Effect of Metformin Combined with Dietary Intervention on Childhood Obesity and Insulin Resistance

Abstract

Background: Obesity is a multifactorial disease with multiple comorbidities such as insulin resistance (IR), cardiovascular disease, diabetes mellitus, and hypertension. Puberty is physiologically responsible for IR. During this stage of life, insulin sensitivity decreases by 25–50% and then improves. A change in lifestyle that promotes healthy nutritional habits and physical activity, as well as complementary treatments such as metformin therapy, is recommended as the first line of treatment. Aim of the Work: To assess the effect of metformin combined with dietary intervention on BMI and IR in obese children and adolescents in the prepubertal and pubertal stages. Methods: This study included 90 children and adolescents divided into two groups: 60 obese children and adolescents with BMIs > the 95th percentile for their sex and age (30 prepubertal and 30 pubertal) and 30 healthy children and adolescents with BMIs between the 5th and 85th percentile for their sex and age (15 prepubertal and 15 pubertal). They underwent a thorough clinical evaluation, which included anthropometric measurements and investigations such as serum adiponectin, leptin, adiponectin-leptin ratio (ALR), plasminogen activator inhibitor-1 (PAI-1), a lipid profile, and HOMA-IR. Obese children and adolescents received metformin with dietary intervention for six months. Results: After the therapeutic intervention, the anthropometric measurements (weights, weight Z-scores, BMIs, BMI Z-scores, waist and hip circumferences, and waist-hip ratios) and the lipid profile (total serum cholesterol, LDL-C, HDL-C, and serum triglycerides) improved significantly in both obese groups (prepubertal and pubertal). Prepubertal obese children significantly improved more than pubertal obese children and adolescents in inflammatory adipokines (leptin, adiponectin, PAF-1, and ALR) and insulin sensitivity markers after the therapy. Conclusion: Puberty is a critical physiologic stage affecting the response to metformin, which should be studied further in pubertal obese children and adolescents, particularly the dose-effect relationship.