Gastrointestinal Symptoms In Diabetic Patients Research Articles

Gastrointestinal symptoms in diabetic patients - diabetic exocrine pancreatopathy or small intestinal bacterial overgrowth?

Gastrointestinal symptoms in diabetic patients - diabetic exocrine pancreatopathy or small intestinal bacterial overgrowth?

17. Peripheral and central nervous contribution to gastrointestinal symptoms in diabetic patients with autonomic neuropathy

To explore the role of diabetic autonomic neuropathy (DAN) in patients with long-standing diabetes mellitus (DM), we investigated psychophysical responses and neuronal activity recorded as evoked brain potentials and dipolar source modelling. Fifteen healthy volunteers and 14 type-1 DM patients with DAN were assessed with a symptom score index characterizing upper GI abnormalities. Multichannel electroencephalography was recorded during painful electrical stimulation of the lower oesophagus. Brain activity to painful stimulations was modelled using Brain Electrical Source Analysis. Diabetic patients had higher stimulus intensities to evoke painful sensation (p ⩽ 0.001), longer latencies of N2 and P2 components (both p ⩽ 0.001), and lower amplitudes of P1–N2 and N2–P2 complexes (p ⩽ 0.001; p = 0.02). Inverse modelling of brain sources showed deeper bilateral insular dipolar source localization (p = 0.002). Symptom score index was negatively correlated with the depth of insular activity (p = 0.004) and positively correlated with insular dipole strength (p = 0.03). DM patients show peripheral and central neuroplastic changes. Moreover, the role of abnormal insular processing may explain the appearance and persistence of GI symptoms related to DAN.

Diagnostic Assessment of Diabetic Gastroparesis

Gastroparesis is characterized by a constellation of upper gastrointestinal (GI) symptoms in association with delayed gastric emptying (GE) in the absence of mechanical outlet obstruction from the stomach. Cardinal symptoms are nausea, vomiting, early satiety or postprandial fullness, bloating, and abdominal or epigastric pain (1). Gastric retention may be asymptomatic in some, possibly due to afferent dysfunction in the setting of vagal denervation (2,3), and delayed GE may be associated with recurrent hypoglycemia in patients without upper GI symptoms (4,5). In these individuals, the term “delayed GE” is preferred to gastroparesis (1), although others have used terms such as “gastric hypoglycemia” (6). Thus, clinical manifestations of impaired GE may include anorexia, weight loss, malnutrition, phytobezoar formation, poorer quality-of-life, or impaired glycemic control due to erratic delivery of nutrients to the small bowel for absorption, and these may occur independent of factors such as age, gender, alcohol consumption, tobacco use, and diabetes type (7–9). Upper GI symptoms in diabetic patients may result from accelerated GE, often in association with vagal neuropathy and impaired proximal gastric accommodation (10). In addition, upper GI symptoms in diabetic patients were not significantly different in those with delayed compared with rapid GE, except possibly for postprandial distress ( P = 0.076 on univariate analysis) (11). Hence, it is essential to measure GE in patients with upper GI symptoms if the right treatment is to be selected, such as choice of a prokinetic agent in those with delayed GE. Similarly, one cannot assume that patients with known vagal neuropathy and upper GI symptoms have gastroparesis, because the measured GE may be normal, fast, or slow in such patients. The magnitude of GE delay may also influence diagnosis; there is overlap in the clinical diagnosis of functional dyspepsia and gastroparesis in patients …

Peripheral and central nervous contribution to gastrointestinal symptoms in diabetic patients with autonomic neuropathy

Long-term diabetes mellitus (DM) has been associated with neuronal changes in the enteric, peripheral and/or central nervous system. Moreover, abnormal visceral sensation and gastrointestinal (GI) symptoms are seen in up to 75% of patients. To explore the role of diabetic autonomic neuropathy (DAN) in patients with long-standing DM, we investigated psychophysical responses and neuronal activity recorded as evoked brain potentials and dipolar source modelling. Fifteen healthy volunteers and 14 type-1 DM patients with DAN were assessed with a symptom score index characterizing upper GI abnormalities. Multichannel (62) electroencephalography was recorded during painful electrical stimulation of the lower oesophagus. Brain activity to painful stimulations was modelled using Brain Electrical Source Analysis (besa). Diabetic patients had higher stimulus intensities to evoke painful sensation (p ≤ 0.001), longer latencies of N2 and P2 components (both p ≤ 0.001), and lower amplitudes of P1-N2 and N2-P2 complexes (p ≤ 0.001; p = 0.02). Inverse modelling of brain sources showed deeper bilateral insular dipolar source localization (p = 0.002). Symptom score index was negatively correlated with the depth of insular activity (p = 0.004) and positively correlated with insular dipole strength (p = 0.03). DM patients show peripheral and central neuroplastic changes. Moreover, the role of abnormal insular processing may explain the appearance and persistence of GI symptoms related to DAN. This enhanced understanding of DAN may have future clinical and therapeutical implications.

