Effectiveness of a novel endoscopy training concept.

BACKGROUND AND STUDY AIMS: Training standards in gastrointestinal endoscopy are poorly defined even though different simulators are increasingly used for skills training. In 2001 a new training concept called "GATE--gastroenterological education-training endoscopy" was established, which provides a combination of background theory, video demonstrations, and simulator training. We aimed to evaluate the acceptance and training effect of this training model. METHODS: In total, 98 physicians participating in four training courses were included. Data were collected on baseline characteristics, acceptance (5-point Likert scale), and pre- and post-course knowledge through a structured questionnaire (A-type and Pick-N multiple choice questions). A total of 13 trainees were randomly selected for additional simulator assessment of training effects on manual skills (5-point Likert scale). RESULTS: A total of 78 trainees (80%) provided complete data sets. The evaluation showed a positive acceptance of the training program (value 1 and 2, Likert scale); for example, 88% of participants suggested the inclusion of the GATE course as an obligatory part of endoscopic education. There was a significant improvement in theoretical knowledge in the post-test set compared with the pre-test set (mean 3.27 ±1.30 vs. 1.69 ±1.01 points; P<0.001). The training effect on practical skill showed a significant reduction in time needed for a procedure (445 ±189 s vs. 274 ±129 s; P<0.01). The mean assessment rating for practical skills improved from 3.05 ±0.65 at baseline to 2.52 ±0.59 on Likert scale ( P=0.085). CONCLUSIONS: The integrated GATE training improved theoretical knowledge and manual skill. The GATE courses have been accredited by the German Society of Gastroenterology, underlining the demand for implementing preclinical training courses in endoscopic training.

Intrarenal resistance index for the assessment of early renal function impairment in patients with liver cirrhosis.

BACKGROUND: Renovascular vasoconstriction in patients with hepatorenal syndrome can be quantified by the renal arterial resistance index (RI). We investigated the value of RI measurement in detection of renal function impairment in patients with different stages of chronic liver disease. METHODS: Subjects were divided into 4 groups containing 21 patients with liver cirrhosis and ascites, 25 patients with liver cirrhosis without ascites, 35 patients with fatty liver disease and 78 control subjects. All patients underwent abdominal ultrasound examination with renal RI measurement and correlation with laboratory results for renal function. RESULTS: RI was significantly higher in ascitic patients compared to non-ascitic patients (0.74 vs. 0.67, p<0.01) and in non-ascitic patients with liver cirrhosis than in control subjects (0.67 vs. 0.62, p<0.01). 48% (19/40) of patients with liver cirrhosis and normal serum creatinine concentration showed elevated RI levels. There were no significant differences in RI levels between patients with fatty liver disease and controls (0.63 vs. 0.62). CONCLUSIONS: Intrarenal RI measurement is a predictor of renal vasoconstriction and serves to detect early renal function impairment in cirrhotic patients. The diagnosis of elevated RI may be taken into account in the clinical management of these patients.

Age dependency of intrarenal resistance index (RI) in healthy adults and patients with fatty liver disease.

BACKGROUND: Our aim was to investigate the influence of age and gender on intrarenal resistance index (RI) measurements in 78 healthy subjects (46 males, 32 females; group 1) and 35 subjects (group 2) with fatty liver disease (28 males and 7 females). SUBJECTS AND METHODS: First, each subject underwent a conventional abdominal ultrasound examination. Then, intrarenal RI values were determined from three distinct interlobar and cortical arteries respectively on both kidneys. The correlation of intrarenal RI with age and gender as a variable was statistically evaluated by linear regression. RESULTS: In group 1, the variables gender, kidney region and comparison of right versus left kidney had no significant effect on intrarenal RI (p>0.05). The variable age, on the other hand, showed a significant positive correlation on all four defined measuring points (p<0.01) with linear correlation coefficients of r = 0.26 (left kidney, central) to r = 0.37 (right kidney, cortical). Therefore normal RI values at ages 25, 45, 65 years could be defined as 0.59, 0.61 and 0.63, respectively. Age dependency can thus be expressed as a function with the formula y = 0.565 + 0.001.x. Patients with fatty liver disease showed age dependency on renal RI (p<0.01) as well. CONCLUSION: In accordance with other studies, the influence of age on intrarenal RI measurement is significant in healthy subjects. Intrarenal RI values from subjects with a fatty liver disease showed age dependency as well. Therefore it is necessary to consider the age of the examined person to interpret RI values correctly.

