Diabetic gastroenteropathy examined with wireless motility capsule

Background Diabetic gastroenteropathy may affect all parts of the gastrointestinal tract. Despite being prevalent, knowledge is limited and treatment often generalised and unsatisfactory. To deliver personalised treatment, there is a need for improved diagnostics. In this study, we have investigated the role of the wireless motility capsule in the evaluation of gastroparesis, diarrhoea, and constipation, the three main manifestations of diabetic gastroenteropathy. Methods We included 72 diabetes patients (49 women; 59 type 1 diabetes) with gastrointestinal symptoms. They were investigated with blood, urinary and faecal samples, questionnaires, autonomic function tests, and gastrointestinal motility and function tests, including wireless motility capsule and gastric emptying scintigraphy. During fasting and examinations, patients were kept on intravenous glucose-insulin infusion. We also investigated 26 healthy participants using wireless motility capsule. Results In paper 1, we found that the wireless motility capsule had high diagnostic accuracy compared to scintigraphy for determining gastric emptying. In paper 2, we found that patients with diarrhoea had increased gastric emptying time, reduced colonic transit time, and altered gastrointestinal pH levels. In paper 3, we found no difference in transit times when comparing diabetes patients with and without constipation, but both diabetes groups had slower whole gut transit than healthy controls. Conclusions The wireless motility capsule may have a role in the investigation of patients with suspected diabetic gastroenteropathy. It has high diagnostic accuracy for measuring gastric emptying and may identify clinically relevant alterations in gastrointestinal transit and pH levels. We recommend further validation of the capsule’s pH and contractility measurements before they are used in routine examinations.Doktorgradsavhandlin

Limb tissue haemodynamic responses and regulation in the heat-stressed human: role of local vs. central thermosensitive mechanisms at rest and during small muscle mass exercise

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University LondonLimb haemodynamic responses during heat-stress and the importance of local vs. central temperature-sensitive mechanisms towards their regulation remain poorly understood, both at a whole-limb level and within individual tissues (i.e. skeletal muscle and skin). The aims of this thesis were to 1) investigate the haemodynamic responses at rest to direct thermal challenges both at a local level and during progressive elevations in systemic heat stress, 2) to ascertain the contribution of local vs. systemic mechanisms towards this regulation, and 3) to investigate the same responses during single-legged small-muscle mass exercise to near maximal levels. Results from Chapters 4 and 5 characterised the haemodynamic responses during isolated cooling and heating of the arm and leg, and provided evidence of alterations in both skin and skeletal muscle blood flow controlled solely through local temperature-sensitive mechanisms. While local cooling led to modest decreases in limb blood flow due to decreases in mean blood velocity alone, increases during heating occurred as a result of an increased antegrade flow, a diminished retrograde flow, and a reduction in the potentially pro-atherogenic oscillatory shear index. In Chapter 6, whole-body heating with isolated single leg cooling displayed the continued control of limb blood flow via local thermosensitive mechanisms alone, as cooled leg blood flow remained unchanged despite significant elevations in core temperature, cardiac output, and opposing heated leg blood flow. Furthermore, elevations in heated leg V̇O2 suggested a possible metabolic contribution to the observed skeletal muscle hyperaemic response. During incremental single-legged knee-extensor exercise to near maximal levels, blood flow was determined by a combination of metabolic workload and local tissue temperatures, regardless of whether systemic heat stress was present. Chapter 7 revealed that whilst skin and muscle blood flow in the leg continued to increase in line with local temperatures to levels of severe heat stress, rapid cooling of the leg when hyperthermic resulted in a similar reverse response in muscle tissues only, as skin blood flow remained elevated despite the abolition of high skin and subcutaneous temperatures. In addition, evidence was provided that moderate levels of whole-body heat stress provided little additional benefit to anti-atherogenic shear profiles than that experienced during isolated limb heating alone. Taken together, these findings suggest that local thermosensitive mechanisms dominate limb blood flow control during direct rapid heating in humans both at rest and during small muscle mass exercise, but that underlying central mechanisms may act to maintain flow when local temperatures are reduced in the face of high core temperatures

Diabetes mellitus type 2; The incretin effect and interaction with the autonomic nervous system

