The association between leptin and proinsulin is lost with central obesity

Area of Science:

• Endocrinology
• Cardiovascular Disease Risk Factors
• Metabolic Syndrome

Background:

• Hyperproinsulinaemia and hyperleptinaemia are key features of insulin resistance syndrome.
• These conditions are linked to increased cardiovascular disease (CVD) risk.
• The relationship between leptin and proinsulin across different CVD risk strata is not well understood.

Purpose of the Study:

• To investigate the association between leptin and proinsulin in men versus women.
• To examine this association in pre- versus postmenopausal women.
• To determine how varying degrees of cardiovascular disease risk influence the leptin-proinsulin relationship.

Main Methods:

• Cross-sectional study of 158 healthy subjects from the Northern Sweden Monitoring of Trends and Determinants in Cardiovascular Disease cohort.
• Measurements included anthropometrics, oral glucose tolerance tests, and assays for insulin, proinsulin, and leptin.
• Analyses involved homeostasis model assessment, partial correlations, and multiple linear regression.

Main Results:

• Leptin was significantly associated with proinsulin in nonobese men, premenopausal women, and obese postmenopausal women, particularly after stratification for waist circumference.
• High fasting proinsulin predicted high leptin in these groups, even after adjusting for age and adiposity.
• This association diminished with increasing central obesity in men and premenopausal women.

Conclusions:

• Adiposity and hormonal milieu significantly influence the leptin-proinsulin association in a general population.
• The insulin resistance syndrome is characterized by a loss of this association.
• Dysfunction of the adipoinsular axis may explain the lost leptin-proinsulin association in insulin resistance syndrome.