The Development of Irritable Bowel Syndrome after Shigella Infection: 3 Year Follow-up Study / 대한소화기학회지

BACKGROUND AND AIMS: Bacterial gastroenteritis seems to be a risk factor of irritable bowel syndrome (IBS). The incidence of post-infectious IBS (PI-IBS) was reported to be in the range of 7-31%, but few studies have reported long term follow-up results. So, we investigated the clinical course and prognosis of PI-IBS three years after shigella infection. METHODS: The subjects were recruited from our previous study, in which we investigated the incidence and risk factors of PI-IBS. We had a questionnaire based on interview with 120 controls and 124 patients who had shigella infection three years ago. Both groups were evaluated for the presence of IBS, functional bowel disorders (FBD) except IBS before, one and three years after the infection, respectively. RESULTS: Ninty-five patients (76.6%) and 105 controls (87.5%) completed the questionnare. In patients group, 7 cases had IBS prior to infection (previous IBS), 12 cases (13.8%) had IBS after 1 year (PI-IBS). Four cases developed IBS newly after 3 years (new IBS). Thirteen cases (14.9%) in patients and 4 cases (4.5%) in controls had IBS over 3 years (OR 3.93: 1.20-12.86). The recovery rate over 3 years were 50.0% (2/4) in previous IBS and 25% (3/12) in PI-IBS. The incidence of PI-IBS after 3 years in previous FBD subjects was 28.6% and was 10.6% in normals (p<0.05). The female gender was a risk factor for FBD. CONCLUSIONS: Bacterial gastroenteritis is a trigger factor of IBS. About a quarter of PI-IBS patients are recovered over 3 years. Previous FBD except IBS is a risk factor after 3 years.

Three Cases of Gastroesophageal Reflux Disease Treated by Laparoscopic Fundoplication / 대한소화기내시경학회지

Medical treatment so far takes the major portion in the treatment of gastroesophageal reflux disease (GERD). Histamine-2 receptor antagonists, proton pump inhibitors and antacids, which are used in the medical treatment of GERD, decreases intragastric acidity, and therefore decreases acid reflux. However, recurrences are frequently observed after the cessation of medication. On the other hand, fundoplication, the surgical management of GERD, aims for physiologic reconstruction of esophagogastric junction, and for correcting the pathogenetic cause of GERD. But fundoplication is linked to risks related to surgery and general anesthesia. Laparoscopic funcoplication minimizes these risks. We recently experienced three cases of GERD improved by laparoscopic 270o fundoplication. One patient was intolerant of long-term proton pump inhibitor treatment, and two patients had hiatal hernia, and one of them showed failure to medical treatment. This report describes these three cases with a brief review of literatures survey.

Relationship of Hemodynamic Indices and Prognosis in Patients with Liver Cirrhosis

BACKGROUND: Hyperdynamic circulation due to reduced peripheral vascular resistance and increased cardiac output, and the development of portal hypertension are the hemodynamic changes observed in patients with liver cirrhosis. Such hemodynamic abnormalities appear in patients with late stage liver cirrhosis. Therefore, hemodynamic indices, which represent hyperdynamic circulation and portal hypertension, are significant for the prognosis of patients with liver cirrhosis. The aim of this study was to determine the hemodynamic indices associated with the prognosis of patients with liver cirrhosis. METHODS: A total of 103 patients diagnosed with liver cirrhosis between December 1999 and June 2003, with a mean follow-up period of 73 weeks, ranging from 7 to 168 weeks, were recruited. Using Child-Pugh classification, the mean arterial pressure, heart rate and hepatic venous pressure gradient (HVPG) were measured. The indices of Doppler ultrasonography, including the portal and splenic venous flows, and the resistance of the hepatic, splenic, and renal arteries were also measured using the arterial pulsatility index (PI). The prognostic values of these indices were determined by their comparison with the patient survivals. RESULTS: Significant hemodynamic indices for a bad prognosis were high HVPG (> or=15 mmHg) and renal arterial PI (> or=1.14) (p or=10 was important for a poor prognosis (p or=15 mmHg) and high renal arterial resistance (PI> or=1.14) were valuable hemodynamic indices for the prognosis of patients with liver cirrhosis. Therefore, it was concluded that the measurement of these hemodynamic indices, in addition to the Child-Pugh classification, is helpful in the prognosis of patients with liver cirrhosis.

