RESUMEN
Chronic inflammation is associated with diabetes and contributes to the development and progression of micro- and macrovascular complications. Transcutaneous vagus nerve stimulation (tVNS) has been proposed to reduce levels of circulating inflammatory cytokines in non-diabetics by activating the cholinergic anti-inflammatory pathway. We investigated the anti-inflammatory potential of tVNS as a secondary endpoint of a randomized controlled trial in people with diabetes (NCT04143269). 131 people with diabetes (type 1: n = 63; type 2: n = 68), gastrointestinal symptoms and various degrees of autonomic neuropathy were included and randomly assigned to self-administer active (n = 63) or sham (n = 68) tVNS over two successive study periods: (1) Seven days with four daily administrations and, (2) 56 days with two daily administrations. Levels of systemic inflammatory cytokines (IL-6, IL-8, IL-10, TNF-α, IFN-γ) were quantified from blood samples by multiplex technology. Information regarding age, sex, diabetes type, and the presence of cardiac autonomic neuropathy (CAN) was included in the analysis as possible confounders. No differences in either cytokine were seen after study period 1 and 2 between active and sham tVNS (all p-values > 0.08). Age, sex, diabetes type, presence of CAN, and baseline levels of inflammatory cytokines were not associated with changes after treatment (all p-values > 0.07). A tendency towards slight reductions in TNF-α levels after active treatment was observed in those with no CAN compared to those with early or manifest CAN (p = 0.052). In conclusion, tVNS did not influence the level of systemic inflammation in people with diabetes.
Asunto(s)
Citocinas , Estimulación Eléctrica Transcutánea del Nervio , Estimulación del Nervio Vago , Humanos , Estimulación del Nervio Vago/métodos , Masculino , Femenino , Persona de Mediana Edad , Estimulación Eléctrica Transcutánea del Nervio/métodos , Citocinas/sangre , Adulto , Anciano , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/terapia , Inflamación/terapia , Inflamación/sangre , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 1/sangre , Neuropatías Diabéticas/terapia , Neuropatías Diabéticas/sangreRESUMEN
AIMS/HYPOTHESIS: Diabetic gastroenteropathy frequently causes debilitating gastrointestinal symptoms. Previous uncontrolled studies have shown that transcutaneous vagal nerve stimulation (tVNS) may improve gastrointestinal symptoms. To investigate the effect of cervical tVNS in individuals with diabetes suffering from autonomic neuropathy and gastrointestinal symptoms, we conducted a randomised, sham-controlled, double-blind (participants and investigators were blinded to the allocated treatment) study. METHODS: This study included adults (aged 20-86) with type 1 or 2 diabetes, gastrointestinal symptoms and autonomic neuropathy recruited from three Steno Diabetes Centres in Denmark. Participants were randomly allocated 1:1 to receive active or sham stimulation. Active cervical tVNS or sham stimulation was self-administered over two successive study periods: 1 week of four daily stimulations and 8 weeks of two daily stimulations. The primary outcome measures were gastrointestinal symptom changes as measured using the gastroparesis cardinal symptom index (GCSI) and the gastrointestinal symptom rating scale (GSRS). Secondary outcomes included gastrointestinal transit times and cardiovascular autonomic function. RESULTS: Sixty-eight participants were randomised to the active group, while 77 were randomised to the sham group. Sixty-three in the active and 68 in the sham group remained for analysis in study period 1, while 62 in each group were analysed in study period 2. In study period 1, active and sham tVNS resulted in similar symptom reductions (GCSI: -0.26 ± 0.64 vs -0.17 ± 0.62, p=0.44; GSRS: -0.35 ± 0.62 vs -0.32 ± 0.59, p=0.77; mean ± SD). In study period 2, active stimulation also caused a mean symptom decrease that was comparable to that observed after sham stimulation (GCSI: -0.47 ± 0.78 vs -0.33 ± 0.75, p=0.34; GSRS: -0.46 ± 0.90 vs -0.35 ± 0.79, p=0.50). Gastric emptying time was increased in the active group compared with sham (23 min vs -19 min, p=0.04). Segmental intestinal transit times and cardiovascular autonomic measurements did not differ between treatment groups (all p>0.05). The tVNS was well-tolerated. CONCLUSIONS/INTERPRETATION: Cervical tVNS, compared with sham stimulation, does not improve gastrointestinal symptoms among individuals with diabetes and autonomic neuropathy. TRIAL REGISTRATION: ClinicalTrials.gov NCT04143269 FUNDING: The study was funded by the Novo Nordisk Foundation (grant number NNF180C0052045).
Asunto(s)
Estimulación Eléctrica Transcutánea del Nervio , Estimulación del Nervio Vago , Humanos , Femenino , Masculino , Persona de Mediana Edad , Método Doble Ciego , Estimulación del Nervio Vago/métodos , Adulto , Anciano , Estimulación Eléctrica Transcutánea del Nervio/métodos , Neuropatías Diabéticas/terapia , Neuropatías Diabéticas/fisiopatología , Enfermedades Gastrointestinales/terapia , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/terapia , Anciano de 80 o más Años , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/terapia , Resultado del Tratamiento , Adulto JovenRESUMEN
The autonomic nervous system delicately regulates the function of several target organs, including the gastrointestinal tract. Thus, nerve lesions or other nerve pathologies may cause autonomic dysfunction (AD). Some of the most common causes of AD are diabetes mellitus and α-synucleinopathies such as Parkinson's disease. Widespread dysmotility throughout the gastrointestinal tract is a common finding in AD, but no commercially available method exists for direct verification of enteric dysfunction. Thus, assessing segmental enteric physiological function is recommended to aid diagnostics and guide treatment. Several established assessment methods exist, but disadvantages such as lack of standardization, exposure to radiation, advanced data interpretation, or high cost, limit their utility. Emerging methods, including high-resolution colonic manometry, 3D-transit, advanced imaging methods, analysis of gut biopsies, and microbiota, may all assist in the evaluation of gastroenteropathy related to AD. This review provides an overview of established and emerging assessment methods of physiological function within the gut and assessment methods of autonomic neuropathy outside the gut, especially in regards to clinical performance, strengths, and limitations for each method.
RESUMEN
Abdominal pain, nausea, vomiting, diarrhoea, constipation, and faecal incontinence are common symptoms of diabetic gastroenteropathy and often have a major impact on quality of life. The symptoms are usually caused by widespread dysfunction of the gastrointestinal tract. Hence, diagnosis requires panenteric assessment. The general principles of management are glycaemic control, diet, prokinetics, laxatives, and in selected cases, gastric electrical stimulation, which is summarised in this review.