Gastrointestinal symptoms in diabetes mellitus, and their relation to anxiety and depression

Prevalence of gastrointestinal (GI) symptoms is increased in patients with diabetes mellitus. In general, GI symptoms are influenced by psychological factors such as anxiety and depression, but little is known about this association in diabetic patients. We tested the hypothesis that anxiety and depression have major impact on GI symptoms in diabetic patients. 280 diabetic patients and 355 non-diabetic, age and sex matched controls were studied by validated questionnaires: (1) PAGI-SYM and GSRS for common GI symptoms and (2) HADS for anxiety and depression. Data were compared using logistic regression analysis. Patients with diabetes scored significantly (p<0.05) higher on the symptoms diarrhea (OR 1.64, 95% CI 1.05-2.56), early satiety (OR 2.50, 95% CI 1.39-4.49) and bloating (OR 1.58, 95% CI 1.03-2.43), but not on other symptoms. Prevalence of anxiety and depression (HADS scores ≥ 8) in diabetics and controls was respectively 27.5% and 20.6% for anxiety (p<0.05), and 19.6% and 13.4% for depression (p<0.05). After adjusting for anxiety and depression only the GI symptom "early satiety" remained significantly more prevalent in the patients with diabetes. The prevalence of the gastrointestinal symptoms diarrhea, bloating and early satiety, and of anxiety and depression is significantly increased in our cohort of predominantly patients with longstanding type 2 diabetes mellitus compared to controls. When adjusted for anxiety and depression, only the gastrointestinal symptom "early satiety" remained more prevalent in these diabetic patients, pointing to a somatic based origin. Thus, in our diabetic population psychological factors to a large extent are associated with gastrointestinal symptoms and should be taken into account when considering treatment of the gastrointestinal symptoms.

Metoclopramide

Metoclopramide

Randomised clinical trial: ghrelin agonist TZP-101 relieves gastroparesis associated with severe nausea and vomiting - randomised clinical study subset data

Limited therapeutic options exist for severe gastroparesis, where severe nausea and vomiting can lead to weight loss, dehydration and malnutrition due to inadequate caloric and fluid intake. TZP-101 (ulimorelin) is a ghrelin receptor agonist that accelerates gastric emptying and improves upper gastrointestinal symptoms in diabetic patients with gastroparesis. To assess effects of TZP-101 in diabetic gastroparesis patients with severe nausea/vomiting and baseline severity scores of ≥3.5 (range: 0-5) on the Gastroparesis Cardinal Symptom Index (GCSI) Nausea/Vomiting subscale. Patients were hospitalised and received four single daily 30-min infusions of one of six TZP-101 doses (range 20-600 μg/kg) or placebo. Efficacy was assessed by symptom improvement. At baseline, 23 patients had a mean severity score for GCSI Nausea/Vomiting of 4.45±0.44. Statistically significant improvements over placebo occurred in the 80 μg/kg group for end of treatment changes from baseline in GCSI Nausea/Vomiting subscale (reduction in score of -3.82±0.76, P=0.011) and the GCSI Total score (-3.14±0.78, P=0.016) and were maintained at the 30-day follow-up assessment (-2.02±1.63, P=0.073 and -1.99±1.33, P=0.032 respectively). The proportion of days with vomiting was reduced significantly (P=0.05) in the 80 μg/kg group (mean of 1.2 days of vomiting for four treatment days) compared with placebo (mean of 3.2 days of vomiting across 4 treatment days). TZP-101 substantially reduced the frequency and severity of nausea and vomiting as well as overall gastroparesis symptoms. The results are consistent with gastrointestinal motility effects of TZP-101, supporting further investigation of TZP-101 in the management of severe gastroparesis.

