Leptin/Adiponectin Ratios Using Either Total Or High-Molecular-Weight Adiponectin as Biomarkers of Systemic Insulin Sensitivity in Normoglycemic Women

Abstract

Plasma leptin/adiponectin ratio (LAR) is negatively associated with insulin sensitivity indexes. High-molecular-weight adiponectin (HMWA) was proposed as the most biologically active form of this insulin-sensitizing adipokine. There are no studies assessing the relative merits of leptin/HMWA ratio over LAR as a biomarker of systemic insulin sensitivity. A standard 2-hour oral glucose tolerance test (OGTT; 75 g of glucose) and a short minimal-model intravenous glucose tolerance test (IVGTT; 0.3 g/kg body weight) were performed in 58 Chilean normoglycemic women (age: 27 ± 6.3 years, BMI 23.6 ± 3.2 kg/m 2 ). LAR was negatively associated with HOMA-S (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mi>r</mml:mi><mml:mo>=</mml:mo><mml:mo>−</mml:mo><mml:mn>0.49</mml:mn></mml:math>; <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mi>p</mml:mi><mml:mo>&lt;</mml:mo><mml:mn>0.0001</mml:mn></mml:math>), Matsuda-ISICOMP (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:mi>r</mml:mi><mml:mo>=</mml:mo><mml:mo>−</mml:mo><mml:mn>0.54</mml:mn></mml:math>; <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M4"><mml:mi>p</mml:mi><mml:mo>&lt;</mml:mo><mml:mn>0.0001</mml:mn></mml:math>), and the calculated sensitivity index (CSi) derived from IVGTT (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M5"><mml:mi>r</mml:mi><mml:mo>=</mml:mo><mml:mo>−</mml:mo><mml:mn>0.38</mml:mn></mml:math>; <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M6"><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn>0.007</mml:mn></mml:math>). In comparison to LAR, leptin/HMWA ratio did not increase neither the linear fit (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M7"><mml:msup><mml:mrow><mml:mi>r</mml:mi></mml:mrow><mml:mrow><mml:mn>2</mml:mn></mml:mrow></mml:msup></mml:math>) nor the magnitude of association with insulin sensitivity indexes (slope of multiple linear regression). The discriminatory capacity of both ratios to classify insulin-resistant versus insulin-sensitive subjects was similar for HOMA-S (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M8"><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn>0.84</mml:mn></mml:math>), Matsuda-ISICOMP (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M9"><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn>0.43</mml:mn></mml:math>), or CSi (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M10"><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn>0.50</mml:mn></mml:math>). In conclusion, LAR showed consistent negative associations with different systemic insulin sensitivity indexes. The use of HMWA to generate leptin/HMWA ratio did not show any advantage over LAR as a biomarker of systemic insulin sensitivity in normoglycemic women.