Altered Colonic Transit in TNBS-induced Experimental Colitis in Guinea Pig and Distribution of Nitric Oxide Synthase in the Colonic Wall / 대한소화기학회지

BACKGROUND/AIMS: Inflammation-induced alterations in smooth muscle contractility may be due to the effects on smooth muscle itself, neurotransmitters or enteric nerves. In dextran sulfate sodium-induced colitic rat, the delay in colonic transit was caused by decreased activity and production of neuronal nitric oxide synthase (nNOS) in the myenteric plexus of the distal colon. The aim of this study was to investigate the relationship between the delay in colonic transit and the distribution of inducible NOS (iNOS) and nNOS immunoreactive cells in the myenteric plexus of trinitrobenzene sulfonic acid (TNBS)-induced colitic guinea pig. METHODS: Sacrificed and their colonic tissues of forty-five TNBS-induced colitic guinea pigs were used to measure the colonic transit, and analyzed by immunohistochemistry. RESULTS: Colonic transit was delayed significantly at 3, 7 and 14 days after administration of TNBS. In control, nNOS immunoreactivity was present in the mucosa, submucosa, lamina propria, and ganglion cells of the myenteric plexus, while after TNBS treatment, reduced nNOS cells were found. However, the number of nNOS ganglion cells in the myenteric plexus was similar to those seen in controls. After administration of TNBS, iNOS immunoreactivity was increased in the mucosa and submucosa, but the number of iNOS positive ganglion cells in the myenteric plexus was not changed compared to control. CONCLUSIONS: It is suggested that in TNBS-induced guinea pig colitis, delayed colonic transit is not associated with the expression of nNOS nor iNOS in the myenteric plexus.

Type of Electric Currents Used for Standard Endoscopic Sphincterotomy Does Not Determine the Type of Complications / 대한소화기학회지

BACKGROUND/AIMS: The blended current is usually used for endoscopic sphincterotomy (EST) to minimize bleeding. The pure cutting current may induce less edema of the ampulla and therefore result in less injury to the pancreas theoretically. The aim of this study was to evaluate effects of electric currents used on the development of serum pancreatic enzyme evaluation, clinical pancreatitis or bleeding after EST. METHODS: One hundred and eighteen consecutive patients who underwent EST with standard papillotome alone for the treatment of choledocholithiasis were reviewed. All EST had been performed by two endoscopists whose experience on EST was similar: one uses 'blended current' (BC group, n=74), while the other uses 'pure cutting current' (PC group, n=44). RESULTS: Baseline clinical, laboratory, and procedural parameters were similar in both groups. The incidences of hyperamylasemia and hyperlipasemia were similar between two groups. There was no significant difference in the incidence of clinical pancreatitis between two groups (BC 6.8% vs PC 0.0%, p=0.1557). All episodes of pancreatitis were mild. No episodes of significant bleeding occurred after EST. The incidences of sepsis, cholangitis and perforation were also not different between two groups. CONCLUSIONS: Development of complications after standard EST such as hyperamylasemia, clinical pancreatitis, and bleeding may not depend on the electric current used.

Sensitivity of Two-Time Immunochemical Fecal Occult-Blood Testing with Sigmoidoscopy for the Detection of Advanced Colon Adenoma / 대한소화기내시경학회지

