The Impact of Alcohol Consumption and Cholecystectomy on Small Intestinal Bacterial Overgrowth

Background

The etiology of small intestinal bacterial overgrowth (SIBO) is diverse and frequently multi-factorial. SIBO is thought to result from structural changes of the gastrointestinal tract, disordered peristalsis of the stomach and/or small intestine, or a disruption of the normal mucosal defenses of the small intestine. Alcoholics are reported to have higher rates of SIBO, as diagnosed by jejunal aspirate; however, no data are available on the association between moderate alcohol consumption and SIBO.

Aim

To evaluate the association between moderate alcohol consumption and SIBO and identify risk factors for SIBO using the lactulose breath test (LBT).

Methods

A retrospective chart review was completed for 210 consecutive patients who underwent the LBT between 2008 and 2010. We reviewed demographic data, including age, race, body mass index, alcohol and tobacco history, medication use, comorbid medical conditions, and history of abdominal surgery.

Results

The study included 196 patients (68 % female; mean age 55 years), 93 of whom had a positive LBT (47.4 %). Of those patients who consumed a moderate amount of alcohol, 58 % had a positive LBT, compared to 38.9 % of abstainers (P = 0.008). Those with a history of cholecystectomy had significantly lower rates of a positive LBT than those who had not (33.3 vs. 51.7 % respectively; P = 0.031). Neither proton pump inhibitor (PPI) use nor tobacco use was associated with a positive LBT.

Conclusion

In this retrospective review, moderate alcohol consumption was a strong risk factor for SIBO. Cholecystectomy appeared to be protective against SIBO. Neither PPI use nor tobacco use was associated with an increased risk of SIBO.     

Small intestinal bacterial overgrowth and delayed orocecal transit time in patients with cirrhosis and low-grade hepatic encephalopathy

Background

Hepatic encephalopathy (HE) is associated with poor prognosis in cirrhosis. Gut-derived nitrogenous substances play a role in pathogenesis of HE. The present study was conducted to assess small intestinal bacterial overgrowth (SIBO) and prolonged orocecal transit time (OCTT) in cirrhosis and low-grade HE.

Methods

In cross-sectional prospective study, 75 patients were divided into 3 groups: group 1 (no HE, n = 31), group 2 (minimal HE, n = 29), and group 3 (early/grade 1 HE, n = 15). Minimal HE (MHE) was diagnosed when psychometric hepatic encephalopathy score (PHES) was ≤5. Early HE was diagnosed, according to West Haven criteria. All patients underwent glucose hydrogen breath test (GHBT) for SIBO and lactulose hydrogen breath test (LHBT) for OCTT.

Results

A total of 29 patients (38.67 %) had MHE and 15 (20 %) had early HE. Prevalence of MHE in Child–Turcotte–Pugh (CTP) class A, B, and C was 33.3, 38.71, and 45 %, respectively, while SIBO was detected in 26 (34.67 %). Prevalence of SIBO was 12.5 % in CTP class A, 41.94 % in CTP class B, and 50 % in CTP class C. Five (16.13 %) patients in no HE group had SIBO as compared to 14 (48.28 %) in MHE group and 7 (46.67 %) in early HE group (p = 0.018). OCTT was 111.13 ± 13.95 min in patients with no HE as compared to 137.59 ± 14.80 min in patients with MHE and 150 ± 15.12 min in patients with early HE (p < 0.001). OCTT was significantly prolonged in patients with SIBO (145 ± 17.49 min) than in those without SIBO (120.71 ± 18.3 min) (p < 0.001).

Conclusion

SIBO and delayed OCTT are more common with MHE and early HE in patients with cirrhosis.     

Low Ileocecal Valve Pressure Is Significantly Associated with Small Intestinal Bacterial Overgrowth (SIBO)

Background

Small intestinal bacterial overgrowth (SIBO) is a significant and increasingly recognized syndrome. While the development may be multifactorial, impairment of the ileocecal valve (ICV), small bowel motility, and gastric acid secretion have been hypothesized to be risk factors. ICV dysfunction remains largely unexplored using standard technology. The wireless motility capsule (WMC) that evaluates pressure, pH, and temperature throughout the GI tract provides the ability to assess these parameters.

Aims

The primary aims of this study were to assess the relationship of ICV pressures, small bowel transit time (SBTT) and intestinal pH with lactulose hydrogen breath testing (LBT) results in subjects with suspected SIBO.

