and arms may parallel the progression of nerve fiber damage at the level of the feet and legs (Kopf et al, 2018a;Yang et al, 2018).…”

Diabetes Increases the Vulnerability of the Cardiac Mitochondrial Network to Criticality

“…Diabetes mellitus is a frequent metabolic disorder with several complications that are typically associated with macroand microangiopathic alterations (Madonna et al, 2017;Jende et al, 2019a). Increased markers of microangiopathy have been implicated in peripheral neuropathy and cardiac myopathy, and linked to mitochondrial dysfunction (Amano, 2016;Jia et al, 2018;Smyrnias et al, 2019;Jende et al, 2020). Although an impressive body of knowledge exists about the role played by mitochondrial dysfunction in diabetes, the mechanisms underlying their impact on diabetic cardiomyopathy, a severe and potentially lethal complication that limits T1DM patients' life expectancy and quality of life, are still not well understood (Aon and Foster, 2015).…”