CharacterIzation of Adult Onset Autoimmune Diabetes

NCT ID: NCT03971955

Last Updated: 2025-03-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ACTIVE_NOT_RECRUITING

Total Enrollment

25 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-07-08

Study Completion Date

2025-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Diabetes

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

OTHER

Study Time Perspective

CROSS_SECTIONAL

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Adult Onset Autoimmune Diabetes/Latent Autoimmune Diabetes

Mixed Meal Test

Intervention Type OTHER

a standard liquid mixed meal will be administered to the participant. The test meal with 1 kcal/ml and with the following caloric distribution Protein: 25%, Carbohydrate: 53%, Fat: 22% is given at a dose of 6 mL per kilogram body weight. Maximum dose is 360 mL and it will be ingested over 5 minutes. Blood samples will be taken 10 min prior to ingestion (t=-10), at baseline (t = 0), and at 15, 30, 60, 90, and 120 minutes.

Dual Energy X-Ray Absorptiometry (DEXA)

Intervention Type OTHER

DEXA Scans will be performed to obtain body composition measures (body fat and estimated muscle mass) using a General Electric (GE) Lunar iDXA whole-body scanner.

Adipose Tissue Biopsy

Intervention Type PROCEDURE

The abdominal skin 6-10 cm lateral to the umbilicus will be cleansed with chlorhexidine. A sterile drape is placed, and the skin and adipose tissue will be anesthetized using Lidocaine. A 3-4 mm Mercedes Liposuction cannula will be inserted for aspiration of up to 2g of adipose tissue.

Type 2 Diabetes

Mixed Meal Test

Intervention Type OTHER

a standard liquid mixed meal will be administered to the participant. The test meal with 1 kcal/ml and with the following caloric distribution Protein: 25%, Carbohydrate: 53%, Fat: 22% is given at a dose of 6 mL per kilogram body weight. Maximum dose is 360 mL and it will be ingested over 5 minutes. Blood samples will be taken 10 min prior to ingestion (t=-10), at baseline (t = 0), and at 15, 30, 60, 90, and 120 minutes.

Dual Energy X-Ray Absorptiometry (DEXA)

Intervention Type OTHER

DEXA Scans will be performed to obtain body composition measures (body fat and estimated muscle mass) using a General Electric (GE) Lunar iDXA whole-body scanner.

Adipose Tissue Biopsy

Intervention Type PROCEDURE

The abdominal skin 6-10 cm lateral to the umbilicus will be cleansed with chlorhexidine. A sterile drape is placed, and the skin and adipose tissue will be anesthetized using Lidocaine. A 3-4 mm Mercedes Liposuction cannula will be inserted for aspiration of up to 2g of adipose tissue.

Type 1 Diabetes

Mixed Meal Test

Intervention Type OTHER

a standard liquid mixed meal will be administered to the participant. The test meal with 1 kcal/ml and with the following caloric distribution Protein: 25%, Carbohydrate: 53%, Fat: 22% is given at a dose of 6 mL per kilogram body weight. Maximum dose is 360 mL and it will be ingested over 5 minutes. Blood samples will be taken 10 min prior to ingestion (t=-10), at baseline (t = 0), and at 15, 30, 60, 90, and 120 minutes.

Dual Energy X-Ray Absorptiometry (DEXA)

Intervention Type OTHER

DEXA Scans will be performed to obtain body composition measures (body fat and estimated muscle mass) using a General Electric (GE) Lunar iDXA whole-body scanner.

Adipose Tissue Biopsy

Intervention Type PROCEDURE

The abdominal skin 6-10 cm lateral to the umbilicus will be cleansed with chlorhexidine. A sterile drape is placed, and the skin and adipose tissue will be anesthetized using Lidocaine. A 3-4 mm Mercedes Liposuction cannula will be inserted for aspiration of up to 2g of adipose tissue.

Healthy Normal Volunteers (HNV)

Mixed Meal Test

Intervention Type OTHER

a standard liquid mixed meal will be administered to the participant. The test meal with 1 kcal/ml and with the following caloric distribution Protein: 25%, Carbohydrate: 53%, Fat: 22% is given at a dose of 6 mL per kilogram body weight. Maximum dose is 360 mL and it will be ingested over 5 minutes. Blood samples will be taken 10 min prior to ingestion (t=-10), at baseline (t = 0), and at 15, 30, 60, 90, and 120 minutes.