Methods

We retrospectively studied consecutive patients referred to our institution for WMC and LBT from 2010–2012. Ileocecal junction pressures (IJP), as a surrogate for ICV pressures, were defined as the highest pressure over a 4-min window prior to the characteristic ileocecal pH drop. SBTT and pH were calculated and compared with LBT results.

Results

Twenty-three patients underwent both WMC and LBT, with positive results observed in 15 (65.2 %). IJP were significantly higher in LBT(?) negative vs. LBT(+) (79.9 vs. 45.1, p < 0.01). SBTT was significantly longer in LBT(+) versus LBT(?) (5.82 vs. 3.81 h, p = 0.05). Among LBT(+) subjects, gastric pH was significantly higher versus LBT(?) subjects (2.76 vs. 1.63, p = 0.01). There was poor correlation between IJP and other parameters (SBTT, small bowel pH, and gastric pH).

Conclusions

Low IJP is significantly associated with SIBO. While this is physiologically plausible, to our knowledge, this is the first study to make this connection. Prolonged SBTT and higher pH are also independently associated with SIBO. Our findings add value of the WMC test as a diagnostic tool in patients with functional gastrointestinal complaints and suggest re-focus of attention on the ileocecal valve as a prominent player in intestinal disorders.     

A Diagnostic Approach to Patients with Suspected Lactose Malabsorption

Background

The lactose breath test (LBT) is the standard technique for diagnosis of lactose malabsorption. However, it is time-consuming, strenuous for the patient and has been reported to have low sensitivity. The lactose intolerance quick test (LIQT) measures lactase activity in duodenal biopsies and may be performed as part of upper gastrointestinal endoscopy.

Aim

The purpose of this study was to assess the role of the LBT and LIQT in the case management of suspected lactose malabsorption.

Methods

The study group included 69 consecutive patients evaluated by the LBT followed by the LIQT. The test results were compared, and the sensitivity, specificity, and predictive values of the LBT were calculated.

Results

Mean age of the patients was 54.4 years, male/female ratio was 1:3, and mean body mass index was 25.2. None had celiac disease on duodenal biopsy. The LIQT was positive for hypolactasia in 55 patients (80 %): mild in 14 (25 %) and severe in 41 (75 %); 10 (18 %) were symptomatic during the LBT. The LBT was positive for lactose malabsorption in 32 patients (46 %). Of the 37 patients with normal findings on the LBT, 24 (65 %) had positive findings on the LIQT: 11 (30 %) mild hypolactasia, 13 (35 %) severe hypolactasia. In one case, the LBT was positive and the LIQT was negative. The LBT had a sensitivity of 56 %, specificity 93 %, positive predictive value 97 %, and negative predictive value 35 %.

Conclusions

The LBT may serve as a diagnostic screening tool for lactose malabsorption. Symptomatic patients with negative LBT results should be referred for second-line testing with the LIQT.     

Small Intestinal Bacterial Overgrowth and Orocecal Transit Time in Patients of Inflammatory Bowel Disease

Background

Inflammatory bowel disease (IBD) consists of Ulcerative colitis (UC) and Crohn’s disease (CD). These two conditions share many common features—diarrhea, bloody stools, weight loss, abdominal pain, fever and fatigue. Small intestinal bacterial overgrowth (SIBO) is frequent in patients with CD but it has not been studied in UC Indian patients.

Aim

The study was planned to measure orocecal transit time (OCTT) and SIBO in UC and CD patients.

Methods

One hundred thirty-seven patients of IBD (95 UC and 42 CD) and 115 healthy controls were enrolled. OCTT and SIBO were measured by lactulose and glucose hydrogen breath test respectively. Concentration of hydrogen and methane were measured by SC microlyser from Quintron, USA.

Results

Mean ± standard deviation (SD) of OCTT in patients of IBD was significantly higher as compared to controls. Furthermore, OCTT was significantly higher in CD patients as compared to UC patients. It was also observed that occurrence of SIBO was significantly higher in IBD patients as compared to controls. The occurrence of SIBO in CD (45.2 %) was significantly higher as compared to patients in UC (17.8 %) group. Percentage of methane positive IBD patients (2.9 %) was significantly lower as compared to methane positive controls (24.4 %).

Conclusion

OCTT was significantly delayed in IBD patients as compared to controls and in CD patients as compared to UC patients. OCTT was significantly higher in SIBO positive IBD patients as compared to SIBO negative patients. Thus, we can suggest that delayed OCTT would have been the cause of increased SIBO in these patients.     

