Adiponectin, Insulin Sensitivity, β-Cell Function, and Racial/Ethnic Disparity in Treatment Failure Rates in TODAY

Diabetes Care. 2017 Jan;40(1):85-93. doi: 10.2337/dc16-0455. Epub 2016 Nov 1.

Abstract

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 (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.

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 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.

Conclusions: 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.

MeSH terms

  • Adiponectin / blood
  • Adolescent
  • African Continental Ancestry Group / statistics & numerical data
  • Blood Glucose / drug effects
  • C-Peptide / analysis
  • Child
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / ethnology*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Drug Combinations
  • Ethnic Groups / statistics & numerical data*
  • European Continental Ancestry Group / statistics & numerical data
  • Female
  • Glucose Tolerance Test
  • Health Status Disparities*
  • Hispanic Americans / statistics & numerical data
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Insulin Resistance / physiology
  • Life Style
  • Male
  • Metformin / administration & dosage
  • Thiazoles / administration & dosage
  • Treatment Failure

Substances

  • ADIPOQ protein, human
  • Adiponectin
  • Blood Glucose
  • C-Peptide
  • Drug Combinations
  • Hypoglycemic Agents
  • Thiazoles
  • rosiglitazone-metformin combination
  • Metformin