Peter Bytzer

Prevalence of Gastrointestinal Symptoms Associated With Diabetes Mellitus: A Population-Based Survey of 15 000 Adults

BACKGROUND Gastrointestinal symptoms are reportedly common in diabetes, but a causal link is controversial and adequate population control data are lacking. OBJECTIVE To determine whether gastrointestinal symptoms are more frequent in persons with diabetes, particularly in those with poor glycemic control. METHODS Fifteen thousand adults were mailed a questionnaire (response rate, 60.0%) containing validated questions on the frequency of troublesome gastrointestinal symptoms within the past 3 months, diabetic status, and self-reported glycemic control. The prevalence of 16 symptoms and 5 symptom complexes, reported to occur often or very often, was compared using logistic regression analysis, adjusting for age and sex. RESULTS Overall, 8657 eligible subjects responded; 423 (4.9%) reported having diabetes. Most (94.8%) had type 2 diabetes mellitus. Adjusting for age and sex, all 16 symptoms and the 5 symptom complexes were significantly more frequent in subjects with diabetes compared with controls. An increased prevalence rate of symptoms was significantly associated with poorer levels of glycemic control but not with duration of diabetes or type of diabetic treatment. CONCLUSIONS Diabetes mellitus is associated with an increased prevalence of upper and lower gastrointestinal symptoms. This effect may be linked to poor glycemic control but not to duration of diabetes or type of treatment.

Initial validation of a diagnostic questionnaire for gastroesophageal reflux disease

OBJECTIVES:Brief, reliable, and valid self-administered questionnaires could facilitate the diagnosis of gastroesophageal reflux disease in primary care. We report the development and validation of such an instrument.METHODS:Content validity was informed by literature review, expert opinion, and cognitive interviewing of 50 patients resulting in a 22-item survey. For psychometric analyses, primary care patients completed the new questionnaire at enrollment and at intervals ranging from 3 days to 3 wk. Multitrait scaling, test–retest reliability, and responsiveness were assessed. Predictive validity analyses of all scales and items used specialty physician diagnosis as the “gold standard.”RESULTS:Iterative factor analyses yielded three scales of four items each including heartburn, acid regurgitation, and dyspepsia. Multitrait scaling criteria including internal consistency, item interval consistency, and item discrimination were 100% satisfied. Test–retest reliability was high in those reporting stable symptoms. Scale scores significantly changed in those reporting a global change. Regressing specialty physician diagnosis on the three scales revealed significant effects for two scales (heartburn and regurgitation). Combining the two significant scales enhanced the strength of the model. Symptom response to self-directed treatment with nonprescription antisecretory medications was highly predictive of the diagnosis also, although the item demonstrated poor validity and reliability.CONCLUSIONS:A brief, simple 12-item questionnaire demonstrated validity and reliability and seemed to be responsive to change for reflux and dyspeptic symptoms.

Proton-Pump Inhibitor Therapy Induces Acid-Related Symptoms in Healthy Volunteers After Withdrawal of Therapy

BACKGROUND & AIMS Rebound acid hypersecretion (RAHS) has been demonstrated after 8 weeks of treatment with a proton-pump inhibitor (PPI). If RAHS induces acid-related symptoms, this might lead to PPI dependency and thus have important implications. METHODS A randomized, double-blind, placebo-controlled trial with 120 healthy volunteers was conducted. Participants were randomized to 12 weeks of placebo or 8 weeks of esomeprazole 40 mg/d followed by 4 weeks with placebo. The Gastrointestinal Symptom Rating Scale (GSRS) was filled out weekly. A score of >2 on 1 of the questions regarding heartburn, acid regurgitation, or dyspepsia was defined as a clinically relevant acid-related symptom. RESULTS There were no significant differences between groups in GSRS scores at baseline. GSRS scores for acid-related symptoms were significantly higher in the PPI group at week 10 (1.4 +/- 1.4 vs 1.2 +/- 0.9; P = .023), week 11 (1.4 +/- 1.4 vs 1.2 +/- 0.9; P = .009), and week 12 (1.3 +/- 1.2 vs 1.0 +/- 0.3; P = .001). Forty-four percent (26/59) of those randomized to PPI reported > or = 1 relevant, acid-related symptom in weeks 9-12 compared with 15% (9/59; P < .001) in the placebo group. The proportion reporting dyspepsia, heartburn, or acid regurgitation in the PPI group was 13 of 59 (22%) at week 10, 13 of 59 (22%) at week 11, and 12 of 58 (21%) at week 12. Corresponding figures in the placebo group were 7% at week 10 (P = .034), 5% at week 11 (P = .013), and 2% at week 12 (P = .001). CONCLUSIONS PPI therapy for 8 weeks induces acid-related symptoms in healthy volunteers after withdrawal. This study indicates unrecognized aspects of PPI withdrawal and supports the hypothesis that RAHS has clinical implications.

