The overall goal of this study is to develop and test a novel method involving ultrasound imaging, in order to detect the development of type 1 diabetes. In this study the investigators will first establish a standard operating procedure for measuring pancreas blood flow speed and volume in the pancreas of human subjects. The investigators will then determine 1) whether these pancreas blood flow factors differ between healthy subjects and those who have recently developed type1 diabetes; and 2) how variable measurements are in healthy subjects and subjects that recently developed type1 diabetes, both between subjects and over time. To address these aims the investigators will perform pancreas ultrasound measurements in each subject using an approved injectable 'bubble' contrast agent that allows measurement of pancreas blood flow. The investigators will compare ultrasound measurement with characteristics of the subject's type 1 diabetes, including genetic factors, glucose levels and other circulating factors, as well as other factors that may influence blood flow in the pancreas independent of type1 diabetes. The successful conclusion of this study will indicate whether measuring pancreas blood flow speed/volume will be helpful in monitoring whether type1 diabetes will emerge and thus will allow a large scale study to answer this question.

Study Design and Research Methods

Part I:

5 subjects from SOP group Goal: Optimize settings for destruction-replenishment contrast-enhanced ultrasound scan

1. Subject recruited at the Barbara Davis Center
2. Subject provides written consent
3. Review medical history (exclusion if required)
4. Subject refrains from eating for ~6h prior to measurement
5. Subject visits University of Colorado Hospital CTRC echo lab
6. CTRC staff places peripheral intravenous line (PIV)
7. Research staff collects vital signs, height and weight
8. Subject received conventional ultrasound scan to locate pancreas tail (by Sonographer, verified by radiologist).
9. Subject receives DEFINITY dose
10. Subject receives destruction-replenishment contrast-enhanced ultrasound scan (adjust settings to optimize)
11. Pause for 30 minutes, allowing subject to stand and move
12. Repeat steps 9-11 (once).
13. Subject de-identified.
14. Analyze data.

Part II:

30 subjects from control group (healthy controls and multiple islet autoantibody positive subjects), 15 subjects from T1D group.

Goal: characterize subject variability and test whether healthy subjects and those with T1D show differing contrast measures

1. Subject recruited at the Barbara Davis Center
2. Subject provides written consent
3. Review medical history (exclusion if required)
4. Subject refrains from eating for ~6h prior to study
5. Subject visits University of Colorado Hospital CTRC echo lab
6. Subject completes questionnaire (family history of diabetes, exclusion criteria)
7. CTRC staff places peripheral intravenous line (PIV)
8. Research staff collects vital signs, height and weight
9. Subject received conventional ultrasound scan to locate pancreas tail (by Sonographer, verified by radiologist).
10. Subject receives DEFINITY dose
11. Subject receives destruction-replenishment contrast-enhanced ultrasound scan (under SOP)
12. Pause for 30 minutes, allowing subject to stand and move
13. Repeat steps 10-12 (once).
14. Subject de-identified
15. Analyze data.

In part I a single repeat measurement may be made to aide in the optimization of data collection. In part II a single repeat measurement is made to assess short-term intra-subject measurement variability.

In part I and part II, a subject will be asked to return on a separate date (within 1 year of the initial scan) for a repeat procedure using an additional DEFINITY delivery method (bolus or infusion, whichever was not given at the initial visit) or if data collection was not of sufficient quality during the first visit.

All Participants:

Inclusion Criteria:

• Male or non-pregnant female age 18-65
• Ability and willingness of patient to participate fully in all aspects of this clinical study
• Written informed consent obtained and documented

Exclusion Criteria:

• Excessive body size preventing effective scan of the pancreas as determined by sonographer
• Evidence of exocrine pancreatic disease, including pancreatitis, cystic fibrosis, pancreatic adenocarcinoma, or neuroendocrine tumor.
• Subjects who are pregnant or breast-feeding
• Subjects incapable of giving assent/informed written consent
• Known or suspected hypersensitivity to perflutren
• Known history or suspected unstable cardiopulmonary conditions (acute myocardial infarction, acute coronary artery syndromes, worsening or unstable congestive heart failure, or serious ventricular arrhythmias)

Group 2 (control subjects, part II):

Inclusion criteria:

No additional inclusion criteria

Exclusion criteria:

• Diagnosis of diabetes according to the ADA recommended criteria (blood glucose and HbA1c will be measured)

• Use of medications used to control high blood sugar (GLP1R agonists, metformin*, sulfonylureas)

  • *Participants taking metformin will be considered eligible if they are willing/able to stop taking the medication for at least two weeks prior to each scan.

• Any person who has received immunomodulatory intervention within 3 months of enrollment

Group 3 (T1D subjects, part II)

Inclusion criteria:

• Diagnosis of diabetes according to the ADA recommended criteria (blood glucose and HbA1c will be measured)
• Evidence of autoantibodies to at least 1 of the following β-cell autoantigens:

insulin, IA-2, GAD65, ZnT8

• Presence of insulin autoantibody will only be valid if taken within the first 14 days of diagnosis.

  • Diagnosis of diabetes within 180 days prior to participation in the study

Exclusion criteria:

• Use of medications used to control high blood sugar (GLP1R agonists, metformin*, sulfonylureas)

  • *Participants taking metformin will be considered eligible if they are willing/able to stop taking the medication for at least two weeks prior to each scan.

• Any person who has received immunomodulatory intervention within 3 months of enrollment

Group 1 subjects will be healthy subjects who will receive contrast-enhanced ultrasound 'destruction-replenishment' measurements, in order to optimize and establish the standard operating procedure (SOP) for this measurement in the pancreas of human subjects. This SOP will then be applied to Group 2 (healthy subjects and autoantibody positive subjects) and Group 3 (recent onset type1 diabetes) subjects as part of the cross-sectional study. Classification of type 1 diabetes includes meeting ADA criteria for diabetes, within 180 days of diagnosis, and evidence of at least 1 islet-associated autoantibody.