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Background The melanocortin 4 receptor (MC4R) critically regulates feeding and satiety. Rare variants in MC4R are predominantly found in obese individuals. Though some rare variants in MC4R discovered in patients have defects in localization, ligand binding and signaling to cAMP, many have no recognized defects. Subjects/Methods In our cohort of 1433 obese subjects that underwent Roux-en-Y Gastric Bypass (RYGB) surgery, we found fifteen variants of MC4R. We matched rare variant carriers to patients with the MC4R reference alleles for gender, age, starting BMI and T2D to determine the variant effect on weight-loss post-RYGB. In vitro, we determined expression of mutant receptors by ELISA and western blot, and cAMP production by microscopy. Results While carrying a rare MC4R allele is associated with obesity, carriers of rare variants exhibited comparable weight-loss after RYGB to non-carriers. However, subjects carrying three of these variants, V95I, I137T or L250Q, lost less weight after surgery. In vitro, the R305Q mutation caused a defect in cell surface expression while only the I137T and C326R mutations showed impaired cAMP signaling. Despite these apparent differences, there was no correlation between in vitro signaling and pre- or post-surgery clinical phenotype. Conclusions These data suggest that subtle differences in receptor signaling conferred by rare MC4R variants combined with additional factors predispose carriers to obesity. In the absence of complete MC4R deficiency, these differences can be overcome by the powerful weight-reducing effects of bariatric surgery. In a complex disorder such as obesity, genetic variants that cause subtle defects that have cumulative effects can be overcome after appropriate clinical intervention.

Enterocutaneous fistulas (ECFs) are a complex topic in terms of classification. ECF-related morbidity and mortality can be high due to fluid loss and electrolyte imbalance, sepsis, and malnutrition. Most prognostic factors influencing the outcome of ECF are now well-known. ECF treatment is complex; and, based on various situations, it can be surgical or conservative/ medical. Depending on fistula site and nutritional status, clinicians have to decide whether total parenteral or enteral nutrition should be established. In cases where total parenteral nutrition alone for 7 days has failed to influence the high output fistulas, overall data support the use of adjuvant drug, somatostatin, or its synthetic analogue, octreotide. Somatostatin 250 microg/d and octreotide 300-600 microg/d have been tried along with total parenteral nutrition to decrease the healing time of ECFs and to reduce the number of complications.

The prevalence of obesity-related health outcomes is increasing among older adults. Because it is thought that nutrition plays an important role in successful aging, there has been considerable interest in the association between dietary patterns of older adults and obesity-related health outcomes. Cluster analysis, utilizing data from four 24-hour dietary recalls, was used to derive dietary patterns in a subgroup of 260 participants from the Geisinger Rural Aging Study (mean age: 78.6 3.9 years). Prevalence (5-year follow-up) of cardiovascular disease, diabetes mellitus, hypertension, and metabolic syndrome was extracted from the outpatient electronic medical records using a validated data abstraction process. Logistic regression, adjusting for relevant covariates, was used to examine the associations between dietary patterns and health outcomes. ‘Sweets and Dairy’ (49%), ‘Health-Conscious’ (27%) and ‘Western’ (24%) dietary patterns were identified at baseline. Prevalence of hypertension in the ’Sweets and Dairy’, ‘Health-conscious’, and ‘Western’ pattern was 81.3%, 65.7%, and 79.0%, respectively. Compared to the ‘Health-Conscious’ pattern, those in the ‘Sweets and Dairy’ pattern had increased odds of hypertension; adjusted odds ratio (95% CI) was 2.17 (1.11-4.27). No significant associations were found for cardiovascular disease, diabetes mellitus, or metabolic syndrome with dietary patterns. Although there was a statistically significant relationship between dietary pattern and prevalence of hypertension, the practical clinical utility remains unclear. The null findings for a 5-year follow-up of any elderly sample for cardiovascular disease, diabetes mellitus andmetabolic syndromedonot address the potential benefits of adopting a healthy dietary pattern at a younger age.

