Adiponectin, Insulin Sensitivity, β-Cell Function, and Racial/Ethnic Disparity in Treatment Failure Rates in TODAY
OBJECTIVE The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study demonstrated that glycemic failure rates in the three treatments combined—metformin plus rosiglitazone, metformin alone, and metformin plus lifestyle—were higher in non-Hispanic blacks (NHBs; 52.8%) versus non-Hispanic whites (NHWs; 36.6%) and Hispanics (Hs; 45.0%). Moreover, metformin alone was less effective in NHB versus NHW versus H youth. This study describes treatment-associated changes in adiponectin, insulin sensitivity, and β-cell function over time among the three racial/ethnic groups to understand potential mechanism(s) responsible for this racial/ethnic disparity.
RESEARCH DESIGN AND METHODS TODAY participants underwent periodic oral glucose tolerance tests to determine insulin sensitivity, C-peptide index, and oral disposition index (oDI), with measurements of total and high-molecular-weight adiponectin (HMWA).
RESULTS At baseline NHBs had significantly lower HMWA than NHWs and Hs, and exhibited a significantly smaller increase (17.3% vs. 33.7% vs. 29.9%, respectively) during the first 6 months overall. Increases in HMWA were associated with reductions in glycemic failure in the three racial/ethnic groups combined (hazard ratio 0.61, P < 0.0001) and in each race/ethnicity separately. Over time, HMWA was significantly lower in those who failed versus did not fail treatment, irrespective of race/ethnicity. There were no differences in treatment-associated temporal changes in insulin sensitivity, C-peptide index, and oDI among the three racial/ethnic groups.
CONCLUSIONS HMWA is a reliable biomarker of treatment response in youth with type 2 diabetes. The diminutive treatment-associated increase in HMWA in NHBs (∼50% lower) compared with NHWs and Hs may explain the observed racial/ethnic disparity with higher therapeutic failure rates in NHBs in TODAY.
This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc16-0455/-/DC1.
- Received March 1, 2016.
- Accepted October 3, 2016.
- © 2016 by the American Diabetes Association.