Obesity, Leptin Resistance, and the Effects of Insulin Reduction

Int J Obes Relat Metab Disord. 2004 Oct;28(10):1344-8. doi: 10.1038/sj.ijo.0802753.

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/m(2)) 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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / metabolism
  • Body Mass Index
  • Energy Metabolism
  • Glucose Tolerance Test
  • Humans
  • Hyperinsulinism / blood
  • Hyperinsulinism / drug therapy*
  • Hyperinsulinism / etiology
  • Insulin / blood
  • Leptin / blood*
  • Obesity / blood
  • Obesity / drug therapy
  • Obesity / physiopathology*
  • Octreotide / therapeutic use*
  • Weight Loss / drug effects

Substances

  • Blood Glucose
  • Insulin
  • Leptin
  • Octreotide