924c The Morbidity of Overweight (Above 85th Percentile) in the First Two Years of Life

63 vs 20 per 10 000 person years, respectively). Postoperatively inpatient care for DM and CVD remained higher among the surgical patients. However, the comparative risk ratio between these cohorts for diabetes was significantly higher before 5.6 (95 % CI 4.1-7.5) than after surgery 2.4 (95% CI 1.7-3.3). There was no such difference in CVD before 3.2 (CI 95% 2.7-3.9) and after surgery 2.8 (CI 95% 2.4-3.3). One year post-operative mortality was 0.6% (n=7). The all-cause mortality risk ratio between the surgical and the comparison cohort after surgery was 1.18 (95% CI 0.86-1.62). Excluding 1-year post-operative mortality, the mortality ratio became 1.05 (95% CI 0.75-1.46). After anti-obesity surgery in men occurrence of inpatient care for diabetes was still higher in the surgical cohort than in the control cohort, but the risk ratio had decreased markedly and all-cause mortality and did not differ from 1.00 (with 95% confidence). These results suggest that in men anti-obesity surgery reduces mortality to levels seen in a comparison cohort. 924c The Morbidity of Overweight (Above 85th Percentile) in the First Two Years of Life Rana Shibli, Lisa Rubin, Hannah Akons, Ron Shaoul Increasing attention in the literature is devoted to childhood obesity and its related morbidity. Most of the papers that deal with this problem focus mainly on older children and adolescents. However, the morbidity in overweight infants and young children, as expressed in hospital admissions and illnesses has not been studied. Our hypothesis was that morbidity related to overweight/obesity is already evident in infants and young toddlers. The major objectives of this study were therefore: 1) to assess the prevalence of overweight in a sample of hospitalized infants. 2) to assess the prevalence of morbidity in overweight infants in a community based sample. Methods: 1) Hospital admissions: The study population included 2139 infants, 24 months and younger, admitted for any reason to our Pediatric Department between 2004-2005. We did not include babies born prematurely or with congenital, genetic or chronic illness. 2) Community based sample. We identified overweight babies (age≤24 months) (weight for height percentile above 85 in at least 2 measurements, at least 3 months apart) in 8 mother and child health care facilities in Haifa subdistrict of Israel. Parents of infants were interviewed using a structured questionnaire. Results: We found that overweight infants (85th-95th percentiles), had less admissions and repeated admissions than expected. Nevertheless, infants above the 95th percentile, had more admissions than expected, as well as a higher number of repeated admissions. In the second part of the study we found that developmental delay (mainly delayed gross motor skills) and snoring were significantly higher in infants above the 85th percentile. In addition, although not statistically significant, infants with overweight suffered more frequently from breathing problems, such as asthma and stridor. When the mothers were asked to assess whether their child is overweight or not only 31.6% of mothers of overweight children thought that the child was overweight. Conclusions: Although the consequences of infant and childhood excess body weight may appear to manifest in later years, this perception is inaccurate. The high admission rates of babies above the 95th percentile and the high incidence of respiratory morbidity, snoring and delayed gross motor skills in overweight infants, supports our hypothesis regarding early morbidity associated with overweight. Our findings indicate a need to actively intervene during these critical years by adopting proper eating habits, active life styles appropriate for this age and increasing the parents' awareness of the importance of adhering to normal weight even in this early age group.

