13C-辛酸呼气试验评估糖尿病胃固体排空功能的研究

目的探讨老年2型糖尿病患者胃固体排空功能及其与心血管自主神经功能的关系。方法老年2型糖尿病组71例，正常对照组30例，应用^13C-辛酸呼气试验技术检测胃固体排空功能，并行心血管自主神经功能评估。结果（1）糖尿病患者胃半排空时间（GET1／2）、延迟相（Tlag）及120min胃残留率（Ret120min）明显高于正常对照组（P均〈0．01）；（2）糖尿病患者胃排空延迟患病率高于正常对照人群（P〈0．01）；（3）糖尿病合并胃排空延迟者心血管自主神经病变患病率明显高于胃排空正常糖尿病患者（P〈0．05）；（4）糖尿病组GET1/2与心血管自主神经功能积分呈显著正相关（r=0．353，P〈0．01）。结论（1）老年2型糖尿病患者胃动力明显下降，胃固体排空延迟常常与心血管自主神经病变合并存在。（2）^13C-辛酸呼气试验是检测胃排空的理想选择。     

13C-octanoic acid breath test for gastric emptying measurement

OBJECTIVES: The purpose of this multicentre study was to assess the accuracy and reproducibility of the 13C-octanoic acid breath test compared to scintigraphy for measurement of gastric emptying. METHODS: Sixty-nine healthy subjects (40 men, 29 women; mean age 30 years, range 21-61) were studied at least once by using the 13C-octanoic breath test. In 34 healthy subjects, gastric emptying was simultaneously measured by gastric scintigraphy, and the 13C-octanoic breath test was then repeated in 18 of these cases. Fifty-four patients (30 men, 24 women; mean age 46 years, range 13-74) with dyspeptic or reflux symptoms were studied according to the same procedure. RESULTS: The correlation between breath test and scintigraphic values was highly significant (r = 0.744, P<0.001). The concordance of results of scintigraphy and breath test (normal versus abnormal) and the reproducibility (Bland and Altman method) of the breath test were good (CVinter = 24%, CVintra = 15%). As compared to scintigraphy, breath test detected an abnormal gastric emptying with 67% sensitivity and 80% specificity (ROC analysis). CONCLUSION: These results confirm the value of breath test as an accurate measurement of gastric emptying. Its excellent reproducibility makes it a method of choice for pharmacological studies. However, at least when scintigraphy is considered the gold standard, breath test sensitivity may be insufficient for the detection of gastroparesis in an individual patient.     

Gastric emptying in diabetic patients by the 13C-octanoic acid breath test: role of insulin in gastric motility

Background Impairment of gastric emptying is well recognized in patients with diabetes mellitus (DM), especially long-standing insulin-dependent diabetes mellitus (IDDM). The aim of this study was to evaluate the cause of delayed gastric emptying in DM patients. Methods In 16 controls, 16 non-insulin-dependent diabetes mellitus (NIDDM) patients and 23 IDDM patients, gastric emptying was studied using the ¹³C octanoic acid breath test. Breath samples were taken before a test meal labeled with 100 mg of ¹³C octanoic acid, and at 15-min intervals over a 300-min period postprandially. Results In all DM patients, the gastric emptying coefficient was lower than that in the controls (P < 0.05), and lag time and half-emptying time were significantly longer (P < 0.05). Both NIDDM and IDDM patients showed delayed ¹³CO₂ excretion compared with the controls, but IDDM patients showed more delayed gastric emptying than NIDDM patients (P < 0.05). There were no significant differences in sex, HbA1c level, or the rate of neuropathy between the two groups. Conclusions IDDM patients showed delayed gastric emptying compared with NIDDM patients, and the ¹³C octanoic acid breath test is useful for evaluating DM patients with delayed gastric emptying.     

