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 goal of the study extension is to see whether the incretin hormone GIP increases insulin secretion in individuals with CF and normal glucose tolerance compared to individuals without CF and normal glucose tolerance. This study includes 3 or 4 visits.

The goal of this study is to investigate the efficacy and safety of Canagliflozin (which is experimental) in children and adolescents ages 10 to 18 years old with Type 2 diabetes and poor control (i.e., an HbA1c of 6.5% to 10.5%). Study drug or placebo would be taken alone or with metformin or insulin as needed. Monitoring tests include blood, urine, physical exams, vital signs, blood sugar and ketone monitoring, diabetes management counseling.

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.

This study is a randomized, double-blind, placebo-controlled study that will evaluate the safety and efficacy of dasiglucagon in children between the ages of 7 days and 12 months who have congenital hyperinsulinism. Dasiglucagon will be given as a subcutaneous infusion while patients are admitted to the hospital. Other treatments for hyperinsulinism may be changed as allowed while maintaining safe blood sugar levels. For the second part of the study, patients may be able to go home on the medication.

The goal of this study is to identify a safe dosing regimen for siplizumab in participants with type 1 diabetes. Siplizumab is a drug used to help treat recent onset type 1 diabetes mellitus (T1DM). This study is interested in participants aged 18-45 years with T1DM, who are within 18 months of receiving their diagnosis. Participants will be randomized (selected at random by the study team) to one of four possible treatment groups. All groups will receive weekly siplizumab doses administered subcutaneously (injected into the body through the skin) for a total of 12 weeks.

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 at the Congenital Hyperinsulinism Center at CHOP is working on a research study to determine whether an experimental gene therapy product, DTX401, is safe and effective in people with glycogen storage disease type Ia (GSDIa). The FDA has not approved this drug for the treatment of GSDIa but has approved us to use this drug as part of this clinical trial. The purpose of this research study is to see if DTX401 can help people with GSDIa have normal blood sugar levels and fewer episodes of hypoglycemia. DTX041 works by delivering copies of the G6PC gene to your liver through a one-time infusion. Participation in this study will last for 2 years and will involve 30 study visits. It is possible that treatment with the study drug infusion may improve your blood sugar levels. Travel costs will be covered by the study and you will receive compensation for participating.

This study will evaluate the safety and effectiveness of the MiniMed 780G insulin pump system used in combination with the DS5 CGM in type 1 diabetic pediatric participants in a home setting.