Peptide YY release in anorectic patients after liquid meal.

Fasting and postprandial levels of human peptide YY (PYY) were recently found to be lower in obesity. To investigate whether PYY levels are correspondingly high in patients with anorexia nervosa, PYY concentrations were analyzed under basal conditions and in response to a liquid meal. We investigated PYY plasma levels in 16 female anorectic (BMI 15.2+/-0.3 kg/m2) and seven lean subjects (BMI 21.3+/-0.6 kg/m2) before and after ingestion of a liquid meal (250 kcal; 15% protein, 55% carbohydrates, and 30% fat). PYY levels were analyzed using PYY ELISA (DSL, USA). Values are given as mean+/-SEM. Basal PYY levels in anorectic patients (89.0+/-14.4 pg/mL) were not significantly different from lean subjects (64.1+/-12.1 pg/mL). Postprandial PYY levels in healthy volunteers increased significantly after 20 and 60 min (80.4+/-12.7 and 96.0+/-19.9 pg/mL, respectively). In anorectic women PYY was increased at 20 min (137.9+/-19.5 pg/mL) and at 60 min (151.3+/-19.2 pg/mL). No difference was found between both groups. We conclude that basal and postprandial PYY levels in normal weight women are not different from anorectic patients. We could not confirm the recently published blunted postprandial PYY response in anorexia, a finding that merits further study.

[Blue rubber-bleb nevus syndrome and therapeutic double balloon enteroscopy]. / Blue-Rubber-bleb-Naevus-Syndrom und therapeutische Doppel-Ballon-Enteroskopie.

This is the first report about the endoscopic removal of hemangiomas in the gastrointestinal tract using the double-balloon enteroscopic technique. We report on a 16-year-old female patient with a 10-year history of chronic anemia due to recurrent gastrointestinal bleeding. Besides permanent iron substitution, up to 3 blood transfusions per week are necessary. At birth a blue rubber-bleb nevus syndrome was diagnosed, with blue angiomatous lesions preferring her skin and digestive tract. In the 8 years before admittance numerous conventional endoscopic procedures and one intraoperative endoscopy with laser coagulation of many cavernous hemangiomas were performed. In our department the successful treatment of 150 hemangiomas with argon plasma coagulation or polypectomy in combination with double-balloon enteroscopy and conventional endoscopy was achieved without complications.

Regulation of ghrelin is related to estimated insulin sensitivity in obese children.

OBJECTIVE: To investigate whether ghrelin concentrations and their changes during weight loss in obese children are associated with parameters of glucose and insulin metabolism. DESIGN: Total plasma ghrelin, insulin and glucose were measured during oral glucose tolerance testing before and after diet-induced weight loss over 6 weeks. SETTING: In-patient rehabilitation program in a pediatric hospital. PARTICIPANTS: Twenty-three obese children (age 10-16 years) and 11 normal weight controls (age 10-15 years). OUTCOME MEASURES: Changes in ghrelin concentrations during weight loss and correlation analysis of changes in ghrelin and changes in parameters of glucose and insulin metabolism. After data collection, subgroup analysis of obese patients with high, medium and low estimated insulin sensitivity whole-body insulin sensitivity index (WBISI) was performed. RESULTS: Weight loss increased the area under the curve (AUC) of ghrelin by 26% (P<0.001). The increase in ghrelin AUC correlated significantly with improved estimated insulin sensitivity (WBISI) (r=0.69, P<0.001). The independent predicting effect of WBISI was confirmed in multivariate analysis. In children with low WBISI, ghrelin reached the level of control values after weight loss. In children with high WBISI, ghrelin increased markedly above control levels. CONCLUSIONS: Changes in ghrelin are independently associated with changes in glucose and insulin metabolism. The increase in plasma ghrelin above control levels was limited to obese children with high WBISI.

[Alternative sonographic determination of liver size by intercostal scans]. / Alternative sonographische Bestimmung der Lebergrösse durch interkostale Schnittführung.

