Outcomes of algorithm-based modifications of insulinotherapy during exercise in MDI vs insulin pump-treated children with type 1 diabetes: Results from the TREAD-DIAB study.

OBJECTIVES: To evaluate the evolution of subcutaneous glucose (SG) after a standardized aerobic exercise in children and adolescents treated with continuous subcutaneous insulin infusion (CSII) or multiple daily injection (MDI) regimen before and after adaptation of insulin doses. RESEARCH DESIGN AND METHODS: Eleven CSII- and 13 MDI-treated patients performed 2 30-minute sessions of moderate to vigorous (70% of age-based maximal heart rate) exercise on a treadmill under continuous glucose monitoring (CGM). First sessions were scheduled without insulin modification (TT#1) while patients performed second sessions (TT#2) after preemptive algorithm-based insulin dose modifications. RESULTS: While insulin adaptations did not modify immediate postexercise drops in blood glucose during TT#2 in either group, CSII-treated patients had their glucose control improved during TT#2 (mean of 141 ± 56 mg/dL vs 144 ± 80 mg/dL in TT#1; P < .05) with up to 86% of SG levels within targets during 16 hours postexercise. Contrarily, SG levels did not normalize during TT#2 in MDI-treated patients who experienced higher rates of hyperglycemia during the afternoon snack. As compared with TT#1, CSII-treated patients had reduced rates of hypoglycemia during 4 hours post-TT#2 (from 19.5% to 2.1%; P < .01) and had shorter duration of nocturnal hypoglycemia (35.5 ± 12.8 vs 204.7 ± 165 minutes; P = .04) whereas in the MDI group no changes in percentages of hypoglycemia were observed during TT#2. CONCLUSION: In our pediatric cohort, algorithmic adaptations of insulin doses were associated with better outcomes in terms of postexercise glucose control in patients with CSII therapy but not with MDI treatment.

Persistence of a chimerical phenotype after hepatocyte differentiation of human bone marrow mesenchymal stem cells.

OBJECTIVES: Recent studies have suggested the potential of mesenchymal stem cells (MSCs) to differentiate into a hepatocyte-like lineage. Here, we evaluate the efficacy of hepatocyte differentiation of MSCs by studying acquisition of hepatocyte-like features together with alteration of the native mesenchymal phenotype. MATERIAL AND METHODS: In vitro, we have investigated protein and mRNA level expression of hepatocyte and mesenchymal markers of mesenchymal-derived hepatocyte-like cells (MDHLCs) and we have evaluated their functionality using metabolic assays. In vivo, we investigated co-expression of hepatocyte (albumin, alpha-foetoprotein, cytokeratin 18) and mesenchymal (fibronectin, vimentin) markers after transplantation of MSCs or MDHLCs into severe combined immune deficiency mice. RESULTS: We observed that while in vitro these cells acquired some phenotypic and functional features of mature hepatocytes, they partially preserved their mesenchymal phenotype. After intrasplenic transplantation, engrafted MSCs with isolated expression of fibronectin and alpha-foetoprotein were observed. When these cells were injected into the liver, they expressed all analysed markers, confirming the chimaeric co-expression observed in vitro. Conversely, liver-engrafted MDHLCs conserved their hepatocyte-lineage markers but lost their chimaeric phenotype. CONCLUSIONS: Hepatocyte differentiation of MSCs predominantly allows the acquisition of phenotypic hallmarks and provides chimaeric cells that maintain expression of initial lineage markers. However, advanced maturation to the hepatocyte-like phenotype could be obtained in vivo by conditioning MSCs prior to transplantation or by infusing cells into the liver micro-environment.