CharacterIzation of Adult Onset Autoimmune Diabetes

NCT03971955 | Active Not Recruiting DMC

• 1 other identifier: 1437923
• Study Type: observational
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Diabetes

Outcome Measures

Primary Outcomes (1)

• Blood collection

  A change in the levels of specific microRNAs (miRNA) isolated from circulating exosomes.

  Screening Visit and Day 1

Study Arms (4)

Adult Onset Autoimmune Diabetes/Latent Autoimmune Diabetes

Other: Mixed Meal Test; Other: Dual Energy X-Ray Absorptiometry (DEXA); Procedure: Adipose Tissue Biopsy

Type 2 Diabetes

Other: Mixed Meal Test; Other: Dual Energy X-Ray Absorptiometry (DEXA); Procedure: Adipose Tissue Biopsy

Type 1 Diabetes

Other: Mixed Meal Test; Other: Dual Energy X-Ray Absorptiometry (DEXA); Procedure: Adipose Tissue Biopsy

Healthy Normal Volunteers (HNV)

Other: Mixed Meal Test; Other: Dual Energy X-Ray Absorptiometry (DEXA); Procedure: Adipose Tissue Biopsy

Interventions

Mixed Meal Test 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.

Adult Onset Autoimmune Diabetes/Latent Autoimmune Diabetes; Healthy Normal Volunteers (HNV); Type 1 Diabetes; Type 2 Diabetes

Dual Energy X-Ray Absorptiometry (DEXA) 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.

Adult Onset Autoimmune Diabetes/Latent Autoimmune Diabetes; Healthy Normal Volunteers (HNV); Type 1 Diabetes; Type 2 Diabetes

Adipose Tissue Biopsy 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.

Adult Onset Autoimmune Diabetes/Latent Autoimmune Diabetes; Healthy Normal Volunteers (HNV); Type 1 Diabetes; Type 2 Diabetes

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This is an observational cross-sectional pilot study that will compare 4 groups of 10 participants each (5±1 of each gender per group) affected by AOnAD, T2D, T1D and Healthy Normal Volunteers (HNV). They will be characterized clinically and biochemically.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AdventHealth Translational Research Institute: lead

Study Sites (1)

Translational Research Institute for Metabolism and Diabetes

Orlando, Florida, 32804, United States

Location

Related Publications (15)

• 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.

  PMID: 30559228 BACKGROUND

• 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.

  PMID: 29115947 BACKGROUND

• 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.

  PMID: 29199115 BACKGROUND

• 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.

  PMID: 18804305 BACKGROUND

• 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.

  PMID: 30969375 BACKGROUND

• 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.

  PMID: 9357409 BACKGROUND

• 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.

  PMID: 16720660 BACKGROUND

• 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.

  PMID: 26404926 BACKGROUND

• 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.

  PMID: 28174261 BACKGROUND

• 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.

  PMID: 29619531 BACKGROUND

• 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.

  PMID: 25239783 BACKGROUND

• 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.

  PMID: 28885622 BACKGROUND

• 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.

  PMID: 23248199 BACKGROUND

• 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.

  PMID: 30041834 BACKGROUND

• 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.

  PMID: 17486113 BACKGROUND

Related Links

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

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

Absorptiometry, Photon

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Radiography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Densitometry; Photometry; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Anna Casu

  Study Principal Investigator

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2019
• First Posted: June 3, 2019
• Study Start: July 8, 2019
• Primary Completion: November 12, 2021
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)