All ETDs from UAB

Advisory Committee Chair

Barbara A Gower

Advisory Committee Members

Olivia Affuso

Paula Chandler-Laney

Amy M Goss

Courtney M Peterson

Document Type

Dissertation

Date of Award

2021

Degree Name by School

Doctor of Philosophy (PhD) School of Health Professions

Abstract

Insulin resistance (IR) is associated with poor metabolic and reproductive outcomes among premenopausal women. Early identification of women with IR might mitigate these outcomes. However, clinically suitable methods to identify women with IR are unavailable due to high cost, high patient burden, or limited reliability. The objective was to examine a bioimpedance-based approach to identifying women with IR using membrane capacitance (CM). CM is a measure of cell membrane health and function, which is independently associated with IR and may be a suitable predictor. We validated the association of CM with IR and established the clinical utility of CM as a biomarker of IR. First, we evaluated the association between CM and the insulin sensitivity index from the euglycemic-hyperinsulinemic clamp (SICLAMP) and determined the accuracy, sensitivity, and specificity of CM as a predictor of IR. Second, we examined extracellular/serum potassium ([K+]S) as a determinant/mechanism for the association between CM and IR. Third, we evaluated clinical determinants, reliability, and between-device consistency of CM measurements. Lastly, we sought to determine whether CM could identify women with IR and IR-related conditions. First, CM was linearly associated with SICLAMP and had high accuracy, sensitivity, and specificity as a predictor of IR, comparable to common surrogate indices (HOMA-IR, QUICKI, 1/insulin0) and higher than body mass index and waist circumference. Second, [K+]S partially mediated the association between IR and CM. Third, CM exhibited high precision and reliability and was influenced by body composition, metabolic activity, and temperature. Lastly, CM did not differ between women with PCOS or infertility vs. healthy controls. Yet, women with IR-phenotypes had significantly higher CM, regardless of group. Collectively, these results suggest that CM is a clinically useful, non-invasive biomarker of IR that acts in part by detecting [K+]S in nondiabetic premenopausal women. CM measurements are sufficiently precise and reliable for clinical use in conditions with body composition or metabolic activity changes. Commonly used bioimpedance analyzers can estimate CM with standardization. CM may be useful for identifying women with the insulin-resistant phenotypes of PCOS and infertility but could not differentiate these conditions independent of IR.

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