title: Suppression of insulin secretion is associated with weight loss and altered macronutrient intake and preference in a subset of obese adults.
abstract: OBJECTIVE
  Hyperinsulinemia is a common feature of many obesity syndromes. We investigated whether suppression of insulin secretion, without dietary or exercise intervention, could promote weight loss and alter food intake and preference in obese adults.
  
  
  METHODS
  Suppression of insulin secretion was achieved using octreotide-LAR 40 mg IM q28d for 24 weeks in 44 severely obese adults (89% female, 39% minority). Oral glucose tolerance testing was performed before and after treatment, indices of beta-cell activity (CIRgp), insulin sensitivity (CISI), and clearance (CP/I AUC) were computed, and leptin levels, 3-day food records and carbohydrate-craving measurements were obtained. DEXA evaluations were performed pre- and post-therapy in an evaluable subgroup.
  
  
  RESULTS
  For the entire cohort, significant insulin suppression was achieved with simultaneous improvements in insulin sensitivity, weight loss, and body mass index (BMI). Leptin, fat mass, total caloric intake, and carbohydrate craving significantly decreased. When grouped by BMI response, high responders (HR; DeltaBMI<-3 kg/m(2)) and low responders (LR; DeltaBMI between -3 and -0.5) exhibited higher suppression of CIRgp and IAUC than nonresponders (NR; DeltaBMI-0.5). CISI improved and significant declines in leptin and fat mass occurred only in HR and LR. Conversely, both leptin and fat mass increased in NR. Carbohydrate intake was markedly suppressed in HR only, while carbohydrate-craving scores decreased in HR and LR. For the entire cohort, DeltaBMI correlated with DeltaCISI, Deltafat mass, and Deltaleptin. DeltaFat mass also correlated with DeltaIAUC and DeltaCISI.
  
  
  CONCLUSIONS
  In a subcohort of obese adults, suppression of insulin secretion was associated with loss of body weight and fat mass and with concomitant modulation of caloric intake and macronutrient preference.
authors.affiliation: Department of Pediatrics, University of Tennessee Health Science Center, Memphis, USA. pvelasquez@utmem.edu
authors.forename: P A
authors.initials: PA
authors.lastname: Velasquez-Mieyer
authors.forename: P A
authors.initials: PA
authors.lastname: Cowan
authors.forename: K L
authors.initials: KL
authors.lastname: Arheart
authors.forename: C K
authors.initials: CK
authors.lastname: Buffington
authors.forename: K A
authors.initials: KA
authors.lastname: Spencer
authors.forename: B E
authors.initials: BE
authors.lastname: Connelly
authors.forename: G W
authors.initials: GW
authors.lastname: Cowan
authors.forename: R H
authors.initials: RH
authors.lastname: Lustig
mesh_terms: D000273:Adipose Tissue / Q000473:pathology; D000328:Adult; D001823:Body Composition; D015992:Body Mass Index; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004435:Eating / Q000187:drug effects*; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D005951:Glucose Tolerance Test; D006728:Hormones / Q000627:therapeutic use; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D015282:Octreotide / Q000627:therapeutic use*; D011446:Prospective Studies; D015431:Weight Loss / Q000187:drug effects*
chemical_list: D004040:Dietary Carbohydrates; D006728:Hormones; D007328:Insulin; D015282:Octreotide