Suppression of insulin secretion is associated with weight loss and altered macronutrient intake and preference in a subset of obese adults

Abstract

PURPOSE: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 b-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; DBMIoÀ3 kg/m 2 ) and low responders (LR; DBMI between À3 and À0.5) exhibited higher suppression of CIRgp and IAUC than nonresponders (NR; DBMI > À0.5). 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, DBMI correlated with DCISI, Dfat mass, and Dleptin. DFat mass also correlated with DIAUC and DCISI. 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.

Obesity, leptin resistance, and the effects of insulin reduction

“…every month. 12 Subjects were admitted to the UT GCRC at the beginning and end of this 6-month trial. On arrival in the morning, each subject underwent REE using indirect calorimetry using a Medical Graphics CPX metabolic cart (St Paul, MN, USA).…”

“…After the REE was completed, an intravenous line was started, serum leptin was obtained, and thereafter each subject underwent 3-h oral glucose tolerance testing (OGTT). 12,15 The insulin area under the curve (IAUC) is an index of the magnitude of the insulinemia and was computed from the insulin excursion. 16 Subjects were also analyzed for total tissue, fat mass, and lean mass at weeks 0 and 24 by DEXA, using a Lunar DPX-L machine (Madison, WI, USA).…”

“…We chose to suppress insulin directly at the b-cell using the somatostatin agonist octreotide-LAR (Novartis; East Hanover, NJ, USA), 9 as this drug has previously been shown to suppress insulin secretion and safely promote weight loss without causing diabetes mellitus, both in children with obesity due to hypothalamic insult 10,11 and in select adults whose obesity is secondary to insulin hypersecretion. 12,13 Other insulin sensitizers, such as thiazoladinediones, while lowering plasma insulin levels, increase energy deposition into adipose tissue. 14 Measurement of leptin sensitivity in humans has been elusive, as there is no static biochemical measure of leptin's effect.…”

A multicenter, randomized, double-blind, placebo-controlled, dose-finding trial of a long-acting formulation of octreotide in promoting weight loss in obese adults with insulin hypersecretion

“…A subpopulation of obese adults without cranial pathology also exhibit insulin hypersecretion, as characterized by a rapid rise in serum insulin during the first 30 min of an OGTT. In a pilot study, 21 suppression of insulin secretion was achieved after 24 weeks of treatment with 40 mg of octreotide LAR and was associated with loss of body weight and fat mass in a subgroup of obese adults. The design of this study is based on the hypothesis that some obese adults with insulin hypersecretion diagnosed via their CIR gp value during an OGTT would respond to insulin suppression using octreotide LAR by losing weight without behavioral intervention.…”

Somatostatin and cancer: Applying endocrinology to oncology

“…Octreotide is already used to suppress insulin secretion in congenital hyperinsulinism, a genetic disorder of insulin regulation, 12,13 and is being tried in the treatment of obesity and hyperinsulinemia. [14][15][16] Via Autocrine/Paracrine Effects. Autocrine/paracrine GH and IGF production are increasingly appreciated as important contributors to normal growth 17 and cancer.…”