RESUMEN
OBJECTIVE: Innate immune responses may be involved in the earliest phases of type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: To test whether blocking innate immaune cells modulated progression of the disease, we randomly assigned 273 individuals with stage 1 T1D to treatment with hydroxychloroquine (n = 183; 5 mg/kg per day to a maximum of 400 mg) or placebo (n = 90) and assessed whether hydroxychloroquine treatment delayed or prevented progression to stage 2 T1D (i.e., two or more islet autoantibodies with abnormal glucose tolerance). RESULTS: After a median follow-up of 23.3 months, the trial was stopped prematurely by the data safety monitoring board because of futility. There were no safety concerns in the hydroxychloroquine arm, including in annual ophthalmologic examinations. Preplanned secondary analyses showed a transient decrease in the glucose average area under the curve to oral glucose in the hydroxychloroquine-treated arm at month 6 and reduced titers of anti-GAD and anti-insulin autoantibodies and acquisition of positive autoantibodies in the hydroxychloroquine arm (P = 0.032). CONCLUSIONS: We conclude that hydroxychloroquine does not delay progression to stage 2 T1D in individuals with stage 1 disease. Drug treatment reduces the acquisition of additional autoantibodies and the titers of autoantibodies to GAD and insulin.
Asunto(s)
Diabetes Mellitus Tipo 1 , Hidroxicloroquina , Humanos , Hidroxicloroquina/uso terapéutico , Autoanticuerpos , Insulina , GlucosaRESUMEN
OBJECTIVE: To assess current rates of complications of diabetic ketoacidosis (DKA), particularly cerebral edema, in a large tertiary-care pediatric hospital with a consistent management protocol. STUDY DESIGN: We report our single-center retrospective experience with 3712 admissions with DKA in 1999-2011. Our DKA protocol features a "3-bag" system using 2 bags of rehydration fluids, identical except for the presence in 1 bag of 10% dextrose, to allow rapid adjustment of glucose infusion rate. The third bag contains insulin. Fluids are administered at a total rate of 2-2.5 times "maintenance" fluid requirements. Total electrolyte concentration is kept approximately isotonic. Billing and medical records databases at Children's Medical Center Dallas were examined for cases of DKA, cerebral edema, other morbidities, and death. RESULTS: We ascertained 20 cases of cerebral edema (0.5%). Most presented early (median duration of treatment 2 hours). Only 10 of 20 computed tomography scans were graded as moderate edema or worse. Only 10 patients received treatment other than routine DKA management. There was 1 death in a patient with sickle cell trait who developed intravascular sickling. Two patients had neurologic sequelae at hospital discharge but both recovered fully. CONCLUSIONS: Compared with data in recent consensus statements, the Dallas protocol is associated with extremely low rates of death and disability (0.08% vs 0.3%) from DKA.
Asunto(s)
Cetoacidosis Diabética/terapia , Fluidoterapia/métodos , Glucosa/uso terapéutico , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Soluciones para Rehidratación/uso terapéutico , Adolescente , Edema Encefálico/epidemiología , Edema Encefálico/etiología , Edema Encefálico/prevención & control , Niño , Preescolar , Protocolos Clínicos , Terapia Combinada , Cetoacidosis Diabética/complicaciones , Cetoacidosis Diabética/mortalidad , Femenino , Humanos , Soluciones Isotónicas , Masculino , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: To examine race/ethnicity and neighborhood income differences in longitudinal patterns of deterioration in hemoglobin A1c (HbA1c) values among youth (age 10 to 18 years) with type 1 diabetes. STUDY DESIGN: A sample of 225 youth (50.2% female), including 81 White, 81 Black, and 63 Hispanic youth with type 1 diabetes, was matched initially on age and sex. Neighborhood median family income was obtained through public census databases. Self-identified race/ethnicity and all HbA1c values (grand mean, 9.09% ± 2.02%) available in patients' medical records between age 10 and 18 years were recorded and analyzed. RESULTS: Hierarchical linear modeling revealed age-related deterioration in HbA1c values that differed by race/ethnicity and income. Controlling for income, White and Hispanic youth had similar HbA1c values at the start of adolescence (age 10) and demonstrated similar rates of deterioration across adolescence. Blacks had higher initial HbA1c values compared with Whites and Hispanics, but a similar rate of deterioration. Higher neighborhood income was associated with slower deterioration in HbA1c value among White teens, but not among Hispanic or Black teens. CONCLUSIONS: Longitudinally, Black youth appear to experience disproportionate risks compared with White and Hispanic youth when income is statistically controlled. Neither Black nor Hispanic youth appear to benefit from living in higher-income neighborhoods.