Effect of long-term dietary protein intake on glucose metabolism in humans.

AIMS/HYPOTHESIS: A meal rich in protein stimulates insulin secretion. Long-term effects of dietary protein on insulin release and glucose metabolism are, however, still not known. Our study focussed on the effect of different protein intake on pancreatic insulin secretion capacity, glycogen turnover and gluconeogenesis. METHODS: Subjects with constant (6 months) dietary protein of 1.87 +/- 0.26 g kg(-1) day(-1) (1.25-2.41) named high protein group and with 0.74 +/- 0.08 (0.57-0.80), normal protein group, were identified by a food questionnaire and were matched (n = 9) according to sex, age and calorie intake. They underwent an intravenous glucose tolerance test and a euglycaemic hyperinsulinaemic clamp with infusion of [6,6-2H2]-glucose combined with indirect calorimetry. To estimate net gluconeogenesis the usual diet was enriched by deuterated water or U-[13C6]-glucose and breath and plasma were sampled. RESULTS: Glucose-stimulated insulin secretion was increased in the high protein group (516 +/- 45 pmol/l vs 305 +/- 32, p = 0.012) due to reduced glucose threshold of the endocrine beta cells (4.2 +/- 0.5 mmol/l vs 4.9 +/- 0.3, p = 0.031). Endogeneous glucose output was increased by 12% (p = 0.009) at 40 pmol/l plasma insulin in the high protein group, but not at higher insulin concentration whereas overall glucose disposal was reduced. Fasting plasma glucagon was 34% increased in the high protein group (p = 0.038). Fractional gluconeogenesis was increased by 40% in subjects receiving a high protein diet as determined by both methods. CONCLUSION/INTERPRETATION: High protein diet is accompanied by increased stimulation of glucagon and insulin within the endocrine pancreas, high glycogen turnover and stimulation of gluconeogenesis.

Comparative clinical evaluation of the 13C-mixed triglyceride breath test as an indirect pancreatic function test.

BACKGROUND: Breath tests using stable isotopes of carbon or hydrogen are increasingly becoming established for the evaluation of various gastrointestinal functions, including measurement of exocrine pancreatic insufficiency. We wanted to evaluate the clinical relevance of the non-invasive, non-radioactive 13C-mixed triglyceride breath test in comparison with the secretin-caerulein test as the 'gold standard' of pancreatic function testing and with faecal chymotrypsin and elastase 1 in patients with mild and severe exocrine pancreatic insufficiency. METHODS: The secretin-caerulein test, faecal fat analysis, 13C-mixed triglyceride breath test, faecal elastase 1, and chymotrypsin and various morphologic investigations were done in 26 patients with mild (n = 13) or severe (n = 13) exocrine pancreatic insufficiency and 25 patients with gastrointestinal diseases of non-pancreatic origin. Twenty-seven healthy volunteers served as normal controls. After a 12-h fast 200 mg mixed triglyceride (1,3-distearyl,2(carboxyl-13C)octanoyl glycerol) were orally administered with a test meal, and breath samples were taken before and at 30-min intervals for 5 h thereafter, and the increase in 13C/12C isotopic ratio in breath was analysed by mass spectrometry. Various modifications of the test procedure were investigated. RESULTS: Specificity for impaired pancreatic function was higher for faecal elastase (90%) and equal for faecal chymotrypsin (82%) as compared with the various variables of the 13C-mixed triglyceride breath test (69-85%). The sensitivity of the 13C-mixed triglyceride breath test for total and separately for mild and severe exocrine pancreatic insufficiency was higher (total, 69-81%) than that of faecal chymotrypsin (total, 56%) but lower than faecal elastase (total, 92%). CONCLUSION: The 13C-mixed triglyceride breath test very sensitively reflects severe exocrine pancreatic insufficiency (steatorrhoea) but has limited sensitivity for the detection of mild cases. With regard to the higher sensitivity and specificity, the higher practicability, and the much lower cost, determination of faecal elastase 1 concentrations is superior to the 13C-mixed triglyceride breath test and therefore remains the most reliable indirect pancreatic function test available today.

13C-starch breath test--comparative clinical evaluation of an indirect pancreatic function test.

