Glucose effectiveness in obese children: relation to degree of obesity and dysglycemia.

OBJECTIVE: Impaired glucose effectiveness (GE) plays a role in the deterioration of glucose metabolism. Our aim was to validate a surrogate of GE derived from an oral glucose tolerance test (OGTT) and to assess the impact of degrees of obesity and of glucose tolerance on it. RESEARCH DESIGN AND METHODS: The OGTT-derived surrogate of GE (oGE) was validated in obese adolescents who underwent an OGTT and an intravenous glucose tolerance test (IVGTT). We then evaluated anthropometric determinants of the oGE and its impact on the dynamics of glucose tolerance in a cohort of children with varying degrees of obesity. RESULTS: The correlation of oGE and IVGTT-derived GE in 98 obese adolescents was r = 0.35 (P < 0.001) as a whole and r = 0.51 (P < 0.001) in subjects with normal glucose tolerance. In a cohort of 1,418 children, the adjusted GE was associated with increasing obesity (P < 0.001 for each category of obesity). Quartiles of oGE and the oral disposition index were associated with 2-h glucose levels (P < 0.001 for both). Among 421 nondiabetic obese subjects (276 subjects with normal glucose tolerance/145 subjects with impaired glucose tolerance who repeated their OGTT after a mean time of 28 ± 16 months), oGE changes were tightly associated with weight (r = 0.83, P < 0.001) and waist circumference changes (r = 0.67, P < 0.001). Baseline oGE and changes in oGE over time emerged as significant predictors of the change in 2-h glucose levels (standardized B = -0.76 and B = -0.98 respectively, P < 0.001 for both). CONCLUSIONS: The oGE is associated with the degree of and changes in weight and waist circumference and is an independent predictor of glucose tolerance dynamics

Therapeutically engineered induced neural stem cells are tumour-homing and inhibit progression of glioblastoma

Transdifferentiation (TD) is a recent advancement in somatic cell reprogramming. The direct conversion of TD eliminates the pluripotent intermediate state to create cells that are ideal for personalized cell therapy. Here we provide evidence that TD-derived induced neural stem cells (iNSCs) are an efficacious therapeutic strategy for brain cancer. We find that iNSCs genetically engineered with optical reporters and tumouricidal gene products retain the capacity to differentiate and induced apoptosis in co-cultured human glioblastoma cells. Time-lapse imaging shows that iNSCs are tumouritropic, homing rapidly to co-cultured glioblastoma cells and migrating extensively to distant tumour foci in the murine brain. Multimodality imaging reveals that iNSC delivery of the anticancer molecule TRAIL decreases the growth of established solid and diffuse patient-derived orthotopic glioblastoma xenografts 230- and 20-fold, respectively, while significantly prolonging the median mouse survival. These findings establish a strategy for creating autologous cell-based therapies to treat patients with aggressive forms of brain cancer