Journal article
Metformin Improves Peripheral Insulin Sensitivity in Youth With Type 1 Diabetes
The journal of clinical endocrinology and metabolism, Vol.104(8), pp.3265-3278
08/01/2019
DOI: 10.1210/jc.2019-00129
PMCID: PMC6584133
PMID: 30938764
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.
Details
- Title: Subtitle
- Metformin Improves Peripheral Insulin Sensitivity in Youth With Type 1 Diabetes
- Creators
- Melanie Cree-Green - University of Colorado Anschutz Medical CampusBryan C. Bergman - University of Colorado Anschutz Medical CampusEda Cengiz - Yale UniversityLarry A. Fox - Nemours FoundationTamara S. Hannon - Indiana UniversityKellee Miller - Jaeb Center for Health ResearchBrandon Nathan - University of MinnesotaLaura Pyle - Colorado School of Public HealthDarcy Kahn - University of Colorado Anschutz Medical CampusMichael Tansey - University of IowaEileen Tichy - Yale UniversityEva Tsalikian - University of IowaIngrid Libman - Children's Hospital of PittsburghKristen J. Nadeau - University of Colorado Anschutz Medical Campus
- Resource Type
- Journal article
- Publication Details
- The journal of clinical endocrinology and metabolism, Vol.104(8), pp.3265-3278
- Publisher
- Endocrine Soc
- DOI
- 10.1210/jc.2019-00129
- PMID
- 30938764
- PMCID
- PMC6584133
- ISSN
- 0021-972X
- eISSN
- 1945-7197
- Number of pages
- 14
- Grant note
- Juvenile Diabetes Research Foundation International; Juvenile Diabetes Research Foundation UL1TR002537 / Iowa CTSA Grant UL1TR001857 / Pittsburgh CTSA Grant UL1TR002535 / National Institutes of Health/National Center for Advancing Translational Sciences Colorado Clinical and Translational Science Awards (CTSA) P30DK048520 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) UL1TR002537 / NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS)
- Language
- English
- Date published
- 08/01/2019
- Academic Unit
- Endocrinology and Diabetes; Stead Family Department of Pediatrics; Fraternal Order of Eagles Diabetes Research Center
- Record Identifier
- 9984353944402771
Metrics
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