Granisetron Transdermal System Improves Refractory Nausea and Vomiting in Gastroparesis

Background

Symptoms of gastroparesis include nausea and vomiting, which can markedly diminish quality of life. Nausea and vomiting can also make treatment with oral antiemetics problematic.

Aim

Our aim was to determine whether treatment-resistant nausea and vomiting in patients with gastroparesis improve after granisetron transdermal patch (GTP) therapy.

Methods

In an open-label pilot study, patients with gastroparesis and symptoms of nausea and vomiting refractory to conventional treatment were treated with GTP. After 2 weeks, patients were asked to assess their therapeutic response using the Clinical Patient Grading Assessment Scale (CPGAS; +7 = completely better; 0 = no change; ?7 = very considerably worse). Responders were defined as CPGAS score >0, non-responders as ≤0.

Results

Patients (n = 36) were treated with GTP. Of these 36 patients, one patient discontinued treatment due to the GTP not adhering to the skin. Of the remaining 35 patients, 18 improved, 15 remained the same, and two worsened. The average CPGAS score was +1.8 ± 0.4 (SEM) (P < 0.05 vs 0). Of the 18 patients with improvement, the average CPGAS score was +3.7 ± 0.3 (SEM), corresponding to “somewhat” to “moderately better” improvement in nausea/vomiting. Side effects occurred in nine patients: four developed constipation, three patients had skin rash, and two reported headaches.

Conclusions

GTP was moderately effective in reducing refractory symptoms of nausea and/or vomiting from gastroparesis in 50 % of patients. Mild side effects were reported by 25 % of patients. GTP may be an effective treatment for nausea and vomiting in gastroparesis, and further study is warranted.     

Use of a High Caloric Liquid Meal as an Alternative to a Solid Meal for Gastric Emptying Scintigraphy

Background

Gastric emptying scintigraphy (GES) using a solid meal is often recommended for the evaluation of gastroparesis. However, some patients cannot tolerate the standardized egg-white sandwich (EWS) solid meal and an alternative meal is needed.

Aim

The aim of this study was to compare GES, regional gastric emptying, and gastric contractility using a liquid nutrient meal (LNM; Ensure Plus^®) to those using EWS.

Methods

Twenty healthy volunteers underwent GES using EWS and LNM on separate days. Gastric emptying was measured using scintigraphy and with a wireless motility capsule (WMC; SmartPill^®).

Results

The gastric emptying half-time with LNM was similar to that with EWS (1.41 ± 0.11 vs 1.52 ± 0.08 h; P = 0.28) and the two were significantly correlated (r = 0.53; P = 0.017). There were time-related differences in gastric emptying of the LNM compared to EWS: in the first hour, gastric retention of EWS was slightly greater than that of LNM, whereas at 3 and 4 h, gastric retention of EWS was slightly less than that of LNM. Regionally, the percentage retention of the meal in the proximal stomach was greater for EWS than for LNM at 0.5 h. WMC gastric emptying times and gastric contractility for the two meals were not significantly different.

Conclusions

Overall gastric emptying of the LNM was similar to that of the EWS meal. The LNM empties without a lag phase and takes slightly longer to empty from the distal stomach, likely due to its higher fat content. These differences are likely due to early accommodation with retention of solids in the proximal stomach and the need for trituration of solids. We conclude that this LNM can serve as an alternative to the conventional solid EWS for GES.     

Prevalence of abnormal lactose breath hydrogen tests in children with functional abdominal pain

Objectives

The study was undertaken to determine the prevalence of abnormal lactose breath hydrogen test in children with non-organic chronic abdominal pain.

Methods

Children with chronic abdominal pain were examined and investigated for organic causes. All children without a known organic cause underwent lactose and glucose breath hydrogen test. After a standard dose of 2 g/kg of lactose to a maximum of 50 g, hydrogen in breath was measured at 15 min intervals for 3 h. A rise of 20 ppm above baseline was considered suggestive of lactose malabsorption.

Results

Of 108 children screened, organic causes were found in 46 children. Sixty-two patients without any organic cause underwent hydrogen breath test. Lactose hydrogen breath test (HBT) was positive in 36 of 62 (58%), while 11 (17%) had positive HBT with glucose suggestive of small intestinal bacterial overgrowth (SIBO). Twenty out of 34 (59%) improved on lactose free diet while 8 out of 11 (72%) children of SIBO improved on antibiotics.

Conclusions

Lactose malabsorption was seen in 58% of children with non-organic chronic abdominal pain.

