Introduction

Autonomic neuropathy affecting multiple organs is a common and severe complication of diabetes¹. Neuropathy of the enteric nervous system and the regulatory autonomic nerve fibers can affect the entire gastrointestinal tract, causing mild to severe gastrointestinal symptoms². The correlation between gastrointestinal symptoms and underlying pathophysiology is generally weak, so objective assessment is important to guide treatment^3-5. Methods for direct evaluation of enteric neuropathy are not yet available in clinical practice. Hence, gastrointestinal transit times and contractile activity are used as proxies for enteric autonomic dysfunction^6,7. Panenteric gastrointestinal assessment is considered essential, yet suitable methods are generally inaccessible, and diagnosing diabetic gastroenteropathy often causes significant challenges^4,8. It is unknown whether measures of extraintestinal autonomic function can reflect diabetic gastroenteropathy and whether these measures could serve as supplementary diagnostic tools.

Aims & Methods

We aimed to assess 1) whether gastrointestinal symptoms are associated with motility measures and 2) whether gastrointestinal symptoms/motility measures are associated with extraintestinal autonomic markers. We included 81 persons with type 1 or type 2 diabetes (65% female, mean age 54) with gastrointestinal symptoms and either symptoms or signs of autonomic neuropathy. The Gastroparesis Cardinal Symptom Index (GCSI) and the Gastrointestinal Symptom Rating Scale (GSRS) were used to assess gastrointestinal symptoms. The wireless motility capsule assessed panenteric transit times and motility indices. Cardiovascular reflex tests performed with the VAGUS device and the cardiac vagal tone assessed with the eMotion Faros device estimated cardiovascular autonomic neuropathy, while the SUDOSCAN evaluated sudomotor function.

Results

Proximal gastrointestinal symptoms were positively associated with the gastric motility index (GCSI: 1.18 (1.04 - 1.35), p=0.01; GSRS: 1.15 (1.03 - 1.29), p=0.02; median ratio (95%CI)), while only satiety reflected gastric emptying time (1.24 (1.03 - 1.49), p=0.02). Diarrhea was associated with decreased small bowel transit time (0.93 (0.89 - 0.98), p=0.005), while constipation was associated with prolonged colonic transit time (1.16 (1.03 - 1.31), p=0.02). Gastrointestinal symptoms increased with the degree of abnormal cardiovascular reflex tests (GCSI: 0.67 (0.16 - 1.19), p=0.03; GSRS: 0.87 (0.30 - 1.45), p=0.01; mean difference (95%CI)) but not with motility measures. Cardiac vagal tone and sudomotor function were not associated with gastrointestinal markers.

Conclusion

Gastrointestinal and extraintestinal autonomic measures were not associated. However, proximal gastrointestinal symptoms were associated with the gastric motility index and cardiovascular reflex tests. Hence, the latter may contribute to evaluating whether proximal gastrointestinal symptoms are autonomically derived.

References

1. Verrotti A, Prezioso G, Scattoni R, Chiarelli F. Autonomic neuropathy in diabetes mellitus. Front Endocrinol (Lausanne). 2014;5:205.
2. Azpiroz F, Malagelada C. Diabetic neuropathy in the gut: pathogenesis and diagnosis. Diabetologia. 2016;59(3):404-408.
3. Arora Z, Parungao JM, Lopez R, Heinlein C, Santisi J, Birgisson S. Clinical utility of wireless motility capsule in patients with suspected multiregional gastrointestinal dysmotility. Dig Dis Sci. 2015;60(5):1350-1357.
4. Kuo B, Maneerattanaporn M, Lee AA, et al. Generalized transit delay on wireless motility capsule testing in patients with clinical suspicion of gastroparesis, small intestinal dysmotility, or slow transit constipation. Dig Dis Sci. 2011;56(10):2928-2938.
5. Rouphael C, Arora Z, Thota PN, et al. Role of wireless motility capsule in the assessment and management of gastrointestinal dysmotility in patients with diabetes mellitus. Neurogastroenterol Motil. 2017;29(9).
6. Kempler P, Amarenco G, Freeman R, et al. Management strategies for gastrointestinal, erectile, bladder, and sudomotor dysfunction in patients with diabetes. Diabetes Metab Res Rev. 2011;27(7):665-677.
7. Camilleri M, Chedid V, Ford AC, et al. Gastroparesis. Nat Rev Dis Primers. 2018;4(1):41.
8. Bertoli D, Mark EB, Liao D, et al. MRI-Based Quantification of Pan-Alimentary Function and Motility in Subjects with Diabetes and Gastrointestinal Symptoms. J Clin Med. 2023;12(18).

Introduction

The proportion of patients who take opioid based analgesics and cannabis has not been studied in a large cohort of patients with cyclical vomiting syndrome (CVS) in the UK. It is also unclear whether the efficacy of prophylactic tricyclic antidepressants (TCAs) is impacted by ongoing opioid or cannabis use.

Aims & Methods

(A) To study the burden of opioid and cannabis use in patients with CVS.
(B) To study the clinical response to prophylactic TCA and whether this was augmented by opioid/cannabis intake.
Clinical characteristics and healthcare outcomes of patients diagnosed with ROME IV CVS in a single neurogastroenterology clinic between January 2016 to December 2023 were retrospectively collected. A standardised clinic template was used to collect data relating to age, sex, gastrointestinal symptoms, medication usage, and patient-reported response to TCA. Patients commenced 10mg TCA for 60 days which was up titrated by 10 mg at each routine outpatient consultation (unless poorly tolerated) until clinical remission was achieved or the maxmum dose (50 mg daily) was prescribed. Clinical remission was defined as the absence of stereotypical episodes of vomiting for at least 6 months prior to the last clinic consultation.

Results

95 patients (male 21%, mean age 30.8±11.8 years) were identified and 84 (88%) were seen on at least two or more occasions with a median duration of follow-up of 22 (IQR: 5, 39) months. The treatment outcomes for all patients treated with TCA are outlined in table 1. At the initial consultation, 35 (37%) and 16 (17%) patients took prescribed opioid analgesics and cannabis, respectively. All were provided with drug cessation advice and were prescribed a TCA: only 12/35 (34%) and 11/16 (69%) of patients adhered to drug cessation advice. On follow-up, 100% of patients who adhered to recommendations to stop opioids and cannabis responded to TCA whilst 0% of patients who continued to take opioids/cannabis responded to TCA. Illicit drugs were found at urine drug screening in 5 patients who failed to respond to TCA (cocaine n=2 and heroin n=3).

Conclusion

This is the first UK study reporting the impact of opioid usage and illicit drugs in patients with CVS. TCAs are useful in treating CVS patients providing they do not consume prescribed opioids or illicit drugs.