OBJECTIVE Like insulin, the adipocyte hormone, leptin, circulates at levels proportionate to body adiposity. Because insulin may regulate leptin secretion, we sought to determine if plasma leptin levels are coupled to body adiposity via changes in circulating insulin levels or insulin sensitivity and whether leptin secretion from adipocytes is impaired in subjects with NIDDM.

RESEARCH DESIGN AND METHODS We used multiple linear regression to analyze relationships between BMI (a measure of body adiposity) and fasting plasma levels of leptin and insulin in 98 nondiabetic human subjects (68 men/30 women) and 38 subjects with NIDDM (27 men/11 women). The insulin sensitivity index (S₁₎ was also determined in a subset of nondiabetic subjects (n = 38).

RESULTS Fasting plasma leptin concentrations were correlated to both BMI (r = 0.66, P = 0.0001) and fasting plasma insulin levels (r = 0.65, P = 0.0001) in nondiabetic men and women (r = 0.58, P = 0.0009 for BMI; r = 0.47, P = 0.01 for insulin). While the plasma leptin level was also inversely related to S₁ (r = −0.35; P = 0.03), this association was dependent on BMI, whereas the association between insulin and S₁ was not. Conversely, the relationship between plasma leptin and BMI was independent of S₁, whereas that between insulin and BMI was dependent on S₁. The relationship between plasma leptin levels and BMI did not differ significantly among NIDDM subjects from that observedin nondiabetic subjects.

CONCLUSIONS We conclude that 1) body adiposity, sex, and the fasting insulin level are independently associated with plasma leptin level; 2) because NIDDM doesnot influence leptin levels, obesity associated with NIDDM is unlikely to result from impaired leptin secretion; and 3) insulin sensitivity contributes to the association between body adiposity and plasma levels of insulin, but not leptin. The mechanisms underlying the association between body adiposity and circulating levels of these two hormones, therefore, appear to bedifferent.