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

2019
https://researcherprofiles.org/profile/228782365
30938764
Cree-Green M, Bergman BC, Cengiz E, Fox LA, Hannon TS, Miller K, Nathan B, Pyle L, Kahn D, Tansey M, Tichy E, Tsalikian E, Libman I, Nadeau KJ
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.

Journal Issue
Volume 104 of Issue 8