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Metformin Improves Peripheral Insulin Sensitivity in Youth With Type 1 Diabetes.

Citation
Cree-Green, M., et al. “Metformin Improves Peripheral Insulin Sensitivity In Youth With Type 1 Diabetes.”. The Journal Of Clinical Endocrinology And Metabolism, pp. 3265-3278.
Center Yale University
Author Melanie Cree-Green, Bryan C Bergman, Eda Cengiz, Larry A Fox, Tamara S Hannon, Kellee Miller, Brandon Nathan, Laura Pyle, Darcy Kahn, Michael Tansey, Eileen Tichy, Eva Tsalikian, Ingrid Libman, Kristen J Nadeau
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.

Year of Publication
2019
Journal
The Journal of clinical endocrinology and metabolism
Volume
104
Issue
8
Number of Pages
3265-3278
Date Published
12/2019
ISSN Number
1945-7197
DOI
10.1210/jc.2019-00129
Alternate Journal
J. Clin. Endocrinol. Metab.
PMID
30938764
PMCID
PMC6584133
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