2 Mar 2018 Abstracts

The complications of a fully closed loop insulin delivery system in adolescents with type 1 diabetes

Jacquelynn Sanders '18

Type 1 diabetes is a growing concern. It is a lifelong commitment that requires constant management of blood glucose levels and insulin injections. For adolescents this is a difficult task due to an active lifestyle, puberty and an unpredictable day. These factors can fluctuate an adolescents glucose levels to extreme levels, which can cause hypoglycemia or hyperglycemia. With the fully closed loop system, a diabetic regains their life, and is able to live their life similar to that of a non-diabetic. A study conducted by Weinzimer et. al, focused on using a pre meal bolus shot of insulin in conjunction with the fully closed loop system, hypothesizing that a small manual pre meal “priming” bolus would reduce glucose levels during and or after a meal. This study consisted of 17 adolescents who were randomly assigned to either a hybrid fully closed loop study, in which those individuals will get a pre meal “priming” bolus. The other group were only assigned to the fully closed loop system. The subjects were equipped with a continuous glucose monitor to establish a baseline before the study, and were kept blind of the results. Once a baseline was established they equipped with subcutaneous glucose sensors that were “closed” the following day. Results of the study showed that a closed loop system does achieve an almost normal glucose range between 100 mg/dl to 120 mg/dl overnight, with the addition of the pre meal priming bolus dose of insulin.

Nonsense Mutation in AIMP2 is Associated with Neurodevelopment Disorder

Nancy Chang '18

Aminoacyl-tRNA synthetases (ARSs) are maintenance enzymes that are needed for translation of genetic information and are known to cause neurodevelopmental disorders such as encephalopathies and sensorineural disorders. Mammalian multi-tRNA synthetase complex (MSC) is one of nine ARSs specialized macromolecular multienzyme complex, provides supplementary support for three proteins (AIMP1/p43, AIMP2/p38, and AIMP3/p18), and plays a role in various signaling pathways and protein synthesis. P38 is a key component and crucial for the MSC complex. P38 protein is extensively expressed in the brain, colon, pancreas, and other human tissues. With the arrival of exome sequencing, several neurological disorders have been identified with defects in these enzymes and proteins. Thus, affected individuals of Indian origin with neurodevelopmental disorders with microcephaly, seizures, and spastic quadriparesis from two unrelated consanguineous families were studied to determine the cause of this neurodevelopmental disorder. MRI showed degeneration of cerebrum, cerebellum and spinal cord, and prominent cisterna magna. Whole-exome sequencing of three affected individuals revealed variants in AIMP2 that lies in a common homozygous region on chromosome 7. The phenotype of the subjects’ revealed similar marks as hypomyelinating leukodystrophy-3 that is caused by mutations that are closely linked to AIMP1/p43. Overall, mutations in AIMP2 are likely to be associated with neurodevelopmental disorders due to the decrease of mRNA levels.