Gastric emptying of a solid meal starts during meal ingestion: combined study using 13C-octanoic acid breath test and Doppler ultrasonography. Absence of a lag phase in 13C-octanoic acid breath test

Scintigraphy and the 13C-octanoic acid breath test are both applied to assess gastric emptying. Using the 13C-octanoic acid breath test, excretion curves show 13C excretion immediately after ingestion of a solid egg meal, in contrast with scintigraphy where gastric emptying is observed after a lag phase. The aim of our study was to investigate whether transpyloric flow occurs during and directly after meal ingestion. Therefore, transpyloric flow was measured during and after ingestion of an egg meal labeled with 13C-octanoic acid, using Doppler ultrasonography. The breath test was performed simultaneously, with samples taken at regular intervals. The first emptying episode was observed 6.9 (3.9-16.2) min after start of meal ingestion. A significant relation between recovery of 13C and total duration of gastric emptying during the first 20 min was observed (partial correlation coefficient r = 0.80, p < 0.001). In conclusion, transpyloric flow starts during ingestion of a solid egg meal and results in detectable excretion of 13C.     

Infrared spectrometry based 13C-octanoic acid breath test in measuring human solid gastric emptying

BACKGROUND AND AIMS: Because of the convenience of non-dispersive infrared spectrometry (NDIRS), we attempted to validate the usefulness of NDIRS compared with scintigraphy in human solid gastric emptying (GE) measurement, and tried to establish the normal range of solid GE based on NDIRS. METHODS: Twelve healthy volunteers (three men, nine women) were recruited for simultaneous scintigraphy and 13C-octanoic acid breath test (13C-OABT) studies. Stomach half-emptying time (t1/2) and lag phase (tlag) were the two main GE parameters measured and correlated. The breath samples were analyzed using NDIRS every 10-15 min for a total of 6 h, while scintigraphy was taken minute by minute for the first 30 min, then hourly for 4 h. Another 32 healthy volunteers (19 men, 13 women) received only the 13C-OABT to measure their solid GE. RESULTS: A significant correlation for t1/2 was found between the breath test and scintigraphy (r = 0.85, P = 0.001), while tlag was also positively correlated (r = 0.73, P = 0.007). The reference range of t1/2B based on all 44 subjects was 89.4-185.1 min (135.9 +/- 21.1 min (mean +/- SD)), while the range for tlagB was 37.1-117.8 min (81.9 +/- 17.4 min). No demographic characteristics were found to influence the GE parameters. CONCLUSIONS: 13C-octanoic acid breath test determined by NDIRS is a simple, non-invasive and reliable measurement, which may provide an 'office-based' tool to detect solid GE.     

Measurement of gastric emptying by 13C-octanoic acid breath test versus scintigraphy in diabetics

In this prospective study, we compared the assessment of gastric emptying by the 13C-octanoic acid breath test to gastric emptying scintigraphy in diabetics. We also examined the relationship between gastric emptying parameters and gastric symptoms and cardiovascular autonomic function. The 13C-octanoic acid breath test and scintigraphy were performed simultaneously in 24 diabetics with a solid test meal (1 egg, doubly labelled with 91 mg 13C-octanoic acid and 50 MBq 99mTechnetium-Nanocoll, 60 g white bread, 5 g margarine and 150 ml water). At fifteen-minute intervals, breath samples were taken over 4 hours and examined by mass spectrometry. In parallel, scintigraphy was performed for 2 hours at one minute intervals. Using breath test data, gastric emptying half time (t (1/2) ), lag-phase (t lag ) and gastric emptying coefficient (GEC) were calculated. Subsequently, the correlation of these results with the equivalent data from scintigraphy were determined employing a regression method. To detect a cardiovascular autonomic neuropathy, a 24-h ECG recording was performed. The prevalence of gastrointestinal symptoms in our collective was assessed by a standardized questionnaire. There was a highly significant positive correlation of both 13C-octanoic acid breath test t (1/2) and scintigraphic t (1/2) (r = 0.8257; p < 0.0001) and 13C-octanoic acid breath test t lag and scintigraphic t lag (r = 0.6302; p < 0.001). The sensitivity of the 13C-octanoic acid breath test was 1 and the specificity was 0.73. In our study, there was no significant association of cardiovascular and gastrointestinal autonomic neuropathy. Furthermore, there was no significant relationship between the prevalence of gastrointestinal symptoms and gastric emptying disorders. We conclude that the 13C-octanoic acid breath test represents a suitable method to measure disordered gastric emptying in diabetics due to its highly significant positive correlation to scintigraphy and due to its validity. It is not possible to predict diabetic gastroparesis on the basis of other autonomic function disorders or because of dyspeptic symptoms.     

