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J Clin Endocrinol Metab. 2019 Aug 1;104(8):3265-3278. doi: 10.1210/jc.2019-00129.

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

Author information

1
Division of Pediatric Endocrinology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
2
Center for Women's Health Research, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
3
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
4
Yale School of Medicine University, New Haven, Connecticut.
5
Nemours Children's Specialty Care, Jacksonville, Florida.
6
Division of Pediatric Endocrinology and Diabetology, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana.
7
Jaeb Center for Health Research, Tampa, Florida.
8
University of Minnesota, Minneapolis, Minnesota.
9
Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
10
Department of Biostatistics and Informatics, Colorado School of Public Health, University of Anschutz Medical Campus, Aurora, Colorado.
11
Stead Family Department of Pediatrics, Endocrinology and Diabetes, University of Iowa, Iowa City, Iowa.
12
Children's Hospital of Pittsburgh at University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
13
Barbara Davis Center for Childhood Diabetes, University of Colorado Anschutz Medical Campus, Aurora, Colorado.

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.

PMID:
30938764
PMCID:
PMC6584133
[Available on 2020-04-02]
DOI:
10.1210/jc.2019-00129

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