Diabetic Autonomic Neuropathy Affects Symptom Generation and Brain-Gut Axis

Abstract

OBJECTIVELong-term diabetes leads to severe peripheral, autonomous, and central neuropathy in combination with clinical gastrointestinal symptoms. The brain-gut axis thus expresses a neurophysiological profile, and heart rate variability (HRV) can be correlated with clinical gastrointestinal symptoms.RESEARCH DESIGN AND METHODSFifteen healthy volunteers and 15 diabetic patients (12 with type 1 diabetes) with severe gastrointestinal symptoms and clinical suspicion of autonomic neuropathy were included. Psychophysics and evoked brain potentials were assessed after painful rectosigmoid electrostimulations, and brain activity was modeled by brain electrical source analysis. Self-reported gastrointestinal symptoms (per the Patient Assessment of Upper Gastrointestinal Disorder Severity Symptom Index) and quality of life (SF-36 Short Form Survey) were collected.RESULTSDiabetic patients had autonomous neuropathy, evidenced by decreased electrocardiographic R-R interval (P = 0.03) and lower HRV (P = 0.008). Patients were less sensitive to painful stimulation (P = 0.007), had prolonged latencies of evoked potentials (P ≤ 0.001), and showed diminished amplitude of the N2–P2 component in evoked potentials (P = 0.01). There was a caudoanterior shift of the insular brain source (P = 0.01) and an anterior shift of the cingulate generator (P = 0.01). Insular source location was associated with HRV assessments (all P < 0.02), and the shift (expressed in mm) correlated negatively with physical health (P < 0.001) and positively with nausea (P = 0.03) and postprandial fullness (P = 0.03). Cingulate source shift was correlated negatively with physical health (P = 0.005) and positively with postprandial fullness (P ≤ 0.001).CONCLUSIONSThis study provides evidence for interaction between autonomic neuropathy and peripheral nervous degeneration, as well as changes in dipole sources in diabetic patients with gastrointestinal symptoms. The findings may lead to improved treatment modalities targeting pharmacological neuroprotection or neuromodulation.

&alpha;-lipoic acid suppresses neuronal excitability and attenuates colonic hypersensitivity to colorectal distention in diabetic rats

“…More than 75% of diabetic patients show one or more GI symptoms such as early satiety, postprandial fullness, bloating, nausea, vomiting, constipation, diarrhea, abdominal pain, and fecal incontinence 35. It was reported that STZ injection led to gastric and colonic hypersensitivity,25,36 in addition to peripheral sensorimotor neuropathy in rats 24,37.…”

Prolonged high fat diet ingestion, obesity, and type 2 diabetes symptoms correlate with phenotypic plasticity in myenteric neurons and nerve damage in the mouse duodenum

“…As frequencies continue to rise, so do the populations of individuals with chronic states of disease (Amos et al 1997). Those with persistent T2D experience a host of secondary complications, including autonomic neuropathy, which affects many organs in the body (Wang et al 2008; Brock et al 2013). Injuries to the enteric nervous system (ENS) manifest through symptoms of gastropathy (dyspepsia, gastroparesis) and gastrointestinal (GI) dysmotility, and these commonly plague T2D patients (Camilleri and Malagelada 1984; Byrtzer et al 2001; Bagyánszki and Bódi 2012; Yarandi and Srinivasan 2014).…”

Associations between Sensorimotor, Autonomic and Central Neuropathies in Diabetes Mellitus

“…The CPM efficacy is likely related to the generalized status of the central nervous system, and hence diabetes induced central impairment may likely interfere with this complex network [13][14][15]. Changes in pain modulation processes, as reflected by dynamic psychophysical tests, are now increasingly recognized as clinically relevant.…”