Key result
Parasympathetic denervation precedes sympathetic injury and perfusion deficits in diabetic cardiac neuropathy.
Why the study?
The precise timeline of cardiac autonomic nerve injury progression in diabetic cardiac autonomic neuropathy and the sensitive imaging window for early diagnosis were not well defined.
Can longitudinal multi-tracer PET/CT accurately track the timeline of sympathetic and parasympathetic denervation in a rat model of diabetic cardiac autonomic neuropathy?
Can longitudinal multi-tracer PET/CT accurately track the timeline of sympathetic and parasympathetic denervation in a rat model of diabetic cardiac autonomic neuropathy?
Multi-tracer longitudinal PET/CT imaging in a diabetic rat model demonstrates that parasympathetic denervation precedes sympathetic denervation, offering a potential noninvasive diagnostic window prior to microvascular and metabolic crises.
May enable preclinical DCAN timeline mapping; leaves open human translation and diagnostic utility.
Rationale and Objective This study utilized micro-positron emission tomography/computed tomography (micro-PET/CT) to track the longitudinal and dynamic progression of cardiac autonomic nerve injury in diabetic rats. Our objective was to map the precise timeline of neural damage relative to disease stages, defining a sensitive imaging window for the early diagnosis of diabetic cardiac autonomic neuropathy (DCAN). Materials and Methods Following streptozotocin induction of type 2 diabetes, rats underwent biweekly micro-PET/CT imaging for up to 17 weeks. Sympathetic and parasympathetic innervations were thoroughly evaluated using [ 11 C]C-MDA and [ 11 C]C-donepezil ([ 11 C]C-DNP), respectively. [ 11 C]C-triphenylmethylphosphonium ([ 11 C]C-TPMP) provided a perfusion baseline to characterize neuro-perfusion mismatches. Quantitative tracer uptake was correlated with histopathological remodeling and the myocardial expression of neurotrophic factors (NGF, GAP-43, CNTF) quantified via quantitative real-time polymerase chain reaction (RT-qPCR). Results Longitudinal PET/CT imaging unveiled a distinct chronological cascade of cardiac deterioration. Parasympathetic denervation ([ 11 C]C-DNP depletion) manifested first at week 6, followed by sympathetic denervation ([ 11 C]C-MDA deficit) at week 8. Conversely, myocardial perfusion deficits ([ 11 C]C-TPMP) remained absent until week 16, escalating to severe metabolic dysfunction by week 17. Histopathology confirmed progressive myocardial inflammation, while RT-qPCR indicated a late-stage, yet insufficient, compensatory upregulation of neurotrophic factors. Conclusion This multi-tracer longitudinal investigation establishes that parasympathetic denervation precedes sympathetic impairment during DCAN development, with both deficits predating microvascular and metabolic crises. These insights offer a critical, noninvasive diagnostic window for early DCAN detection and clinical monitoring.
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Gu et al. (2026) studied Diabetic cardiac autonomic neuropathy (DCAN). Streptozotocin-induced type 2 diabetes progression was evaluated on Chronological progression of cardiac autonomic nerve injury and myocardial perfusion deficits. In diabetic rats, longitudinal PET/CT showed parasympathetic denervation at week 6 preceded sympathetic impairment at week 8 and myocardial perfusion deficits at week 16.
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