Dual Energy X-Ray Absorptiometry (DEXA)

Intervention Type OTHER

DEXA Scans will be performed to obtain body composition measures (body fat and estimated muscle mass) using a General Electric (GE) Lunar iDXA whole-body scanner.

Adipose Tissue Biopsy

Intervention Type PROCEDURE

The abdominal skin 6-10 cm lateral to the umbilicus will be cleansed with chlorhexidine. A sterile drape is placed, and the skin and adipose tissue will be anesthetized using Lidocaine. A 3-4 mm Mercedes Liposuction cannula will be inserted for aspiration of up to 2g of adipose tissue.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Mixed Meal Test

a standard liquid mixed meal will be administered to the participant. The test meal with 1 kcal/ml and with the following caloric distribution Protein: 25%, Carbohydrate: 53%, Fat: 22% is given at a dose of 6 mL per kilogram body weight. Maximum dose is 360 mL and it will be ingested over 5 minutes. Blood samples will be taken 10 min prior to ingestion (t=-10), at baseline (t = 0), and at 15, 30, 60, 90, and 120 minutes.

Intervention Type OTHER

Dual Energy X-Ray Absorptiometry (DEXA)

DEXA Scans will be performed to obtain body composition measures (body fat and estimated muscle mass) using a General Electric (GE) Lunar iDXA whole-body scanner.

Intervention Type OTHER

Adipose Tissue Biopsy

The abdominal skin 6-10 cm lateral to the umbilicus will be cleansed with chlorhexidine. A sterile drape is placed, and the skin and adipose tissue will be anesthetized using Lidocaine. A 3-4 mm Mercedes Liposuction cannula will be inserted for aspiration of up to 2g of adipose tissue.

Intervention Type PROCEDURE

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

AdventHealth Translational Research Institute

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Anna Casu

Role: PRINCIPAL_INVESTIGATOR

Study Principal Investigator

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Translational Research Institute for Metabolism and Diabetes

Orlando, Florida, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2019. Diabetes Care. 2019 Jan;42(Suppl 1):S13-S28. doi: 10.2337/dc19-S002.

Reference Type BACKGROUND
PMID: 30559228 (View on PubMed)

Rogers MAM, Kim C, Banerjee T, Lee JM. Fluctuations in the incidence of type 1 diabetes in the United States from 2001 to 2015: a longitudinal study. BMC Med. 2017 Nov 8;15(1):199. doi: 10.1186/s12916-017-0958-6.

Reference Type BACKGROUND
PMID: 29115947 (View on PubMed)

Thomas NJ, Jones SE, Weedon MN, Shields BM, Oram RA, Hattersley AT. Frequency and phenotype of type 1 diabetes in the first six decades of life: a cross-sectional, genetically stratified survival analysis from UK Biobank. Lancet Diabetes Endocrinol. 2018 Feb;6(2):122-129. doi: 10.1016/S2213-8587(17)30362-5. Epub 2017 Nov 30.

Reference Type BACKGROUND
PMID: 29199115 (View on PubMed)

Thunander M, Petersson C, Jonzon K, Fornander J, Ossiansson B, Torn C, Edvardsson S, Landin-Olsson M. Incidence of type 1 and type 2 diabetes in adults and children in Kronoberg, Sweden. Diabetes Res Clin Pract. 2008 Nov;82(2):247-55. doi: 10.1016/j.diabres.2008.07.022. Epub 2008 Sep 18.

Reference Type BACKGROUND
PMID: 18804305 (View on PubMed)

Thomas NJ, Lynam AL, Hill AV, Weedon MN, Shields BM, Oram RA, McDonald TJ, Hattersley AT, Jones AG. Type 1 diabetes defined by severe insulin deficiency occurs after 30 years of age and is commonly treated as type 2 diabetes. Diabetologia. 2019 Jul;62(7):1167-1172. doi: 10.1007/s00125-019-4863-8. Epub 2019 Apr 10.

Reference Type BACKGROUND
PMID: 30969375 (View on PubMed)

Turner R, Stratton I, Horton V, Manley S, Zimmet P, Mackay IR, Shattock M, Bottazzo GF, Holman R. UKPDS 25: autoantibodies to islet-cell cytoplasm and glutamic acid decarboxylase for prediction of insulin requirement in type 2 diabetes. UK Prospective Diabetes Study Group. Lancet. 1997 Nov 1;350(9087):1288-93. doi: 10.1016/s0140-6736(97)03062-6.