The clinical relevance of the 13C-starch breath test was evaluated in comparison to the secretin-caerulein test as the "gold standard" of pancreatic function testing, fecal elastase concentration, and fecal chymotrypsin activity in 30 patients with mild (n = 15) or severe (n = 15) exocrine pancreatic insufficiency. 23 patients with gastrointestinal diseases of non-pancreatic origin and 31 healthy volunteers served as controls. 50 g of natural starch of maize were orally administered after a 12-h fast and breath samples were taken before and in 30 min intervals for five hours after oral ingestion and the increase of 13C/12C-isotopic ratio was analyzed by mass spectrometry. Specificity of fecal elastase (93%) and fecal chymotrypsin (93%) for impaired pancreatic function were much higher compared to the various parameters of the 13C-starch breath test (69-74%). Sensitivities of the 13C-starch breath test for all and separately for mild and severe exocrine pancreatic insufficiency were higher (total 70-77%) compared to fecal chymotrypsin (total 60%), but lower compared to fecal elastase (total 93%). With regard to the higher sensitivity and specificity, the higher practicability, and the lower costs determination of fecal elastase concentrations is superior to the 13C-starch breath test and therefore remains to be the most reliable indirect pancreatic function test available today.

Validity of a novel biopsy urease test (HUT) and a simplified 13C-urea breath test for diagnosis of Helicobacter pylori infection and estimation of the severity of gastritis.

This prospective study was designed to validate a novel biopsy urease test as well as a simplified 13C-urea breath test for the detection of Helicobacter pylori. In addition, the hypothesis was tested that both the reaction velocity of the urease test and the 13CO2 excess of the urea breath test may allow a prediction of the severity of gastritis. Seventy dyspeptic patients with unknown H. pylori status were included. The H. pylori status was assessed by means of culture and histology after Warthin and Starry stain. One antral and one body biopsy specimen were separately analyzed by the novel biopsy urease test (HUT). Also, a 13C-urea breath test using 75 mg 13C-labelled urea and orange juice as test meal was performed in all patients. Forty-seven patients (67%) were H. pylori positive as judged from histology and culture. In 46 patients, H. pylori infection was also detected by the novel biopsy urease test and by the urea breath test as well (sensitivity 97.9%). False-positive results were not observed by either method (specificity 100%). Both the reaction velocity of the urease test and the 13CO2 excess of the breath test significantly correlated with H. pylori density and grade and activity of gastritis. The determination coefficients, however, indicated that both methods allow a reliable prediction of the severity of gastritis only in about 40-50% of the patients. In conclusion, the novel biopsy urease test and the simplified 13C-urea breath test proved to be highly accurate in diagnosing H. pylori infection. Despite a significant correlation, neither the reaction velocity of the urease test nor the 13CO2 excess of the breath test are clinically useful for the prediction of the severity of gastritis.

Improved resolution of magnetic resonance microscopy in examination of skin tumors.

Magnetic resonance imaging has become increasingly important for visualization and tissue differentiation of internal organs. Because of limited resolution, investigation of skin has been of little diagnostic value so far. We combined a homogeneous magnetic field of 9.4 T, as used in magnetic resonance spectroscopy, with gradient fields of 11.7 G/cm and an imaging unit to obtain a voxel resolution of 40 x 40 x 300 microm(3). With this magnetic resonance microscopy unit, we studied normal skin, 12 nevocellular nevi, 20 basal cell carcinomas, 8 melanomas, and 8 seborrheic keratoses after excision in vitro. The specimens were visualized in spin-echo images. The proton relaxation times T1 and T2 were determined for the different skin layers and tumor tissues. Interpretation of the spin-echo images was based on comparison with the correlating histology. Epidermis, dermis, subcutaneous tissue, and hair follicle complexes could be distinguished. Stratum corneum and hairs emitted no signal. All tumors presented as distinct, signal-rich, homogeneous structures within the dark, signal-poor dermis. Their shape corresponded to their outline in the histologic sections. Buds of superficial basal cell carcinomas could be resolved. The proton relaxation times T1 and T2 were significantly different among all skin layers and tumors. Our results demonstrate that with sufficient resolution, differentiation of skin tumors is possible using magnetic resonance imaging.

[Non-invasive 13C octanoic acid breath test for measuring stomach emptying of a solid test meal--correlation with scintigraphy in diabetic patients and reproducibility in healthy probands]. / Nicht-invasiver 13C-Oktansäureatemtest zur Messung der Magenentleerung einer festen Testmahlzeit--Korrelation mit der Szintigraphie bei Diabetikern und Reproduzierbarkeit bei gesunden Probanden.