Bakgrunn: Inkretineffekten er kroppens evne til økt insulinsekresjon når glukose inntas peroralt sammenliknet med administrert intravenøst, utløst av spesifikke hormoner fra tarmen. En redusert inkretineffekt leder til forhøyet blodsukker etter måltid, og er et tidlig fenomen ved diabetes type 2, også påvist i forstadier til diabetes, såkalt prediabetes, og ved fedme. En bevart inkretineffekt ser delvis ut til å være avhengig av et intakt autonomt nervesystem. Autonom nevropati har vært betraktet som en sen komplikasjon til diabetes mellitus, men det er økende evidens for at nevropati også kan oppstå tidlig i forløpet. Kjennskap til disse faktorene ledet oss til en hypotese om at tidlig autonom nevropati kan bidra til den reduserte inkretineffekten ved diabetes type 2. Mål: Vårt primære mål var å undersøke om det var assosiasjon mellom inkretineffekt og grad av autonom nevropati. Sekundære mål var å se på inkretineffekten relatert til grad av hyperglykemi og varighet av diabetes, og sammenlikne en ny test som innebærer ballongdilatasjon i rektum, som mål for tarmens sensitivitet og videre signaloverføring, med mer etablerte tester for nevropati. Et siste sekundærmål var å undersøke gjennomførbarheten av en norsk versjon av spørreskjemaet, «Composite Autonomic Symptom Score» (COMPASS) 31, som kan påvise mulige symptomer fra autonom dysfunksjon, og vi testet om dette var assosiert med øvrige nerveundersøkelser. Metode: Tre grupper ble inkludert; en gruppe med diabetes type 2 varighet >10 år, en gruppe med nyoppdaget type 2 diabetes siste året, uten behov for medikamentell behandling, og en kontrollgruppe matchet for alder, kjønn og kroppsmasseindeks. Inkretineffekten ble kalkulert fra c-peptid (areal under kurven) ved oral glukosebelastning sammenliknet med intravenøs isoglykemisk glukose infusjon. Gastrointestinal glukose-håndtering (GIGD) ble kalkulert fra glukose gitt oralt sammenliknet med glukose tilført intravenøst. Tester for nevropati inkluderte kardiovaskulære reflekstester, hjertefrekvensvariabilitet, svettefunksjon, nerveledningshastighet i nervus suralis og monofilament test. Som mål på gastrointestinal visceral nervefunksjon utførte vi rektal ballongdilatasjon med registrering av trykk for første følelse av dilatasjon og ubehagelig følelse av dilatasjon. Evokerte hjernepotensial ble målt som respons på ballongdilatasjon ved gjentatte stimuli av nevnte trykk. Spørreskjemaet COMPASS 31 ble besvart digitalt. Resultat: Deltakerne med diabetes trengte høyere trykk for å oppnå første følelse av ballongdilatasjon i rektum, uavhengig av diabetesvarighet. Økt behov for trykk korrelerte med nedsatt GIGD, men ikke med inkretineffekt. Økt behov for trykk korrelerte også med nedsatt følelse på monofilament test. GIGD og inkretineffekt korrelerte signifikant med både grad av hyperglykemi og diabetesvarighet. Det ble funnet få tilfeller av nevropati totalt sett, og få forskjeller mellom gruppene. Det var en tendens til at lenger latenstid og mindre amplituder på evokerte hjernepotensial var assosiert med lavere hjertefrekvensvariabilitet og kardiovaskulære reflekstester, sural nerveledning og monofilament test, men ikke statistisk signifikant etter korreksjon for multippel testing. Høyere score på COMPASS 31 ble funnet hos dem med langvarig diabetes og hos kvinner, med best sensitivitet og negativ prediktiv verdi for score <10. Konklusjon: Vi fant rektal hyposensitivitet både ved langvarig og tidlig type 2 diabetes og dette var assosiert med redusert GIGD, men ikke med redusert inkretineffekt. Dette kan tyde på at adekvat nervefunksjon i tarmen er viktig for andre faktorer enn inkretineffekten i håndteringen av glukose. Redusert GIGD og inkretineffekt er assosiert med økende hyperglykemi og varighet av diabetes, som viser et kontinuum i tarmens glukosehåndtering fra normo- til hyperglykemi. Vi fant klinisk plausible tegn på at sentral nerveledning er assosiert med perifer nervefunksjon, men resultatene må tolkes med forsiktighet, gitt multippel testing. Rektal ballongdilatasjon med måling av sensitivitet og evokerte hjernepotensial synes å være en lovende metode for undersøkelse av nervefunksjon i tarmen, også når øvrige autonome tester er normale. Til sist finner vi spørreskjemaet COMPASS 31 lovende til bruk både i forskning, men også i den kliniske hverdag, hvor autonome symptomer ofte er neglisjert. I en liknende populasjon som vår vil en score på 