TY - JOUR
T1 - Alteration of Gastric Functions and Candidate Genes Associated With Weight Reduction in Response to Sibutramine
AU - Vazquez Roque, Maria I.
AU - Camilleri, Michael
AU - Clark, Matthew M.
AU - TePoel, Debra A.
AU - Jensen, Michael D.
AU - Graszer, Karen M.
AU - Kalsy, Sarah A.
AU - Burton, Duane D.
AU - Baxter, Kari L.
AU - Zinsmeister, Alan R.
N1 - Funding Information:
Supported by a General Clinical Research Center (grant M01-RR00585) from the National Institutes of Health. Dr Camilleri is supported by grants R01 DK67071 and K24 DK02638 and Dr Jensen was supported in part by the Minnesota Obesity Center grant DK50456 from the National Institutes of Health. Dr Camilleri participates as a member of a Mayo Clinic advisory group for the development of devices for the treatment of obesity. The Mayo Clinic owns equity in the company Enteromedics, and Dr Camilleri first received an annual royalty in 2005. There is no individual or institutional financial interest in the drug under study, subutramine.
PY - 2007/7
Y1 - 2007/7
N2 - Background & Aims: It is unclear whether weight loss with the noradrenergic (norepinephrine) and serotonergic (5-hydroxytryptamine) reuptake inhibitor, sibutramine, is associated with altered stomach functions and whether genetics influence treatment response. Methods: Forty-eight overweight and obese but otherwise healthy participants were randomized to placebo or sibutramine (15 mg/day for 12 weeks). At baseline and posttreatment we measured the following: gastric emptying for solids and liquids by scintigraphy, gastric volumes by single-photon emission computed tomography, maximum tolerated volume and 30-minute postnutrient challenge symptoms, and selected gastrointestinal hormones. All participants received structured behavior therapy for weight management. The influence of candidate gene polymorphisms involved in norepinephrine and 5-hydroxytryptamine or receptor function (phenylethanolamine N-methyltransferase, guanine nucleotide binding protein β polypeptide 3, α2A adrenoreceptor, and solute carrier family 6 [neurotransmitter transporter, serotonin] member 4 [homo sapiens] [SLC6A4]) on weight loss and gastric functions was evaluated. Results: The overall average weight loss posttreatment was 5.4 ± 0.8 (SEM) kg with sibutramine and 0.9 ± 0.9 kg with placebo (P < .001). The sibutramine group showed significant retardation in gastric emptying of solids (P = .03), reduced maximum tolerated volume (P = .03), and increased postprandial peptide YY compared with the placebo group. Obese females showed greater effects of sibutramine on weight loss and gastric emptying of solids and liquids. Gastric volumes and postchallenge symptoms were not significantly different in the 2 treatment groups. The LS/SS genotype of the promoter for SLC6A4 was associated with enhanced weight loss with sibutramine. Conclusions: Weight reduction with sibutramine is associated with altered gastric functions and increased peptide YY and is significantly associated with SLC6A4 genotype. The role of genetic variation in SLC6A4 on weight loss in response to sibutramine deserves further study.
AB - Background & Aims: It is unclear whether weight loss with the noradrenergic (norepinephrine) and serotonergic (5-hydroxytryptamine) reuptake inhibitor, sibutramine, is associated with altered stomach functions and whether genetics influence treatment response. Methods: Forty-eight overweight and obese but otherwise healthy participants were randomized to placebo or sibutramine (15 mg/day for 12 weeks). At baseline and posttreatment we measured the following: gastric emptying for solids and liquids by scintigraphy, gastric volumes by single-photon emission computed tomography, maximum tolerated volume and 30-minute postnutrient challenge symptoms, and selected gastrointestinal hormones. All participants received structured behavior therapy for weight management. The influence of candidate gene polymorphisms involved in norepinephrine and 5-hydroxytryptamine or receptor function (phenylethanolamine N-methyltransferase, guanine nucleotide binding protein β polypeptide 3, α2A adrenoreceptor, and solute carrier family 6 [neurotransmitter transporter, serotonin] member 4 [homo sapiens] [SLC6A4]) on weight loss and gastric functions was evaluated. Results: The overall average weight loss posttreatment was 5.4 ± 0.8 (SEM) kg with sibutramine and 0.9 ± 0.9 kg with placebo (P < .001). The sibutramine group showed significant retardation in gastric emptying of solids (P = .03), reduced maximum tolerated volume (P = .03), and increased postprandial peptide YY compared with the placebo group. Obese females showed greater effects of sibutramine on weight loss and gastric emptying of solids and liquids. Gastric volumes and postchallenge symptoms were not significantly different in the 2 treatment groups. The LS/SS genotype of the promoter for SLC6A4 was associated with enhanced weight loss with sibutramine. Conclusions: Weight reduction with sibutramine is associated with altered gastric functions and increased peptide YY and is significantly associated with SLC6A4 genotype. The role of genetic variation in SLC6A4 on weight loss in response to sibutramine deserves further study.
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U2 - 10.1016/j.cgh.2007.02.037
DO - 10.1016/j.cgh.2007.02.037
M3 - Article
C2 - 17544870
AN - SCOPUS:34447095717
VL - 5
SP - 829
EP - 837
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
SN - 1542-3565
IS - 7
ER -