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Title: Predictors of response to insulin therapy in youth with poorly controlled type 2 diabetes in the TODAY trial

item BACHA, FIDA - Children'S Nutrition Research Center (CNRC)
item EL GHORMLI, LAURE - George Washington University
item ARSLANIAN, SILVA - University Of Pittsburgh Medical Center
item ZEITLER, PHILIP - University Of Colorado
item LAFFEL, LORI - Joslin Diabetes Center
item LEVITT KATZ, LORRAINE - Children'S Hospital - Philadelphia, Pennsylvania
item GANDICA, RACHELLE - Columbia University - New York
item CHANG, NANCY - Children'S Hospital Los Angeles
item SPRAGUE, JENNIFER - Washington University
item MACLEISH, SARAH - Case Western Reserve University (CWRU)

Submitted to: Pediatric Diabetes
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/30/2019
Publication Date: 8/16/2019
Citation: Bacha, F., El Ghormli, L., Arslanian, S., Zeitler, P., Laffel, L.M., Levitt Katz, L.E., Gandica, R., Chang, N.T., Sprague, J.E., Macleish, S.A., The TODAY Study Group. 2019. Predictors of response to insulin therapy in youth with poorly controlled type 2 diabetes in the TODAY trial. Pediatric Diabetes. 20(7):871-879.

Interpretive Summary: Up to 50% of youth with type 2-diabetes do not respond adequately to oral medications and need insulin to improve their sugar control. We wanted to understand the factors that will lead to better response to insulin once started. We investigated this in the TODAY multicenter study. We found that the response to insulin was very variable. Only about a third had a clinically meaningful decline in their glucose in response to insulin. In general, the response to insulin was not related to age, sex, body mass index or race ethnicity. We found that youth who have better sensitivity to insulin and higher levels of the hormone called adiponectin, had a greater response to insulin and more improvement in their diabetes control. Future studies should examine adherence to medication intake and psychosocial factors that may also have an effect on response to treatment.

Technical Abstract: To understand the factors associated with glycemic control after starting insulin in youth with type 2 diabetes following glycemic failure (persistent HbA1c >=8%) with metformin alone, metformin + rosiglitazone or metformin + lifestyle in the TODAY study. Change in HbA1c after add-on insulin therapy and the factors predictive of glycemic response were evaluated. At 1-year postinsulin initiation, 253 youth had a mean of 3.9 +/- 1.0 visits since the time of insulin initiation. Participants were divided into three groups according to glycemic control: consistent decrease in HbA1c by >=0.5%, change <0.5%, or consistent increase in HbA1c >=0.5%, at 75% or more of the visits. Within 1-year postinsulin initiation, 33.2% of participants had a consistent HbA1c decrease of >=0.5%, 46.2% changed HbA1c <0.5%, and 20.6% had an increase >=0.5%. At randomization into TODAY and at time of insulin initiation, the three glycemia groups were similar in age, sex, race-ethnicity, pubertal stage, BMI z-score, diabetes duration, and insulin secretion indices. Consistent HbA1c improvement was associated with higher insulin sensitivity (1/fasting insulin) at randomization and at time of failure, higher adiponectin at randomization, and was not associated with indices of B-cell function. Response to add-on insulin was highly variable among youth in TODAY. Greater insulin sensitivity and higher adiponectin concentrations at randomization were associated with improved glycemic control after initiation of insulin. Due to limited information on adherence to insulin injections, the roles of adherence to the prescribed insulin regimen or psychosocial factors are unknown.