BACKGROUND: The evaluation of hepatic size is a daily question in abdominal ultrasound, especially to determine the presence of hepatomegaly. In the literature, different methods of measurement are described, mostly as a subcostal measured organ diameter in one direction. This method has its limits in patients with obesity, accumulation of abdominal gas or in uncooperative patients (lack of coordinative respiration) so that alternative measurements are necessary. METHODS: In 241 patients hepatic size was first measured in two conventional sections: midclavicular line (MCL) and anterior axillary line (AAL). Additionally, we measured the organs in midaxillary line craniocaudal (MAL) by determination of the cranio-caudal diameter. In 58 patients additional computed tomography was performed due to special diagnostical reasons so that liver size in MCL could be revealed and compared with ultrasonographical values. RESULTS: The mean value in MCL was 10.7 +/- 2.1 cm measured by ultrasound, 11.4 +/- 3.7 cm measured by computed tomography, 14.0 +/- 1.9 cm in AAL and 14.9 +/- 2.0 cm in MAL. In 5% of the cases the liver could not be measured in the conventional subcostal sections due to obesity or masking by gas, but this was possible in MAL. CONCLUSIONS: We revealed a good correlation of liver size in MCL between ultrasound and computed tomography, as well as in the measurement of AAL and MAL diameters. However, even in cases with difficult subcostal approach intercostal diameters allow for an accurate determination of hepatic size.

The Munich Polypectomy Study (MUPS): prospective analysis of complications and risk factors in 4000 colonic snare polypectomies.

BACKGROUND AND STUDY AIMS: Screening colonoscopy with polypectomy has been shown to reduce the morbidity and mortality associated with colorectal cancer. However, there is a lack of large and systematic prospective studies of the complications of polypectomy. PATIENTS AND METHODS: Data on all snare polypectomies performed in 13 institutions (six hospitals and seven gastroenterology offices) were recorded prospectively during a 20-month period, including data on a 30-day follow-up period. The primary end points of the study were polypectomy complications, which were classed as "major" or "minor". Risk factors for complications were analyzed for both patient characteristics and polyp parameters. RESULTS: A total of 3976 snare polypectomies in 2257 patients (mean age 64.5 years) were included in the study. The mean polyp size was 1.1 cm, and 72% were sessile. Complications occurred in 9.7% of patients (6.1% of polyps); 75% of these complications were minor; and the mortality rate was zero. Multivariate regression analysis revealed polyp size as the main risk factor, both for complications overall (odds ratio 6.56, 95%CI 4.45-9.67) and for major complications (odds ratio 31.01, 95%CI 7.53-128.1). Right-sided polyp location was a significant risk factor for major complications (odds ratio 2.40, 95%CI 1.34-4.28). Setting a cut-off value of 3% as an acceptable rate for major complications, polyps larger than 1 cm in the right colon or 2 cm in the left colon, and multiple polyps carried an increased risk. CONCLUSIONS: Colonoscopic polypectomy is associated with a 10% rate of complications, but three-quarters of these are of minor clinical significance. More than 90% of the complications can be managed conservatively if adequate endoscopic expertise is available. Guidelines for intensified follow-up after polypectomy should be based on the size, location, and number of a patient's polyps.

A prospective study of serum ghrelin levels in patients treated with clozapine.

We investigated serum ghrelin levels (SGL) in 12 patients with schizophrenia over a 10-week period after initiation of clozapine treatment. In contrast to increments of body mass indices (BMI, kg/m2) and serum leptin levels (SLL), no significant change in SGL was detected. Inverse correlations between delta SGL and delta SLL did not reach statistical significance. Linear mixed model analysis could not detect effects of age, sex, BMI, SLL and serum clozapine levels on SGL. Our results do not support a causal involvement of ghrelin in clozapine-related weight gain.

Postprandial ghrelin release in anorectic patients before and after weight gain.

The appetite-modulating hormone ghrelin transmits changes in food intake to the central nervous system. In patients with anorexia nervosa, weight gain reduces elevated fasting ghrelin levels to normal, however, less is known about the effects on postprandial ghrelin levels. In 20 female anorectic in-patients (25.6 +/- 1.0 years; body mass index (BMI) 15.1 +/- 0.3 kg/m2) a standardized test with 250 ml fluid meal (250 kcal: 9.4 g protein, 34.4 g carbohydrates, and 8.3 g fat) was performed at three different times (at admission, after partial weight gain of at least 2 kg, and at discharge) and compared to healthy controls (n = 6; BMI 21.1 +/- 0.7 kg/m2). Plasma ghrelin levels were measured preprandially as well as 20 and 60 min postprandially by a commercially available radioimmunoassay (Phoenix Pharmaceuticals, USA). At admission plasma ghrelin levels significantly decreased postprandially (from 871.9 +/- 124 to 620.3 +/- 80 pg/ml 60 min after meal; P < 0.005). After partial weight gain (2.8 +/- 0.1 kg; BMI 16.1 +/- 0.3 kg/m2) postprandial ghrelin concentrations decreased from 597.0 +/- 79 to 414.7 +/- 39 pg/ml (P < 0.0001), at discharge (weight gain: 7.6 +/- 0.5 kg; BMI 17.9 +/- 0.4 kg/m2) from 570.4 +/- 78 to 395.4 +/- 44 pg/ml (P < 0.0001). Mean postprandial ghrelin decrease was not significantly different between the three tests (29, 25, and 26%, respectively) or to controls (20%). In anorectic patients mean postprandial ghrelin decrease did not change during weight gain. These findings indicate that in anorexia nervosa the suppression of ghrelin release by acute changes of energy balance (feeding) is not disturbed and that it is independent from chronic changes in energy balance (weight gain).