Gut sensations in diabetic autonomic neuropathy

The pathogenesis of gastrointestinal symptoms in diabetes mellitus is complex and multi-factorial. Diabetes induced peripheral and central changes in the neuronal pain matrix may be of importance and were explored using a new multi-modal and multi-segmental sensory testing approach. The sensitivity to mechanical, thermal and electrical stimulations in the oesophagus and duodenum was assessed in 12 type-1 diabetic patients with proven autonomic neuropathy and severe gastrointestinal symptoms using a comprehensive stimulation device aiming to activate different gut nerves and pain mechanisms. Twelve healthy subjects served as controls. The sensory response and the somatic referred pain areas were recorded. In the diabetic patients an overall hyposensitivity to the combination of all stimulations was found in the oesophagus and duodenum ( P = 0.02). Post hoc analysis revealed hyposensitivity to mechanical stimulations in the oesophagus ( P = 0.006) and duodenum ( P = 0.002), and to thermal ( P < 0.001) and electrical ( P = 0.005) stimulations in the oesophagus and duodenum combined. The hyposensitivity in the gut was accompanied by a 46% increase in the somatic referred pain areas ( P = 0.04) indicating central neuronal changes. The multi-modal and multi-segmental sensory testing approach indicates that the sensory nerves are widely affected in the GI tract and generalized to nerves in all layers of the gut. Changes in the neuronal pain matrix including interactions between peripheral and central pain mechanisms may be involved in the pathogenesis of gastrointestinal symptoms in long-standing diabetes. Future targets in the treatment of gastrointestinal symptoms in diabetic patients with autonomic neuropathy could be based on modulation of the central nervous system excitability.

Intussusception as a gastrointestinal complication of diabetes: case report and literature review

This is the first reported case of intussusception in a patient with type 1 diabetes mellitus complicated by gastroparesis and autonomic neuropathy. Literature on the reported cases of intussusception in patients with diabetes, its aetiopathology and possible association with gastroparesis has been systematically reviewed following a Medline database search (1951 to June 2003) Intussusception should be considered in the differential diagnosis of gastrointestinal symptoms in diabetic patients presenting with hyperglycaemia.

Oral hypoglycaemic drugs and gastrointestinal symptoms in diabetes mellitus.

Gastrointestinal symptoms are commonly reported as side-effects of oral hypoglycaemic drugs. It may be very difficult to distinguish between spontaneous and truly drug-related symptoms due to the high background incidence of gastrointestinal symptoms. Gastrointestinal symptoms in diabetic patients have also been linked to factors associated with long-standing disease and suboptimal control. To explore the association between gastrointestinal symptoms and treatment with oral hypoglycaemic drugs in a large cohort of subjects with type 2 diabetes. 956 subjects with type 2 diabetes participated in the study. All subjects completed a validated, self-administered questionnaire on gastrointestinal symptoms, diabetes, drug use and various potential risk factors for gastrointestinal symptoms. The association between oral hypoglycaemics and nine gastrointestinal symptom groups was assessed based on logistic regression. 405 of the 956 patients used oral hypoglycaemic drugs. Metformin use was independently associated with chronic diarrhoea (odds ratio 3.08, 95% CI: 1.29-7.36, P < 0.02) and with faecal incontinence (odds ratio 1.95, 95% CI: 1.10-3.47, P < 0.05). Use of sulphonylureas was associated with less abdominal pain, but not with any other gastrointestinal symptom. Troublesome gastrointestinal symptoms do not appear to be caused by oral hypoglycaemics, except for diarrhoea and faecal incontinence, which are strongly and independently associated with metformin use.

Diabetic state affects the innervation of gut in an animal model of human type 1 diabetes.

Gastrointestinal symptoms in diabetic patients are commonplace, and are believed to be due, at least partly, to neuropathy of the gut. In the present study, therefore, some important neurotransmitters in the myenteric plexus were investigated in non-obese diabetic mice, an animal model of human type 1 diabetes. For this purpose, immunocytochemistry was applied on sections from antrum, duodenum and colon, subsequently quantified by computerized image analysis. Whereas the number of vasoactive intestinal peptide (VIP)-positive neurons was increased in antral myenteric ganglia of diabetic mice, there was a decreased density of nerve fibres in muscularis propria. No difference was seen in the VIP of duodenum and colon. Acetylcholine-containing nerve fibres showed an increased volume density in muscularis propria of antrum and duodenum, but a decreased density in colon of diabetic mice, as compared with controls. There was a decreased number of neurons containing nitric oxide synthase (NOS) in myenteric ganglia of antrum and duodenum. No difference was seen in density of NOS-containing nerve fibres in muscularis propria. There was no difference regarding neuropeptide Y (NPY) and galanin between diabetic and control mice; nor was there any difference between pre-diabetic NOD mice and controls regarding all bioactive substances investigated. It is concluded that the diabetic state affects the innervation of gut in this animal model. The present findings may be of some relevance to the gastrointestinal symptoms seen in patients with diabetes.

