Metformin is the only first-line oral agent for youth with type 2 diabetes mellitus (Y-T2D) , but efficacy and adherence is complicated by gastrointestinal (GI) side effects. Prebiotic microbiome modulators (MM) may reduce side effects by shifting the microbial flora and promoting metabolism of short-chain fatty acid producing bacteria. The feasibility and tolerability of prebiotic use in Y-T2D is unknown. We hypothesized that a prebiotic MM would be safe, tolerable, and decrease GI symptoms in youth. We compared lower GI symptoms and glycemia in Y-T2D at initiation of daily metformin therapy in a 1-week, randomized, double-blind, crossover trial of a daily prebiotic MM versus placebo shake (Phase 1) followed by a 1 month open-labeled extension (Phase 2) . We assessed stool frequency, stool consistency (King’s Stool Chart) , and used principal component analysis to create a composite GI symptom score (urgency, bloating, flatulence, consistency) . Mixed effects models were used to compare continuous glucose monitor profiles and quality of life metrics (Pediatric Quality of Life Inventory™) . In six Y-T2D (17.2±1.7y (mean±SD) , 66% female, BMI 42±9 kg/m2, HbA1c 6.4±0.6%) stool frequency was assessed every 1-2 days. Stool frequency, stool composition, GI symptom score, and quality of life scores were not different by group or study phase. There were no severe adverse effects during the trial. One youth had increased bloating and discontinued the prebiotic in Phase 2. During phase 1, prebiotic MM tended to have lower average glucose (122±26 vs. 135±23 mg/dL, P=0.07) but this was not sustained in phase 2 (136±31 vs.135±23, P=0.8) . Time in range, standard deviation, and coefficient of variation of glucose were similar during the study.
In summary, the prebiotic MM was well tolerated during short-term metformin therapy in Y-T2D, but was not associated with GI symptom, quality of life, or metabolic changes. Future studies should explore localized gut and systemic metabolic effects of prebiotics in youth.
K. Tuttle: None. L. Mabundo: None. M.S. Stagliano: None. K.B. Dietsche: None. A.B. Courville: None. D.E. Estrada: None. S.T. Chung: None.
NIDDK/NIH Intramural Research Program