Accuracy of the diagnosis of GORD by questionnaire, physicians and a trial of proton pump inhibitor treatment: the Diamond Study

Objective The aim of this study was to determine the accuracy of the diagnosis of gastro-oesophageal reflux disease (GORD) by the Reflux Disease Questionnaire (RDQ), family practitioners, gastroenterologists and a test of esomeprazole therapy. Methods This was a single-blind, single-arm study over 3–4 weeks from September 2005 to November 2006. Each symptom-based diagnostic assessment was made blinded to prior diagnoses. Patients were those presenting to their family practitioner with troublesome upper gastrointestinal symptoms (n=308). The RDQ was completed and a symptom-based diagnosis was made by the family practitioner. Placebo esomeprazole was started. Gastroenterologists made a symptom-based diagnosis and then performed endoscopy with 48 h oesophageal pH and symptom association monitoring to determine the presence/absence of GORD. Symptoms were recorded during treatment with 40 mg of esomeprazole for 2 weeks. The main outcome measure was RDQ scoring for the presence of GORD compared with symptom-based diagnosis by family physicians and gastroenterologists. Results GORD was present in 203/308 (66%) patients. Only 49% of the patients with GORD selected either heartburn or regurgitation as the most troublesome symptom. Sensitivity and specificity, respectively, of the symptom-based diagnosis of GORD, were 62% and 67% for the RDQ, 63% and 63% for family practitioners, and 67% and 70% for gastroenterologists. Symptom response to esomeprazole was neither sensitive nor specific for the diagnosis of GORD. Conclusions The RDQ, family practitioners and gastroenterologists have moderate and similar accuracy for diagnosis of GORD. Symptom response to a 2 week course of 40 mg of esomeprazole does not add diagnostic precision. Clinical trial number NCT00291746.

Impact of chronic gastrointestinal symptoms in diabetes mellitus on health-related quality of life

OBJECTIVES:Morbidity from GI symptoms in diabetes is considered to be high, but no studies have quantified the impact of GI symptoms in diabetes on health-related quality of life. We hypothesized that diabetics reporting increased GI symptoms would experience more impaired quality of life.METHODS:Subjects from the community with diabetes (n = 892) and outpatients with diabetes (n = 209) were recruited for this study. Subjects were divided into type 1 (diabetes diagnosed at age <30 yr and requiring insulin) and type 2. A validated questionnaire measuring GI symptoms and diabetes status and the Short Form-36 were completed. The results were compared with Australian normal data. GI symptom groups measured were frequent abdominal pain, bowel-related abdominal pain, reflux, dyspepsia, constipation, diarrhea, and fecal incontinence.RESULTS:There was a clinically significant decrease in quality-of-life scores in diabetics compared with population norms across all subscales. The impact on quality of life in diabetes was predominantly observed in type 2 diabetics. The quality-of-life scores in all subscales decreased markedly with increasing numbers of distinct GI symptom groups, and this was similar in community and outpatient diabetics. For all the Short Form-36 subscales, GI symptom groups were significantly (all p < 0.0001) associated with poorer quality of life in diabetes, independent of age, gender, smoking, alcohol use, and type of diabetes.CONCLUSIONS:GI symptoms impact negatively on health-related quality of life in diabetes mellitus.

A randomised controlled trial assessing the efficacy and safety of repeated tegaserod therapy in women with irritable bowel syndrome with constipation

Background: It has been proposed that treatments for irritable bowel syndrome with constipation (IBS-C) should provide rapid symptomatic relief, be intermittent, and effective upon repeated use. Aims: To evaluate the efficacy and safety of tegaserod on IBS symptoms, and its impact on quality of life and health economic measures. Patients: Women (⩾18 years of age) with IBS-C according to the Rome II criteria. Methods: Prospective, double blind, placebo controlled, randomised trial. Women with IBS-C either received tegaserod 6 mg twice daily or placebo for one month. Patients with at least a partial response entered a treatment free interval. Upon symptom recurrence, tegaserod treated patients were re-randomised to tegaserod or placebo for an additional month. Primary efficacy variables were response (overall IBS symptoms and abdominal discomfort/pain) to first and repeated treatment. Analysis was by intention to treat. Results: 2660 patients and 1191 patients were randomised for first and repeated treatment respectively. Tegaserod was superior to placebo for each primary efficacy variable (first treatment: 33.7% v 24.2% responders respectively for relief of IBS symptoms and 31.3% v 22.1% for relief of abdominal discomfort/pain; repeated treatment: 44.9% v 28.7%, and 42.4% v 27.1%, all p<0.0001). Tegaserod was superior to placebo for every secondary efficacy variable (relief of abdominal discomfort/pain, bloating and constipation; stool frequency and consistency). A response to tegaserod was observed within the first treatment week. Tegaserod produced greater satisfaction, work productivity, and improved quality of life than placebo (p<0.05). Conclusion: Tegaserod provides rapid and sustained relief of IBS-C symptoms both during first and repeated treatment.

GI symptoms in diabetes mellitus are associated with both poor glycemic control and diabetic complications.

