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

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.

• Authors: 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
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 104 Issue 8 Pg. 3265-3278 (08 01 2019) ISSN: 1945-7197 [Electronic] United States
• PMID: 30938764 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Endocrine Society.

Chemical References

• Blood Glucose
• Hypoglycemic Agents
• Metformin

Topics

• Adipose Tissue (metabolism)
• Adolescent
• Adult
• Blood Glucose (analysis)
• Child
• Diabetes Mellitus, Type 1 (drug therapy, metabolism)
• Double-Blind Method
• Female
• Humans
• Hypoglycemic Agents (therapeutic use)
• Insulin Resistance
• Liver (metabolism)
• Male
• Metformin (adverse effects, therapeutic use)
• Young Adult