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Association of serum leptin with hypoventilation in human obesity
  1. P R Phipps1,
  2. E Starritt1,
  3. I Caterson2,
  4. R R Grunstein1
  1. 1Centre for Respiratory Failure and Sleep Disorders, Royal Prince Alfred Hospital, Sydney, NSW 2050 and Institute of Respiratory Medicine, University of Sydney, NSW 2006, Australia
  2. 2Human Nutrition Unit, Department of Biochemistry, University of Sydney, Sydney, NSW 2006, Australia
  1. Correspondence to:
    Associate Professor R R Grunstein, Institute of Respiratory Medicine, University of Sydney, NSW 2006, Australia;


Background: Leptin is a protein hormone produced by fat cells of mammals. It acts within the hypothalamus via a specific receptor to reduce appetite and increase energy expenditure. Plasma leptin levels correlate closely with total body fat mass operating via a central feedback mechanism. In human obesity serum leptin levels are up to four times higher than in lean subjects, indicating a failure of the feedback loop and central leptin resistance. In leptin deficient obese mice (ob/ob mice) leptin infusion reverses hypoventilation. It was hypothesised that a relative deficiency in CNS leptin, indicated by high circulating leptin levels, may be implicated in the pathogenesis of obesity hypoventilation syndrome (OHS).

Methods: Fasting morning leptin levels were measured in obese and non-obese patients with and without daytime hypercapnia (n=56). Sleep studies, anthropometric data, spirometric parameters, and awake arterial blood gas tensions were measured in each patient.

Results: In the whole group serum leptin levels correlated closely with % body fat (r=0.77). Obese hypercapnic patients (mean (SD) % body fat 43.8 (6.0)%) had higher fasting serum leptin levels than eucapnic patients (mean % body fat 40.8 (6.2)%), with mean (SD) leptin levels of 39.1 (17.9) and 21.4 (11.4) ng/ml, respectively (p<0.005). Serum leptin (odds ratio (OR) 1.12, 95% CI 1.03 to 1.22) was a better predictor than % body fat (OR 0.92, 95% CI 0.76 to 1.1) for the presence of hypercapnia.

Conclusions: Hyperleptinaemia is associated with hypercapnic respiratory failure in obesity. Treatment with leptin or its analogues may have a role in OHS provided central leptin resistance can be overcome.

  • leptin
  • obesity hypoventilation syndrome
  • hypercapnia

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