10 poeng eller mindre nærmest utelukke kardiovaskulær autonom nevropati.Background: The incretin effect refers to the amplified insulin response when glucose is administered orally compared to intravenously. A reduced incretin effect is found at early stages of type 2 diabetes, even in prediabetes and obesity, but the mechanisms behind are unknown. Evidence suggests that part of the effect of incretin hormones are mediated through vagal nerve transmission. Diabetic autonomic neuropathy is considered a late complication of diabetes mellitus, but there is an increasing awareness that neuropathy can exist in both prediabetes and early stages of diabetes. This led us to the hypothesis that the incretin effect could be affected by early autonomic neuropathy because of a reduced transmission of signals. Aims: Our main objective was to explore whether a reduced incretin effect could be associated with autonomic neuropathy. Secondarily, we aimed to explore the incretin effect in relation to degree of dysglycemia and the duration of diabetes. Other secondary objectives were to explore a novel test of gut visceral sensitivity and central transmission of peripheral signals, and to compare it with established tests for diabetic neuropathy, including assessment of symptoms using the Composite Autonomic Symptom Score (COMPASS) 31. Methods: This was case-control study including three groups of participants: People with type 2 diabetes for >10 years (longstanding), people with newly discovered type 2 diabetes within the last year, without the need for antidiabetic medication (early), and a group of matched controls in age, sex, and body mass index. An oral glucose tolerance test followed by an intravenous isoglycemic glucose infusion were performed to calculate the incretin effect (from c-peptide area under the curve). Gastrointestinal-mediated glucose disposal (GIGD) was calculated as an estimate of the body’s ability to cope with the challenge of a carbohydrate ingestion. Neuropathy tests included cardiovascular reflex tests, heart rate variability, sudomotor function, sural nerve, and the monofilament test. Rapid rectal balloon distention measuring visceral sensitivity and evoked potentials was performed as a proxy for gut autonomic nerve function. The COMPASS 31 questionnaire was distributed and answered online. Results: Both groups of diabetes were hyposensitive to first sensation performing rapid rectal balloon distention. Also, those with reduced sensation performing the monofilament test showed hyposensitivity. A correlation was found between rectal hyposensitivity at the first sensation and reduced GIGD, but not with the incretin effect. Both GIGD and the incretin effect were found to correlate with degree of dysglycaemia and duration of diabetes, and were comparable to previous studies. Overall, few cases of confirmed neuropathy were detected, and there were few differences between groups regarding established neuropathy tests. Longer evoked potential latencies and smaller amplitudes plausibly correlated with lower heart rate variability and cardiovascular reflex test score, reduced parameters in the sural nerve test and monofilament sensation, but not statistically significant considering multiple testing. Higher scores in COMPASS 31 were correlated with longstanding diabetes and female sex. We found an acceptable negative predictive value for cardiovascular autonomic neuropathy at a 10-point cut-off . Conclusions: Rectal hyposensitivity may be an early manifestation of type 2 diabetes, and associated with GIGD, but not with the incretin effect. GIGD and the incretin effect are associated with degree of dysglycemia and duration of diabetes, indicating a continuum in the diminished effect. Central neuronal signal processing appears to be affected in parallel with peripheral neuronal function, but the results must be interpreted with caution. In general, we found that investigating evoked potentials following rapid rectal balloon distention may be a useful research tool for evaluating gut autonomic neuropathy, also when other autonomic neuropathy tests are normal. The Norwegian version of COMPASS 31 was easy to use and for assessing autonomic neuropathy in diabetes, and we suggest a cut off at ten points for screening purposes. Symptoms of autonomic neuropathy seems to be more frequent in people with longstanding diabetes and in women.Doktorgradsavhandlin