BACKGROUND/AIMS: Because detection and removal of colonic adenoma provided an opportunity to prevent colorectal cancer, advanced adenoma (>10 mm, villous or high grade dysplasia) should be the major target of screening. In this study, we assessed the diagnostic sensitivity of one- or two-time immunochemical fecal occult blood test (i-FOBT), flexible sigmoidoscopy and their combination in patients with advanced adenoma or non-advanced adenoma. MEHTODS: From January to October 2002, we performed colonoscopy with i-FOBT using latex agglutination method in 879 individuals. Among these, we diagnosed 234 polyps in 93 patients with advanced adenoma and 179 polyps in 109 patients with non-advanced adenoma. After the diagnosis of adenoma, second i-FOBT was done before polypectomy. Based on these data, we evaluated the diagnostic sensitivities of i-FOBT, flexible sigmoidoscopy and their combination for patients with advanced adenoma or non-advanced adenoma. RESULTS: The diagnostic sensitivity of one- or two-time i-FOBT, flexible sigmoidoscopy and flexible sigmoidoscopy with two-time i-FOBT in patients with advanced adenoma vs.non-advanced adenoma were 17.2% vs. 18.3%, 28.0% vs. 29.4%, 70.1% vs. 66.1% and 81.7% vs. 78.0%. Although repeated application of i-FOBT enhanced diagnostic sensitivity for colon adenoma, this test or combination with flexible sigmoidoscopy did not differentiate advanced adenoma from non-advanced adenoma. CONCLUSIONS: Although it fails to detect one fifth of colon adenoma, combined two-time i-FOBT testing with flexible sigmoidoscopy is an effective and feasible screening modality for advanced colon adenoma.

Usefulness of Urinary Trypsinogen-2 Dipstick Test for Diagnosis of Acute Pancreatitis / 대한소화기학회지

BACKGROUND/AIMS: The clinical usefulness of urinary trypsinogen-2 dipstick test is still in controversy. We evaluated the usefulness of urinary trypsinogen-2 dipstick test in patients with acute pancreatitis. METHODS: Urinary trypsinogen-2 dipstick test was prospectively performed in 50 patients with acute pancreatitis, 50 patients with non-pancreatic abdominal pain, and 50 healthy controls. RESULTS: On admission, urinary trypsinogen-2 dipstick test was positive in 36 of 50 patients with acute pancreatitis (sensitivity, 72%) and in 4 of 50 patients with non-pancreatic abdominal pain (specificity, 92%). On the other hand, it was all negative in controls. The sensitivity and specificity of serum lipase were 78% and 94%, respectively. At 24 hours after admission, the positive rate of urinary trypsinogen-2 dipstick test rose from 72% to 94% (p=0.02). The results of urinary trypsinogen-2 dipstick test was positive in 14 of 15 patients with severe pancreatitis and 22 of 35 patients with mild pancreatitis according to the criteria by Atlanta International Symposium, 1992. CONCLUSIONS: Urinary trypsinogen-2 dipstick test is comparable to serum lipase in diagnosing acute pancreatitis. Delayed measurement and severe pancreatitis are more likely to yield positive results with urinary trypsinogen-2 dipstick test. Thus, we suggest that the cut-off value of urinary trypsinogen-2 dipstick test should be lowered to increase its sensitivity.

A Case of a Giant Brunner's Gland Hamartoma Originating from the Pyloric Ring / 대한소화기내시경학회지

Brunner's gland hamartoma, also called as Brunner's gland adenoma or Brunner's gland hyperplasia, is a relatively rare disease that results from benign proliferation of the Brunner's gland normally present in the duodenum. It is mostly located at the duodenal bulb, occasionally second or third portion, but is rarely found at the pyloric ring, jejunum or proximal ileum. In Korea, total 27 cases of Brunner's gland hamartoma have been reported, but none of them had their origin at the pyloric ring only. We report a case of Brunner's gland hamartoma, found incidentally, originating from the pyloric ring in a 54-year-old woman, which was resected endoscopically after retracting the tumor into the stomach.

