The 13CO2 breath test for liver glycogen oxidation after 3-day labeling of the liver with a naturally 13C-enriched diet.

OBJECTIVE: When naturally (13)C-enriched carbohydrate is used to label hepatic glycogen, (13)C-liver glycogen oxidation can be monitored subsequently by measuring the (13)C enrichment of breath CO(2) during a sedentary fast. In our previous breath test studies, we used a 1-d labeling protocol to enrich liver glycogen. Others found that after 3 d of labeling the liver glycogen (13)C enrichment is identical to the dietary carbohydrate (13)C enrichment. METHODS: We compared a diet protocol in which naturally (13)C-enriched carbohydrate was given for 3 d before the breath test with our previously applied 1-d labeling design. The (13)CO(2) breath test was combined with indirect calorimetry. The results were compared with those from our previous studies. In addition, we compared liver glycogen oxidation rates with those from our present technique and different techniques as used in other published studies. RESULTS: Six healthy volunteers were included in this study. The (13)C enrichment of breath CO(2) at plateau excretion level did not differ after 1 or 3 d on a labeling diet. However, the end of plateau time tended to be later after the 3-d diet, 14.3 h versus 12.5 to 13.5 h postprandially in the 1-d labeling studies. Also, the return to baseline time was later in the 3-d study, at 25.8 h versus 19.0 to 23.2 h postprandially after 1 d of labeling. The liver glycogen oxidation rate was similar in both techniques until 17 h postprandially. After this time the 3-d labeling protocol showed a higher level of liver glycogen oxidation. CONCLUSION: The results indicated that the labeling of liver glycogen is slightly less complete after 1 d on a (13)C-enriched diet as compared with 3-d labeling. Our (13)C breath test results compared rather well with studies from the literature using the (13)C-NMR technique, the D(2)O technique, or the (13)CO(2) breath method to measure liver glycogen oxidation.

Muscle glycogen does not interfere with a 13CO2 breath test to monitor liver glycogen oxidation.

Naturally 13C-enriched carbohydrate has been used to label the liver glycogen pool for metabolic studies. The utilization of this glycogen was then monitored by the appearance of 13CO2 in breath. Using this method, it is assumed that during sedentary fasting the contribution of muscle glycogen towards oxidation is negligible. We investigated the influence of a different level of 13C enrichment of muscle glycogen on the 13C enrichment of breath CO2 while the breath test was carried out. In six healthy volunteers, the muscle glycogen stores were grossly depleted by a cycling exercise prior to consumption of the 13C-enriched diet which was given over a 10 h period. The oxidation of liver glycogen was measured during an 18 h sedentary fast. The results were compared with a control group who had not depleted their muscle glycogen before labelling. A higher 13C enrichment of muscle glycogen did not interfere with two parameters of liver glycogen oxidation, i.e. the duration of the plateau phase of 13CO2 and the return to baseline time. It was also shown that the 13C-labelled muscle glycogen was still available after the 18 h fast because a strenuous exercise led to a rapid 13CO2 enrichment. It is concluded that muscle glycogen 13C enrichment does not invalidate a 13CO2 breath test to measure liver glycogen oxidation during a sedentary fast.

Influence of the 13C-enrichment of the habitual diet on a 13CO2 breath test used as an index of liver glycogen oxidation: a validation study in western Europe and Africa.

A diet containing naturally 13C-enriched carbohydrate combined with a 13CO2 breath-test analysis can be used to monitor liver glycogen oxidation in persons used to a diet low in 13C, e.g., the Western European diet. In this study, we evaluated this test principle further by changing the way we label the glycogen pool. The 13C enrichment of exhaled CO2 was studied in two groups, one in Europe and one in Africa. The European group (n = 12) was accustomed to a diet low in 13C, and they went on a 13C-enriched study diet to identify liver glycogen. The African group (n = 6) was accustomed to a diet naturally high in 13C, and they went on a diet low in 13C. The basal 13C abundance in exhaled CO2 was higher in the African group (1.0879 At%; atmospheric 1.1 atom percent) than in the European group (1.0821 At%). During the study period, the parameters for liver glycogen oxidation--the 13CO2 enrichment plateau, the plateau duration, and the return to baseline time--did not differ between groups. The abundance of 13CO2 in exhaled CO2 over time in the two groups was similar but inverse. This study confirms the use of a 13CO2 breath test to monitor liver glycogen oxidation and demonstrates how to use such a test in persons accustomed to a diet high in 13C.

