Extracellular Vesicles, Insulin Action, and Exercise

NCT06546085 | Recruiting

• 2 other identifiers: Pro2024000230R01DK133598-01A1
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 3

Brief Summary

Extracellular vesicles (EVs) play a role in obesity-induced insulin resistance and likely impact the development of cardiovascular disease. However, little is known on how EVs affect vascular insulin action in people. The purpose of this study is to understand how EVs play a role in type 2 diabetes related cardiovascular disease. This research will also study if exercise can change how EVs impact blood flow and metabolic health. This study will contribute to designing precision medicine to treat/prevent cardiovascular disease in type 2 diabetes.

Conditions

Type 2 Diabetes; Obesity

Outcome Measures

Primary Outcomes (1)

• Change in Extracellular Vesicles during insulin infusion

  Extracellular vesicles (CD41 -CD31+, CD45, Tx, CD31, CD105) will be isolated from plasma before and during insulin stimulation.

  From enrollment to the end of treatment at 16 weeks.

Secondary Outcomes (6)

• Change in Metabolic Insulin Sensitivity by the Isoglycemic Clamp

  From enrollment to the end of treatment at 16 weeks.

• Change in Contrast Enhanced Ultrasound

  From enrollment to the end of treatment at 16 weeks.

• Change in Flow Mediated Dilation of the brachial artery

  From enrollment to the end of treatment at 16 weeks.

• Change in Pulse Wave Velocity

  From enrollment to the end of treatment at 16 weeks.

• Change in Augmentation Index

  From enrollment to the end of treatment at 16 weeks.

Study Arms (3)

Lean with Normal Glucose Tolerance

NO INTERVENTION

Participants will not receive the study intervention and will be healthy controls.

Obesity with Normal Glucose Tolerance

EXPERIMENTAL

Participants with obesity and normal glucose tolerance will participate in 3 supervised exercise training sessions at 85% VO2max that expends \~400 kcal for 16 weeks.

Behavioral: Exercise

Obesity with Type 2 Diabetes

EXPERIMENTAL

Participants with obesity and type 2 diabetes will participate in 3 supervised exercise training sessions at 85% VO2max that expends \~400 kcal for 16 weeks.

Behavioral: Exercise

Interventions

Exercise BEHAVIORAL

Supervised treadmill exercise at 85% VO2max, 3x/wk for 16 weeks. Exercise duration will be adjusted based on individual VO2-heart rate (HR) relationship so that \~400 kcals will be expended during each training session.

Obesity with Normal Glucose Tolerance; Obesity with Type 2 Diabetes

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female 30 - 80 years old.
• HbA1c \<5.7% and fasting glucose \<100mg/dl to be considered NGT
• T2D diagnosis or confirmation HbA1c ≥6.5% and fasting glucose ≥126 mg/dl
• Prescribed metformin, GLP-1 agonists (oral/injectable), TZDs, DPP-IV inhibitors, Acarbose, SGLT-2 inhibitors ≥6 year.
• Has a body mass index of 20-24.99 or 25.0-45 kg/m2.
• Not diagnosed with Type 1 diabetes.
• Not currently engaged in \>150 min/wk of exercise.

You may not qualify if:

• Participants with morbid obesity (BMI \>45 kg/m2) and underweight patients (BMI: ≤18 kg/m2).
• Intolerance to insulin
• Evidence of type 1 diabetes and diabetics requiring insulin therapy.
• Participants who have not been weight stable (≥2 kg weight change in past 6 months)
• Participants who have been recently active in past 6 months via health screening questions (≥150 min of moderate/high intensity exercise)
• T2D with HbA1c ≥10.0%
• Participants who are smokers or who have quit smoking ≤2 years ago
• Participants prescribed metformin, GLP-1 agonists (oral/injectable), TZDs, DPP-IV inhibitors, Acarbose, SGLT-2 inhibitors within 6 year.
• Hypertriglyceridemic (≥400 mg/dl) and hypercholesterolemic (≥260 mg/dl) participants as determined from LabCorp samples.
• Kidney dysfunction as determined from LabCorp biochemical outcomes (e.g. creatinine (≥1.0 mg/dl), eGFR (≤59 ml/min/1.73), BUN (≥24 mg/dl) as derived from comprehensive metabolic panels).
• Hypertensive (≥160/100 mmHg) at time of screening.
• Abnormal liver function (reflective from comprehensive panel liver enzymes Alk (≥121 IU/L), AST (≥40 IU/L) and ALT (≥32 IU/L) via LabCorp).
• History of significant metabolic, cardiac, cerebrovascular, hematological, pulmonary, gastrointestinal, liver, renal, or endocrine disease or cancer that in the investigator's opinion would interfere with or alter the outcome measures, or impact subject safety.
• Pregnant (as evidenced by positive pregnancy test) or nursing women
• Participants with contraindications to participation in an exercise training program