Investigation into the Effects of Mosapride on Motility of Guinea Pig Stomach, Ileum, and Colon

Mosapride citrate (Mosapride) is a new prokinetic agent that enhances the gastrointestinal (GI) motility by stimulation of 5-HT4 receptors. This agent stimulates acetylcholine release from enteric cholinergic neurons in the GI wall. It was reported in several studies that mosapride selectively enhanced the upper, but not lower, GI motor activity. However, in these studies other 5-HT4 receptor agonists exerted stimulating effects on the motility of the colon. Moreover, it is well known that the receptors of 5-HT4 are also located in the colon. The purpose of this study was to estimate the effect of mosapride on the motility of the stomach, ileum and colon in the guinea pig and to investigate whether or not mosapride influenced the colonic motility. Mosapride significantly increased the amplitude of the contraction waves in the guinea pig stomach by electrical stimulation. In addition, it significantly increased the number of peaks, the area under the curve and the propagation velocity of the peristaltic contraction of the guinea pig ileum in a concentration dependent fashion. Mosapride also significantly shortened the transit time of the guinea pig colon. Accordingly, we concluded that mosapride exerted prokinetic effect on the entire GI tract of the guinea pig. Based on the possibility of similar results in humans, we suggest the potential use of mosapride for lower GI motor disorders such as constipation and upper GI motor disorders such as gastroesophageal reflex disease or gastroparesis.

Altered Colonic Motor Functions in Experimental Colitis of Guinea Pigs / 대한소화관운동학회지

BACKGROUND/AIMS: Trinitrobenzene sulphonic acid (TNBS)-induced colonic inflammation in rat alters colonic motor function. The aims of this study were to investigate the effect of TNBS-induced colitis on the colonic motor function of a guinea pig along the course of colitis and to document persistently altered colonic motor function after resolution of inflammation. METHODS: Colitis was induced in about 300 g male guinea pigs (Hartley) by intrarectal administration of 0.3 mL TNBS in 50% ethanol, while controls received 0.3 mL of 50% ethanol or not. After 24 hours, 48 hours, 72 hours, 1 week, and 2 weeks, the distal colon was taken for the investigation of gross and microscopic findings, muscle tension, and colonic transit. RESULTS: Maximal mucosal injury and inflammation were evident from the 2nd day following the induction of colitis. Seven days after the induction of colitis, some portions of the damaged mucosa began to recover. Development of tension in response to carbachol was not altered significantly along the course of colitis. Colonic transit was delayed significantly at 3, 7, and 14 days after administration of TNBS. CONCLUSIONS: Colonic transit in TNBS-induced colitis of guinea pigs is delayed, but not linearly related to the degree of inflammation. Delayed colonic transit is not related to the muscarinic receptor-mediated contractions of circular muscle from the inflamed colon. Further studies are required to determine the mechanism(s) involved in this motor change.

Migration of Pyloric Self-Expanding Metallic Stent to the Esophagus / 대한소화기내시경학회지

Self-expandable metallic stent (SEMS) has been reported to provide effective treatment alternatives with minimal morbidity for patients with malignant gastroduodenal obstruction. Limitations of SEMSs are stent occlusion due to tumor ingrowth or overgrowth and stent migration. Migrated stents may remain in the stomach or travel distally. To our knowledge, however, migration of pyloric SEMS to the esophagus has not been reported. We experienced such a case in a 65-year-old woman who had undergone a gastrojejunostomy and choledochojejunostomy due to unresectable pancreatic head cancer. Pyloric SEMSs (Niti-S Pyloric Bare Stent, 18x60 mm, Taewoong Medical, Korea) were deployed at the obstructed efferent and afferent loops. After severe vomiting, a pyloric SEMS placed at the afferent loop migrated into the esophagus, which caused severe chest pain and intractable hiccup. It was removed endoscopically. This case illustrates that pyloric SEMS can migrate to the esophagus through the lower esophageal sphincter.

