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Title: Initial presentation of type 2 diabetes in adolescents predicts durability of successful treatment with metformin monotherapy: Insights from the pediatric diabetes consortium T2D registry

Author
item BACHA, FIDA - Children'S Nutrition Research Center (CNRC)
item CHENG, PEIYAO - Jaeb Center For Health Research
item GAL, ROBIN - Jaeb Center For Health Research
item KOLLMAN, CRAIG - Jaeb Center For Health Research
item TAMBORLANE, WILLIAM - Yale University
item KLINGENSMITH, GEORGEANNA - University Of Colorado
item MANSEAU, KATHERINE - University Of Colorado
item WOOD, JAMIE - Cleveland State University
item BECK, ROY - Jaeb Center For Health Research

Submitted to: Hormone Research in Paediatrics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/21/2017
Publication Date: 10/31/2017
Citation: Bacha, F., Cheng, P., Gal, R.L., Kollman, C., Tamborlane, W.V., Klingensmith, G.J., Manseau, K., Wood, J., Beck, R.W. 2017. Initial presentation of type 2 diabetes in adolescents predicts durability of successful treatment with metformin monotherapy: Insights from the pediatric diabetes consortium T2D registry. Hormone Research in Paediatrics. https://doi.org/10.1159/000481912.

Interpretive Summary: Youth with type 2 diabetes have rapid deterioration of glucose control on oral medication within 2 years of diagnosis. We investigated the risk factors for the rapid deterioration in diabetes control in 276 adolescents enrolled in a diabetes registry with greater than 2 years since diabetes diagnosis. They were divided in 2 groups. Group 1 consisted continued to have good control on oral medicine (metformin) and Group 2 required insulin. The 2 groups had similar age and body mass index at enrollment in the registry. Our analyses showed that lower glucose index (hbA1c) at diagnosis and shorter diabetes duration were associated with adequate diabetes control on oral medicine alone. We also found poor diabetes control in group 2 despite insulin treatment. We concluded that early diagnosis of diabetes is related to better long term diabetes control on oral medicine alone. There is a need for additional studies to understand the reasons underlying poor diabetes control in those receiving insulin.

Technical Abstract: Many adolescents with type 2 diabetes (T2D) have rapid deterioration of glycemic control on metformin monotherapy within 2 years of diagnosis. Enrollment data from the Pediatric Diabetes Consortium T2D registry were used to categorize 276 youth with a T2D duration >/-2 years into two groups: (1) participants with HbA1C <7.5% on metformin monotherapy (group 1, n = 75) and (2) participants treated with insulin +/- metformin (group 2, n = 201). The characteristics of the groups were compared. At enrollment, groups 1 and 2 did not differ in age (16.2 vs. 16.8 years) or BMI percentile (99 vs. 98%); group 2 had higher HbA1C (9.9% [85 mmol/mol] vs. 5.9% [41 mmol/mol], p < 0.001). Lower HbA1C and metformin monotherapy at diagnosis were associated with a greater likelihood of adequate control with metformin alone (p < 0.001). In multivariable analysis, HbA1c at diagnosis (p = 0.001) and diabetes duration (p = 0.009) were associated with adequate control on metformin. The HbA1C trajectory after diagnosis was worse in group 2. Durable metabolic control of T2D with metformin monotherapy is most likely in youth presenting with lower HbA1C and with shorter diabetes duration, independent of age, race-ethnicity, and BMI. Elevated HbA1C levels in those on insulin therapy highlight the importance of early diagnosis and a better understanding of glycemic control barriers.