CharacterIzation of Adult Onset Autoimmune Diabetes

The purpose of the study is to identify new biomarkers of Adult Onset Autoimmune Diabetes (AOnAD).


Eligibility Criteria:
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