Sponsors & Collaborators

• Rutgers, The State University of New Jersey: lead
• University of Virginia: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (3)

Institute for Food, Nutrition, and Health

New Brunswick, New Jersey, 08901, United States

RECRUITING

Robert Wood Johnson University Hospital Clinical Research Center

New Brunswick, New Jersey, 08901, United States

RECRUITING

Rutgers University Loree Gymnasium

New Brunswick, New Jersey, 08901, United States

RECRUITING

Related Publications (9)

• Zhang M, Wang L, Chen Z. Research progress of extracellular vesicles in type 2 diabetes and its complications. Diabet Med. 2022 Sep;39(9):e14865. doi: 10.1111/dme.14865. Epub 2022 May 20.

  PMID: 35509124 BACKGROUND

• Nozaki T, Sugiyama S, Koga H, Sugamura K, Ohba K, Matsuzawa Y, Sumida H, Matsui K, Jinnouchi H, Ogawa H. Significance of a multiple biomarkers strategy including endothelial dysfunction to improve risk stratification for cardiovascular events in patients at high risk for coronary heart disease. J Am Coll Cardiol. 2009 Aug 11;54(7):601-8. doi: 10.1016/j.jacc.2009.05.022.

  PMID: 19660689 BACKGROUND

• Ragland TJ, Heiston EM, Ballantyne A, Stewart NR, La Salvia S, Musante L, Luse MA, Isakson BE, Erdbrugger U, Malin SK. Extracellular vesicles and insulin-mediated vascular function in metabolic syndrome. Physiol Rep. 2023 Jan;11(1):e15530. doi: 10.14814/phy2.15530.

  PMID: 36597186 BACKGROUND

• Heiston EM, Ballantyne A, Stewart NR, La Salvia S, Musante L, Lanningan J, Erdbrugger U, Malin SK. Insulin infusion decreases medium-sized extracellular vesicles in adults with metabolic syndrome. Am J Physiol Endocrinol Metab. 2022 Oct 1;323(4):E378-E388. doi: 10.1152/ajpendo.00022.2022. Epub 2022 Jul 20.

  PMID: 35858245 BACKGROUND

• Heiston EM, Ballantyne A, La Salvia S, Musante L, Erdbrugger U, Malin SK. Acute exercise decreases insulin-stimulated extracellular vesicles in conjunction with augmentation index in adults with obesity. J Physiol. 2023 Nov;601(22):5033-5050. doi: 10.1113/JP282274. Epub 2022 Feb 16.

  PMID: 35081660 BACKGROUND

• Eichner NZM, Gilbertson NM, Heiston EM, Musante L, LA Salvia S, Weltman A, Erdbrugger U, Malin SK. Interval Exercise Lowers Circulating CD105 Extracellular Vesicles in Prediabetes. Med Sci Sports Exerc. 2020 Mar;52(3):729-735. doi: 10.1249/MSS.0000000000002185.

  PMID: 31609300 BACKGROUND

• Hallmark R, Patrie JT, Liu Z, Gaesser GA, Barrett EJ, Weltman A. The effect of exercise intensity on endothelial function in physically inactive lean and obese adults. PLoS One. 2014 Jan 20;9(1):e85450. doi: 10.1371/journal.pone.0085450. eCollection 2014.

  PMID: 24465565 BACKGROUND

• Steinberg HO, Chaker H, Leaming R, Johnson A, Brechtel G, Baron AD. Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance. J Clin Invest. 1996 Jun 1;97(11):2601-10. doi: 10.1172/JCI118709.

  PMID: 8647954 BACKGROUND

• Solomon TP, Malin SK, Karstoft K, Haus JM, Kirwan JP. The influence of hyperglycemia on the therapeutic effect of exercise on glycemic control in patients with type 2 diabetes mellitus. JAMA Intern Med. 2013 Oct 28;173(19):1834-6. doi: 10.1001/jamainternmed.2013.7783. No abstract available.

  PMID: 23817567 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Obesity

Interventions

Exercise

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Steven K Malin, PhD

  Rutgers University - New Brunswick

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Steven K Malin, PhD

CONTACT

848-932-7540; steven.malin@rutgers.edu

Emily M Heiston, PhD

CONTACT

848-932-7540; emily.heiston@rutgers.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: This is a between-within clinical trial study design. Groups (lean, obese/normal glucose tolerance, type 2 diabetes) will be matched on age and sex while those with obesity and normal glucose tolerance (NGT) will have matched BMI to type 2 diabetes (T2D) for cross-sectional comparisons. People with obesity and NGT as well as obesity with T2D will undergo exercise training for 16 weeks to determine EV changes in comparison to lean controls.

Study Record Dates

• First Submitted: August 6, 2024
• First Posted: August 9, 2024
• Study Start: February 10, 2025
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): April 1, 2029
• Last Updated: January 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)