Noninvasive (13)C-octanoic acid breath test shows delayed gastric emptying in patients with amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive loss of motor neurons. However, ALS has been recognized to also involve non-motor systems. Subclinical involvement of the autonomic system in ALS has been described. The recently developed (13)C-octanoic acid breath test allows the noninvasive measurement of gastric emptying. With this new technique we investigated 18 patients with ALS and 14 healthy volunteers. None of the patients had diabetes mellitus or other disorders known to cause autonomic dysfunction. The participants received a solid standard test meal labeled with (13)C-octanoic acid. Breath samples were taken at 15-min intervals for 5 h and were analyzed for (13)CO(2) by isotope selective nondispersive infrared spectrometry. Gastric emptying peak time (t(peak)) and emptying half time (t(1/2)) were determined. All healthy volunteers displayed normal gastric emptying with a mean emptying t(1/2) of 138 +/- 34 (range 68-172) min. Gastric emptying was delayed (t(1/2) > 160 min) in 15 of 18 patients with ALS. Emptying t(1/2) in ALS patients was 218 +/- 48 (range 126-278) min (p < 0.001). These results are compatible with autonomic involvement in patients with ALS, causing delayed gastric emptying of solids and encouraging the theory that ALS is a multisystem disease rather than a disease of the motor neurons only.     

Evaluation of gastric emptying measured with the 13C-octanoic acid breath test in patients with functional dyspepsia: comparison with ultrasonography

BACKGROUND: As a non-invasive modality by which to evaluate the gastric emptying of a solid meal, the 13C-octanoic acid breath test has recently become more widely used. Previously, we reported that ultrasonography was another non-invasive and reliable method for assessing gastric motility. The aim of this study was to compare the reliability of these two methods. METHODS: Seventeen patients with functional dyspepsia and 10 healthy volunteers were studied. The solid test meal consisted of a scrambled egg labeled with 13C-octanoic acid (100 mg) and served with a bowl of rice and boiled chicken (total 424 kcal). After ingestion of the test meal, all subjects were examined in the sitting position. Ultrasonography images were obtained every 15 min for 3 h. Breath sampling followed the same time schedule as for the ultrasonography, with an additional 3 h of sampling at 30-min intervals. We investigated the half emptying time (T1/2) and the lag phase with both methods. RESULTS: The T1/2 by the ultrasonography method and the breath test were positively correlated (r2 = 0.638); however, there was no significant agreement between the study groups. Both the T1/2 and the lag phase were prolonged in the functional dyspepsia patients compared with the healthy volunteers, regardless of the method of measurement. The lag phase was significantly correlated (r2=0.864) with the T1/2 by the breath test. CONCLUSIONS: Although the 13C-octanoic acid breath test cannot assess the gastric emptying of solids as reliably as ultrasonography, both tests are useful for evaluating functional dyspepsia patients with delayed gastric emptying.     

Delayed gastric emptying in the obese: an assessment using the non-invasive (13)C-octanoic acid breath test

AIM: Much of the controversy surrounding the correlation between obesity and gastric emptying lies in the inconsistency of methodology and analysis. This study was designed to overcome some of the discrepancies encountered in previous studies and to test the hypothesis that obese individuals have altered gastric emptying compared to lean individuals. METHODS: Gastric emptying was measured using the (13)C-octanoic acid breath test in 16 lean and 16 obese women pair-matched for age. Following an overnight fast, subjects were given a standard 2 MJ egg meal labelled with 100 microl of [1-(13)C]-octanoic acid. Breath samples were collected at regular intervals over a 6-h period. (13)C-isotopic enrichment in the breath was analysed using isotope ratio mass spectrometry and the data fitted to the established gastric emptying model. The lag times (t(lag)), half excretion times (t(1/2)), latency phase (t(lat)) and ascension times (t(asc)) were calculated. RESULTS: The mean t(1/2)-values (+/-standard error of the mean) were 3.67 +/- 0.14 h and 4.23 +/- 0.18 h for lean and obese respectively, indicating significantly delayed gastric emptying in the obese (p = 0.019). The obese group also showed a significantly slower lag time (t(lag), p = 0.005) and latency phase (t(lat), p = 0.005), but no significant difference was found in the ascension time (t(asc), p = 0.154). Within groups, no correlation was found between half excretion times and body weight or half excretion times and body mass index. CONCLUSIONS: The present study demonstrated a prolonged lag phase and delayed gastric emptying in obese women when compared to lean women. This delay may be as a consequence of high-fat diets, a sedentary lifestyle and increased gastric distension associated with obesity, or a contributing factor in the pathogenesis of obesity resulting from the inactivation of gastrointestinal satiety signals and in an increase in food intake.     