The Munich Barrett follow up study: suspicion of Barrett's oesophagus based on either endoscopy or histology only--what is the clinical significance?

BACKGROUND: The incidence of distal oesophageal adenocarcinoma is rising, with chronic reflux and Barrett's oesophagus being considered risk factors. Reliable detection of Barrett's oesophagus during upper endoscopy is therefore mandatory but requires both endoscopy and histology for confirmation. Appropriate management of patients with endoscopic suspicion but negative on histology, or vice versa, or of patients with no endoscopic suspicion but with a biopsy diagnosis of intestinal metaplasia at the gastro-oesophageal junction, has not yet been studied prospectively. PATIENTS AND METHODS: In a prospective multicentre study, 929 patients (51% male, mean age 50 years) referred for upper gastrointestinal endoscopy were included; 59% had reflux symptoms. The endoscopic aspect of the Z line and any suspicion of Barrett's oesophagus were noted, and biopsies were taken in all patients from the Z line (n = 4), gastric cardia (n = 2), and body and antrum (n = 2 each). Biopsies positive for specialised intestinal metaplasia (SIM) were reviewed by a reference pathologist for a final Barrett's oesophagus diagnosis. All patients with endoscopic and/or histological suspicion of Barrett's oesophagus were invited for a follow up endoscopy; the remaining cases (no endoscopic or histological suspicion of Barrett's oesophagus) were followed clinically. RESULTS: Of 235 patients positive for Barrett's oesophagus on endoscopy and/or histology, 63% agreed to undergo repeat endoscopy (mean follow up period 30.5 months). 46% of patients with an endoscopic Barrett's oesophagus diagnosis but no histological confirmation (group A) showed the same distribution, a further 42% did not have Barrett's oesophagus, and 11% had confirmed Barrett's oesophagus on both endoscopy and biopsy on follow up. In the group with a histological Barrett's oesophagus diagnosis but negative on initial endoscopy (group B), follow up showed the same in 26% whereas 46% had no Barrett's oesophagus, and confirmed Barrett's oesophagus (endoscopy plus histology) was diagnosed in 17%. Of the study population, 16 patients had Barrett's oesophagus on initial endoscopy confirmed by histology which remained constant in 70% at follow up (group C). Of the remaining patients without an initial Barrett's oesophagus diagnosis on either endoscopy or histology (group D) and only clinical follow up (mean follow up period 38 months), one confirmed Barrett's oesophagus case was found among 100 patients re-endoscoped outside of the study protocol. However, no single case of dysplasia or cancer of the distal oesophagus was detected in any patient during the study period. CONCLUSIONS: Even in a specialised gastroenterology setting, reproducibility of presumptive endoscopic or histological diagnoses of Barrett's oesophagus at follow up were poor. Only 10-20% of cases with either endoscopic or histological suspicion of Barrett's oesophagus had established Barrett's oesophagus after 2.5 years of follow up. The risk of dysplasia in this population was very low and hence meticulous follow up may not be required.

Ultrasound in emergency patients: better detection of free intraabdominal fluids by the use of tissue harmonic imaging.

BACKGROUND: Ultrasound examination is one of the main investigative procedures in emergency patients who are hospitalized due to abdominal pain. Detectable free fluid collections are important hints to the definite, sometimes life-threatening diagnosis, but their detection in cases of only small amounts is difficult to perform by conventional sonography. PATIENTS AND METHODS: We report about 25 cases of patients who suffered from acute abdominal pain and who were presented as emergency patients to our department of ultrasound. First, the examination was performed by conventional sonography (3.4 MHz). Only with the additional tissue harmonic imaging (THI, 2.3 MHz, pulse inversion) thin borders of free fluids around the liver or other abdominal organs (gallbladder, spleen, pancreas, bowel) could be detected leading to other important diagnostic or therapeutic steps. In this way, the diagnosis of pancreatitis, cholezystitis, peritonitis, peritoneal carcinosis, ascites (liver cirrhosis, serositis, postoperative status after laparotomy), bleeding or paralytic ileus could be elucidated. CONCLUSION: THI sonography improves the detection of small amounts of free abdominal fluid collections. Therefore, this technique is helpful in the diagnostic procedure of emergency patients.

