Leptin predicts a worsening of the features of the metabolic syndrome independently of obesity.
OBJECTIVE
The term metabolic syndrome (MS) describes a cluster of cardiovascular risk factors including dyslipidemia, glucose intolerance, insulin resistance, and hypertension. Obesity increases the risk of MS, but as obesity is neither necessary nor sufficient to cause the syndrome, there is considerable interest in identifying obesity-independent pathways. One such pathway may involve the actions of the adipokine leptin, which is associated cross-sectionally with MS and prospectively with coronary heart disease and stroke, independently of obesity. Our goal was to test the hypothesis that leptin predicts the development of the features of MS independently of obesity.


METHODS
This study used a prospective population-based cohort of 748 middle-aged whites in whom baseline measures of leptin and repeated measurement of the subcomponents of the MS at 5 and 10 years were available. The features of the MS were characterized as five factors (obesity, dyslipidemia, elevated blood pressure, glucose intolerance, and insulin resistance), which were combined to create an MS summary score.


RESULTS
Baseline leptin significantly predicted the development of obesity (p = 0.001) and, after adjustment for BMI, development of glucose intolerance (p = 0.016) and insulin resistance (p < 0.0001). Leptin levels did not independently predict a change in lipids or blood pressure. Leptin levels significantly predicted the development of the MS (p = 0.036), independently of baseline BMI.


CONCLUSIONS
Leptin predicts the development of the MS independently of baseline obesity. This association is specifically related to the development of glucose intolerance and insulin resistance. The extent to which these relationships are explained through residual confounding by obesity remains to be determined.
Franks
Paul W
PW
Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Phoenix, AZ 85014, USA. pfranks@niddk.nih.gov
Brage
Soren
S
Luan
Jian'an
J
Ekelund
Ulf
U
Rahman
Mushtaquar
M
Farooqi
I Sadaf
IS
Halsall
Ian
I
O'Rahilly
Stephen
S
Wareham
Nicholas J
NJ
D000328:Adult; D015331:Cohort Studies; D005260:Female; D006801:Humans; D020738:Leptin / Q000097:blood*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000209:etiology; D009765:Obesity / Q000097:blood* / Q000209:etiology; D011446:Prospective Studies; D012307:Risk Factors
D020738:Leptin