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Sa1354 Effect of a Test Meal on Insulin Sensitivity and Meal Responses of Satiety Hormones and Their Association to Insulin Resistance in Obese and Normal Weight Adolescents
AGA Abstracts
was independent of sex, age and height and operation type (laparoscopic standard, distal RYGB and biliopancreatic diversion). Conclusions: The ratio of length of common limb/ total length of the small bowel is an important factor for weight loss after gastric bypass surgery, defining an optimal ratio between 0.14 and 0.33 with a least of 100 cm as common limb length. Bariatric surgeons could individualize their surgery by choosing the length of the common channel according to total small bowel length measured during laparoscopic RYGB. Sa1354 Effect of a Test Meal on Insulin Sensitivity and Meal Responses of Satiety Hormones and Their Association to Insulin Resistance in Obese and Normal Weight Adolescents Jean-Pierre Gutzwiller, Christoph Beglinger Background. Gastrointestinal (GI) hormones are involved in satiety regulation and in glucose metabolism. The pathophysiology of these hormones in obesity during normal meal intake remains, however, unclear. Insulin resistance in children is difficult to define, but underlies the metabolic syndrome, a clustering of obesity, hyperinsulinemia, hyperglycemia, dyslipidemia and hypertension that increase risk for type 2 diabetes mellitus and cardiovascular disease as early as mid-puberty. Methods A total of 16 obese (BMI ≥97th percentile for age and gender) and 14 control (BMI between 25th and 75th percentiles) Caucasian adolescents were recruited from the University Children's Hospital Basel Endocrinology Clinic. An intravenous catheter was placed for drawing blood. Blood samples were drawn starting at least 30 min after placement, at t = −5, 30, 60, and 120 min relative to meal intake. Adolescents were presented with the meal at t = 0, and instructed to eat the meal within 15 min, blood samples were collected and Glucagon-like Peptide-1, Glucagon, Amylin and Ghrelin were measured. Basal Insulin and Glucose was obtained to determine Insulin sensitivity (HOMA-Index). Postprandial gut hormone levels were associated to HOMA-Index using multiple linear regression analysis. Results HOMA index was defined as the dependent variable. Fasting amylin and glucagon values were included as independent variables in the model, as was done with postprandial GLP-1 plasma values (GLP-1 AUC). The model with these 3 factors explained a variability of 66%. Looking at the weights of these factors in the model, fasting glucagons had about 50%, whereas for fasting amylin and postprandial GLP1 values, each contributed about 25%. Conclusion We conclude that hyperglucagonemia, hyperamylinemia and reduced postprandial GLP-1 secretion are important pathophysiological steps in the development of metabolic syndrome in adolescents.
Sa1356 Visceral Obesity As Risk Factor of Progression of Reflux Esophagitis: A Longitudinal 5 Year Cohort Study Su Jin Chung, Donghee Kim, Min Jung Park, Joo Sung Kim OBJECTIVES: To investigate the potential roles of visceral adiposity on the natural course of reflux esophagitis (RE). MATERIAL AND METHODS: The cohort population included 1500 subjects [750 patients with endoscopically proven RE vs age-, sex- and waist circumference (WC)-matched controls] who underwent abdominal fat computed tomography (CT) scan were followed at Seoul National University Hospital Healthcare System Gangnam Center between Oct 2005 and Dec 2012. The baseline areas of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) measured by abdominal fat CT scan were calculated. Effects of visceral adiposity on the course of RE were estimated with hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression. RESULTS: During the study periods, a total of 982 subjects underwent repeated upper endoscopy and were finally included [625 (63.6%) to No-change group, 92 (9.4%) to Progression group and 265 (27.0%) to Regression group] with a mean follow-up period of 4.6 yr (0.9 to 8.4 yr). VAT area increased the risk of progression of RE (HR=1.87 and 1.85; 95% CI, 1.1-3.4 and 1.0-3.4, lowest vs. 3rd and 4th quartiles, respectively) in univariate analysis. There were no specific correlations between SAT area and progression or regression of the disease. Adjustments for age, sex, smoking, alcohol, diabetes, Helicobacter pylori status, difference of waist circumference and SAT area attenuated this risk, but large amount of VAT area still increased risk for disease progression of RE (P for trend=0.020). CONCLUSIONS: Visceral obesity is an independent risk factor with the progression of RE in this 5 year longitudinal study.