Endogenous and exogenous glucocorticoids decrease plasma ghrelin in humans.

OBJECTIVE: The orexigenic and adipogenic peptide hormone ghrelin is predominantly produced and secreted by the stomach and seems to transduce changes in food intake to specific neuronal circuits in the brain. The activity of ghrelin also includes stimulatory effects on the corticotropic system. However, little is known about the influence of glucocorticoids on ghrelin levels. We therefore studied human plasma ghrelin levels in the presence and absence of elevated glucocorticoid levels of either endogenous or exogenous origin. METHODS: Plasma ghrelin levels were measured in five patients with chronic hypercortisolism (aged 29-58, median 46 years) due to Cushing's syndrome before and after successful surgery for the adenoma, and in eight healthy controls (aged 24-39, median 27.5 years) before and after 30 mg prednisolone (for 5 days) once a day in the morning (median body mass index (BMI) 22.7 kg/m(2)). Plasma ghrelin levels were measured with a commercially available radioimmunoassay. RESULTS: In patients with Cushing's syndrome, plasma ghrelin levels were low (median 363.2 pg/ml, range 161.9-525.7 pg/ml) and significantly increased by 26.6% (P=0.04) after successful surgery, while BMI decreased (median 26.2-24.0 kg/m(2), P=0.04). A strong negative correlation (r=-0.9, P=0.04) between changes in BMI and plasma ghrelin was observed. In healthy controls, plasma ghrelin levels (median 288.7 pg/ml, range 119.6-827.8 pg/ml) were significantly suppressed by 18.3% (P=0.04) after prednisolone treatment. CONCLUSIONS: We have shown for the first time that plasma ghrelin levels are decreased under endogenously or exogenously induced hypercortisolism, making ghrelin an unlikely candidate for causing the changes in energy balance or body composition characteristic of Cushing's disease. However, the reduced ghrelin secretion could reflect a compensation mechanism in reaction to the metabolic consequences of chronic hypercortisolism.

Lower esophageal sphincter pressure in patients with gastroesophageal reflux diseases and posture and time patterns.

Gastroesophageal reflux disease is caused predominantly by lower esophageal sphincter insufficiency. Reports suggest that it is possible to distinguish between two main mechanisms causing reflux: low basal sphincter pressure leading to free reflux, mostly occurring at night in the supine position, and increased transient lower esophageal sphincter relaxations with normal or increased resting pressure leading to reflux during the day in an upright position. Lower esophageal sphincter pressure (LESP)-- s determined by stationary pull-through manometry--was compared to profiles of acidic reflux measured by 24-h pH monitoring in 207 patients with proven gastroesophageal reflux disease. Differences in LESP were not significant among patients with reflux predominantly during the day in an upright position and those with reflux predominantly at night in a supine position (16.1 +/- 7.4 mmHg versus 15.1 +/- 7.8 mmHg; t-test: P = 0.355). For both patterns of LESP, there was a slight negative correlation with the amount of acidic reflux (determined as a percentage of time with pH < 4). Pearson correlation coefficients were -0.196 for upright refluxers and -0.137 for bipositional/supine refluxers (P = 0.006 and P = 0.049, respectively). As there are no differences in LESP with regard to posture or time patterns of acidic reflux it seems unlikely that upright reflux is associated with increased LESP, whereas supine reflux manifests due to a hypotensive LESP. Alternatively, it may be concluded that stationary pull-through manometry is inadequate for determining the cause of gastroesophageal reflux disease and is therefore of limited use in its routine diagnosis.

Inter- and intra-observer variability of magnification chromoendoscopy for detecting specialized intestinal metaplasia at the gastroesophageal junction.

