Background:As adolescents with obesity and insulin resistance may be refractory to lifestyle intervention therapy alone, additional off-label metformin therapy is often used. In this study, the long-term efficacy and safety of metformin versus placebo in adolescents with obesity and insulin resistance is studied.Methods:In a randomized placebo-controlled double-blinded trial, 62 adolescents with obesity aged 10–16 years old with insulin resistance received 2000 mg of metformin or placebo daily and physical training twice weekly over 18 months. Primary end points were change in body mass index (BMI) and insulin resistance measured by the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR). Secondary end points were safety and tolerability of metformin. Other end points were body fat percentage and HbA1c.Results:Forty-two participants completed the 18-month study (66% girls, median age 13 (12–15) years, BMI 30.0 (28.3 to 35.0) kg m−2 and HOMA-IR 4.08 (2.40 to 5.88)). Median ΔBMI was +0.2 (−2.9 to 1.3) kg m−2 (metformin) versus +1.2 (−0.3 to 2.4) kg m−2 (placebo) (P=0.015). No significant difference was observed for HOMA-IR. No serious adverse events were reported. Median change in fat percentage was −3.1 (−4.8 to 0.3) versus −0.8 (−3.2 to 1.6)% (P=0.150), in fat mass −0.2 (−5.2 to 2.1) versus +2.0 (1.2–6.4) kg (P=0.007), in fat-free mass +2.0 (−0.1 to 4.0) versus +4.5 (1.3 to 11.6) kg (P=0.047) and in ΔHbA1c +1.0 (−1.0 to 2.3) versus +3.0 (0.0 to 5.0) mmol mol−1 (P=0.020) (metformin versus placebo).Conclusions:Long-term treatment with metformin in adolescents with obesity and insulin resistance results in stabilization of BMI and improved body composition compared with placebo. Therefore, metformin may be useful as an additional therapy in combination with lifestyle intervention in adolescents with obesity and insulin resistance.
Introduction Obesity is a risk factor to develop metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM). Insulin resistance (IR) plays a major part in both. With increasing incidence of childhood obesity, this retrospective study aimed to identify predictors of IR in children/adolescents with obesity to optimize screening for IR. Method Patients aged ≥ 2–≤ 18 years with obesity (BMI-SDS > 2.3) were included. IR was defined as HOMA-IR ≥ 3.4, and MetS if ≥3 of the following criteria were present: waist circumference and blood pressure ≥ 95th age percentile, triglycerides ≥ 1.7 mmol/l, HDL < 1.03 mmol/l, and fasting plasma glucose ≥ 5.6 mmol/l. Results In total, 777 patients were included. Of the 306 children, 51, 38, and 0 were diagnosed with IR, MetS, and T2DM, respectively. Of the 471 adolescents, 223, 95, and 0 were diagnosed with IR, MetS, and T2DM, respectively. In the multivariable regression model, BMI-SDS, preterm birth, and Tanner stage were associated with IR in children (6.3 (95% CI 1.3–31.1), 5.4 (95% CI 1.4–20.5), 2.2 (95% CI 1.0–4.8)), and BMI-SDS and waist circumference in adolescents (4.0 (95% CI 1.7–9.2), 3.7 (95% CI 1.5–9.4)). Conclusion Different IR predictors were observed in children/adolescents with obesity. These predictors can be used to optimize screening for IR in pediatric populations.
Background: Gut immaturity is linked with postnatal intestinal disorders. However, biomarkers to assess the intestinal developmental stage around birth are lacking. The aim of this study was to gain more insight on intestinal fatty acid-binding protein (I-FABP) as an indicator of gut maturity. Methods: Antenatal I-FABP distribution and release was investigated in extremely premature, moderately premature, and term lambs, and these findings were verified in human urinary samples. Ileal I-FABP distribution was confirmed in autopsy material within 24 h postnatally. results: Median (range) serum I-FABP levels were lower in extremely premature lambs compared with moderately premature lambs (156 (50.0-427) vs. 385 (100-1,387) pg/ml; P = 0.02). Contrarily, median early postnatal urine I-FABP levels in human infants were higher in extremely premature compared with moderately premature and term neonates (1,219 (203-15,044) vs. 256 (50-1,453) and 328 (96-1,749) pg/ml; P = 0.008 and P = 0.04, respectively). I-FABP expression was most prominent in nonvacuolated enterocytes and increased with rising gestational age (GA) in ovine and human tissue samples. The epithelial distribution pattern changed from a phenotype displaying I-FABP-positive enterocytes merely in the crypts early in gestation into a phenotype with I-FABP expressing cells exclusively present in the villus tips at term in ovine and human tissue. conclusion: In this ovine and human study, increasing GA is accompanied by an increase in I-FABP tissue content. Cord I-FABP levels correlate with gestation in ovine fetuses, identifying I-FABP as a marker for gut maturation. Raised postnatal urine I-FABP levels in preterm human infants may indicate intestinal injury and/or inflammation in utero.
BackgroundThe prevalence of childhood obesity and insulin resistance is rising, increasing the risk of diabetes mellitus type 2. To prevent these complications, lifestyle intervention is the corner stone in treatment. However, long-term efficacy of lifestyle intervention is questionable. In addition to lifestyle intervention, pharmacological treatments have been explored. Metformin has been shown to be moderately effective to reduce BMI in obese adolescents with hyperinsulinemia. However, data on pharmacokinetics and long-term efficacy and safety are lacking as well as an evidence-based dosing regimen for this age group. The primary objective of the METFORMIN study is to determine the effect of adding metformin treatment to lifestyle intervention in reducing BMI in obese adolescents with insulin resistance. In addition, the pharmacokinetics of metformin in obese adolescents will be studied.Methods/designThe METFORMIN study is a multi-centre prospective study that consists of two 18-month phases: a double-blind randomized placebo-controlled trial (part 1) and an open-label follow-up study (part 2). During part 1, the participants will be given metformin 1,000 mg or placebo twice daily and will be offered a lifestyle intervention programme; 144 participants will be included, 72 in each arm. Primary endpoints are reduction in body mass index, insulin resistance, and percentage body fat.DiscussionThis study will provide data on short- and long-term efficacy and safety of metformin and on the pharmacokinetics of metformin in obese adolescents.Trial registrationClinicalTrials.gov number NCT01487993; EudraCT nr. 2010-023980-17. Registration date: 06-01-2011
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.