Sa1355 Morphological Imaging-Based Brain Signatures Discriminate Overweight From Lean Subjects: Examining Central Mechanisms With Obesity Arpana Gupta, Emeran A. Mayer, Claudia P. Sanmiguel, Ivo D. Dinov, Kirsten Tillisch, Jennifer S. Labus Background Behavioral and neuroimaging based observations have identified similarities between brain mechanisms involved in maladaptive obesity-related ingestive behaviors and addictive behaviors, resulting in the concept of food addiction. These studies have demonstrated that structural alterations in key regions of an extended reward network are linked to increased food related behaviors in obesity. Aim: To apply multivariate pattern analysis/ recognition methods from machine-based learning approaches to identify obesity related structural alterations. Hypothesis: Data driven morphological brain signatures can discriminate overweight from lean healthy control subjects. Methods: Structural brain images were obtained from 325 male and female healthy control subjects (159 overweight subjects). The UCLA Laboratory of Neuroimaging (LONI) pipeline was used for image preprocessing, volumetric, shape analysis, and cortical thickness analysis using the LONI probabilistic brain atlas (LBPA 40) and the ICBM (International Consortium for Brain Mapping) atlas, yielding 56 regions. For each cortical region, measures of gray matter (GM) morphometry (volume, mean curvature, surface area and cortical thickness) were computed. Each subjects' structural values were entered as a data matrix into a Sparse Partial Least Square-Discrimination Analysis (sPLS-DA) to examine whether the morphological measures can distinguish overweight from lean individuals. Results: The classification algorithm indicated that two multivariate brain signatures comprising 20 regions each achieved 76% accuracy in discriminating overweight from lean individuals (See Figure), based on 10 fold cross-validation performed 10 times. Both signatures were primarily comprised of GM reductions in hippocampus, parietal (precuneus, postcentral gyrus), and temporal regions, and GM increases in insular, brainstem, frontal and occipital regions in overweight compared to lean. The two signatures accounted for 68% of the variance in the data set, with the first component explaining 63% of the variance and the second component explaining 5% of the variance. Binary classification measures included sensitivity at 76%, specificity at 92%, negative predictive value at 86%, and positive predictive value at 85%. Conclusions: 1. Obesity and overweight in healthy subjects are associated with structural brain changes. 2. Classification algorithms based on the morphometry of regional brain structure alone can identify specific targets for future mechanistic studies and treatments aimed at abnormal ingestive behavior and obesity.
Sa1357 Histologic NASH Is Associated Lack of Improvement of Metabolic Conditions Post Bariatric Surgery James M. Estep, Ashley Greer, Rohini Mehta, Elzafir Elsheikh, Thomas Jeffers, Zachary D. Goodman, Hazem A. Elarainy, Amir H. Moazez, Zobair M. Younossi It is estimated that 85% of morbidly obese patients have some degree of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Aim: To assess if underlying NAFLD improves in the first year following bariatric surgery. Obese patients undergoing weight loss surgery (N=44) received a liver biopsy at the time of surgery. Biopsies were read by a single hepatopathologist and categorized as having no liver diagnosis, non-NASH NAFLD, and NASH Clinical and laboratory values, such as BMI, circulating triglycerides, ALT, AST,LDL, HDL, glucose, and total cholesterol were collected at the time of surgery and during follow up visits 3-12 months after surgery and compared. Spearman correlations were calculated to compare initial histologic features with the improvement rate of individual values. Of the study cohort, 59% were female, 47% were Caucasian, 27% with diabetes mellitus, 31% with hyperlipidemia, and 38% with hypertension. Histologic assessment indicated that 5% of patients did not have any liver disease but 95% had some degree of NAFLD with 75% histologic criteria for NASH. During a median 6.12 months of follow-up, patient BMI (P<0.001), fasting glucose (P<0.01), total cholesterol (P<0.05), and circulating triglycerides (P<0.05) all showed significant improvement. Diagnosis of NASH was negatively correlated with improvement for ALT (r=-0.39, P<0.05), AST (r=-0.30, P<0.05), HDL (r=0.56, P<0.05), and serum triglycerides (r=-0.29, P<0.05). When individual histologic features were examined, initial stage of pericellular fibrosis negatively correlated with improvement in ALT (r=-0.36, P<0.05) and AST (r=-0.43, P<0.05), while degree of steatosis negatively correlated with improvement for HDL (r=-0.4, P<0.05) and triglycerides (r=-5.1, P<0.05). Presence of histologic NASH at the time of bariatric surgery may identify patients who may be resistant or have slower rate of improvement of their metabolic conditions. Larger cohorts and longer treatment duration is important to clarify this potential association.
