Exercise Physiology Study

NCT03090451 | Completed

• 1 other identifier: 16761
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

People with type 1 diabetes often find exercise very difficult to manage, because of the high risk for low blood glucose levels. This can occur very quickly once exercise starts and presents many risks for subjects, such as severe symptoms, confusion, passing out, seizures, and even coma or death in very severe cases. Preventing low blood glucose levels during and after exercise is important because physical exercise is a key component of managing diabetes. It is often hard to correctly adjust insulin infusion rates or doses before exercise as the relationship between exercise and changes in glucose levels in those who have type 1 diabetes is still not fully understood. Therefore, the investigators propose this study to further our understanding in this area. This study is designed to help separate the effects of insulin from those of muscle work (non-insulin effects) on the changes in blood glucose levels during aerobic exercise. The main hypothesis is that the non-insulin effects occur quickly during exercise and account for the rapid change in blood glucose levels once aerobic exercise begins. These effects can be separated from the slower changes in insulin sensitivity that occur because of exercise, and which account for reduced insulin demand even after exercise has stopped. The investigators will investigate the effects of both moderate and intense aerobic exercise at different levels of insulin in the body to help separate the insulin and non-insulin effects. The investigators wish to recruit 26 subjects to take part in this study. Subjects will be randomly divided into two groups, with 13 in each group. Group 1 will undergo moderate aerobic exercise, while group 2 will undergo intense aerobic exercise. Each subject will repeat the exercise study three times on three separate days at least 2 weeks apart, while having insulin infused at a low, a medium, and a high rate. Subjects will have an IV line placed in each arm, one for drawing blood relatively frequently during the study, and another for infusion of insulin, glucose, and a special glucose tracer (non-radioactive). Each study lasts about 9 hours. Information from this study will be used to help develop a mathematical model of how glucose changes during exercise in type 1 diabetes. Such a model of type 1 diabetes and exercise will be very useful for adjusting insulin doses in patients who use multiple daily injections of insulin, and can help to guide an automated insulin delivery system, such as the artificial pancreas.

Conditions

Type 1 Diabetes Mellitus; Hypoglycemia

Keywords

Insulin; Glucose Clamp; Glucose Tracer; Artificial Pancreas; Exercise; Aerobic

Outcome Measures

Primary Outcomes (1)

• Non-insulin mediated glucose uptake (NIMGU)

  Rate of disappearance of glucose in \[mg/kg\]/min during exercise that is not related to the insulin effect, as calculated using a non-steady state model of glucose dynamics. This will be compared to the baseline NIMGU before exercise.

  At baselin and at 30 minutes into physical exercise

Secondary Outcomes (5)

• Insulin mediated glucose uptake (IMGU)

  At baseline and at 30 minutes into physical exercise

• Mean glucose level

  9 hours

• Time spent in severe hypoglycemia

  9 hours

• Time spent in hypoglycemia

  9 hours

• Time spent in hyperglycemia

  9 hours

Study Arms (2)

Moderate Aerobic Exercise

EXPERIMENTAL

Subjects will undergo moderate aerobic physical exercise (40-45% of VO2-max) on three separate days at i) low insulin levels, ii) medium insulin levels, and iii) high insulin levels.

Behavioral: Aerobic Exercise

Intense Aerobic Exercise

EXPERIMENTAL

Subjects will undergo intense aerobic physical exercise (60-65% of VO2-max) on three separate days at i) low insulin levels, ii) medium insulin levels, and iii) high insulin levels.

Behavioral: Aerobic Exercise

Interventions

Aerobic Exercise BEHAVIORAL

Aerobic physical exercise on treadmill, with intensity based on prior VO2-max testing during the screening visit.

Intense Aerobic Exercise; Moderate Aerobic Exercise

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosis of type 1 diabetes mellitus for at least 1 year.
• Male or female subjects 18 to 45 years of age.
• Physically willing and able to perform 45 minutes of physical exercise, as determined by the investigator after reviewing the subject's activity level.
• A hemoglobin A1c (HbA1c) less than 10%.
• Willingness to follow all study procedures, including attending all study visits.
• Willingness to sign informed consent and HIPAA documents.

