Eligibility Details:
Inclusion Criteria:
Type 1 Diabetes (T1D)
- age 18-35 years
- age at diagnosis 13 to 30 years
- Body Mass Index (BMI) 25 to 35 kg/m2 with a stable body weight (±3 kg in the past 6
months)
- diagnosis of T1D according to American Diabetes Association (ADA) criteria
continuously requiring insulin for survival (if in doubt, diagnosis can be confirmed
by positivity of 2 or more IAAb* at time of diagnosis, at any time or at time of
recruitment)
- diabetes diagnosis performed within the previous 5 years,
- requiring insulin continuously since diagnosis to prevent ketosis
- Fasting C-peptide levels < 0.3 nmol/l
Type 2 Diabetes (T2D)
- age 40-75 years
- age at diagnosis 40 to 70 years
- BMI 25 to 35 kg/m2 with a stable body weight (±3 kg in the past 6 months)
- diagnosis of diabetes according to ADA criteria
- Diabetes diagnosis performed within the previous 5 years
- Not requiring insulin
- Fasting C-peptide levels > 0.3 nmol/l
Adult Onset Autoimmune Diabetes/Latent Autoimmune Diabetes of Adults (AOnAD/LADA)
- age 40-75 years
- age at diagnosis 40 to 70 years
- BMI 25 to 35 kg/m2 with a stable body weight (±3 kg in the past 6 months)
- diagnosis of diabetes according to ADA criteria
- fasting C-peptide > 0.3 nmol/l
- positive for at least one islet autoantibody (IAAb* - at time of diagnosis, at any
time or at time of recruitment)
- not requiring insulin or, if on insulin, treatment started at least 6 months after
diagnosis
Healthy Normal Volunteers (HNV)
- age 40-75 years
- BMI 25 to 35 kg/m2 with a stable body weight (±3 kg in the past 6 months)
- No personal history of diabetes according to ADA criteria
- No history of diabetes in first degree relatives (FDRs)
- Fasting C-peptide levels > 0.3 nmol/l
- IAAbs are Insulin AutoAntibodies (IAA), Thyrosine phosphatase IA-2 Antibodies
(IA-2 Ab), Glutamic Acid Decarboxylase Antibodies (GAD Ab), Zinc Transporter 8
Antibodies (ZnT8 Ab), Islet Cell Antibodies (ICA).
Exclusion Criteria:
- For T2D participants: treatment with insulin or with thiazolidinediones (TZDs).
- For T1D and AOnAD/LADA participants: treatment with TZDs.
- Presence of unstable cardiovascular disease (unstable angina, myocardial infarction or
coronary revascularization within 6 months, clinically significant abnormalities on
EKG, presence of cardiac pacemaker, implanted cardiac defibrillator)
- Evidence of acute or chronic liver disease even if asymptomatic (AST or ALT >2.5 times
the upper limit of normal)
- Kidney disease (creatinine >1.6 mg/dl or estimated GFR<60 ml/min)
- Triglycerides >500 mg/dl, LDL >200 mg/dl
- Uncontrolled hypertension (Blood Pressure BP>160 mmHg systolic or >100 mmHg diastolic)
- Recent important weight loss (>3 kg in 3 months)
- History of drug or alcohol abuse (> 3 drinks per day) within the last 5 years.
- History of cancer within the last 5 years (skin cancers, with the exception of
melanoma, may be acceptable).
- History of organ transplant.
- History of bariatric surgery
- Bleeding or coagulation disorders requiring chronic use of blood thinners.
- Current treatment with blood thinners or antiplatelet medications that cannot be
safely stopped for study procedures
- History of chronic pancreatitis or pancreatic surgery
- Acute or chronic infections
- History of HIV, active Hepatitis B or C, or Tuberculosis.
- Anemia (hemoglobin <12 g/dl in men, <11 g/dl in women) or other chronic hematology
disorders.
- Use of any medications known to influence glucose, fat and/or energy metabolism within
the last 3 months (e.g., growth hormone therapy, glucocorticoids [steroids], etc.)
other than the treatment for diabetes
- Thyroid dysfunction. Participants with a Thyroid Stimulating Hormone TSH > 10 µ IU or
less than 0.4 µ IU are excluded. Participants on thyroid replacement medication or on
antithyroid drugs may be enrolled providing they have been on a stable dose of
medication for at least 6 weeks prior to screening and their TSH is within the range
specified above.
- Severe asthma or chronic obstructive pulmonary disease
- Initiation or change in hormone replacement therapy within the past 3 months
(including, but not limited to birth control or estrogen replacement therapy)
- Cushing's disease or syndrome
- Drugs that affect immune, weight or metabolic function, including but not limited to:
oral corticosteroids, oral or injectable anti-obesity medications. Drugs for
dyslipidemia (statins, ezetimibe, etc.) and a daily full strength or baby aspirin for
atherosclerosis prevention will be allowed, provided patients have been on stable
doses for at least 6 weeks prior to screening and that aspirin could be safely
temporarily stopped for the study
- Weight >450 lbs. (This is Dual X-ray Absorptiometry (DEXA) table weight limit)
- Gastrointestinal disorders associated with malabsorption.
- Pregnant or nursing females or females less than 6 months postpartum from the
scheduled date of collection.
- Had major surgery within 4 weeks prior to the pre-trial (screening) visit
- Participation in studies involving investigational drug(s) within 30 days prior to
Screening Visit 1
- Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more
within 56 days prior to Screening Visit
- Allergies to milk derived or soy derived products, lactose intolerance (due to the
composition of the standard liquid meal that will be used for the test)
- Allergies and reactions to lidocaine.
- History of eating disorders
- Psychiatric disease prohibiting adherence to study protocol
- Unable to provide a reliable informed consent
- Presence of any condition that, in the opinion of the investigator and clinical team,
compromises participant safety or data integrity or the participant's ability to
complete study visits
common.study.methods.has-drugs-no
common.study.methods.is-healthy-no