924a Candidate Genes Predict Weight Loss in Response to Sibutramine: A Pharmacogenetic Study in 181 Obese or Overweight Patients April Grudell, Seth R. Sweetser, Paula Carlson, Duane D. Burton, Maria Vazquez Roque, Deborah J. Eckert, Autumn Braddock, Matthew Clark, Karen Graszer, Sarah Kalsy, Alan R. Zinsmeister, Michael Camilleri Background: Sibutramine is a noradrenergic (NE) and serotonergic (5-HT) reuptake inhibitor approved for treatment of obesity. Aim: To assess the influence of candidate α2A receptor, 5-HT transporter (SLC6A4) and GNβ3 genes on weight loss in response to sibutramine or placebo treatment. Methods: 181 healthy overweight and obese (BMI >25, <50) participants received behavior therapy and were randomly assigned to receive placebo or sibutramine, 10 or 15 mg daily, for 12 weeks; all received structured behavioral therapy for weight management. Blood DNA was analyzed for SLC6A4 (5HTTLPR), α2A C1291G, and GNβ3 C825T genotypes. Separate ANCOVA models were used to assess associations of each candidate gene with weight loss. Results: The 3 treatment groups had similar demographic (weight, BMI, waist), fasting blood glucose and genotype distributions at baseline. Sibutramine, 10 and 15 mg doses, resulted in overall significant weight loss (4.5±0.5 kg on 10 mg, 4.9±0.6 kg on 15 mg vs. 1.4±0.7 kg on placebo). For each candidate gene, treatment effects were most pronounced for one genotype variant. There was a statistically significant gene by dose interaction for GNβ3 genotype. Specifically, weight loss on sibutramine (averaged over 2 doses) vs. placebo was observed for α2A CC (~5kg loss, p=0.009), GNβ3 TC/TT (~6kg loss over 2 doses, p<0.001). For SLC6A4 LS/SS genotype, there was a weight loss of ~4.5kg (p=0.014) on sibutramine. There were also significant treatment effects for specific pairwise combinations of genotype variants, with greater weight loss on sibutramine compared to placebo for: SLC6A4 LS/SS and GNβ3 TC/TT, ~6.7kg loss, p<0.002; α2A CC and GNβ3 TC/TT, ~6.5kg loss, p<0.001. Conclusions: Selection of patients for sibutramine treatment of obesity based on these candidate genes that modulate function of α2A receptor, 5-HT transporter and GNβ3 may enhance response to sibutramine and behavioral therapy.

924d Occipital C1-C2 Neuromodulation Modifies Eating Behavior and Decreases Body Mass and Fat Stores in Morbidly Obese Patients - a Preliminary Results Jacek Sobocki, Roman M. Herman, Piotr Walega Introduction. Autonomic and vagal neuromodulation has been suggested for the treatment of morbid obesity. C1 and C2 occipital nerves remain in close anatomical relation to vagal nerve roots at the entrance to medulla oblongata. Moreover, some patients undergoing C1C2 stimulation for other pathologies have reported decreased appetite. Aim. The aim of the study was to evaluate effect of C1-C2 occipital neuromodulation on eating behavior, autonomic activity, blood biochemistry and body mass and composition. Material. Six obese patients were included in the study (3 women, 3 men, BMI 42-49, avg.age 43,8, range 2455). Method. Under local anesthesia two Octrode® leads (ANS, Plano, TX) were placed bilaterally in C1-C2 region subcutaneously in horizontal direction from the midline. Stimulation was started 24 hours after implantation and continued for 8 weeks. An external stimulator (MTS® trial stimulation system, ANS, Plano, TX) was used for stimulation and programming was standardized. Patients activated stimulators for 12 hours every day and turned the stimulators off at night. No other treatment including diet or change in the lifestyle was introduced throughout the duration of the study. The following parameters were evaluated: body mass (0, 4 and 8 weeks) and blood tests (blood count, K, Na, BUN, Glu, LDL, HLD, Total Cholesterol, Triglycerides), body composition (bioimpedance study), Heart Rate Variability (0 and 8 weeks). Electrodes were removed without complication after completion of the study. The study was approved by a local ethical committee. Results. No adverse events or site effects were observed in this group. One patient reported amelioration of constipation for which she suffered for several years another reported two incidents of salivation and one of headache, but relation of these effects with stimulation is not clear. The average body mass decrease was 5.33 kg in 1st and 8.16 kg in 2nd month. Body composition study showed two-months decrease in body fat of 7.9 kg on average. HRV revealed increased parasympathetic tone (LF/HF 5.4+/-4.3 vs. 1.5+/-1.1). No changes in blood tests were observed. Conclusion. C1-C2 occipital stimulation is capable of modifying eating behavior, decreasing body mass and affecting a positive shift in body composition. The applicability of this treatment method for obesity should be confirmed through future trials. The authors thank to Advance Neuromodulation Systems (Plano,TX) for Educational Grant that supported this study.

