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Metformin Improves Peripheral Insulin Sensitivity in Youth With Type 1 Diabetes.
- Source :
-
The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2019 Aug 01; Vol. 104 (8), pp. 3265-3278. - Publication Year :
- 2019
-
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.<br />Objective: Measure peripheral, hepatic, and adipose insulin sensitivity before and after metformin or placebo therapy in youth with obesity with type 1 diabetes.<br />Design: Double-blind, placebo-controlled clinical trial.<br />Setting: Multi-center at eight sites of the T1D Exchange Clinic Network.<br />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.<br />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.<br />Main Outcome Measures: Peripheral insulin sensitivity, endogenous glucose release, rate of lipolysis.<br />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.<br />Conclusions: Metformin appears to improve whole-body and peripheral IR in youth who are overweight/obese with type 1 diabetes.<br /> (Copyright © 2019 Endocrine Society.)
- Subjects :
- Adipose Tissue metabolism
Adolescent
Adult
Blood Glucose analysis
Child
Diabetes Mellitus, Type 1 metabolism
Double-Blind Method
Female
Humans
Liver metabolism
Male
Metformin adverse effects
Young Adult
Diabetes Mellitus, Type 1 drug therapy
Hypoglycemic Agents therapeutic use
Insulin Resistance
Metformin therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1945-7197
- Volume :
- 104
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- The Journal of clinical endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 30938764
- Full Text :
- https://doi.org/10.1210/jc.2019-00129