ABSTRACT
AIMS/HYPOTHESIS: We hypothesised that type 1 diabetic patients with established diabetic sensorimotor polyneuropathy (DSPN) would have segmental and/or pan-enteric dysmotility in comparison to healthy age-matched controls. We aimed to investigate the co-relationships between gastrointestinal function, degree of DSPN and clinical symptoms. METHODS: An observational comparison was made between 48 patients with DSPN (39 men, mean age 50 years, range 29-71 years), representing the baseline data of an ongoing clinical trial (representing a secondary analysis of baseline data collected from an ongoing double-blind randomised controlled trial investigating the neuroprotective effects of liraglutide) and 41 healthy participants (16 men, mean age 49 years, range 30-78) who underwent a standardised wireless motility capsule test to assess gastrointestinal transit. In patients, vibration thresholds, the Michigan Neuropathy Screening Instrument and Patient Assessment of Upper Gastrointestinal Symptom questionnaires were recorded. RESULTS: Compared with healthy controls, patients showed prolonged gastric emptying (299 ± 289 vs 179 ± 49 min; p = 0.01), small bowel transit (289 ± 107 vs 224 ± 63 min; p = 0.001), colonic transit (2140, interquartile range [IQR] 1149-2799 min vs 1087, IQR 882-1650 min; p = 0.0001) and whole-gut transit time (2721, IQR 1196-3541 min vs 1475 (IQR 1278-2214) min; p < 0.0001). Patients also showed an increased fall in pH across the ileocaecal junction (-1.8 ± 0.4 vs -1.3 ± 0.4 pH; p < 0.0001), which was associated with prolonged colonic transit (r = 0.3, p = 0.001). Multivariable regression, controlling for sex, disease duration and glycaemic control, demonstrated an association between whole-gut transit time and total GCSI (p = 0.02). CONCLUSIONS/INTERPRETATION: Pan-enteric prolongation of gastrointestinal transit times and a more acidic caecal pH, which may represent heightened caecal fermentation, are present in patients with type 1 diabetes. The potential implication of delayed gastrointestinal transit on the bioavailability of nutrition and on pharmacotherapeutic and glycaemic control warrants further investigation. TRIAL REGISTRATION: EUDRA CT: 2013-004375-12.
Subject(s)
Cecum/microbiology , Cecum/physiopathology , Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 1/physiopathology , Gastrointestinal Transit/physiology , Peripheral Nervous System Diseases/metabolism , Peripheral Nervous System Diseases/physiopathology , Adult , Aged , Female , Gastric Emptying/physiology , Humans , Hydrogen-Ion Concentration , Male , Middle Aged , Time FactorsABSTRACT
The global prevalence of diabetes mellitus is increasing; arguably as a consequence of changes in diet, lifestyle and the trend towards urbanization. Unsurprisingly, the incidence of both micro and macrovascular complications of diabetes mirrors this increasing prevalence. Amongst the complications with the highest symptom burden, yet frequently under-diagnosed and sub-optimally treated, is diabetic autonomic neuropathy, itself potentially resulting in cardiovascular autonomic neuropathy and gastrointestinal (GI) tract dysmotility. The aims of this review are fourfold. Firstly to provide an overview of the pathophysiological processes that cause diabetic autonomic neuropathy. Secondly, to discuss both the established and emerging cardiometric methods for evaluating autonomic nervous system function in vivo. Thirdly, to examine the tools for assessing pan-GI and segmental motility and finally, we will provide the reader with a summary of putative non-invasive biomarkers that provide a pathophysiological link between low-grade neuro inflammation and diabetes, which may allow earlier diagnosis and intervention, which in future may improve patient outcomes.
