Browsing by Author "Fox, Larry A."

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Glycemic outcomes of children 2–6 years of age with type 1 diabetes during the pediatric MiniMed™ 670G system trial
    (Wiley, 2022) Forlenza, Gregory P.; Ekhlaspour, Laya; DiMeglio, Linda A.; Fox, Larry A.; Rodriguez, Henry; Shulman, Dorothy I.; Kaiserman, Kevin B.; Liljenquist, David R.; Shin, John; Lee, Scott W.; Buckingham, Bruce A.; Pediatrics, School of Medicine
    Background: Highly variable insulin sensitivity, susceptibility to hypoglycemia and inability to effectively communicate hypoglycemic symptoms pose significant challenges for young children with type 1 diabetes (T1D). Herein, outcomes during clinical MiniMed™ 670G system use were evaluated in children aged 2-6 years with T1D. Methods: Participants (N = 46, aged 4.6 ± 1.4 years) at seven investigational centers used the MiniMed™ 670G system in Manual Mode during a two-week run-in period followed by Auto Mode during a three-month study phase. Safety events, mean A1C, sensor glucose (SG), and percentage of time spent in (TIR, 70-180 mg/dl), below (TBR, <70 mg/dl) and above (TAR, >180 mg/dl) range were assessed for the run-in and study phase and compared using a paired t-test or Wilcoxon signed-rank test. Results: From run-in to end of study (median 87.1% time in auto mode), mean A1C and SG changed from 8.0 ± 0.9% to 7.5 ± 0.6% (p < 0.001) and from 173 ± 24 to 161 ± 16 mg/dl (p < 0.001), respectively. Overall TIR increased from 55.7 ± 13.4% to 63.8 ± 9.4% (p < 0.001), while TBR and TAR decreased from 3.3 ± 2.5% to 3.2 ± 1.6% (p = 0.996) and 41.0 ± 14.7% to 33.0 ± 9.9% (p < 0.001), respectively. Overnight TBR remained unchanged and TAR was further improved 12:00 am-6:00 am. Throughout the study phase, there were no episodes of severe hypoglycemia or diabetic ketoacidosis (DKA) and no serious adverse device-related events. Conclusions: At-home MiniMed™ 670G Auto Mode use by young children safely improved glycemic outcomes compared to two-week open-loop Manual Mode use. The improvements are similar to those observed in older children, adolescents and adults with T1D using the same system for the same duration of time.
  • Thumbnail Image
    Item
    Metformin Improves Peripheral Insulin Sensitivity in Youth With Type 1 Diabetes
    (Endocrine Society, 2019-08) Cree-Green, Melanie; Bergman, Bryan C.; Cengiz, Eda; Fox, Larry A.; Hannon, Tamara S.; Miller, Kellee; Nathan, Brandon; Pyle, Laura; Kahn, Darcy; Tansey, Michael; Tichy, Eileen; Tsalikian, Eva; Libman, Ingrid; Nadeau, Kristen J.; Pediatrics, School of Medicine
    Context: Type 1 diabetes in adolescence is characterized by insulin deficiency and insulin resistance (IR), both thought to increase cardiovascular disease risk. We previously demonstrated that adolescents with type 1 diabetes have adipose, hepatic, and muscle IR, and that metformin lowers daily insulin dose, suggesting improved IR. However, whether metformin improves IR in muscle, hepatic, or adipose tissues in type 1 diabetes was unknown. Objective: Measure peripheral, hepatic, and adipose insulin sensitivity before and after metformin or placebo therapy in youth with obesity with type 1 diabetes. Design: Double-blind, placebo-controlled clinical trial. Setting: Multi-center at eight sites of the T1D Exchange Clinic Network. Participants: A subset of 12- to 19-year-olds with type 1 diabetes (inclusion criteria: body mass index ≥85th percentile, HbA1c 7.5% to 9.9%, insulin dosing ≥0.8 U/kg/d) from a larger trial (NCT02045290) were enrolled. Intervention: Participants were randomized to 3 months of metformin (N = 19) or placebo (N = 18) and underwent a three-phase hyperinsulinemic euglycemic clamp with glucose and glycerol isotope tracers to assess tissue-specific IR before and after treatment. Main outcome measures: Peripheral insulin sensitivity, endogenous glucose release, rate of lipolysis. Results: Between-group differences in change in insulin sensitivity favored metformin regarding whole-body IR [change in glucose infusion rate 1.3 (0.1, 2.4) mg/kg/min, P = 0.03] and peripheral IR [change in metabolic clearance rate 0.923 (-0.002, 1.867) dL/kg/min, P = 0.05]. Metformin did not impact insulin suppression of endogenous glucose release (P = 0.12). Adipose IR was not assessable with traditional methods in this highly IR population. Conclusions: Metformin appears to improve whole-body and peripheral IR in youth who are overweight/obese with type 1 diabetes.