     

Antibiotic Treatment of Constipation-Predominant Irritable Bowel Syndrome

Background

The antibiotic rifaximin is used to treat non-constipated irritable bowel syndrome (IBS). Methane production is associated with constipation and its severity in constipation-predominant IBS (C-IBS). A previous retrospective study suggested that rifaximin and neomycin was superior to neomycin alone in improving symptoms in methane-positive subjects.

Aims

To determine the effectiveness of neomycin alone or with rifaximin in improving symptoms in methane-positive C-IBS subjects.

Methods

A double-blind, randomized, placebo-controlled trial was performed from 2010 to 2013 at three tertiary care centers. Subjects aged 18–65 with C-IBS (Rome II criteria) and breath methane (>3 ppm) meeting the inclusion and exclusion criteria were recruited. Subjects completed a baseline symptom questionnaire rating the severity of abdominal and bowel symptoms on a visual analog scale and were randomized to receive neomycin and placebo or neomycin and rifaximin for 14 days. Symptom severity was assessed by weekly questionnaire for 2 weeks of therapy and 4 additional weeks of follow-up.

Results

Thirty-one subjects (16 neomycin and placebo, 15 neomycin and rifaximin) were included in the intention-to-treat analysis. Constipation severity was significantly lower in the neomycin and rifaximin group (28.6 ± 30.8) compared to neomycin alone (61.2 ± 24.1) (P = 0.0042), with greater improvement in constipation (P = 0.007), straining (P = 0.017) and bloating (P = 0.020), but not abdominal pain. In the neomycin and rifaximin group, subjects with methane <3 ppm after treatment reported significantly lower constipation severity (30.5 ± 21.8) than subjects with persistent methane (67.2 ± 32.1) (P = 0.020).

Conclusions

Rifaximin plus neomycin is superior to neomycin alone in improving multiple C-IBS symptoms. This effect is predicted by a reduction in breath methane.     

Diagnosing Small Intestinal Bacterial Overgrowth: A Comparison of Lactulose Breath Tests to Small Bowel Aspirates

Background

Duodenal aspiration (DA) and lactulose breath tests (LBT) are commonly performed to diagnose small intestinal bacterial overgrowth (SIBO). There are no data directly comparing these tests.

Aims

To investigate the agreement between DA and LBT for the diagnosis of SIBO.

Methods

A retrospective cohort study of adult patients who underwent a LBT and a DA at a tertiary care center over 9 years was assembled. LBT was considered positive if the hydrogen baseline or peak change measurement was ≥?20 ppm, and/or if the methane baseline or peak change was ≥?10 ppm. DA was considered positive if >?100,000 cfu/mL of gram-negative flora was identified on culture, and contaminated if >?100,000 cfu/mL of gram-positive flora was identified.

Results

A total of 106 patients were evaluated; 81 (76.4%) were female; the mean age was 53.4?±?15.9 years. 21 patients (19.8%) had evidence of contamination on DA. 14 (16.5%) patients had a positive DA result. Patients with diabetes mellitus and those with PPI use were more likely to have a positive DA (94.4% vs. 71.4%, p?=?0.007; 62% vs. 28.6%, p?=?0.021, respectively). 33 (31.1%) patients had a positive LBT. Patients with a history of small bowel resection were more likely to have a positive LBT (12.1% vs. 1.4%, p?=?0.016). DA and LBT results agreed in 54 patients (63.5%; kappa?=???0.02), indicating poor agreement.

Conclusions

The agreement between LBT and DA in evaluation for SIBO was poor. LBT may be favorable to DA, as LBT is safer, cheaper, and less likely to yield a contaminant result.

     

Cholecystectomy and Clinical Presentations of Gastroparesis

Background

Many patients with gastroparesis have had their gallbladders removed.

Aim

To determine if clinical presentations of patients with gastroparesis differ in those with prior cholecystectomy compared to patients who have not had their gallbladder removed.

Methods

Gastroparetic patients were prospectively enrolled in the NIDDK Gastroparesis Registry. Detailed history and physical examinations were performed; patients filled out questionnaires including patient assessment of GI symptoms.