Azathioprine in inflammatory bowel disease, a safe alternative?

Azathioprine and its metabolite 6-mercaptopurine are effective in the treatment of inflammatory bowel disease. They are mostly used for reduction of the use of steroids, maintenance therapy after remission induction by cyclosporin and treatment of fistulae in Crohn's disease. Adverse effects occur in about 15% of patients. The main side effects are pancreatitis, allergic reactions, fever and bone marrow suppression. Symptoms, management and prevention are discussed. A blood monitoring schedule is suggested. Azathioprine and 6-mercaptopurine seem to be safe in pregnancy. There may be a slight increased risk for developing a non-Hodgkin's lymphoma.

Human liver glycogen metabolism assessed with a 13C-enriched diet and a 13CO2 breath test.

BACKGROUND: Adequate liver glycogen stores to maintain hepatic glucose output by glycogenolysis in the post-absorptive state are essential to prevent protein loss through gluconeogenesis. There are no simple techniques to monitor liver glycogen use. METHODS: In this study, we labelled liver glycogen with naturally 13C-enriched carbohydrate and measured the pattern of 13CO2 excretion and the post-prandial time during which oxidation of 13C-labelled liver glycogen was demonstrable by 13CO2 enrichment in breath. Two experiments were performed in 24 healthy volunteers. RESULTS: In the first experiment we observed that breath 13CO2 enrichment returned to baseline values at 20.3 (SD 2.3, n = 12) hours post-prandially, indicating exhaustion of the 13C-labelled liver glycogen at that time. In a second experiment, breath 13CO2 enrichment in the early hours of the post-prandial phase was studied. After a steep decline, which started 2-4 h after the last meal, the 13CO2 enrichment reached a plateau phase 6 h post-prandially. This plateau phase lasted for about 6-8 h, suggesting steady-state glycogenolysis during this period. The plateau phase was followed by a further decline in 13CO2 excretion, suggesting a gradually diminishing contribution of 13C-labelled liver glycogen to substrate oxidation. CONCLUSION: It is possible to label liver glycogen with a diet of naturally 13C-enriched carbohydrate. The oxidation of the labelled liver glycogen can be monitored by measuring 13C-enrichment in breath CO2.

[Percutaneous drainage of benign nonparasitic liver cysts]. / Percutane drainage van benigne niet-parasitaire levercysten.

OBJECTIVE: To evaluate the treatment of symptomatic benign non-parasitic cysts of the liver by percutaneous drainage and sclerotherapy with alcohol. DESIGN: Descriptive, prospective. SETTING: Ikazia Hospital, Rotterdam. PATIENTS: All patients who presented with symptomatic benign non-parasitic cysts of the liver during the period 1988-1992 and in whom percutaneous drainage was not contraindicated. After drainage sclerotherapy with absolute alcohol was carried out, after which suction was applied until oozing stopped. RESULTS: Four patients were treated, all women, 51, 53, 53 and 64 years old. In 3 patients the cyst did not recur during the follow-up period, which ranged from 8 to 60 months. The 4th patient needed surgical treatment after the percutaneous drainage failed twice. No complications of the drainage were encountered. CONCLUSION: Percutaneous drainage followed by alcohol sclerotherapy and suction is the treatment of choice in patients with symptomatic benign non-parasitic cysts of the liver. Surgical treatment should be reserved for patients who fail to respond to repeated percutaneous drainage and cases in which the location of the cyst makes it technically difficult to use a percutaneous route.