Biomarker May Predict Treatment Response in Type 2 Diabetes

High-molecular-weight adiponectin (HMWA) appears to be a reliable predictor of glycemic response to treatment in children and adolescents with type 2 diabetes, according to data published in Diabetes Care.

In the TODAY study (Treatment Options for Type 2 Diabetes in Adolescents and Youth; ClinicalTrials.gov identifier: NCT00081328), researchers found higher rates of glycemic failure in black patients vs white and Hispanic patients for all 3 treatments (metformin plus rosiglitazone, metformin alone, and metformin plus lifestyle). This study sheds light on why these differences exist.

“[Non-Hispanic black] youth, normal or with diabetes, have lower peripheral insulin sensitivity, an upregulated beta-cell function, and lower insulin clearance compared with their [non-Hispanic white] counterparts “Moreover, adiponectin, an insulin-sensitizing adipokine predictive of glycemic efficacy in adult type 2 diabetes, is lower in [non-Hispanic black] vs [non-Hispanic white] youth, and adults,” the researchers wrote.

“We therefore hypothesized that the higher glycemic failure rates in [non-Hispanic black patients] could stem from these differences in the pathophysiological components of type 2 diabetes and/or differences in adiponectin levels.”

The TODAY study included 699 obese children and adolescents aged 10 to 17 years with type 2 diabetes. Primary outcomes were loss of glycemic control defined as an HbA1c of greater than 8% over 6 months or persistent metabolic decompensation. During the study, insulin sensitivity, C-peptide index, and oral disposition index were assessed via periodic oral glucose tolerance tests. Total and HMWA were also measured.

Results showed that HMWA was significantly lower in black patients than in white and Hispanic patients at baseline, while the increase in HMWA was also smaller during the first 6 months (17.3% vs 33.7% and 29.9%, respectively). Increases in HMWA were linked to decreases in glycemic failure in all 3 racial/ethnic groups combined (hazard ratio [HR]: 0.61; P <.0001) as well as in each group separately.

Regardless of race/ethnicity, patients who failed treatment vs those who did not had significantly lower HMWA over time. Treatment-associated changes in insulin sensitivity, C-peptide index, and oral disposition index also did not differ among the 3 groups.

“In summary, these observations support the validity and the value of HMWA as a biomarker predictive of glycemic response to treatment in youth with type 2 diabetes. The significantly lower increase in HMWA in the first 6 months in [non-Hispanic black patients] may explain the higher therapeutic failure rates in [non-Hispanic black patients] compared with the other 2 racial/ethnic groups,” the researchers concluded. “Therapeutic modalities that more effectively increase adiponectin levels may yet prove beneficial in [non-Hispanic black patients] as well as all youth with type 2 diabetes.”

Disclosures: The authors report no conflicts of interest.

Reference

1. Arslanian S, El ghormli L, Bacha F, et al; for the TODAY Study Group. Adiponectin, insulin sensitivity, beta-cell function, and racial/ethnic disparity in treatment failure rates in TODAY. Diabetes Care. 2016 Nov 1. doi:10.2337/dc16-0455 [Epub ahead of print].