Results

Of 391 subjects with diabetic or idiopathic gastroparesis (IG), 142 (36 %) had a prior cholecystectomy at the time of enrollment. Patients with prior cholecystectomy were more often female, older, married, and overweight or obese. Cholecystectomy had been performed in 27/59 (46 %) of T2DM compared to 19/78 (24 %) T1DM and 96/254 IG (38 %) (p = 0.03). Patients with cholecystectomy had more comorbidities, particularly chronic fatigue syndrome, fibromyalgia, depression, and anxiety. Postcholecystectomy gastroparesis patients had increased health care utilization, and had a worse quality of life. Independent characteristics associated with prior cholecystectomy included insidious onset (OR = 2.06; p = 0.01), more comorbidities (OR = 1.26; p < 0.001), less severe gastric retention (OR(severe) = 0.68; overall p = 0.03) and more severe symptoms of retching (OR = 1.19; p = 0.02) and upper abdominal pain (OR = 1.21; p = 0.02), less severe constipation symptoms (OR = 0.84; p = 0.02), and not classified as having irritable bowel syndrome (OR = 0.51; p = 0.02). Etiology was not independently associated with a prior cholecystectomy.

Conclusions

Symptom profiles in patients with and without cholecystectomy differ: postcholecystectomy gastroparesis patients had more severe upper abdominal pain and retching and less severe constipation. These data suggest that prior cholecystectomy is associated with selected manifestations of gastroparesis.     

Time Trends in Gastroparesis Treatment

Introduction

While delayed emptying is the defining criterion for gastroparesis, prokinetics often only have a limited impact on symptoms and have been associated with potentially serious adverse effects. The goal of this study was to determine how this information and regulatory changes affected gastroparesis management.

Methods

The electronic medical records of patients seen between 2003 and 2012 in the outpatient clinic of a large tertiary center were retrieved based on the billing diagnosis of gastroparesis. Demographic, clinical, and survival data were abstracted.

Results

A total of 709 patients were identified, with diabetes (21.2 %) and prior surgery (9.8 %) being the most common identifiable causes. The majority of patients (56 %) had idiopathic gastroparesis. The cohort was female predominant (79.5 %) with an average age of 45.4 ± 0.6 years. At the index encounter, 61.8 % received prokinetics. About one-third (37.7 %) used antiemetics at least intermittently. Between 2003 and 2012, prokinetic use dropped from 81 to 43 %, while the use of antiemetics increased from 14 to 41 %. Similarly, there was a significant increase in prescribed opioids and antidepressants. During the period of the study, 44 patients (6.2 %) died. Increasing age, a higher comorbidity burden, anxiety, and medication use were associated with higher mortality risks.

Conclusion

This large outpatient cohort suggests that treatment trends move away from prokinetics and focus on symptom-oriented therapy and/or confounding mood disorders.     

Severity of Dyspeptic Symptoms Correlates with Delayed and Early Variables of Gastric Emptying

Background

A simplified report of gastric retention values at select times is now recommended for scintigraphic gastric emptying test (GET).

Aims

The purpose of this study was to assess correlation between severity of gastroparetic symptoms and all variables of GET, compared to select variables in clinical use.

Methods

This was a prospective study of patients referred for scintigraphic GET. The Gastroparesis Cardinal Symptom Index questionnaire was obtained prior to the scintigraphy. Variables determined were lag time, half emptying time (T1/2), retention at 30 min, 1, 2 and 4 h. Statistical analysis was by Spearman rank correlation and Wilcoxon rank test with a significance set at p ≤ 0.05.

Results

Seven hundred seventeen patients had GET from 03/09 to 03/11. Results are from 325 patients who did not take medications known to affect GET were analyzed (64.9 % females, mean age 47 ± 18.9 years, 21.8 % diabetics, 78.2 % non-diabetic, of which 7.6 % were post-surgical, primarily post-fundoplication). Combined gastric retention at 2 and 4 h detected delayed GET in 83.5 % non-diabetics and 76.6 % of diabetics. Rapid GET was present in 11 % of patients at 30 min and 4 % at 1 h. Significant positive correlation was observed between nausea, vomiting, loss of appetite and variables of GET, but not with the half-time of emptying (T1/2). Bloating negatively correlated with retention at 2 h. There was no association between duration of symptoms and GET variables.

Conclusions

Gastroparetic symptoms correlate with different retention times of GET, but not with T1/2. However, symptoms poorly distinguish between categories of gastroparesis or status of gastric emptying. Delayed GE is best detected by 2 and 4 h retention times, while 30 min and 1 h retention times detect rapid GE.     

Low-grade small intestinal bacterial overgrowth is common in patients with non-alcoholic steatohepatitis on quantitative jejunal aspirate culture

Background

Though pathogenesis of non-alcoholic steatohepatitis (NASH) is unclear, association with small intestinal bacterial overgrowth [SIBO] and fecal dysbiosis is suggested. We evaluated SIBO in NASH using quantitative jejunal aspirate culture (conventional criteria: ≥?10⁵ colony forming unit (CFU)/mL and newer cutoff ≥?10³ CFU/mL) and glucose hydrogen breath test.