A Clinical Study on the Effect of Transcatheter Arterial Embolization in the Treatment of Peptic Ulcer Bleeding / 대한소화기내시경학회지

BACKGROUND/AIMS: Transcatheter arterial embolization (TAE) has been increasingly used in the treatment of patients with gastrointestinal bleeding due to improved catheter and guidewire technologies and emergence of safer embolization materials. We evaluated the clinical characteristics of patients in whom TAE was performed and the outcome of the treatment. METHODS: Eleven patients (M:F=9:2, mean age=60.6 years) underwent TAE between April 2001 and August 2002. Causes of bleeding were gastric ulcer in 9 cases and duodenal ulcer in 2 cases. Seven patients had comorbid diseases, but 4 patients did not. RESULTS: Successful TAE without rebleeding was achieved in 10 of 11 patients (90.9%). One patient failed to respond to TAE and died due to multiorgan failure. Another patient died due to other causes despite a successful TAE. There were no TAE-related complications. CONCLUSIONS: TAE is a safe and effective modality in the treatment of patients with peptic ulcer bleeding who do not respond to endoscopic hemostasis. Thus, TAE seems to be included in the treatment algorithm of peptic ulcer bleeding regardless of surgical risks of patients and be placed before surgery, but prospective randomized studies are needed.

A Case of Malignant B-Cell Lymphoma Involving the Stomach in a Patient with Neurofibromatosis Type 1 / 대한소화기내시경학회지

Neurofibromatosis type 1, an autosomal dominant disorder, is clinically characterized by the presence of cafe-au-lait spots and cutaneous neurofibromas. Malignancy is a frequently cited and feared complication of neurofibromatosis. Neurofibromatosis has been reported to be associated with some CNS tumors, neurofibrosarcoma, pheochromocytoma, and nonlymphocytic leukemia. Also malignant lymphoma may develop in patients with neurofibromatosis. In Korea, only a case of lung cancer and a case of pheochromocytoma have been reported to develop in patients with neurofibromatosis type 1. Recently, we experienced a case of malignant lymphoma involving the stomach in a 70-year-old woman with neurofibromatosis type 1. An esophagogastroduodenoscopy revealed a 5 cm sized ulcerofungating mass on the greater curvature of the upper body. Histologic diagnosis of the biopsied specimen was B-cell diffuse small and large cell lymphoma. This case illustrates that malignant lymphoma should be included in the differential diagnosis of gastric tumors in patients with neurofibromatosis type 1.

A Case of Congenital Anomaly of the Pancreatic Duct Discovered in a Child with Recurrent Acute Pancreatitis / 대한소화기내시경학회지

Congenital pancreatic duct anomalies result from an error in the complex developmental process. Congenital pancreatic duct anomalies may be categorized by their mechanisms into migration anomaly, fusion anomaly, and duplication anomaly. These ductal abnormalities have been implicated to be potential causes for both acute and chronic pancreatitis. We have recently observed a congenital anomaly of the pancreatic ducts in which bifurcated main pancreatic ducts drain through the major papilla in a 10 year-old boy presenting with recurrent acute pancreatitis. Although its causal relationship with acute pancreatitis is unclear, this kind of pancreatic ductal anomaly has not been found in the literature.

A case of primary hepatic actinomycosis coinfected with alpha-streptococcus / 대한내과학회지

Actinomycosis is a chronic suppurative and granulomatous disease caused by gram-positive bacteria, the Actinomyces, which normally resides in the mouth cavity and large bowel. Actinomyces and other bacterial species are concomitantly, on occasion, found, having been designated "companion microbes". Designing a therapeutic regimen that includes coverage for "companion microbes" during the initial treatment course is reasonable. Primary hepatic actinomycosis, which was not found in possible source or associated disease and was coinfected with alpha-strepotcoccus, has not yet been reported in Korea. We report a case of primary hepatic actinomycosis coinfected with alpha-streptococcus presenting fever, chill, right upper quadrant abdominal pain as chief complaints in a 63-year-old woman. Primary hepatic actinomycosis was confirmed by identification of the sulfur granule, which was obtained by ultrasonography-guided percutaneous needle aspiration and biopsy.

