Hydroxychloroquine in Stage 1 Type 1 Diabetes.

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.

Abatacept for Delay of Type 1 Diabetes Progression in Stage 1 Relatives at Risk: A Randomized, Double-Masked, Controlled Trial.

Objective: Previous studies showed that inhibiting lymphocyte costimulation reduces declining β-cell function in individuals newly diagnosed with type 1 diabetes. We tested whether abatacept would delay or prevent progression of type 1 diabetes from normal glucose tolerance (NGT) to abnormal glucose tolerance (AGT) or to diabetes and the effects of treatment on immune and metabolic responses.

Research Design And Methods: We conducted a phase 2, randomized, placebo-controlled, double-masked trial of abatacept in antibody-positive participants with NGT who received monthly abatacept/placebo infusions for 12 months.

Innate inflammation drives NK cell activation to impair Treg activity.

IL-12 and IL-18 synergize to promote T1 responses and have been implicated as accelerators of autoimmune pathogenesis in type 1 diabetes (T1D). We investigated the influence of these cytokines on immune cells involved in human T1D progression: natural killer (NK) cells, regulatory T cells (Tregs), and cytotoxic T lymphocytes (CTL). NK cells from T1D patients exhibited higher surface CD226 versus controls and lower CD25 compared to first-degree relatives and controls.

Application of a Genetic Risk Score to Racially Diverse Type 1 Diabetes Populations Demonstrates the Need for Diversity in Risk-Modeling.

Prior studies identified HLA class-II and 57 additional loci as contributors to genetic susceptibility for type 1 diabetes (T1D). We hypothesized that race and/or ethnicity would be contextually important for evaluating genetic risk markers previously identified from Caucasian/European cohorts. We determined the capacity for a combined genetic risk score (GRS) to discriminate disease-risk subgroups in a racially and ethnically diverse cohort from the southeastern U.

Depressive Symptoms at Critical Times in Youth With Type 1 Diabetes: Following Type 1 Diabetes Diagnosis and Insulin Pump Initiation.

Purpose: Depressive symptoms occur at various times during the life cycle in persons with type 1 diabetes. We investigated depressive symptoms prospectively in youth with new-onset type 1 diabetes and in those beginning pump therapy.

Methods: Youth with type 1 diabetes (N = 96), ages 10-17 years, completed the Children's Depression Inventory (CDI) at baseline and at 1, 6, and 12 months after diabetes onset or pump start; scores ≥13 indicated clinical elevation.

T cells display mitochondria hyperpolarization in human type 1 diabetes.

T lymphocytes constitute a major effector cell population in autoimmune type 1 diabetes. Despite essential functions of mitochondria in regulating activation, proliferation, and apoptosis of T cells, little is known regarding T cell metabolism in the progression of human type 1 diabetes. In this study, we report, using two independent cohorts, that T cells from patients with type 1 diabetes exhibited mitochondrial inner-membrane hyperpolarization (MHP).

Examination of Psychosocial and Physiological Risk for Bulimic Symptoms in Youth With Type 1 Diabetes Transitioning to an Insulin Pump: A Pilot Study.

Objectives: This study tested hypotheses drawn from a risk model positing that psychosocial risk plus disease-related and treatment factors contribute to bulimic symptoms in youth with type 1 diabetes (T1D) transitioning to an insulin pump. The goal of this study was to examine whether disease-related factors, particularly disease- and treatment-based disruption in hunger and satiety, contribute to report of bulimic symptoms in youth with T1D after accounting for psychosocial risk factors.

Methods: 43 youth (ages 10-17, 54% female) with established T1D were recruited before transition from multiple daily injections to insulin-pump therapy from three tertiary pediatric diabetes centers.

Serum polybrominated diphenyl ether concentrations and thyroid function in young children.

Thyroid hormones are essential for proper neurodevelopment in early life. There is evidence that exposure to polybrominated diphenyl ethers (PBDEs) affects thyroid function, but previous studies have been inconsistent, and no studies among children have been conducted in the United States where PBDE levels are particularly high. Serum levels of seven PBDE congeners and thyroid hormones and other thyroid parameters were measured in 80 children aged 1-5 years from the southeastern United States between 2011 and 2012.

