Dietary Fiber and Metformin Combined Therapy in Pediatric Obesity and Insulin  Resistance
Creators: Basuray, Nandini
Publisher: name: University of Alberta Library
Year: 2024

<p>Pediatric obesity is associated with insulin resistance (IR) and low-grade inflammation, which increases the risk of developing early-onset type 2 diabetes mellitus (T2DM). Early-onset T2DM presents with a more aggressive disease trajectory than adult-onset; necessitating therapeutic approaches to manage obesity and IR. Conventional therapies include lifestyle modifications (i.e., changes in diet and physical activity) or pharmacotherapies; however, such therapies alone have limited effectiveness. Therefore, the MetFiber study combines dietary fiber supplements and metformin, both of which have been associated with reductions in IR and inflammation.</p>

<p>The first objective of this research was to summarize gastrointestinal, immune, and metabolic health benefits associated with dietary fiber consumption in children and adolescents with obesity. The resulting narrative review supports the use of specific dietary fiber supplements in the MetFiber study. Findings show that children and adolescents fail to meet daily fiber recommendations, which may be related to fiber intolerance. The fiber gap impedes the ability to achieve physiological benefits associated with dietary fibers (improved insulin sensitivity, glycemic response, and satiety). Employing strategies such as consuming fiber-rich whole foods and mixtures of fiber, and increasing slow fermenting fibers may improve fiber tolerance and thus help improve metabolic and gut microbial health in pediatric populations. </p>

<p>The second objective was to describe baseline profiles of enrolled MetFiber study participants. The third objective was to present preliminary findings from the ongoing MetFiber study, which is a 12-month parallel, three-arm, double-blind, randomized controlled trial to assess the effectiveness of all treatments together (dietary fiber (35 g/day) and metformin (1700 mg daily) alone and in combination) on reducing IR in adolescents with obesity. Parameters assessed in the study include; homeostatic model assessment for insulin resistance (HOMA-IR), inflammation (high-sensitivity C-reactive protein [hs-CRP]), body mass index (BMI) z-score, fat-mass, perceived satiety, and gastrointestinal tolerance. </p>

<p>Adolescents (12-18 years) with obesity (BMI &gt;95th percentile for age/sex), HOMA-IR &gt;3.16, and a family history of T2DM were enrolled and randomized. Fasting blood samples, 120-minute oral glucose tolerance test, body composition assessment using air displacement plethysmography, and questionnaires (sexual maturation, physical activity) were completed at baseline and every 6 months. Anthropometric measurements, questionnaires (gastrointestinal tolerance, quality of life [QoL], perceived satiety), and 3-day food records were completed at baseline and every 3 months. Friedman rank sum test and Wilcoxon signed rank tests were performed to assess changes in the identified parameters between baseline, 3-, 6-, and 12-months; statistical significance was considered as p&lt;0.05. </p>

<p>Nineteen adolescents (52.1% males, age: 15 years [IQR:13,16], 94.7% in mid-late puberty, BMI z-score: 3.2 [IQR: 2.7,4.1]) were enrolled. Participants demonstrated variable levels of IR (HOMA-IR: 7.00 [IQR: 4.79, 8.55], Matsuda index: 1.18 [IQR: 0.92, 1.74], and QUICKI index: 0.29 [IQR: 0.28, 0.30]), and hs-CRP: 3.4 mg/L (IQR: 1.0, 4.5 mg/L) at baseline. Participants had a median BMI ≥99.0th percentile, waist circumference &gt;90th percentile, percent fat mass (%FM) of 45.9% (IQR: 42.3%, 49.2%), fat-free mass (FFM) of 56.5 kg (IQR: 50.9, 65.3kg), and a load-capacity index (LCI) of 0.85 (IQR: 0.73, 0.97) at baseline. Variable levels of perceived satiety, low levels of physical activity, and little impairment in QoL were reported at baseline. A majority of participants (95%) did not meet their recommended fiber intakes (13.2 g/day [IQR: 8.8, 17.2 g/day]). </p>

<p>No significant changes were noted in HOMA-IR (p=0.247), Matsuda index (p=0.247), QUICKI index (p=0.247), hs-CRP (p=0.692), BMI z-scores (p=0.292), waist circumference z-scores (p=0.594), waist-to-height ratio (p=0.564), %FM (p=0.819), FFM (p=0.165), or LCI (p=0.819) between baseline and 12-months (n=5). Despite non-significant changes in BMI z-scores, 60% of participants at 12 months (n=3) had reductions in BMI z-score (change ≥-0.20), suggesting a clinical reduction in weight in this subset of participants. Perceived satiety varied among participants during the intervention, suggesting possible treatment-dependent responses. Gastrointestinal symptoms were mild at 3 months (p= 0.147), while changes were non-significant between baseline and 12 months, suggesting the intervention was well tolerated overall.   </p>

<p>Baseline findings were consistent with literature describing adolescents with obesity and IR. Preliminary analysis of a limited sample size revealed no significant change in HOMA-IR, hs-CRP, %FM, or perceived satiety; however, a clinically significant reduction in BMI z-score in a subset of participants suggests that the interventions may promote weight loss. Future analysis of an unblinded and complete data set will be performed, which may offer insight into treatment-dependent effects on IR.</p>