Affective-autonomic states of domestic pigs in the context of coping and animal welfare

Gaining better insight in affective states of farm animals is of importance for understanding their welfare state. One important step in this context is to establish valid proxy measures to objectively assess and interpret an individual’s subjective perception of its environment. This thesis presents a reliable tool for the objective evaluation of affective-autonomic states in free-moving pigs and gains insight into the neurophysiological mechanisms underlying the individual processing of affective states in relation to their valence and arousal dimensions.Die Untersuchung affektiver Zustände von Nutztieren ist für das Verständnis ihres Wohlbefindens von essentieller Bedeutung. Ein wichtiger Schritt in diesem Kontext ist die Etablierung zuverlässiger Messmethoden zur objektiven Beurteilung und Interpretation individueller subjektiver Wahrnehmung. Diese Arbeit stellt eine valide Methode zur objektiven Beurteilung affektiv-autonomer Zustände bei Schweinen dar und vermittelt einen Einblick in die neurophysiologischen Mechanismen, die der individuellen Verarbeitung affektiver Zustände zugrunde liegen

Effects of effortful swallowing on cardiac autonomic control in individuals with neurogenic dysphagia: A prospective observational analytical study

Considering that neurogenic oropharyngeal dysphagia is a prevalent condition with or without cardiac disease we should contemplate issues surrounding cardiovascular difficulties during rehabilitation. This study aims to evaluate the effects of effortful swallowing maneuver (ESM) on heart rate variability (HRV) in subjects with neurogenic oropharyngeal dysphagia. We studied 22 individuals [8 Stroke and 14 Parkinson Disease (PD) subjects aged between 41 and 75 years old] with neurogenic oropharyngeal dysphagia regardless of gender. HRV was assessed under two circumstances: spontaneous swallowing versus ESM. Surface electromyography of the suprahyoid muscles was undertaken to measure the swallowing muscle excitation, which then confirmed higher muscle activity during ESM. We attained no changes in HRV between the two swallowing events [HR: spontaneous swallowing 78.68 ± 13.91 bpm vs. ESM 102.57 ± 107.81 bpm, p = 0.201; RMSSD (root-mean square of differences between adjacent normal RR intervals in a time interval): spontaneous swallowing 16.99 ± 15.65 ms vs. ESM 44.74 ± 138.85 ms, p = 0.312; HF (high frequency): spontaneous swallowing 119.35 ± 273 ms2 vs. ESM 99.83 ± 194.58 ms2, p = 0.301; SD1 (standard deviation of the instantaneous variability of the beat-to-beat heart rate): spontaneous swallowing 12.02 ± 1.07 ms vs. ESM 31.66 ± 98.25 ms, p = 0.301]. The effortful swallowing maneuver did not cause clinically significant changes in autonomic control of HR in this group of subjects with oropharyngeal dysphagia

Heart Rate Variability (HRV) analysis : a methodology for organizational neuroscience

Recently, the application of neuroscience methods and findings to the study of organizational phenomena has gained significant interest and converged in the emerging field of organizational neuroscience. Yet, this body of research has principally focused on the brain, often overlooking fuller analysis of the activities of the human nervous system and associated methods available to assess them. In this paper, we aim to narrow this gap by reviewing heart rate variability (HRV) analysis, which is that set of methods assessing beat-to-beat changes in the heart rhythm over time, used to draw inference on the outflow of the autonomic nervous system (ANS). In addition to anatomo- physiological and detailed methodological considerations, we discuss related theoretical, ethical, and practical implications. Overall, we argue that this methodology offers the opportunity not only to inform on a wealth of constructs relevant for management inquiries, but also to advance the organizational neuroscience research agenda and its ecological validity

Neuroprotective Effects of Long-term Endurance Training on the Cortical Autonomic Network in the Aging Brain

This study tested whether long-term endurance training in older adults (ET; n = 15, 55 ± 4 years, relative VO2max = 50 ± 8 ml/kg/min) would alter cardiovagal control and preserve the cortical autonomic network compared to age-matched controls (CON; n = 15, 56 ± 4 years, relative VO2max = 37 ± 9 ml/kg/min). The hypothesis predicts 1) altered deactivation patterns of the ventral medial prefrontal cortex (vMPFC) in response to isometric hand grip (IHG) and 2) greater indices of cardiovagal control; a) increased baroreflex sensitivity at rest, b) greater heart rate change (ΔHR) and c) reductions in high frequency heart rate variability (ΔHF HRV) in the ET group. Functional magnetic resonance imaging was utilized to observe BOLD signal changes. There was no difference in measured indices of cardiovagal control between groups and both exhibited vMPFC deactivation with IHG. Overall, ET does not preserve cortical functional patterns in the older brain or enhance cardiovagal control compared to age-matched controls

Neuroenhancement in Military Personnel::Conceptual and Methodological Promises and Challenges

Military personnel face harsh conditions that strain their physical and mental well-being, depleting resources necessary for sustained operational performance. Future operations will impose even greater demands on soldiers in austere environments with limited support, and new training and technological approaches are essential. This report highlights the progress in cognitive neuroenhancement research, exploring techniques such as neuromodulation and neurofeedback, and emphasizes the inherent challenges and future directions in the field of cognitive neuroenhancement for selection, training, operations, and recovery