Reference Type BACKGROUND
PMID: 9357409 (View on PubMed)

Barinas-Mitchell E, Kuller LH, Pietropaolo S, Zhang YJ, Henderson T, Pietropaolo M. The prevalence of the 65-kilodalton isoform of glutamic acid decarboxylase autoantibodies by glucose tolerance status in elderly patients from the cardiovascular health study. J Clin Endocrinol Metab. 2006 Aug;91(8):2871-7. doi: 10.1210/jc.2005-2667. Epub 2006 May 23.

Reference Type BACKGROUND
PMID: 16720660 (View on PubMed)

Insel RA, Dunne JL, Atkinson MA, Chiang JL, Dabelea D, Gottlieb PA, Greenbaum CJ, Herold KC, Krischer JP, Lernmark A, Ratner RE, Rewers MJ, Schatz DA, Skyler JS, Sosenko JM, Ziegler AG. Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association. Diabetes Care. 2015 Oct;38(10):1964-74. doi: 10.2337/dc15-1419.

Reference Type BACKGROUND
PMID: 26404926 (View on PubMed)

Acevedo-Calado M, James EA, Morran MP, Pietropaolo SL, Ouyang Q, Arribas-Layton D, Songini M, Liguori M, Casu A, Auchus RJ, Huang S, Yu L, Michels A, Gianani R, Pietropaolo M. Identification of Unique Antigenic Determinants in the Amino Terminus of IA-2 (ICA512) in Childhood and Adult Autoimmune Diabetes: New Biomarker Development. Diabetes Care. 2017 Apr;40(4):561-568. doi: 10.2337/dc16-1527. Epub 2017 Feb 7.

Reference Type BACKGROUND
PMID: 28174261 (View on PubMed)

Achenbach P, Hawa MI, Krause S, Lampasona V, Jerram ST, Williams AJK, Bonifacio E, Ziegler AG, Leslie RD; Action LADA consortium. Autoantibodies to N-terminally truncated GAD improve clinical phenotyping of individuals with adult-onset diabetes: Action LADA 12. Diabetologia. 2018 Jul;61(7):1644-1649. doi: 10.1007/s00125-018-4605-3. Epub 2018 Apr 4.

Reference Type BACKGROUND
PMID: 29619531 (View on PubMed)

Brooks-Worrell BM, Boyko EJ, Palmer JP. Impact of islet autoimmunity on the progressive beta-cell functional decline in type 2 diabetes. Diabetes Care. 2014 Dec;37(12):3286-93. doi: 10.2337/dc14-0961. Epub 2014 Sep 19.

Reference Type BACKGROUND
PMID: 25239783 (View on PubMed)

Buzzetti R, Zampetti S, Maddaloni E. Adult-onset autoimmune diabetes: current knowledge and implications for management. Nat Rev Endocrinol. 2017 Nov;13(11):674-686. doi: 10.1038/nrendo.2017.99. Epub 2017 Sep 8.

Reference Type BACKGROUND
PMID: 28885622 (View on PubMed)

Hawa MI, Kolb H, Schloot N, Beyan H, Paschou SA, Buzzetti R, Mauricio D, De Leiva A, Yderstraede K, Beck-Neilsen H, Tuomilehto J, Sarti C, Thivolet C, Hadden D, Hunter S, Schernthaner G, Scherbaum WA, Williams R, Brophy S, Pozzilli P, Leslie RD; Action LADA consortium. Adult-onset autoimmune diabetes in Europe is prevalent with a broad clinical phenotype: Action LADA 7. Diabetes Care. 2013 Apr;36(4):908-13. doi: 10.2337/dc12-0931. Epub 2012 Dec 17.

Reference Type BACKGROUND
PMID: 23248199 (View on PubMed)

Mishra R, Hodge KM, Cousminer DL, Leslie RD, Grant SFA. A Global Perspective of Latent Autoimmune Diabetes in Adults. Trends Endocrinol Metab. 2018 Sep;29(9):638-650. doi: 10.1016/j.tem.2018.07.001. Epub 2018 Jul 23.

Reference Type BACKGROUND
PMID: 30041834 (View on PubMed)

Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007 Jun;9(6):654-9. doi: 10.1038/ncb1596. Epub 2007 May 7.

Reference Type BACKGROUND
PMID: 17486113 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

https://www.adventhealth.com/research/translational-research-institute-metabolism-and-diabetes

Translational Research Institute for Metabolism and Diabetes (TRI-MD)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

1437923

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Lipoprotein Kinetics in T1D
NCT05179954 RECRUITING NA
Early Markers of Disease and Response to Therapy
NCT04118153 COMPLETED EARLY_PHASE1