You may not qualify if:

• Female of childbearing potential who is pregnant, intending to become pregnant, breast-feeding, or is not using adequate contraceptive methods. Acceptable contraception includes birth control pill/patch/vaginal ring, Depo-Provera, Norplant, an IUD, the double barrier method (the woman uses a diaphragm and spermicide and the man uses a condom), or abstinence.
• Renal insufficiency (GFR \< 60 ml/min, using the MDRD equation as reported by the OHSU laboratory).
• Liver failure, cirrhosis, or any other liver disease that compromises liver function as determined by the investigator.
• Hematocrit of less than 34%.
• Hypertension with systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg despite treatment or who have treatment-refractory hypertension (e.g. requiring four or more medications).
• History of severe hypoglycemia during the past 12 months prior to screening visit or hypoglycemia unawareness as judged by the investigator. Subjects will complete a hypoglycemia awareness questionnaire (included in Appendix A). Subjects will be excluded for four or more 'R' responses.
• Adrenal insufficiency.
• Any active infection.
• Known of suspected abuse of alcohol, narcotics, or illicit drugs.
• Seizure disorder.
• Active foot ulceration.
• Severe peripheral arterial disease characterized by ischemic rest pain or severe claudication.
• Major surgical operation within 30 days prior to screening.
• Use of an investigational drug within 30 days prior to screening.
• Chronic usage of any immunosuppressive medication (such as cyclosporine, azathioprine, sirolimus, or tacrolimus).

Sponsors & Collaborators

• Oregon Health and Science University: lead

Study Sites (1)

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Related Publications (13)

• American Diabetes Association. Economic costs of diabetes in the U.S. in 2012. Diabetes Care. 2013 Apr;36(4):1033-46. doi: 10.2337/dc12-2625. Epub 2013 Mar 6.

  PMID: 23468086 BACKGROUND

• Livingstone SJ, Levin D, Looker HC, Lindsay RS, Wild SH, Joss N, Leese G, Leslie P, McCrimmon RJ, Metcalfe W, McKnight JA, Morris AD, Pearson DW, Petrie JR, Philip S, Sattar NA, Traynor JP, Colhoun HM; Scottish Diabetes Research Network epidemiology group; Scottish Renal Registry. Estimated life expectancy in a Scottish cohort with type 1 diabetes, 2008-2010. JAMA. 2015 Jan 6;313(1):37-44. doi: 10.1001/jama.2014.16425.

  PMID: 25562264 BACKGROUND

• Rusavy Z, Lacigova S. [Life expectancy of people with type 1 diabetes in the past and today]. Vnitr Lek. 2014 Sep;60(9):765-71. Czech.

  PMID: 25294766 BACKGROUND

• Naik RG, Brooks-Worrell BM, Palmer JP. Latent autoimmune diabetes in adults. J Clin Endocrinol Metab. 2009 Dec;94(12):4635-44. doi: 10.1210/jc.2009-1120. Epub 2009 Oct 16.

  PMID: 19837918 BACKGROUND

• Yardley JE, Hay J, Abou-Setta AM, Marks SD, McGavock J. A systematic review and meta-analysis of exercise interventions in adults with type 1 diabetes. Diabetes Res Clin Pract. 2014 Dec;106(3):393-400. doi: 10.1016/j.diabres.2014.09.038. Epub 2014 Oct 7.

  PMID: 25451913 BACKGROUND

• Quirk H, Blake H, Tennyson R, Randell TL, Glazebrook C. Physical activity interventions in children and young people with Type 1 diabetes mellitus: a systematic review with meta-analysis. Diabet Med. 2014 Oct;31(10):1163-73. doi: 10.1111/dme.12531.

