Metformin Improves Peripheral Insulin Sensitivity in Youth With Type 1 Diabetes
dc.contributor.author | Cree-Green, Melanie | |
dc.contributor.author | Bergman, Bryan C. | |
dc.contributor.author | Cengiz, Eda | |
dc.contributor.author | Fox, Larry A. | |
dc.contributor.author | Hannon, Tamara S. | |
dc.contributor.author | Miller, Kellee | |
dc.contributor.author | Nathan, Brandon | |
dc.contributor.author | Pyle, Laura | |
dc.contributor.author | Kahn, Darcy | |
dc.contributor.author | Tansey, Michael | |
dc.contributor.author | Tichy, Eileen | |
dc.contributor.author | Tsalikian, Eva | |
dc.contributor.author | Libman, Ingrid | |
dc.contributor.author | Nadeau, Kristen J. | |
dc.contributor.department | Pediatrics, School of Medicine | en_US |
dc.date.accessioned | 2020-06-23T20:00:34Z | |
dc.date.available | 2020-06-23T20:00:34Z | |
dc.date.issued | 2019-08 | |
dc.description.abstract | Context: Type 1 diabetes in adolescence is characterized by insulin deficiency and insulin resistance (IR), both thought to increase cardiovascular disease risk. We previously demonstrated that adolescents with type 1 diabetes have adipose, hepatic, and muscle IR, and that metformin lowers daily insulin dose, suggesting improved IR. However, whether metformin improves IR in muscle, hepatic, or adipose tissues in type 1 diabetes was unknown. Objective: Measure peripheral, hepatic, and adipose insulin sensitivity before and after metformin or placebo therapy in youth with obesity with type 1 diabetes. Design: Double-blind, placebo-controlled clinical trial. Setting: Multi-center at eight sites of the T1D Exchange Clinic Network. Participants: A subset of 12- to 19-year-olds with type 1 diabetes (inclusion criteria: body mass index ≥85th percentile, HbA1c 7.5% to 9.9%, insulin dosing ≥0.8 U/kg/d) from a larger trial (NCT02045290) were enrolled. Intervention: Participants were randomized to 3 months of metformin (N = 19) or placebo (N = 18) and underwent a three-phase hyperinsulinemic euglycemic clamp with glucose and glycerol isotope tracers to assess tissue-specific IR before and after treatment. Main outcome measures: Peripheral insulin sensitivity, endogenous glucose release, rate of lipolysis. Results: Between-group differences in change in insulin sensitivity favored metformin regarding whole-body IR [change in glucose infusion rate 1.3 (0.1, 2.4) mg/kg/min, P = 0.03] and peripheral IR [change in metabolic clearance rate 0.923 (-0.002, 1.867) dL/kg/min, P = 0.05]. Metformin did not impact insulin suppression of endogenous glucose release (P = 0.12). Adipose IR was not assessable with traditional methods in this highly IR population. Conclusions: Metformin appears to improve whole-body and peripheral IR in youth who are overweight/obese with type 1 diabetes. | en_US |
dc.eprint.version | Final published version | en_US |
dc.identifier.citation | Cree-Green, M., Bergman, B. C., Cengiz, E., Fox, L. A., Hannon, T. S., Miller, K., Nathan, B., Pyle, L., Kahn, D., Tansey, M., Tichy, E., Tsalikian, E., Libman, I., & Nadeau, K. J. (2019). Metformin Improves Peripheral Insulin Sensitivity in Youth With Type 1 Diabetes. The Journal of clinical endocrinology and metabolism, 104(8), 3265–3278. https://doi.org/10.1210/jc.2019-00129 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/23059 | |
dc.language.iso | en_US | en_US |
dc.publisher | Endocrine Society | en_US |
dc.relation.isversionof | 10.1210/jc.2019-00129 | en_US |
dc.relation.journal | Journal of Clinical Endocrinology and Metabolism | en_US |
dc.rights | Publisher Policy | en_US |
dc.source | PMC | en_US |
dc.subject | Type 1 diabetes | en_US |
dc.subject | Adolescence | en_US |
dc.subject | Insulin deficiency | en_US |
dc.subject | Insulin resistance | en_US |
dc.subject | Metformin efficacy | en_US |
dc.title | Metformin Improves Peripheral Insulin Sensitivity in Youth With Type 1 Diabetes | en_US |
dc.type | Article | en_US |
ul.alternative.fulltext | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584133/ | en_US |
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