Methods

Thirty-eight patients with NASH (age 37.5 years, range 20–54, 9, 24% female), diagnosed by ultrasonography, alanine aminotransferase >1.5 times normal and liver biopsy (in 27/38, 71%) and exclusion of other causes and 12 constipation-predominant irritable bowel syndrome as historical controls (age 39.5-y, 26–44; 3, 25% female) without fatty liver were studied.

Results

Jejunal aspirates, obtained in 35/38 patients, were sterile in 14/35 (40%) and bacteria isolated in 21 (60%) (all aerobic, in one anaerobe also; Gram positive 5, negative 13, both 3). In contrast, bacteria (two Gram negative) were isolated in 3/12 (25%) controls (odds ratio 4.5, 95% CI 1.0–19.5; p = 0.04); colony counts were higher in NASH than controls (median 380 CFU/mL, 0–200,000 vs. 0 CFU/mL, 0–1000; p = 0.02). Gram negative bacteria tended to be commoner in NASH than controls (16/35 vs. 2/12; p = 0.07). Seven out of 35 (20%) patients with NASH (≥?10⁵ CFU/mL in 5 and 2 other on glucose hydrogen breath test) and no control had SIBO (p = ns); low-grade SIBO (≥10³ CFU/mL) was commoner in NASH than controls (14/35, 40%, vs. 1/12, 8.3%; p = 0.04). There was no correlation between bacterial colony count and bacterial type and anthropometric and biochemical parameters.

Conclusion

Low-grade bacterial overgrowth, particularly with Gram negative bacteria, was commoner in NASH than controls.

     

‘Exercise snacks’ before meals: a novel strategy to improve glycaemic control in individuals with insulin resistance

Aims/hypothesis

The aim of this study was to investigate whether small doses of intense exercise before each main meal (‘exercise snacks’) would result in better blood glucose control than a single bout of prolonged, continuous, moderate-intensity exercise in individuals with insulin resistance.

Methods

Nine individuals completed three exercise interventions in randomised order. Measures were recorded across 3 days with exercise performed on the middle day, as either: (1) traditional continuous exercise (CONT), comprising 30 min moderate-intensity (60% of maximal heart rate [HR_max]) incline walking before dinner; (2) exercise snacking (ES), consisting of 6?×?1 min intense (90% HR_max) incline walking intervals 30 min before each meal; or (3) composite exercise snacking (CES), encompassing 6?×?1 min intervals alternating between walking and resistance-based exercise, 30 min before meals. Meal timing and composition were controlled within participants for exercise interventions.

Results

ES attenuated mean 3 h postprandial glucose concentration following breakfast (by 1.4?±?1.5 mmol/l, p?=?0.02) but not lunch (0.4?±?1.0 mmol/l, p?=?0.22), and was more effective than CONT following dinner (0.7?±?1.5 mmol/l below CONT; p?=?0.04). ES also reduced 24 h mean glucose concentration by 0.7?±?0.6 mmol/l (p?=?0.01) and this reduction persisted for the subsequent 24 h (lower by 0.6?±?0.4 mmol/l vs CONT, relative to their baselines; p?=?0.01). CES was just as effective as ES (p?>?0.05 for all glycaemic variables) at improving glycaemic control.

Conclusions/interpretation

Dosing exercise as brief, intense ‘exercise snacks’ before main meals is a time-efficient and effective approach to improve glycaemic control in individuals with insulin resistance.     

Genetics correlates with lung function and nocturnal ventilation in myotonic dystrophy

Background

Dystrophia myotonica (DM) is the most frequent adult-onset muscular dystrophy. Type 1 is caused by the cytosine–thymine–guanine (CTG) repeat expansion in the DM protein kinase gene. Respiratory muscle weakness and altered central ventilatory control lead to hypercapnia and lung volume restriction.

Purpose

This study aims to review the respiratory involvement in DM patients and study its relation with genetics.

Methods

Retrospective study of patients with DM referred for respiratory assessment was made. Noninvasive ventilation (NIV) was considered to daytime hypercapnia or symptoms of nocturnal hypoventilation.

