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Effect of Metformin on Vascular Function in Children With Type 1 Diabetes: A 12-Month Randomized Controlled Trial
Jemma J A Anderson1,2, Jennifer J Couper1,2, Lynne C Giles3
1Discipline of Paediatrics, Robinson Research Institute, University of Adelaide, Australia.
Insights
Metformin improved vascular function and glycemic control in children with type 1 diabetes. This intervention also reduced insulin dosage, showing potential for cardiovascular disease prevention.
Area of Science:
- Pediatric Endocrinology
- Cardiovascular Research
- Pharmacology
Background:
- Type 1 diabetes in children is associated with vascular dysfunction, a precursor to atherosclerosis.
- Early interventions are crucial to mitigate long-term cardiovascular disease risk in this population.
Purpose of the Study:
- To assess the impact of metformin on vascular function in pediatric patients diagnosed with type 1 diabetes.
- To evaluate metformin's effect on cardiovascular risk factors in children with type 1 diabetes.
Main Methods:
- A 12-month, double-blind, randomized, placebo-controlled trial was conducted.
- Ninety children (8-18 years) with type 1 diabetes and elevated BMI received either metformin or a placebo.
- Vascular function was assessed using brachial artery ultrasound, measuring flow-mediated and glyceryl trinitrate-mediated dilatation (GTN).
Main Results:
- Metformin significantly improved glyceryl trinitrate-mediated dilatation (GTN) by 3.3 percentage units (P=0.03), independent of HbA1c.
- Participants on metformin showed a reduction in insulin dose by 0.2 U/kg/d (P=0.001) and improved HbA1c levels.
- No significant effects were observed on BMI, lipids, blood pressure, or intima-media thickness; gastrointestinal side effects were more common with metformin.
Conclusions:
- Metformin enhances vascular smooth muscle function and glycemic control in children with type 1 diabetes.
- The drug also leads to a reduced insulin requirement, suggesting a potential role in managing cardiovascular risk.
- The observed benefits and acceptable safety profile support further investigation into metformin's use in this pediatric cohort.
Context:
Children with type 1 diabetes have vascular dysfunction preceding atherosclerosis. Early interventions are needed to reduce cardiovascular disease.
Objective:
To evaluate the effect of metformin on vascular function in children with type 1 diabetes.
Design:
Twelve-month double-blind, randomized, placebo-controlled trial.
Setting:
Tertiary pediatric diabetes clinic.
Participants:
Ninety children (8 to 18 years of age), >50th percentile body mass index (BMI), with type 1 diabetes.
Intervention:
Metformin (up to 1 g twice a day) or placebo.
Main Outcome Measure:
Vascular function measured by brachial artery ultrasound [flow-mediated dilatation/glyceryl trinitrate-mediated dilatation (GTN)].
Results:
Ninety participants were enrolled [41 boys, 13.6 (2.5) years of age, 45 per group], 10 discontinued intervention, and 1 was lost to follow-up. On metformin, GTN improved, independent of glycosylated hemoglobin (HbA1c), by 3.3 percentage units [95% confidence interval (CI) 0.3, 6.3, P = 0.03] and insulin dose reduced by 0.2 U/kg/d (95% CI 0.1, 0.3, P = 0.001) during 12 months, with effects from 3 months. Metformin had a beneficial effect on HbA1c at 3 months (P = 0.001) and difference in adjusted HbA1c between groups during 12 months was 1.0%; 95% CI 0.4, 1.5 (10.9 mmol/mol; 95% CI 4.4, 16.4), P = 0.001. There were no effects on carotid/aortic intima media thickness, BMI, lipids, blood pressure, or other cardiovascular risk factors. Median (95% CI) adherence, evaluated by electronic monitoring, was 75.5% (65.7, 81.5), without group differences. More gastrointestinal side effects were reported on metformin (incidence rate ratio 1.65, 95% CI 1.08, 2.52, P = 0.02), with no difference in hypoglycemia or diabetic ketoacidosis.
Conclusions:
Metformin improved vascular smooth muscle function and HbA1c, and lowered insulin dose in type 1 diabetes children. These benefits and good safety profile warrant further consideration of its use.