Gastric emptying after pylorus-preserving gastrectomy: assessment using the 13C-acetic acid breath test

BACKGROUND/AIMS: Gastric emptying after PPG is directly associated with postoperative QOL. Few studies have investigated gastric emptying after a gastrectomy for stomach cancer using carbon-labeled acetic acid breath test. METHODOLOGY: We analyzed gastric emptying in 28 patients who underwent a gastrectomy for gastric carcinoma. Among the patients, 14 underwent pylorus-preserving gastrectomy and 14 underwent distal gastrectomy. We recruited 15 healthy subjects as controls. Gastric emptying was evaluated with the 13C-Acetic acid breath test was performed. Postprandial breath samples were collected at a 15-min interval for 2 hours and at a 30-min interval thereafter. We calculated the ratio of (13)CO2 expired per hour and determined the time required to reach peak (13)CO2 expiration level. RESULTS: The time required to reach peak (13)C02 expiration level were 1.78 hours for the patients who underwent pylorus-preserving gastrectomy, 1.19 hours for the control group and 0.70 hours for the patients who underwent distal gastrectomy. CONCLUSIONS: Our 13C-Acetic acid breath test following an intake of solid foods showed that gastric retention can be preserved after a pylorus-preserving gastrectomy.     

Influence of caloric intake on gastric emptying of solids assessed by 13C-octanoic acid breath test

BACKGROUND: The 13C-octanoic breath test (13C-OBT), a recently developed technique to evaluate gastric emptying of solids, has been validated in comparison to scintigraphy with low caloric meals (250 kcal). However, there is consensus that for clinical studies total caloric load should be in excess of 300 kcal, but studies comparing 13C-OBT results after low and medium caloric meals are lacking. METHODS: Ten healthy subjects were given a 250-kcal and a 550-kcal meal in randomized order. Gastric emptying was assessed simultaneously by ultrasonography and 13C-OBT. Breath samples were taken according to both classic (21 samples over 5 h) and simplified (11 samples) schedules. RESULTS: Increasing the meal energy content resulted in significantly longer half emptying time (T(1/2)) estimates by both ultrasonography (P < 0.01, Wilcoxon test) and 13C-OBT (P < 0.05). T(1/2) estimates by the two methods significantly correlated for both the 250 (r(s) = 0.733, P = 0.018) and the 550 (r(s) = 0.637, P = 0.035) kcal meal. However, differences between T(1/2) estimates by 13C-OBT and ultrasonography were greater after the 550- than the 250-kcal meal (median 172.5 versus 76.5 min, P < 0.05). Interindividual variability was also 2-fold greater for indexes estimated by 13C-OBT with the 550-kcal meal compared with the 250-kcal meal. For both meals 13C-OBT yielded similar results with the classic and simplified schedules. CONCLUSIONS: In healthy subjects caloric intake is a major determinant of gastric emptying rate. However, after a medium caloric meal 13C-OBT shows some inaccuracy, which raises questions about its routine clinical application. Nevertheless, when using 13C-OBT one must take into account that the simplified schedule is just as effective as the classic one, and is far lower in cost.     

Gastric and oesophageal emptying in patients with Type 2 (non-insulin-dependent) diabetes mellitus

Summary Gastric emptying of a digestible solid and liquid meal and oesophageal emptying of a solid bolus were measured with scintigraphic techniques in 20 randomly selected Type 2 (non-insulin-dependent) diabetic patients receiving oral hypoglycaemic therapy and 20 control subjects. In the diabetic patients, the relationships between oesophageal emptying, gastric emptying, gastrointestinal symptoms, autonomic nerve function and glycaemic control were examined. The percentage of the solid meal remaining in the stomach at 100 min (p<0.001), the 50% gastric emptying time for the liquid meal (p<0.05) and oesophageal emptying (p<0.05) were slower in the diabetic patients compared to the control subjects. Scores for upper gastrointestinal symptoms and autonomic nerve dysfunction did not correlate significantly (p>0.05) with oesophageal, or gastric emptying. The 50% gastric emptying time for the liquid meal was positively related (r=0.58, p<0.01) to the plasma glucose concentration at the time of the performance of the gastric emptying test and the lag period, before any solid food emptied from the stomach, was longer (p<0.05) in subjects with plasma glucose concentrations during the gastric emptying measurement greater than the median, compared to those with glucose concentrations below the median. These results indicate that delayed gastric and oesophageal emptying occur frequently in Type 2 diabetes mellitus and that delayed gastric emptying relates, at least in part, to plasma glucose concentrations.     