Effect of Sildenafil on Esophageal Motor Function in Healthy Volunteers / 대한소화관운동학회지

BACKGROUND/AIM: Nitric oxide (NO), the nonadrenergic, noncholinergic inhibitory neurotransmitter, plays a role in controlling esophageal motor function by causing guanosine 3', 5'-cyclic monophosphate (cGMP) accumulation in circular smooth muscle of the esophagus and lower esophageal sphincter (LES). Increase in the intracellular concentration of cGMP as a second messenger produces relaxation of smooth muscle. It is metabolized by phosphodiesterase (PDE). Sildenafil, a drug used to improve the functional impotence, shows an inhibitory effect on the smooth muscle cells of the human corpus cavernosum by blocking type V PDE that destroys cGMP. The aim of this study was to investigate the effects of sildenafil on the esophageal motility. METHODS: Eight male subjects without any evidence of esophageal motor dysfunction were enrolled in this study. On first day, 20 ml of distilled water (placebo) was infused into the stomach. On second day, 0.8 mg/kg of sildenafil powder dissolved in water was infused into the stomach. We measured the amplitude of esophageal body contractions and LES pressure at each day. In addition, plasma cGMP levels were assayed by ELISA method. RESULTS: There were no significant differences in esophageal manometric findings in the placebo group, but significant decreases in LES pressure as well as amplitude of peristaltic contractions at smooth muscle portion of esophagus were noted in sildenafil group. Sildenafil showed its maximum effect in lowering LES pressure on 30 minutes after ingestion, and also in decreasing the amplitude of peristaltic contractions at smooth muscle portion of esophagus on 15 minutes after ingestion. There was no difference in the propagation velocity of peristalsis and plasma cGMP levels after sildenafil treatment. CONCLUSION: Sildenafil showed inhibitory effects on smooth muscle of esophageal body and LES in human.

A Comparison and Validity of Various Diagnostic Criteria of Irritable Bowel Syndrome / 대한소화관운동학회지

BACKGROUNDS: There has been some discordance in the prevalence of irritable bowel syndrome (IBS) probably due to different diagnostic criteria used by different study groups. The aims of this study was to determine the degree of agreement between different standard definitions and to test the validity of applying these different standards in epidemiological investigations of IBS among Korean population. METHODS: We recruited 1,038 patients who visited Yongdong Severance Hosipital for medical checkup and gave out the prepared questionnaires. Based on the returned questionnaires, degree of agreement between Manning, Rome I, and Rome II criteria was investigated by percent agreement and calculating kappa statics. Furthermore, clinical characteristics in different definition groups and patients of self-reported IBS were investigated and compared. RESULTS: Complete questionnaires were returned by 928 out of 1,038 subjects. The percent agreements ranged from 80.7 to 96.7 percent and kappa values ranged from 0.20 to 0.59. Best agreement occurred between Manning and Rome I criteria. Many subjects diagnosed as not having IBS by various diagnostic criteria of IBS thought themselves as having IBS. More sizable number of patients were suspected to have structural gastrointestinal diseases in IBS patients diagnosed by Manning, Rome I, and Rome II criteria compared with self-reported IBS subjects. CONCLUSIONS: It could be suspected that results of epidemiological investigations might be different according to standard definitions applied on each studies. Furthermore, some modifications of existing standard definitions of Western world would be required before applying them among Korean population.

Defecographic Findings of Rectal Intussusception / 대한소화관운동학회지

OBJECTIVES: To analyze the findings of rectal intussusception and to find the other accompanied functional anorectal diseases. MATERIALS AND METHODS: We analyzed defecograms in 25 patients with rectal intussusception among 77 patients taken with obstructed defecatory symptom. Females were 16 (64%), males were 9 (36%), and the mean age was 55 years old. The changes of anorectal angle (ARA) and movement of anorectal junction were measured, and the morphologic changes of rectal wall during defecation were analyzed. RESULTS: ARAs measured by central axis method (CAM), the mean angles were 114.6, 102.2, and 119.8 degree, respectively in resting, squeezing, and straining period. By posterior wall methods (PWM), those were 86.7, 72.0, 93.3 degree. The differences of ARA between resting and straining period were 5.2, 6.6 degree, respectively by CAM and PWM. The mean descent of anorectal junction during defecation was 0.83 cm. The most frequent finding associated with rectal intussusception was rectocele (12 cases;48%). The other accompanied findings were 9 spastic pelvic floor syndrome (36%) and 4 fecal incontinence (16%). Total 18 patients out of 25 patients were accompanied with other functional anorectal diseases (72%). CONCLUSIONS: Recognition of rectal intussusception with accompanied diseases would be important for the proper treatment planning.