Gastrointestinal symptoms in Chinese patients with Type 2 diabetes mellitus.

To examine and compare gastrointestinal (GI) symptoms in Hong Kong Chinese Type 2 diabetic outpatients and non-diabetic control subjects. A total of 149 Chinese Type 2 diabetic patients (66 men and 83 women, age (mean +/- SD) 46.8+/-11.1 years) newly referred to the diabetes clinic of the Prince of Wales Hospital, Hong Kong were examined. Sixty-five age and sex-matched non-diabetic subjects were recruited from the community as controls (22 men and 43 women, age (mean +/- SD) 46.5+/-6.6 years, P = 0.820). All patients were interviewed regarding GI symptoms over the past year, using a questionnaire that covered 14 items. A scoring system from 0 to 4 was used to grade severity. Diabetic patients had higher blood pressure, fasting plasma glucose and glycated haemoglobin and were more often smokers than control subjects. Of the 149 diabetic subjects, 105 (70.5+/-45.8%) had GI symptoms while only 20 (30.8%) of the 65 control subjects had GI symptoms (P<0.001). The respective percentages of upper and lower GI symptoms in diabetic and normal subjects were 44.3% vs. 24.6% (P = 0.006) and 54.4% vs. 13.9% (P<0.001). The three commonest GI symptoms in diabetic patients were diarrhoea (34.9%), constipation (27.5%) and epigastric fullness (16.8%). After adjustment for age, sex, duration of diagnosed diabetes and smoking, patients with or without metformin had similar percentages or scores for GI symptoms. On multivariate analysis using age, body mass index, fasting plasma glucose, glycated haemoglobin, duration of diagnosed diabetes and presence of peripheral neuropathy as independent variables, duration of diabetes was the only independent parameter associated with total score for GI symptoms (beta = 0.116, P = 0.003), for upper GI symptoms (beta = 0.073, P = 0.005) and for lower GI symptom (beta = 0.043, P = 0.020). Up to 70% of the Chinese Type 2 diabetic outpatients have GI symptoms, which is a much higher rate than in non-diabetic control subjects. Duration of diabetes is the most important factor associated with the presence of such GI symptoms.

Helicobacter pylori infection and insulin-dependent diabetes mellitus

Helicobacter pylori is associated with different diseases: duodenal ulcer, rosacea, ischaemic heart disease and gastric cancer. Given the abnormal immunological response and the high prevalence of gastrointestinal symptoms in diabetic patients, we conducted a study on H. pylori prevalence among these patients. We designed a case control study of a population-based cohort. Eighty insulin-dependent diabetes mellitus (IDDM) patients with an average age (24.05±8.3 years), and 100 control subjects (25±7.1 years) were selected to verify the seroprevalence of Helicobacter pylori in these populations. One serum sample was obtained from each subject for evaluation of antibodies against Helicobacter pylori, parietal cells (APA) and pancreatic islets cells (ICA). The seroprevalence of H. pylori among IDDM patients aged less than 24 years was significantly higher than among control subjects; the corresponding rate among IDDM aged greater than 24 years was significantly lower than among control subjects. Antibodies against parietal cells (APA) and islet cells (ICA) among H. pylori positive diabetic patients were significantly higher than among H. pylori negative diabetic patients. IDDM patients were subdivided on the basis of the evolutive course of diabetes. Seroprevalence of H. pylori as well as prevalence of ICAs decreased with IDDM duration. Nevertheless, no variation in the prevalence of APAs during the course of diabetes was observed. We observed an association between the seroprevalence of Helicobacter pylori and the duration of IDDM. The seroprevalence of H. pylori and ICA decreased with the evolutive course of diabetes mellitus among IDDM. The prevalence of ICA and APA in IDDM H. pylori positive subjects was higher than among controls.