Results

Forty-two consecutive patients (37.9?±?13.6 years) were evaluated. Mean CTG length was 642.8?±?439.2 repeats. In the first evaluation, mean forced vital capacity (FVC) was 74.4?±?20.2 %, maximal expiratory pressure (MEP) 35?±?16 %, maximal inspiratory pressure 52?±?23 %, peak cough flow (PCF) 327.3?±?97.7 L/min, arterial pressure of oxygen 79.7?±?11.3 mmHg, arterial pressure of carbon dioxide 45.5?±?6.2 mmHg, overnight minimal peripheral oxygen saturation (SpO₂) 79.6?±?11.6 %, and apnea–hypopnea index 13.9?±?9.9. CTG length was found to be related with MEP (r?=??0.67; p?=?0.001) and SpO₂ (r?=??0.37; p?=?0.039). NIV was started in 25 patients. Ventilated patients had lower FVC (2.19 to 3.21 L; p?<?0.001) and PCF (285.3 to 388.5 L/min; p?=?0.003) and more CTG repeats (826.6 to 388.5 repeats; p?=?0.02). NIV compliance was poor in seven patients (28 %) and related with hypercapnia (r?=?0.87; p?=?0.002) and inspiratory positive airway pressure setting (r?=?0.65; p?=?0.009). Ventilation improved symptoms and nocturnal hypoventilation. Comparing the first and last evaluations, only PCF was significantly lower (275.0 to 310.8 L/min; p?=?0.019).

Conclusions

Ventilatory insufficiency is very common in patients with DM and CTG length may be useful to predict it. Prolonged NIV improves symptoms, nocturnal hypoventilation and maintains daily blood gases. Routine evaluation of PCF should not be forgotten and assisted coughing training provided.     

Regional Differences in Healthcare Delivery for Gastroparesis

Aim

Few studies have examined the effects of various interventions in gastroparesis. The goal of the present study was to determine whether inpatient management and outcomes differed among states across the United States.

Methods

Using population statistics and the State Inpatient Database (Agency for Healthcare Research and Quality), regional differences in admissions for gastroparesis, inpatient mortality, length of stay, nursing home transfers, and rates of endoscopy, gastrostomy placement, and nutritional support were assessed.

Results

Admissions for gastroparesis ranged from 24.3 ± 0.8/100,000 in Utah to 117.1 ± 9.7/100,000 in Maryland, with mortality rates similarly varying fourfold from 0.5 ± 0.1/100,000 in Colorado to 2.3 ± 0.1/100,000 in Florida. Intervention rates differed between states (endoscopy: 6.8 ± 0.8 % in Wyoming versus 23.1 ± 0.4 % in Florida; gastrostomy: 0.8 ± 0.1 % in North Carolina versus 3.3 ± 0.8 % in Hawaii; nutritional support: 1.2 ± 0.2 % in West Virginia versus 7.0 ± 0.6 % in New Jersey). Admissions rates were independently predicted by high overall hospitalizations within a state. Higher population density, median incomes and admissions to for-profit hospitals correlated with endoscopy rates. Coexisting heart failure and male gender were associated with higher likelihood of gastrostomy placement, while initiation of nutritional support was predicted by physician supply and insurance status. Age cohort, Medicare coverage, poverty rates and endoscopic testing independently predicted mortality, while length of stay correlated with diagnostic and therapeutic interventions.

Conclusions

There is a significant variability in admissions, interventions and outcomes for gastroparesis. While biological factors, such as comorbidities and age, contribute to this variability, the data suggest that socioeconomic variables significantly affect approaches to gastroparesis treatment in the United States.     

Willingness score obtained after a short CPAP trial predicts CPAP use at 1 year

Purpose

To predict continuous positive airway pressure (CPAP) adherence at 1 year.

Methods

We followed consecutive OSA patients scheduled for CPAP initiation for 1 year. Patients completed a self-efficacy questionnaire (5 = low, 25 = high score) before CPAP initiation. After CPAP initiation, we enquired about patients’ satisfaction in CPAP trial and their eagerness and willingness to continue CPAP therapy (0 = unsatisfied, uneager, or refused CPAP; 100 = satisfied, eager, or willing to continue CPAP treatment).

Results

Of the 580 patients we followed, 377 continued CPAP therapy beyond 1 year. A low willingness score (<50) was expressed by 77 patients but only 7 of them used CPAP >4 h daily at 1 year, yielding a specificity of 97 % in predicting CPAP failure. At 1 year, patients with a self-efficacy score >20, expressed prior to CPAP initiation, used CPAP more often than the patients with a score <20 (average use 4.4?±?2.2 h vs. 3.7?±?2.3 h, p?<?0.001).