  PMID: 24965376 BACKGROUND

• Breton MD, Brown SA, Karvetski CH, Kollar L, Topchyan KA, Anderson SM, Kovatchev BP. Adding heart rate signal to a control-to-range artificial pancreas system improves the protection against hypoglycemia during exercise in type 1 diabetes. Diabetes Technol Ther. 2014 Aug;16(8):506-11. doi: 10.1089/dia.2013.0333. Epub 2014 Apr 4.

  PMID: 24702135 BACKGROUND

• Jacobs PG, Resalat N, El Youssef J, Reddy R, Branigan D, Preiser N, Condon J, Castle J. Incorporating an Exercise Detection, Grading, and Hormone Dosing Algorithm Into the Artificial Pancreas Using Accelerometry and Heart Rate. J Diabetes Sci Technol. 2015 Oct 5;9(6):1175-84. doi: 10.1177/1932296815609371.

  PMID: 26438720 BACKGROUND

• Tansey MJ, Tsalikian E, Beck RW, Mauras N, Buckingham BA, Weinzimer SA, Janz KF, Kollman C, Xing D, Ruedy KJ, Steffes MW, Borland TM, Singh RJ, Tamborlane WV; Diabetes Research in Children Network (DirecNet) Study Group. The effects of aerobic exercise on glucose and counterregulatory hormone concentrations in children with type 1 diabetes. Diabetes Care. 2006 Jan;29(1):20-5. doi: 10.2337/diacare.29.1.20.

  PMID: 16373890 BACKGROUND

• Diabetes Research in Children Network (DirecNet) Study Group; Tsalikian E, Kollman C, Tamborlane WB, Beck RW, Fiallo-Scharer R, Fox L, Janz KF, Ruedy KJ, Wilson D, Xing D, Weinzimer SA. Prevention of hypoglycemia during exercise in children with type 1 diabetes by suspending basal insulin. Diabetes Care. 2006 Oct;29(10):2200-4. doi: 10.2337/dc06-0495.

  PMID: 17003293 BACKGROUND

• Schiavon M, Dalla Man C, Kudva YC, Basu A, Cobelli C. In silico optimization of basal insulin infusion rate during exercise: implication for artificial pancreas. J Diabetes Sci Technol. 2013 Nov 1;7(6):1461-9. doi: 10.1177/193229681300700606.

  PMID: 24351172 BACKGROUND

• Jacobs PG, El Youssef J, Castle JR, Engle JM, Branigan DL, Johnson P, Massoud R, Kamath A, Ward WK. Development of a fully automated closed loop artificial pancreas control system with dual pump delivery of insulin and glucagon. Annu Int Conf IEEE Eng Med Biol Soc. 2011;2011:397-400. doi: 10.1109/IEMBS.2011.6090127.

  PMID: 22254332 BACKGROUND

• Nguyen TP, Jacobs PG, Castle JR, Wilson LM, Kuehl K, Branigan D, Gabo V, Guillot F, Riddell MC, Haidar A, El Youssef J. Separating insulin-mediated and non-insulin-mediated glucose uptake during and after aerobic exercise in type 1 diabetes. Am J Physiol Endocrinol Metab. 2021 Mar 1;320(3):E425-E437. doi: 10.1152/ajpendo.00534.2020. Epub 2020 Dec 28.

  PMID: 33356994 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Hypoglycemia; Insulin Resistance; Motor Activity

Interventions

Exercise

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Hyperinsulinism; Behavior

Intervention Hierarchy (Ancestors)

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

Study Officials

• Joseph El Youssef, MD

  Oregon Health and Science University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: No masking for this study.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Two main arms: 1) moderate aerobic exercise, 2) intense aerobic exercise. In each arm, subjects will undergo three separate studies, i) at low insulin levels, ii) at medium insulin levels, and iii) at high insulin levels.

Study Record Dates

• First Submitted: March 7, 2017
• First Posted: March 24, 2017
• Study Start: May 1, 2017
• Primary Completion: December 14, 2018
• Study Completion: June 18, 2019
• Last Updated: August 28, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)