Two-Year Follow-up From the T1GER Study: Continued Off-Therapy Metabolic Improvements in Children and Young Adults With New-Onset T1D Treated With Golimumab and Characterization of Responders.

OBJECTIVE: The T1GER (A Study of SIMPONI to Arrest ß-Cell Loss in Type 1 Diabetes) study showed many metabolic benefits of the tumor necrosis factor-α blocker golimumab in children and young adults with type 1 diabetes (T1D). Off-therapy effects are reported. RESEARCH DESIGNS AND METHODS: T1GER was a phase 2, placebo-controlled, randomized trial in which golimumab or placebo was administered for 52 weeks to participants 6-21 years old diagnosed with T1D within 100 days of randomization. Assessments occurred during the 52-week on-therapy and 52-week off-therapy periods. RESULTS: After treatment was stopped, C-peptide area under the curve (AUC) remained greater in the treatment versus control group. At weeks 78 and 104, the golimumab group had lower reductions in the 4-h C-peptide AUC baseline than the placebo group, where specifically the golimumab group had reductions of 0.31 and 0.41 nmol/L, and the placebo group had reductions of 0.64 and 0.74 nmol/L. There were also trends in less insulin use, higher peak C-peptide levels and those in partial remission, and higher peak C-peptide levels in the golimumab group. Golimumab responders, defined as having an increase or minimal loss of C-peptide AUC and/or being in partial remission at week 52, showed even greater improvements in most metabolic parameters on and off therapy and had less hypoglycemia during the off-therapy period versus placebo. Adverse events, including infections, were similar between the groups during all time periods of the study. CONCLUSIONS: In children and young adults with new-onset T1D, golimumab preserved endogenous ß-cell function and resulted in other favorable metabolic parameters on and off therapy. A subpopulation had disease stabilization while on therapy, with improved metabolic parameters off therapy.

Pediatric critical illness hyperglycemia: risk factors associated with development and severity of hyperglycemia in critically ill children.

OBJECTIVE: To determine which children are susceptible to critical illness hyperglycemia (CIH) and whether CIH severity and duration correlate with diagnosis or illness severity. STUDY DESIGN: We developed a standard approach to identify and treat CIH in our medical/surgical pediatric intensive care unit. We define CIH as persistent blood glucose (BG) >140 mg/dL and titrate infused insulin to maintain BG 80 to 140 mg/dL. We conducted a retrospective analysis of patients with hyperglycemia from June 2006 through May 2007. Main outcomes were risk of development of CIH in different patient subgroups and CIH severity and duration. RESULTS: Average peak BG, CIH duration, and peak insulin requirements were 199 mg/dL, 6.3 days, and 0.09 units/kg/h, respectively, in patients with CIH. CIH severity and duration were highest in neurosurgical and patients with sepsis, those requiring mechanical ventilation and vasopressors, extracorporeal support, and those with highest illness severity scores. CONCLUSIONS: CIH severity and duration correlate with diagnosis and illness severity. Certain "risk factors" may be predictive of who develops CIH.