Interactions among Thyroid Function, Insulin Sensitivity, and Serum Lipid Concentrations: The Fremantle Diabetes Study

Context: Recent observations in healthy subjects showed that insulin resistance modifies the relationship between serum cholesterol and thyroid function.Objective: The aim of the study was to determine whether insulin sensitivity modifies the association between thyroid dysfunction and lipid parameters in diabetic patients.Design: This is a cross-sectional study.Setting: This is a community-based observational study.Patients: One hundred seventeen females with type 2 diabetes who were not taking oral hypoglycemic therapy, insulin, or lipid-lowering therapy participated in the study.Intervention: Serum TSH, insulin, total and high-density lipoprotein cholesterol, and triglycerides were measured.Main Outcome Measures: Age-adjusted multiple linear regression analysis of serum lipid concentrations and derived parameters, as functions of serum TSH and homeostasis model assessment-derived insulin sensitivity (HOMA-S), were measured.Results: The relationship among serum lipid concentrations, serum TSH, and HOMA-S was significantly modified by an interaction term ln(TSH)*ln(HOMA-S). In three-dimensional graphs, there were strong positive associations between TSH and lipid parameters with adverse cardiac risks at low insulin sensitivity that were absent at higher insulin sensitivity. The effect was strongest for lipid risk factors associated with insulin resistance.Conclusions: The interaction between thyroid function and insulin sensitivity is an important contributor to diabetic dyslipidemia and may justify T-4 replacement in some patients.