BACKGROUND AND STUDY AIMS: Magnification endoscopy after contrast enhancement with acetic acid or staining with methylene blue has been reported to be highly accurate in predicting specialized intestinal metaplasia (SIM) in Barrett's esophagus. So far, however, no data have been published on the interobserver and intra-observer variability of these new methods. PATIENTS AND METHODS: Fifty-one patients with reflux symptoms were prospectively evaluated. Endoscopy was carried out with a magnification endoscope, and video sequences were recorded in standard and zoom modes (at the 12-o'clock, 3-o'clock, 6-o'clock, and 9-o'clock positions) before and after instillation of 1.5 % acetic acid (n = 26) or staining with 0.5 % methylene blue (n = 25). Biopsies were obtained from the same locations for histopathological examination. The 102 video sequences were shown to four experienced endoscopists in a mixed and blinded fashion. The evaluation criteria used followed the published criteria; classification was carried out according to the pit-pattern structure, methylene blue positivity, and the presence of villous structures. Finally, a general statement on suspected SIM in relation to Barrett's esophagus was requested. RESULTS: With regard to the criteria selected for evaluation, there was a high level of interobserver variability among the four examiners (all kappa < 0.4). SIM was histologically detectable in 60.8 % of the patients. The accuracy of all of the examiners for predicting SIM by magnification endoscopy was around 50 %, with no differences observed before and after instillation of acetic acid or methylene blue staining. CONCLUSIONS: The suggested criteria for identifying SIM using magnification endoscopy are associated with a high level of interobserver variability. When evaluated in a blinded manner, staining techniques do not significantly improve the yield for detecting SIM at the esophagogastric junction.

Improved ultrasound examination of pancreas grafts in type 1 (insulin-dependent) diabetic patients using tissue harmonic imaging.

BACKGROUND: Combined kidney/pancreas transplantation is an established therapy for type 1 diabetic patients with end-stage renal disease. Ultrasound examinations are valuable noninvasive methods for postoperative monitoring of transplant recipients. Kidney grafts are easily to detect, whereas pancreas grafts are surrounded or covered by small bowel loops, which makes the examination much more difficult. PATIENTS AND METHODS: Thirty-three simultaneous pancreas and kidney recipients (SPK) were examined by conventional sonography at 3.4 MHz and THI sonography (pulse inversion, 2.3 MHz) by an investigator experienced in abdominal ultrasound. The images were graded by two "blinded readers" using a scale (1-best image quality, 2-second best, 3-worst) with regard to tissue penetration and detail characterization of the pancreas grafts. The graders were unaware of the sonographic technique, respectively. Statistical evaluation was performed by the Mann-Whitney U test. RESULTS: In 25 cases (78%) pancreas grafts were detected by conventional sonography. The detection rate was higher using THI sonography, namely 29 cases (91%). Grading for tissue penetration revealed a mean value of 2.05 +/- 0.5 for conventional and 1.94 +/- 0.5 for THI sonography (P =.27). Detail characterization of the pancreas grafts was determined to show a mean value of 2.50 +/- 0.5 for conventional sonography and a significantly better mean value of 1.78 +/- 0.6 for THI sonography (P <.0001). CONCLUSION: THI sonography improves the detection and the judgment of tissue characteristics of pancreas grafts. Penetration of ultrasound waves is not relevantly decreased by this new technique.

Post-prandial decrease of human plasma ghrelin in the absence of insulin.

Ghrelin is the most powerful orexigenic hormone in mammalian physiology. Ghrelin plasma concentrations increase prior to meal onset, but decrease post-prandially. We and others reported previously that insulin reduces circulating ghrelin levels and might therefore be a driving force for post-prandial suppression of ghrelin. To test the influence of insulin on post-prandial ghrelin regulation, a patient with Type I diabetes with complete insulin deficiency received a low glycemic index meal and subsequently an additional high glycemic index meal in the absence of insulin substitution. Subsequently, a sc injection of 0.08 IU Lispro insulin per kg body weight was given. Results were compared to those of a healthy control subject matched for sex, age and body mass index, which was undergoing the same test series (without Lispro bolus) in the presence of endogenous post-prandial insulin secretion. A substantial decrease of plasma ghrelin levels was observed in the insulin-deficient patient following low glycemic index carbohydrate load (27% plasma ghrelin decrease). The subsequent exposure to a high glycemic index meal resulted in a slight additional reduction of ghrelin levels (32% from baseline), while Lispro bolus did not induce further changes in circulating ghrelin (27% of baseline at termination). This post-prandial response was comparable to that of the healthy control subject (33% reduction after the first meal, 40% after the second meal). These data tentatively suggest that post-prandial secretion of ghrelin is not exclusively regulated by plasma insulin or plasma glucose but may depend on other metabolic factors yet to be identified.