Background: A widely accepted method for estimating weight loss following gastric bypass surgery is percent of excess body mass index (BMI) loss (%EBL). Because the amount of excess body weight is higher in patients with higher BMIs, the %EBL during the postoperative period is commonly lower despite the higher absolute weight loss (i.e., pounds lost); thus patients may be considered failures despite substantial weight loss. We developed a method to standardize weight loss following gastric bypass surgery that accounts for pre-operative BMI. Methods: Roux-en-Y gastric bypass patients with 12 months of post-operative follow-up were included (12 month follow-up rate is 90%). After stratifying by baseline BMI, the distribution of 18-month BMI measures was analyzed to calculate the 10th%tile within each group (i.e. the 10% of patients with the lowest BMI at 18-months). Linear regression was used to create a formula for post-operative BMI using baseline BMI as the independent variable. Results: A total of 1,349 patients (81% female) with a mean age of 46.6 years were studied. Baseline BMI was grouped as 35-39 (n 113), 40-44 (n 342), 45-49 (n 318), 50-54 (n 273), 55-59 (n 144), and 60 (n 159) kg/m. The 10th %tile for 18-month BMI highly correlated with baseline BMI (r-squared 0.9987, pvalue .0001; 18-month BMI 4.564 (0.558*baseline BMI). Conclusion: Establishing %EWL criteria based upon initial BMI as a goal/measure of success, after Roux-en-Y gastric bypass accounts for absolute differences in weight loss across BMI categories. This measure defines an achievable goal for new patients and provides a new standard of post-operative weight loss measurement. More research is needed to validate this measure with co-morbidity resolution and improvement in other health outcomes in a larger, more diverse cohort.

Background/Aims: Obesity has a strong genetic component. Recent genome-wide association studies have identified single nucleotide polymorphisms (SNPs) in or near over a dozen genes that are related to body mass index (BMI). Despite the association of these SNPs with BMI, the mechanism by which they influence the determination of body weight is not yet known. Recently, the fat- mass and obesity-associated (FTO) obesity SNP was related to energy intake and preference for foods of high caloric density in children. FTO genotype was not associated with resting energy expenditure. We have extended this type of analysis to eating behaviors in the morbidly obese. Methods: DNA was obtained from approximately 900 morbidly obese (BMI>40 kg/m2) patients and used to genotype obesity SNPs in or near the FTO, INSIG2, MC4R, and PCSK1 genes. Binge eating status (normal, episodic overeating, or any binge eating) was determined using the validated Questionnaire on Eating and Weight Patterns (QEWP). Binge eating status was correlated with each individual genotype, the combined obesity allele burden, and the combined homozygous obesity gene burden. Results: Binge eating data was obtained from 640 patients who had completed the QEWP. Of these 640, 116 (18%) were classified as manifesting binge eating behavior. No association was present between heterozygous or homozygous FTO (P=0.59), MC4R (P=0.30), or PSK1 (P=0.77) obesity SNPs. However, 29% of those who were homozygous for the INSIG2 obesity SNP were classified as binge eaters, versus 17% of heterozygous or homozygous normal patients (P=0.006). Association was also found with binge eating status and the presence of 2 or more homozygous obesity genotypes (28% versus 17%, P=0.041), likely due to the INSIG2 gene. Cumulative obesity allele burden (0–8 alleles for the 4 genes) was not associated with binge eating status (P=0.42). Conclusions: The INSIG2 obesity SNP appears to influence binge eating behavior in morbidly obese adults. The FTO obesity SNP appears to influence eating behavior in children suggesting that different genes may influence obesity at different ages. For both genes, excess caloric intake appears to be the major mechanism influencing BMI. How other obesity genes influence body weight regulation has not yet been determined.

Hypothesis: Modest, preoperative weight loss will improve perioperative outcomes among high-risk, morbidly obese patients undergoing Roux-en-Y gastric bypass. Design: A prospective, longitudinal assessment of characteristics and outcomes of gastric bypass patients. Setting: All patients undergoing open or laparoscopic Roux-en-Y gastric bypass surgery for morbid obesity or its comorbid medical problems at Geisinger Medical Center in Danville, Pennsylvania, during a 3-year period from May 31, 2002, to February 24, 2006, were included in this analysis. Patients were required to participate in a standardized multidisciplinary preoperative program that encompasses medical, psychological, nutritional, and surgical interventions and education. In addition, patients were encouraged to achieve a 10% loss of excess body weight prior to surgical intervention. Results: Of the 884 subjects, 425 (48%) lost more than 10% of their excess body weight prior to the operation. After surgery (mean follow-up, 12 months), this group was more likely to achieve 70% loss of excess body weight (P.001). Those who lost more than 5% of excess body weight prior to surgery were statistically less likely to have a length of stay of greater than 4 days (P=.03). Conclusions: This study shows that high-risk morbidly obese candidates for bariatric surgery who are able to achieve a loss of 5% to 10% excess body weight prior to surgery have a higher probability of a shorter length of hospital stay and more rapid postoperative weight loss.