Type 1 diabetic patients with peripheral neuropathy have pan-enteric prolongation of gastrointestinal transit times and an altered caecal pH profile

TY - JOUR

T1 - Type 1 diabetic patients with peripheral neuropathy have pan-enteric prolongation of gastrointestinal transit times and an altered caecal pH profile

AU - Farmer, Adam D

AU - Pedersen, Anne Grave

AU - Brock, Birgitte

AU - Jakobsen, Poul Erik

AU - Karmisholt, Jesper

AU - Mohammed, Sahar D

AU - Scott, S Mark

AU - Drewes, Asbjørn Mohr

AU - Brock, Christina

PY - 2017/4/1

Y1 - 2017/4/1

N2 - 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

AB - 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

KW - Adult

KW - Aged

KW - Cecum

KW - Diabetes Mellitus, Type 1

KW - Female

KW - Gastric Emptying

KW - Gastrointestinal Transit

KW - Humans

KW - Hydrogen-Ion Concentration

KW - Male

KW - Middle Aged

KW - Peripheral Nervous System Diseases

KW - Time Factors

KW - Journal Article

KW - Randomized Controlled Trial

U2 - 10.1007/s00125-016-4199-6

DO - 10.1007/s00125-016-4199-6

M3 - Journal article

C2 - 28105520

SN - 0012-186X

VL - 60

SP - 709

EP - 718

JO - Diabetologia

JF - Diabetologia

IS - 4

ER -