Defecographic Findings of Rectal Intussusception / 대한소화관운동학회지

OBJECTIVES: To analyze the findings of rectal intussusception and to find the other accompanied functional anorectal diseases. MATERIALS AND METHODS: We analyzed defecograms in 25 patients with rectal intussusception among 77 patients taken with obstructed defecatory symptom. Females were 16 (64%), males were 9 (36%), and the mean age was 55 years old. The changes of anorectal angle (ARA) and movement of anorectal junction were measured, and the morphologic changes of rectal wall during defecation were analyzed. RESULTS: ARAs measured by central axis method (CAM), the mean angles were 114.6, 102.2, and 119.8 degree, respectively in resting, squeezing, and straining period. By posterior wall methods (PWM), those were 86.7, 72.0, 93.3 degree. The differences of ARA between resting and straining period were 5.2, 6.6 degree, respectively by CAM and PWM. The mean descent of anorectal junction during defecation was 0.83 cm. The most frequent finding associated with rectal intussusception was rectocele (12 cases;48%). The other accompanied findings were 9 spastic pelvic floor syndrome (36%) and 4 fecal incontinence (16%). Total 18 patients out of 25 patients were accompanied with other functional anorectal diseases (72%). CONCLUSIONS: Recognition of rectal intussusception with accompanied diseases would be important for the proper treatment planning.

The Growth Hormone (GH) - Binding Protein in Obesity with Varying Glucose Tolerance: Relationship to Body fat Distribution Sex Hormones, Insulin and GH-Insulin-Like Growth Factor (IGF)-1 Axis / 대한내분비학회지

BACKGROUND: As GHBP is believed to be derived from proteolytic cleavage of the extracellular domain of the GH receptor and may be regarded as an intrinsic part of the GH-IGF-1 axis, an effect of body composition on circulating GHBP levels may be expected. We investigated GHBP variations in obesity with varying glucose tolerance and its relationship to body fat distribution, sex hormones, insulin secretion, and the GH-IGF-1 axis. METHODS: Bioelectrical impedence for measurement of total body fat and computed tomography for visceral fat and subcutaneous fat at umbilicus level were performed in 69 obese Koreans and 21 lean Koreans. Insulin secretion in response to an oral glucose tolerance test (OGTT) and a GH stimulation test by L-dopa, growth hormone-binding protein (GHBP), insulin-like growth factor (IGF)-1 and sex hormones (estrone, estradiol, total and free testosterone) were measured. RESULTS: Obese type 2 DM group had the highest GHBP levels and the most visceral fat amount. GHBP levels were most strongly correlated with the ratio of visceral fat area to body weight (VWR) above other parameters (r=0.725, p<0.001). Insulin- and free fatty acid-area under the curve (AUC) during OGTT and IGF-1 level were also positively correlated with GHBP levels (r=0.474, p<0.005; r=0.572, p<0.005; r=0.453, p<0.005). GH-AUC to L-dopa stimulation test was negatively correlated with GHBP levels (r=0.432, p<0.005). The GHBP level was slightly higher in females than in male in the same glucose tolerance category. In males, total and free testosterone levels were negatively correlated with GHBP levels (r=-0.516, p<0.001;r=-0.653, p<0.001). Stepwise multiple linear regression analysis showed that VWR, FFA-and insulin-AUC significantly contributed to the variability of GHBP (r=0.58). CONCLUSION: We demonstrated that 1) visceral fat amount was mainly determined GHBP levels in obese subjects with varying glucose tolerance; 2) hyperglycemia per se did not influence GHBP level, whereas insulin and FFA could play a role in regulation of GHBP level. 3) The constant concentration of IGF-1 despite GH hyposecretion suggests that increased GHBP level retlect GHBP hypersensitivity in order to compensate for decreased GH secretion in obesity; 5) the lower level of GHBP in males might be explained at least in part by a suppressive effect of androgen.