Depressive Symptoms, Emotion Dysregulation, and Bulimic Symptoms in Youth With Type 1 Diabetes: Varying Interactions at Diagnosis and During Transition to Insulin Pump Therapy.

This study evaluated the associations between depressive symptoms, emotion dysregulation and bulimic symptoms in youth with type 1 diabetes (T1D) in the context of the diagnosis and treatment of T1D. Study participants were 103 youth in 2 distinct groups: newly diagnosed (New) or transitioning to pump therapy (continuous subcutaneous insulin infusion [CSII]; "Pump"), who completed questionnaires regarding symptoms of depression, emotion dysregulation, and bulimia. Glycemic control (A1c), height, weight, and questionnaires were evaluated within 10 days of diagnosis (n = 58) or at education/clinic visit before starting insulin utilizing CSII (n = 45).

Outcomes analysis of radioactive iodine and total thyroidectomy for pediatric Graves' disease.

Background: The majority of pediatric patients with Graves' disease will ultimately require definitive therapy in the form of radioactive iodine (RAI) ablation or thyroidectomy. There are few studies that directly compare the efficacy and complication rates between RAI and thyroidectomy. We compared the relapse rate as well as the acute and long-term complications of RAI and total thyroidectomy among children and adolescents with Graves' disease treated at our center.

Inter-individual variation in weaning among rhesus macaques (Macaca mulatta): Serum stable isotope indicators of suckling duration and lactation.

Weaning is a transition in early development with major implications for infant survival and well-being, and for maternal lifetime reproductive success. The particular strategy a primate mother adopts in rearing her offspring represents a negotiation between her ability to invest and her need to invest, and can be considered adaptive and influenced by biological and social factors. Any investigation into how and why maternal weaning strategies differ among non-human primates is limited by the precision of the measurement tool used to assess infants' weaning ages.

Growth velocity and weaning δ(15)N "Dips" during ontogeny in Macaca mulatta.

Objectives: A "dip" in the stable nitrogen isotope ratios (δ(15)N) of subadults in the late weaning/early post-weaning phase of growth and development has been observed. Speculatively, this is the mechanism of positive nitrogen balance operating among rapidly growing subadults. An alternate hypothesis for δ(15)N dips is that during weaning, subadults eat lower-(15)N foods than adults.

A novel TRPS1 gene mutation causing trichorhinophalangeal syndrome with growth hormone responsive short stature: a case report and review of the literature.

The role of growth hormone (GH) and its therapeutic supplementation in the trichorhinophalangeal syndrome type I (TRPS I) is not well delineated. TRPS I is a rare congenital syndrome, characterized by craniofacial and skeletal malformations including short stature, sparse, thin scalp hair and lateral eyebrows, pear-shaped nose, cone shaped epiphyses and hip dysplasia. It is inherited in an autosomal dominant manner and caused by haploinsufficiency of the TRPS1 gene.

Do obese children with diabetic ketoacidosis have type 1 or type 2 diabetes?

Objective: Many obese children with unprovoked diabetic ketoacidosis (DKA) display clinical features of type 2 diabetes during follow up. We describe the clinical presentation, autoimmune markers and the long-term course of obese and lean children with DKA.

Research Design And Methods: We reviewed the medical records on the initial acute hospitalization and outpatient follow-up care of 21 newly diagnosed obese and 20 lean children with unprovoked DKA at Emory University affiliated children's hospitals between 1/2003 and 12/2006.

Improved access to subspecialist diabetes care by telemedicine: cost savings and care measures in the first two years of the FITE diabetes project.

We have used telemedicine clinics supplemented by online education to provide effective care for children with diabetes. Before the programme began, the mean interval between visits was 149 days; in year 1 of the programme it was 98 days, and in year 2 it was 89 days. Before the programme, there were on average 13 hospitalizations a year (47 days) and this decreased to 3.

Cerebral edema in childhood diabetic ketoacidosis: natural history, radiographic findings, and early identification.

Objective: Children who develop cerebral edema (CE) during diabetic ketoacidosis (DKA) exhibit definable signs and symptoms of neurological collapse early enough to allow intervention to prevent brain damage. Our objective was to develop a model for early detection of CE in children with DKA.

Research Design And Methods: A training sample of 26 occurrences of DKA complicated by severe CE and 69 episodes of uncomplicated DKA was reviewed.