S-271
AGA Abstracts
was independent of sex, age and height and operation type (laparoscopic standard, distal RYGB and biliopancreatic diversion). Conclusions: The ratio of length of common limb/ total length of the small bowel is an important factor for weight loss after gastric bypass surgery, defining an optimal ratio between 0.14 and 0.33 with a least of 100 cm as common limb length. Bariatric surgeons could individualize their surgery by choosing the length of the common channel according to total small bowel length measured during laparoscopic RYGB. Sa1354 Effect of a Test Meal on Insulin Sensitivity and Meal Responses of Satiety Hormones and Their Association to Insulin Resistance in Obese and Normal Weight Adolescents Jean-Pierre Gutzwiller, Christoph Beglinger Background. Gastrointestinal (GI) hormones are involved in satiety regulation and in glucose metabolism. The pathophysiology of these hormones in obesity during normal meal intake remains, however, unclear. Insulin resistance in children is difficult to define, but underlies the metabolic syndrome, a clustering of obesity, hyperinsulinemia, hyperglycemia, dyslipidemia and hypertension that increase risk for type 2 diabetes mellitus and cardiovascular disease as early as mid-puberty. Methods A total of 16 obese (BMI ≥97th percentile for age and gender) and 14 control (BMI between 25th and 75th percentiles) Caucasian adolescents were recruited from the University Children's Hospital Basel Endocrinology Clinic. An intravenous catheter was placed for drawing blood. Blood samples were drawn starting at least 30 min after placement, at t = −5, 30, 60, and 120 min relative to meal intake. Adolescents were presented with the meal at t = 0, and instructed to eat the meal within 15 min, blood samples were collected and Glucagon-like Peptide-1, Glucagon, Amylin and Ghrelin were measured. Basal Insulin and Glucose was obtained to determine Insulin sensitivity (HOMA-Index). Postprandial gut hormone levels were associated to HOMA-Index using multiple linear regression analysis. Results HOMA index was defined as the dependent variable. Fasting amylin and glucagon values were included as independent variables in the model, as was done with postprandial GLP-1 plasma values (GLP-1 AUC). The model with these 3 factors explained a variability of 66%. Looking at the weights of these factors in the model, fasting glucagons had about 50%, whereas for fasting amylin and postprandial GLP1 values, each contributed about 25%. Conclusion We conclude that hyperglucagonemia, hyperamylinemia and reduced postprandial GLP-1 secretion are important pathophysiological steps in the development of metabolic syndrome in adolescents.
Sa1356 Visceral Obesity As Risk Factor of Progression of Reflux Esophagitis: A Longitudinal 5 Year Cohort Study Su Jin Chung, Donghee Kim, Min Jung Park, Joo Sung Kim OBJECTIVES: To investigate the potential roles of visceral adiposity on the natural course of reflux esophagitis (RE). MATERIAL AND METHODS: The cohort population included 1500 subjects [750 patients with endoscopically proven RE vs age-, sex- and waist circumference (WC)-matched controls] who underwent abdominal fat computed tomography (CT) scan were followed at Seoul National University Hospital Healthcare System Gangnam Center between Oct 2005 and Dec 2012. The baseline areas of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) measured by abdominal fat CT scan were calculated. Effects of visceral adiposity on the course of RE were estimated with hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression. RESULTS: During the study periods, a total of 982 subjects underwent repeated upper endoscopy and were finally included [625 (63.6%) to No-change group, 92 (9.4%) to Progression group and 265 (27.0%) to Regression group] with a mean follow-up period of 4.6 yr (0.9 to 8.4 yr). VAT area increased the risk of progression of RE (HR=1.87 and 1.85; 95% CI, 1.1-3.4 and 1.0-3.4, lowest vs. 3rd and 4th quartiles, respectively) in univariate analysis. There were no specific correlations between SAT area and progression or regression of the disease. Adjustments for age, sex, smoking, alcohol, diabetes, Helicobacter pylori status, difference of waist circumference and SAT area attenuated this risk, but large amount of VAT area still increased risk for disease progression of RE (P for trend=0.020). CONCLUSIONS: Visceral obesity is an independent risk factor with the progression of RE in this 5 year longitudinal study.