The recently developed 13C-octanoic acid breath test allows the measurement of gastric emptying of solids. In this prospective study we wanted to investigate, whether the 13C-octanoic acid breath test using breath samples every half an hour is suitable in assessing gastric emptying in comparison to scintigraphy in diabetics. Furthermore, we examined the intraindividual reproducibility in healthy volunteers. 20 consecutive diabetics with clinical symptoms of gastroparesis received a solid double-labeled standard test meal. The meal consisted of 1 scrambled egg, labeled with 75 mg 13C-octanoic acid and 0.5 mCi 99mTc colloid, 50 g rye bread, 20 g butter, 200 ml orange juice; 280 kcal. Breath samples were taken at half hour intervals for 4 hours and analyzed for 13CO2 by isotope ratio mass spectrometry. Using a regression method gastric emptying half times (t 1/2) were determined and correlations to simultaneous 99mTc-scintigraphy were calculated. There was a moderate significant correlation of 13C-octanoic acid breath test t 1/2 and scintigraphic t 1/2 (R = 0.6; p = 0.008). The 13C-octanoic acid breath test t 1/2 obtained in 20 healthy volunteers measured at two separate days showed a coefficient of variation (VC), that was greater between subjects (VK = 42%) than between two measurements in the same subject (VK = 24%), which reflects a moderate intraindividual reproducibility. Taking breath samples every half an hour the 13C-octanoic acid breath test only reveals a moderate intraindividual reproducibility and a moderate correlation to scintigraphy in diabetics. For detailed assessment of solid gastric emptying in diabetics a 13C-octanoic acid breath test using shorter breath sampling intervals is recommended.

[The modified 13C-urea breath test in the diagnosis of Helicobacter pylori colonization of the gastric mucosa]. / Modifizierter 13C-Harnstoff-Atemtest in der Diagnostik der Helicobacter-pylori-Besiedlung der gastralen Mucosa.

The value of a modified 13C-urea breath test for the detection of Helicobacter pylori was analysed in a prospective study of 50 consecutive patients (28 women, 22 men, aged 20-90 years) with unknown Helicobacter pylori status about to undergo upper intestinal endoscopy. Four biopsies each were obtained in each patient from the antrum and the body of the stomach and examined for Helicobacter pylori infection of the gastric mucosa histologically (haematoxylin-eosin and Giemsa stain), with the rapid urease test and by culture. The patients then underwent a modified 13C-urea breath test. Results were positive histologically and(or) by culture in 29 patients, while the breath test was positive in 28 (sensitivity 96.3%). The breath test was falsely positive in two (specificity 91.3%). The biopsy urease test had a sensitivity of 96.3% with a 100% specificity. These results demonstrate that the modified 13C-urea breath test is a simple and accurate way of demonstrating Helicobacter pylori infection, equal in diagnostic value to the biopsy urease test.

[Qualitative and semiquantitative invasive and noninvasive diagnosis of Helicobacter pylori colonization of gastric mucosa]. / Qualitative und semiquantitative invasive und nicht-invasive Diagnostik der Helicobacter pylori-Kolonisation der gastralen Mukosa.

In 110 patients with unknown Helicobacter pylori status and without anti-bacterial treatment submitted for routine endoscopy of the upper gastrointestinal tract biopsies were taken from the antral and body mucosa, which were assessed for H. pylori colonisation and/or gastritis by an urease test (Jatrox H. p.-Test), microscopy after methylene-blue staining of a mucosal smear, specific culture and histology (stains: haematoxylin & eosin and Warthin-Starry). In addition, a simplified 13C-urea breath test was validated. A complete set of data was available from 104 patients (64 women - 40 men, median of age: 55 years [range: 17-92 years], H. pylori positive histologically and/or culturally [goldstandard]: n = 67). The test criteria sensitivity, specificity, positive and negative predictive value were calculated to be 100%/100%/100%/100% for the urease test, 76.1%/100%/100%/69.8% for microscopy of a mucosal smear, and 92.5%/97.3%/98.4%/88.1% for 13C-urea breath test (two-point measurement). Statistical analysis demonstrated highly significant (p < 0.0001) correlations between the reaction velocity of the urease test, the histologically visible degree of Helicobacter pylori colonisation and the differences of the delta-values of the 13C-urea breath test on the one hand and between grade and activity of gastritis as well as between the gastritis and activity scores, respectively, and the semi-quantitatively categorized results of the urease test, the histological degree of H. pylori colonisation and the 13C-urea breath test on the other hand.(ABSTRACT TRUNCATED AT 250 WORDS)