characterization of adult onset autoimmune diabetes

Conditions: Diabetes

Summary: 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