Adiponectin, Insulin Sensitivity, β-Cell Function, and Racial/Ethnic Disparity in Treatment Failure Rates in TODAY.
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 (NHB; 52.8%) versus non-Hispanic whites (NHW; 36.6%) and Hispanics (H; 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.



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).



At baseline NHB had significantly lower HMWA than NHW and H 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.



HMWA is a reliable biomarker of treatment response in youth with type 2 diabetes. The diminutive treatment-associated increase in HMWA in NHB (∼50% lower) compared with NHW and H may explain the observed racial/ethnic disparity with higher therapeutic failure rates in NHB in TODAY.
Children's Hospital of Pittsburgh, Pittsburgh, PA.
Silva
S
Arslanian
Biostatistics Center, George Washington University, Rockville, MD elghorml@bsc.gwu.edu.
Laure
L
El Ghormli
Texas Children's Hospital, Baylor College of Medicine, Houston, TX.
Fida
F
Bacha
Yale University School of Medicine, New Haven, CT.
Sonia
S
Caprio
Columbia University, New York, NY.
Robin
R
Goland
Texas Children's Hospital, Baylor College of Medicine, Houston, TX.
Morey W
MW
Haymond
Massachusetts General Hospital for Children, Boston, MA.
Lynne
L
Levitsky
University of Colorado Anschutz Medical Campus, Aurora, CO.
Kristen J
KJ
Nadeau
Washington University in St. Louis, St. Louis, MO.
Neil H
NH
White
Children's Hospital of Philadelphia, Philadelphia, PA.
Steven M
SM
Willi
D052242:Adiponectin / Q000097:blood; D000293:Adolescent; D044383:Black People / Q000706:statistics & numerical data; D001786:Blood Glucose / Q000187:drug effects; D002096:C-Peptide / Q000032:analysis; D002648:Child; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000208:ethnology* / Q000503:physiopathology; D004338:Drug Combinations; D005006:Ethnicity / Q000706:statistics & numerical data*; D005260:Female; D005951:Glucose Tolerance Test; D054624:Health Status Disparities; D006630:Hispanic or Latino / Q000706:statistics & numerical data; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007333:Insulin Resistance / Q000502:physiology; D008019:Life Style; D008297:Male; D008687:Metformin / Q000008:administration & dosage; D013844:Thiazoles / Q000008:administration & dosage; D017211:Treatment Failure; D044465:White People / Q000706:statistics & numerical data
C499918:ADIPOQ protein, human; D052242:Adiponectin; D001786:Blood Glucose; D002096:C-Peptide; D004338:Drug Combinations; D007004:Hypoglycemic Agents; D013844:Thiazoles; C471074:rosiglitazone-metformin combination; D008687:Metformin