Sa1355 Morphological Imaging-Based Brain Signatures Discriminate Overweight From Lean Subjects: Examining Central Mechanisms With Obesity Arpana Gupta, Emeran A. Mayer, Claudia P. Sanmiguel, Ivo D. Dinov, Kirsten Tillisch, Jennifer S. Labus Background Behavioral and neuroimaging based observations have identified similarities between brain mechanisms involved in maladaptive obesity-related ingestive behaviors and addictive behaviors, resulting in the concept of food addiction. These studies have demonstrated that structural alterations in key regions of an extended reward network are linked to increased food related behaviors in obesity. Aim: To apply multivariate pattern analysis/ recognition methods from machine-based learning approaches to identify obesity related structural alterations. Hypothesis: Data driven morphological brain signatures can discriminate overweight from lean healthy control subjects. Methods: Structural brain images were obtained from 325 male and female healthy control subjects (159 overweight subjects). The UCLA Laboratory of Neuroimaging (LONI) pipeline was used for image preprocessing, volumetric, shape analysis, and cortical thickness analysis using the LONI probabilistic brain atlas (LBPA 40) and the ICBM (International Consortium for Brain Mapping) atlas, yielding 56 regions. For each cortical region, measures of gray matter (GM) morphometry (volume, mean curvature, surface area and cortical thickness) were computed. Each subjects' structural values were entered as a data matrix into a Sparse Partial Least Square-Discrimination Analysis (sPLS-DA) to examine whether the morphological measures can distinguish overweight from lean individuals. Results: The classification algorithm indicated that two multivariate brain signatures comprising 20 regions each achieved 76% accuracy in discriminating overweight from lean individuals (See Figure), based on 10 fold cross-validation performed 10 times. Both signatures were primarily comprised of GM reductions in hippocampus, parietal (precuneus, postcentral gyrus), and temporal regions, and GM increases in insular, brainstem, frontal and occipital regions in overweight compared to lean. The two signatures accounted for 68% of the variance in the data set, with the first component explaining 63% of the variance and the second component explaining 5% of the variance. Binary classification measures included sensitivity at 76%, specificity at 92%, negative predictive value at 86%, and positive predictive value at 85%. Conclusions: 1. Obesity and overweight in healthy subjects are associated with structural brain changes. 2. Classification algorithms based on the morphometry of regional brain structure alone can identify specific targets for future mechanistic studies and treatments aimed at abnormal ingestive behavior and obesity.
Sa1357 Histologic NASH Is Associated Lack of Improvement of Metabolic Conditions Post Bariatric Surgery James M. Estep, Ashley Greer, Rohini Mehta, Elzafir Elsheikh, Thomas Jeffers, Zachary D. Goodman, Hazem A. Elarainy, Amir H. Moazez, Zobair M. Younossi It is estimated that 85% of morbidly obese patients have some degree of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Aim: To assess if underlying NAFLD improves in the first year following bariatric surgery. Obese patients undergoing weight loss surgery (N=44) received a liver biopsy at the time of surgery. Biopsies were read by a single hepatopathologist and categorized as having no liver diagnosis, non-NASH NAFLD, and NASH Clinical and laboratory values, such as BMI, circulating triglycerides, ALT, AST,LDL, HDL, glucose, and total cholesterol were collected at the time of surgery and during follow up visits 3-12 months after surgery and compared. Spearman correlations were calculated to compare initial histologic features with the improvement rate of individual values. Of the study cohort, 59% were female, 47% were Caucasian, 27% with diabetes mellitus, 31% with hyperlipidemia, and 38% with hypertension. Histologic assessment indicated that 5% of patients did not have any liver disease but 95% had some degree of NAFLD with 75% histologic criteria for NASH. During a median 6.12 months of follow-up, patient BMI (P<0.001), fasting glucose (P<0.01), total cholesterol (P<0.05), and circulating triglycerides (P<0.05) all showed significant improvement. Diagnosis of NASH was negatively correlated with improvement for ALT (r=-0.39, P<0.05), AST (r=-0.30, P<0.05), HDL (r=0.56, P<0.05), and serum triglycerides (r=-0.29, P<0.05). When individual histologic features were examined, initial stage of pericellular fibrosis negatively correlated with improvement in ALT (r=-0.36, P<0.05) and AST (r=-0.43, P<0.05), while degree of steatosis negatively correlated with improvement for HDL (r=-0.4, P<0.05) and triglycerides (r=-5.1, P<0.05). Presence of histologic NASH at the time of bariatric surgery may identify patients who may be resistant or have slower rate of improvement of their metabolic conditions. Larger cohorts and longer treatment duration is important to clarify this potential association.
S-271
AGA Abstracts