Conclusions

A low score of willingness to continue CPAP therapy after a short trial predicts CPAP failure and poor CPAP adherence at 1 year.     

Effects of 12 weeks’ treatment with a proton pump inhibitor on insulin secretion, glucose metabolism and markers of cardiovascular risk in patients with type 2 diabetes: a randomised double-blind prospective placebo-controlled study

Aims/hypothesis

Recent studies suggest that proton pump inhibitor treatment may increase insulin secretion and improve glucose metabolism in type 2 diabetes. In a randomised double-blind prospective placebo-controlled 2 × 2 factorial study, we examined the effect of esomeprazole on insulin secretion, HbA_1c and cardiovascular risk factors in type 2 diabetes.

Methods

Forty-one patients with type 2 diabetes using dietary control or oral glucose-lowering treatment were randomised to receive add-on esomeprazole 40 mg (n?=?20) or placebo (n?=?21) for 12 weeks. Randomisation was carried out prior to inclusion on the basis of a computer-generated random-number list. The allocation sequence was concealed in sealed envelopes from the researcher enrolling and assessing participants. The study was undertaken at Steno Diabetes Center, Gentofte, Denmark. The primary outcome was change in AUC for insulin levels during a meal test. Secondary outcomes were the levels of HbA_1c and biochemical markers of cardiovascular risk, including lipids, coagulation factors, inflammation markers, markers of endothelial function and 24 h ambulatory BP measurements.

Results

Forty-one participants were analysed. In the esomeprazole-treated group the AUC for insulin did not change (before vs after treatment: 28,049?±?17,659 vs 27,270?±?32,004 pmol/l × min (p?=?0.838). In the placebo group AUC for insulin decreased from 27,392?±?14,348 pmol/l × min to 22,938?±?11,936 pmol/l × min (p?=?0.002). Esomeprazole treatment (n?=?20) caused a ninefold increase in the AUC for gastrin. HbA_1c increased from 7.0?±?0.6% (53?±?5 mmol/mol) to 7.3?±?0.8% (56?±?6 mmol/mol) in the esomeprazole-treated group and from 7.0?±?0.6% (53?±?5 mmol/mol) to 7.4?±?0.8% (57?±?6 mmol/mol) in the placebo group (n?=?21) (p for difference in change >0.05). Except for BP, there were no differences between the groups in the markers of cardiovascular risk (p?>?0.05). Monitoring of 24 h ambulatory BP showed a significant decrease in daytime systolic BP, daytime diastolic BP and 24 h diastolic BP in the placebo group (p?<?0.05). No change in BP was seen in the patients treated with esomeprazole.

Conclusions/interpretation

Treatment with esomeprazole over 12 weeks did not improve insulin secretion, glycaemic control or cardiovascular disease biomarkers in patients with type 2 diabetes.

Trial registration

ClinicalTrials.gov NCT00699426

Funding

The study was funded by Novo Nordisk A/S and Christian Hansen A/S.     

Effect of Amiloride on Experimental Acid-Induced Heartburn in Non-erosive Reflux Disease

Background

Acid-sensing ion channels (ASICs) are esophageal nociceptors that are candidates to mediate heartburn in non-erosive reflux disease (NERD). Amiloride, a diuretic, is known to inhibit ASICs. For this reason, we sought a role for ASICs in mediating heartburn by determining whether amiloride could block heartburn in NERD induced by esophageal acid perfusion.

Methods

In a randomized double-blind crossover study, we perfused the esophagus with amiloride or (saline) placebo prior to eliciting acid-induced heartburn in patients with a history of proton pump inhibitor-responsive NERD. Those with NERD and positive modified Bernstein test were randomized to perfusion with amiloride, 1 mmol/l, or placebo for 5 min, followed by repeat acid-perfusion. Heartburn severity and time to onset was measured and the process repeated following crossover to the alternative agent.

Results

14 subjects completed the study. Amiloride did not reduce the frequency (100 vs. 100 %) or severity of acid-induced heartburn (Mean 2.50 ± SEM 0.33 vs. 2.64 ± 0.45), respectively. There was a trend towards longer time to onset of heartburn for amiloride versus placebo (Mean 2.93 ± SEM 0.3 vs. 2.36 ± 0.29 min, respectively), though these differences did not reach statistical significance (p > 0.05).

Conclusions

Amiloride had no significant effect on acid-induced heartburn frequency or severity in NERD, although there was a trend towards prolonged time to onset of symptoms.