This study is sponsored by Children's Hospital of Philadelphia Department of Radiology. The purpose of this research is to study 18F-L-Fluoro-DOPA (F-DOPA), a tracer, which is used to take pictures of the pancreas. This imaging test is called an F-DOPA PET scan. The F-DOPA tracer is used to highlight areas of the pancreas that make too much insulin on the PET scan images. The test includes a CT scan (computerized tomography) done at the same time on the same machine, to help define exactly where the highlighted area is located within the pancreas and determine the location of blood vessels and other vital structures. Who can participate:

• Infants, children and adults with hyperinsulinemic hypoglycemia, diagnosed by a fasting test and/or response to glucagon stimulation
• Any age, from birth on
• Requiring surgery to remove part or all of the pancreas

The purpose of this research study is to examine and understand the various mechanisms that contribute to CFRD and gain a better understanding of potential means to treat CFRD. Participation will include 2-3 visits, home monitoring, and will last about 2 years.

The aim of this study is to evaluate safety, and tolerability of insulin LY3209590 following a single dose given to children with type 2 diabetes mellitus (T2DM). This will be the first study to evaluate LY3209590 in pediatric patients with T2DM.

Screening:

All participants will be screened up to 28 days prior to dosing.

Treatment and Assessment Period:

On Day 1, participants will receive a single 100-Unit subcutaneous dose of LY3209590 at the clinical research unit.

Follow up research visits will be performed on Days 3, 5, 7, 15, 29, 43, and 65. Blood sampling and safety assessments will be performed at each in clinic visit. Before each study visit, subjects will need to fast for at least 8 hours.

A follow-up telephone call will be performed on approximately Day 72. The total time for participation is the study is about 100 days.

The DISCOVERY Study is a new, national effort to learn about the causes of type 2 diabetes in children. DISCOVERY is for children 9-14 years old who are at higher risk of developing type 2 diabetes. We want to figure out why some children get type 2 diabetes and others do not.

Our team has partnered with Moderna on a clinical trial for patients with glycogen storage disease type 1a (GSD1a). We would like to invite you to take part in a clinical trial for an mRNA investigational drug that could potentially correct the cause of GSD1a, by teaching your body to break down glycogen, correct low glucose, and avoid starch intake. The purpose of this trial is to see if a new investigational mRNA study drug, called mRNA-3745, is safe and if it works in the way researchers expect. mRNA technology uses messenger ribonucleic acid (mRNA), an instructional molecule that naturally occurs in the body and carries information to cells. In this case, we are studying if mRNA-3745 given through an IV infusion can instruct the body to make the protein that is missing in people with GSD1a.

mRNA-3725 is not approved by the FDA; the FDA has allowed us to provide this investigational medicine to patients enrolled in this phase 1/2 trial. Phase 1/2 clinical trials like this one aim to test the safety, side effects, and best dose of an investigational medication. In the phase 2 part, participants usually receive the highest dose of treatment discovered in the phase 1 part. This is the first study in which humans are administered this study drug.

If successful, mRNA-3745 would enable certain organs in the body to effectively break down glycogen and avoid low glucose levels and starch intake. If mRNA-3745 could correct the cause of GSD1a, it would help keep your glucose levels where they need to be all the time.

Participation in this clinical trial could last up to approximately two years, depending on which stage you enroll in and whether or not you decide to participate in the long-term follow-up period of the study. Some of the visits in this trial will require you to stay overnight at the hospital, and some of the visits will require you to visit the hospital or doctors office. Most of the visits in this clinical trial can be done at your home, where a home health nurse will perform the assessments needed.

All study-related procedures, travel, and compensation are provided.

The purpose of the study is to determine changes in lactate and creatine in calf muscle of healthy adult volunteers. Males and females of different ages (18 - 30 years, 45-55 years, and 70-80 years) will be asked to attend a single in-person study visit. Prior to the completing the MRI scan, the study team will review the health status of individuals.

The purpose of this research study is to learn more about Graves disease and PTC/Hypothyroidism, How it effects brain function and brain function changes after starting medical treatment.

Congenital Hyperinsulinism is the most common cause of low blood sugar (hypoglycemia) in infants and children.Infants who are born with this problem have low blood sugar, which can cause seizures or brain damage.

We are doing this study to see if the patterns of abnormalities in controlling insulin in children and adults with hyperinsulinism are related to any underlying genetic cause and to identify possible new genetic causes.This will be done by standard clinical tests of insulin control: a glucose tolerance test, a protein tolerance test, and a fasting test.

Our team is working on a study to better understand neurological problems, including seizures and developmental delays, that occur in children with hyperinsulinism, including HI/HA syndrome, and type 1 diabetes mellitus. The study involves a one-day visit to The Children's Hospital of Philadelphia and The University of Pennsylvania for a specialized magnetic resonance imaging scan (MRI) of the brain, an electroencephalogram (EEG), blood draw, and completion of questionnaires to evaluate development and behavior. The entire study visit is expected to take about five hours. If you are interested in learning more, please contact us at HIResearch@email.chop.edu.

You or your child are being asked to take part in this research study because you have Glycogen Storage Disease Type III (GSD III). The purpose of this research study is to better understand blood sugar variability, muscle strength and function, and impact of Glycogen Storage Disease Type III (GSD III) on overall health. You will not receive any treatment for your GSD III as part of this study, but the information you provide will be helpful for the study sponsor, Ultragenyx Pharmaceutical Inc., to develop a new therapy for GSD III.

If you agree to take part, your participation will last for about 26 weeks and will involve up to 2 study visits to the hospital along with up to 26 phone calls. There will be no changes to your treatment regimen for GSD III as part of this study.

As a participant in the research you will:

• come to the hospital for 1-2 in person visits to complete interviews and questionnaires,
• wear a blinded continuous glucose monitor (CGM) 3 months and an unblinded CGM for 3 months,
• complete fingerstick blood sugar checks, maintain a nutrition diary for 3 or more weeks throughout the study,
• maintain a hypoglycemia symptom diary, and
• upload CGM and HHG device data to a study-provided laptop weekly.

The main risks of this study are from hypoglycemia related to your diagnosis of GSD III and a loss of confidentiality. There are no direct benefits to you for participating in this study but the information collected as part of this study will help researchers better understand GSD III.