924b Anti-Obesity Surgery in Swedish Men Reduces Morbidity and Lowers Mortality to Population Levels Richard Marsk, Erik Naslund, Per Tynelius, Jacob Freedman, Finn Rasmussen Several studies of anti-obesity surgery with mainly women have demonstrated lower all cause mortality compared to obese controls. The aim of the present study was to examine the effect of anti-obesity surgery on mortality and morbidity in a male obese cohort who underwent anti-obesity surgery (purely restrictive (67%), gastric bypass (32%), jejunuoileal bypass (11 %)) compared a non-operated cohort. 1,192 operated men born 1951 to 1983 were identified in the national Inpatient Care Registry (ICR) who had their BMI calculated at military conscription at age 18-19 years were identified by record-linkage to the Military Service Conscription Registry (MSCR). A comparison cohort of 246,322 men was identified in the MSCR. For both cohorts data were gathered on diabetes mellitus (DM) and cardiovascular disease (CVD) from conscription to surgery (mean time 21.0±6.7 (1SD) years) and from surgery to time of emigration, death (Cause of Death Registry) or end of follow-up 31 December 2006, whichever came first (mean observation time 6.6 ±4.7 years). Mean BMI at conscription was 31.2 ±5.4 in the surgical cohort and 23.9±3.1 kg/m2 in the comparison cohort. Mean age at time of surgery was 35.1 ±7.6 years. Occurrence of DM and CVD was higher in the surgical cohort than in the comparison cohort prior to surgery (23 vs 4 and

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AGA Abstracts

AGA Abstracts

September 2007 were treated with IFX [61 (30%) <3 mon from dx, 64 (32%) 3-12 mon, 47 (23%) 12-24 mon, 30 (15%) >24 mon]. Mean age at time of first IFX dose was 12.7±2.9yr, range 1.5-18.3yr. Treatment was for luminal disease only in 80%, fistulizing disease in 10%, and both in 10%. 159 received scheduled maintenance IFX and 28 received IFX episodically (7 of whom were ultimately converted to scheduled maintenance); in 15 follow-up was inadequate to determine pattern. Concomitant medications at first IFX infusion were corticosteroids (CS) 60%, AZA/6MP (79%), MTX (6%). The study population received a total of 2360 infusions (mean per person 12±8, median 10, range 1-36). CS were stopped in ≤3 mon in 73% of those receiving them and in 79% CS were not restarted. Following IFX, maximum CD severity was inactive or mild in 73%. Hospitalization and surgery after starting IFX were required in 22% and 11% respectively. Increased IFX dose or decreased infusion interval was required in 44%. Kaplan-Meier analysis showed the proportion still receiving IFX at 6 mon 89%, 12 mon 84%, 18 mon 78%, 24 mon 71%, 36 mon 61%. IFX was discontinued in 54 subjects: 6 (11%) primary non-response, 7 (13%) loss of response, 14 (26%) allergy, 24 (44%) elective, 2 (4%) other, 1 (2%) unknown. At last follow-up 38% of subjects were receiving IFX/immunomodulator (IM) dual therapy, 26% IFX alone, 19% IM alone, 4% adalimumab/IM, 2% adalimumab alone, 5% other, and 6% unable to determine. There was one death (cardiac arrhythmia unrelated to IFX) and one malignancy (Hodgkin's disease of intestine noted at surgery following loss of response). CONCLUSIONS: In the largest cohort of children receiving IFX reported to date, inactive/mild CD was observed in almost 75% of subjects following IFX. CS were stopped and not restarted in most subjects receiving CS at the start of IFX therapy. More than two-thirds of those starting IFX are still receiving this therapy for at least 2 yrs. Discontinuation of IFX is most commonly elective or due to development of allergy.