title: HOMA and Matsuda indices of insulin sensitivity: poor correlation with minimal model-based estimates of insulin sensitivity in longitudinal settings.
abstract: OBJECTIVE
  Little is known about the performance of surrogates in assessing changes in insulin sensitivity over time. This report compared updated HOMA of insulin sensitivity (HOMA2-%S) and the Matsuda index from OGTTs with minimal model-based estimates of insulin sensitivity (SI) from frequently sampled IVGTTs (FSIGTs) in longitudinal settings and cross-sectional settings.
  
  
  METHODS
  Two longitudinal studies were used: one a natural observational study in which 338 individuals were followed for a median of 4 years; one a clinical treatment study in which 97 individuals received pioglitazone treatment and were followed for 1 year. Pairs of OGTTs and FSIGTs were performed at baseline and follow-up. Correlations were computed. Impact of measurement uncertainty was investigated through simulation studies.
  
  
  RESULTS
  Correlations between HOMA2-%S and SI from baseline or follow-up data were in the range reported previously (0.61-0.69). By contrast, correlations for changes over time were only 0.35-0.39. The corresponding correlations between the Matsuda index and SI were 0.66-0.72 for cross-sectional data and 0.40-0.48 for longitudinal change. Correlations for changes were significantly lower than the cross-sectional correlations in both studies (p < 0.03). Simulation results demonstrated that the reduced correlations for change were not explained by error propagation, supporting a real limitation of surrogates to fully capture longitudinal changes in insulin sensitivity.
  
  
  CONCLUSIONS
  HOMA and Matsuda indices derived from cross-sectional data should be used cautiously in assessing longitudinal changes in insulin sensitivity.
authors.affiliation: Department of Research and Evaluation, Kaiser Permanente Southern California, 100 S. Los Robles, 5th Floor, Pasadena, CA, 91101, USA, anny.h.xiang@kp.org.
authors.forename: A H
authors.initials: AH
authors.lastname: Xiang
authors.forename: R M
authors.initials: RM
authors.lastname: Watanabe
authors.forename: T A
authors.initials: TA
authors.lastname: Buchanan
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D005215:Fasting; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism* / Q000627:therapeutic use; D007333:Insulin Resistance; D008137:Longitudinal Studies; D008297:Male; D000077205:Pioglitazone; D015203:Reproducibility of Results; D045162:Thiazolidinediones / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D000077205:Pioglitazone