OBJECTIVE:Diabetes mellitus is associated with an increased prevalence of GI symptoms, but the mechanisms underlying symptoms are poorly defined and controversial. We aimed to determine whether there is a relationship between GI symptoms and both diabetic complications and glycemic control.METHODS:We performed a cross-sectional questionnaire study of 1101 subjects with diabetes mellitus recruited from outpatient clinics (n = 209) and the community (n = 892). Data on eight GI symptom groups, complications of diabetes (retinopathy, neuropathy, nephropathy), and self-reported glycemic control were obtained from a validated questionnaire. Glycated hemoglobin was measured in 463 of the subjects. The association between diabetic complications, glycemic control, and GI symptoms was assessed using logistic regression analysis, adjusted for demographic and clinical factors.RESULTS:Of the 1101 subjects, 57% reported at least one complication. Diabetic complications were independently associated with both symptom complexity (number of symptom groups reported) (adjusted odds ratio = 1.92 per symptom group [95% CI = 1.51–2.45]) and seven of the eight GI symptom groups. For all symptom groups, the association was explained by self-reported symptoms of peripheral neuropathy. Poor glycemic control measured by both self-report and Hb A1c was an independent risk factor for upper GI symptoms, whereas other potential risk indicators, including duration and type of diabetes, were not significant.CONCLUSIONS:GI symptoms in diabetes mellitus may be linked to diabetic complications, particularly peripheral neuropathy, and to poor glycemic control.

Low socioeconomic class is a risk factor for upper and lower gastrointestinal symptoms: a population based study in 15 000 Australian adults

BACKGROUND The association of social class with health has been extensively studied, yet relationships between social class and gastrointestinal symptoms remain almost unexplored. AIMS To examine relationships between social class and gastrointestinal symptoms in a population sample. METHODS The prevalence of 16 troublesome gastrointestinal symptoms was determined by a postal questionnaire sent to 15 000 subjects (response rate 60%) and compared with a validated composite measure of socioeconomic status (index of relative socioeconomic disadvantage). Comparisons across social class were explored for five symptom categories (oesophageal symptoms; upper dysmotility symptoms; bowel symptoms; diarrhoea; and constipation). Results are reported as age standardised rate ratios with the most advantaged social class as the reference category. RESULTS There were clear trends for the prevalence rates of all gastrointestinal symptoms to increase with decreasing social class. These trends were particularly strong for the five symptom categories. Lower social class was associated with a significantly (p<0.0001) higher number of symptoms reported overall and with a higher proportion of individuals reporting 1–2 symptoms and more than five symptoms. In both sexes, the most pronounced effects for subjects in the lowest social class were found for constipation (males: rate ratio 1.83 (95% confidence intervals (CI) 1.16–2.51); females: rate ratio 1.68 (95% CI 1.31–2.04)) and upper dysmotility symptoms (males: rate ratio 1.45 (95% CI 1.02–1.88); females: rate ratio 1.35 (95% CI 1.07–1.63)). Oesophageal symptoms and diarrhoea were not associated with social class. CONCLUSIONS Troublesome gastrointestinal symptoms are linked to socioeconomic status with more symptoms reported by subjects in low socioeconomic classes. Low socioeconomic class should be considered a risk factor for both upper and lower gastrointestinal symptoms.

Six-month trial of on-demand rabeprazole 10 mg maintains symptom relief in patients with non-erosive reflux disease

Background : Compliance studies have shown that patients with reflux symptoms generally take their medication only when experiencing these symptoms.

Non-Steroidal Anti-Inflammatory Drugs and Ulcer Complications: a Risk Factor Analysis for Clinical Decision-Making

BACKGROUND Use of non-steroidal anti-inflammatory drugs (NSAIDs) is recognized as an important cause of peptic ulcer complications. The aim of this nested case-control study was to identify risk factors for NSAID-related ulcer complications. METHODS Cases were consecutive NSAID users admitted with an ulcer complication (n = 118), and controls were a random sample of all NSAID users without ulcer complication identified by a pharmacoepidemiologic database (n = 540). RESULTS Ninety-four of 118 cases were interviewed, and 324 of 540 controls answered the questionnaire. Analysis showed no difference between included and non-included subjects. Risk factors for patients at start of NSAID therapy were high age: 60-75 years (odds ratio (OR), 3.5 (95% confidence interval (Cl), 1.8-7.1); > 75 years (OR, 8.9 (4.3-18.3)); male sex (OR 1.7 (1.0-3.0)); ulcer history (OR 2.5 (1.2-5.1)); steroid treatment (OR 2.0 (0.8-4.6)); smoking (OR 1.6 (0.9-2.7)); and alcohol use (OR 1.8 (0.9-3.6)). Risk factors for patients receiving NSAID therapy were high age, male sex, ulcer history, smoking and, furthermore, dyspepsia (OR 2.0 (1.0-4.2)), especially NSAID-related dyspepsia (OR 8.7 (4.0-18.9)). Risk was lower for patients treated more than 3 months. CONCLUSION Risk measured from this design can be shown to correlate strongly with the rate difference, a measure that is more clinically relevant than conventional relative risk estimates. Strong risk factors for NSAID-related ulcer complication are high age, male sex, ulcer history, and dyspepsia related to the NSAID therapy. Avoiding NSAID therapy in these high-risk patients, whenever possible, might prevent many adverse events.