1. ¹Department of Pediatrics, University of California, San Francisco, CA, USA
2. ²Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA
3. ³Department of Internal Medicine, University of Tennessee Health Science Center, Memphis, TN, USA
4. ⁴Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, USA

Correspondence: Dr R Lustig, Department of Pediatrics, University of California San Francisco, Box 0434, 513 Parnassus Avenue, San Francisco, CA 94143-0434, USA. E-mail: rlustig@peds.ucsf.edu

Received 4 January 2004; Revised 3 May 2004; Accepted 15 June 2004; Published online 17 August 2004.

Abstract

Leptin resistance is a hallmark of obesity, but its etiology is unknown, and its clinical measurement is elusive. Leptin-sensitive subjects have normal resting energy expenditure (REE) at a low leptin concentration, while leptin-resistant subjects have a normal REE at a higher leptin concentration; thus, the ratio of REE:Leptin may provide a surrogate index of leptin sensitivity. We examined changes in REE and leptin in a cohort of 17 obese subjects during experimental weight loss therapy with the insulin-suppressive agent octreotide-LAR, 40 mg i.m. q28d for 6 months. Six subjects lost significant weight (>10%) and BMI (>-3 kg/m²) with a 34% decline in leptin and a 46% decrease in insulin area under the curve (IAUC) to oral glucose tolerance testing. These subjects maintained their pretreatment REE, and thus exhibited a rise in REE:Leptin, while the other 11 showed minimal changes in each of these parameters. For the entire cohort, the change in IAUC correlated negatively with the change in REE:Leptin. These results suggest that the REE:Leptin ratio, while derivative, may serve as a useful clinical indicator of changes in leptin sensitivity within obese subjects. They also support the possibilities that hyperinsulinemia may be a proximate cause of leptin resistance, and that reduction of insulinemia may promote weight loss by improving leptin sensitivity.