Effects of Helicobacter pylori eradication therapy on gastric emptying measured using the 13C-octanoic acid breath test and the acetaminophen method

BACKGROUND: The relationship between Helicobacter pylori eradication and gastric emptying has been reported; however, the effect of eradication therapy on gastric emptying is still unclear. This study evaluated the relationship between three gastric emptying techniques, the scintigraphic technique, the 13C-octanoic acid breath test, and the acetaminophen method, measured simultaneously, and the effect of H. pylori eradication therapy on gastric emptying and abdominal symptoms in patients with functional dyspepsia who were H. pylori positive. METHODS: Fifty-three consecutive patients with positive H. pylori infection were enrolled in this study. In the first 14 patients, gastric emptying was measured using the three gastric emptying techniques. In 42 patients cured of H. pylori infection, the 13C-octanoic acid breath test and the acetaminophen method were performed before and 3 months after eradication. RESULTS: Significant correlations were found between the scintigraphic technique, the 13C-octanoic acid breath test, and the acetaminophen method. Gastric emptying determined by the 13C-octanoic acid breath test and the acetaminophen method was not changed after eradication, on average. In 14 (33.3%) patients a decrease in symptom score after eradication was observed. In four (9.5%) patients, accelerated gastric emptying after eradication may have led to a reduction in the abdominal symptoms. CONCLUSIONS: The 13C-octanoic acid breath test and the acetaminophen method are appropriate for investigating gastric emptying. A causal relationship between improvement of symptoms and accelerated gastric emptying was not found, and the efficacy of H. pylori eradication therapy in patients with functional dyspepsia was minimally exhibited.     

A pilot study of mitochondrial DNA point mutation A3243G in a sample of Croatian patients having type 2 diabetes mellitus associated with maternal inheritance

Abstract In this work, patients having type 2 diabetes mellitus and diabetic mothers were tested for the presence of mitochondrial DNA point mutation A3243G. This mutation is associated with the MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes), diabetes and deafness. Twenty-two diabetic persons were screened. DNA was isolated from peripheral blood lymphocytes and from swabs of oral mucosa. The mitochondrial DNA point mutation A3243G was detected using PCR-RFLP test. The mutation was detected in oral mucosal DNA of two patients (but not from lymphocyte DNA). One patient was a man with hearing and visual impairments and proteinuria; the other was a woman having proteinuria but no hearing impairment. The mutation was not detectable in oral mucosal DNA from the control persons: 20 diabetic patients having diabetic fathers and 22 healthy, nondiabetic volunteers. The incidence of mitochondrial DNA point mutation A3243G in this study of Croatian diabetic patients is in line with data in the literature.     

Renal complications in patients with diabetes mellitus associated with an A to G mutation of mitochondrial DNA at the 3243 position of leucine tRNA.

The substitution of guanine for adenine at position 3243 of the leucine tRNA gene of mitochondrial DNA was originally described in association with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes). Diabetes mellitus associated with the mutation (mitochondrial diabetes) is a different phenotype from MELAS. We identified 11 patients with the mutation among 385 Japanese diabetic patients: two had MELAS and nine had mitochondrial diabetes. We present data on a male patient with mitochondrial diabetes who developed the nephrotic syndrome at the age of 23. Light microscopy revealed mesangial expansion, PAS-positive deposits and segmental sclerosis in the glomeruli. Scattered mesangial electron-dense deposits and thickening of the basement membrane were found on electron microscopy, suggesting that diabetic glomerulosclerosis accompanied by focal glomerulosclerosis (FGS). Mitochondrial diabetes may pre-dispose patients to renal complications, including forms of glomerulonephritis, such as FGS.