Breaking up Sedentary Time to Improve Glucose Control in a Population at Risk for Developing Type 2 Diabetes

Pre-diabetes Clinical Trial

— BURST2D  

Official title:

Breaking up Sedentary Time to Improve Glucose Control in a Population at Risk for Developing Type 2 Diabetes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05041491
• Other study ID #: 20-1900
• Status: Recruiting
• Phase: Early Phase 1
• Start date: November 30, 2021
• Est. completion date: October 15, 2025

Study information

• Verified date: April 2024
• Source: University of Colorado, Denver
• Contact: Patricia Smith, MS, RDN
• Phone: 303.724.6821
• Email: trish.smith[@]cuanschutz.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Newly released guidelines recommend increased physical activity (PA) and reduced sedentary behaviors (SB) to improve glycemia and prevent the onset and progression of type 2 diabetes (T2D). Typically, 30-60 min bouts of PA are advocated per day. Although this approach increases PA, it does not decrease the length of the sedentary periods through the day. This is important because recent epidemiological data suggest that frequently interrupting sedentary time improves glucose control even in people who achieve the recommended levels of PA. Preliminary experimental data suggest that breaking up prolonged sedentary time by performing multiple short bouts (5 min) of PA throughout the day, may improve glycemia more than performing a single continuous bout of PA, and thereby potentially be a novel strategy to prevent T2D. The improvement in glycemia was observed even when the total amount of PA and total energy expenditure were matched, suggesting that how and when PA is performed over the day may matter more than how much PA is done. However, important gaps in knowledge remain including: (1) whether similar benefits on glucose control would be observed in adults with prediabetes, a clinically relevant population that is at high risk of developing T2D; (2) whether these effects are sustained or diluted over time, and (3) what are the mechanistic underpinnings. To address these gaps, the investigators propose to measure the acute and chronic effects of PA breaks on glucose control and the underlying mechanisms in individuals at risk of developing T2D. Sedentary men and women with prediabetes (n=66, 50% F) will be randomized to either an intervention designed to interrupt SB with 5-min bouts of brisk walking performed hourly for 9 hours/day, 5 days/week (BREAK) or a control condition consisting of 45-min of brisk walking performed as a single daily continuous bout, 5 days/week (ONE). The two 3-months interventions will be matched for total active time.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 66
• Est. completion date: October 15, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

Inclusion Criteria:

• Male and female

• BMI of 18.5-40 kg/m2and weight stable over the previous 6 months.

• Age, 18-64 years old.

• Fasting glucose of 100-125 mg/dL or fasting HbA1c of 5.7-6.4%, or 2h OGTT blood glucose of 140-199mg/dL based on the American Diabetes Association (ADA) criteria for pre-diabetes.

• Less than 150 minutes of moderate-to-vigorous physical activity (MVPA) per week and more than 6 hours of sitting time per day, as self-reported by the volunteers using the International Physical Activity Questionnaire (IPAQ).

• Less than 6500 of steps per day as measured by a pedometer over 5 days (at least 1 weekend day).

• Passing medical and physical screening, and analysis of blood and urine screening samples.

• Low-moderate caffeine use (<3 cups/day).

• Agree to refrain from any other structured exercise than the physical activity prescribed in each arm of the study.

• Agree to eat control diets for 3 days before and during the Clinical and Translational Research Center (CTRC) visits;

• Agree to refrain from taking any over-the-counter (including nonsteroidal anti-inflammatory drugs) or prescribed medication (apart from oral contraceptives) for 3 days prior to the inpatient CTRC visits;

• Agree to wear a Fitbit® activity monitor and upload data on the website on a daily basis for the whole duration of the study.

• Agree to follow the physical activity interventions and to be randomly assigned to one of the two arms of the study.

• Agree to complete all the study procedures.

Exclusion Criteria:

• Pregnancy, breast-feeding or post-menopause for women.

• Being considered unsafe to participate as determined by the study physician.

• Ever having a history of systemic, psychiatric, neurological disease, or drug and alcohol abuse.

• History of cardiovascular disease, diabetes, uncontrolled hypertension, untreated thyroid, renal, hepatic diseases, dyslipidemia or any other medical condition affecting weight or lipid metabolism.

• Being positive for human immunodeficiency virus or hepatitis B or C.

• Taking medications affecting weight, triglycerides, energy intake/energy expenditure, or sleep in the last 3 months.

• Having abnormal blood chemistry and/or hematology as deemed significant by the study physician.

• Being a smoker or having been a smoker in the 3 months prior to their screening visit.

• Having donated over 400 mL of blood within 3 months (90 days) of screening for the study;

• Working night shifts or traveling across more than 2 time zones within 1 month of and throughout the study.

• Not completing the trial days of BREAK and ONE during the screening period to assess the willingness and ability of the participant to perform each of the interventions.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Glucose Intolerance
• Pre-diabetes
• Prediabetic State

Intervention

Behavioral:
• BREAK
The BREAK intervention is a physical activity regimen.
• ONE
The ONE intervention is a physical activity regimen.

Locations

Country	Name	City	State
United States	University of Colorado Anschutz Medical Campus	Aurora	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
University of Colorado, Denver

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glycemia	Plasma glucose concentration in mg/dL measured before and 30, 60, 90 and 120 min after an oral glucose tolerance test (OGTT, 75g glucose).	Glucose concentration in mg/dl, measured at fasting, during a 2 hour OGTT and after
Secondary	Insulinemia	Plasma insulin concentration in milli-international units per milliliter (mUI/mL) measured before and 30, 60, 90 and 120 min after an oral glucose tolerance test (OGTT, 75g glucose).	Plasma insulin concentration in mUI/mL, measured at fasting, during a 2 hour OGTT and after
Secondary	Mean interstitial glucose concentration	Mean interstitial glucose concentration measured continuously by a glucose monitor placed on the tricep for 24hours for 10 days.	Before and after 1 month and 3 months of intervention
Secondary	Daily glycemia variability	Standard deviation (SD) of interstitial glucose concentration measured continuously by a glucose monitor placed on the tricep 24hours throughout 10 days.	Before and after 1 month and 3 months of intervention
Secondary	Fasting A1c concentration	Fasting A1c concentration expressed in %	Time Frame: Before and after 1 month and 3 months of intervention
Secondary	Fasting fructosamine concentration	Fasting fructosamine concentration in umol/L	Before and after 1 month and 3 months of intervention
Secondary	12-hour exogenous glucose oxidation	Rates of carbon-13 (13C) recovery (% of the dose) in expired carbon dioxide (CO2) following the ingestion of U-13C-glucose in both breakfast and lunch meals.	Before and after 1 month of intervention
Secondary	12-hour endogenous glucose oxidation	Rates of D2 recovery (% of the dose) in expired urines following the infusion of (2,2H2) glucose.	Before and after 1 month of intervention
Secondary	12 hour CO2 production	CO2 production measured by indirect calorimetry (ParvoMedics TrueOne® 2400, Salt Lake City) for 20 minutes every hour from 0800h to 1800h.	Before and after 1 month of intervention
Secondary	12 hour O2 production	O2 production measured by indirect calorimetry (ParvoMedics TrueOne 2400, Salt Lake City) for 20 minutes every hour from 0800h to 1800h.	Before and after 1 month of intervention
Secondary	12 Urine excretion	Urine will be measured every hour from 0730h to 1830h	Before and after 1 month of intervention
Secondary	Glucose kinetics	Steele's equation for non-steady-state will be used to compute rate of appearance of total glucose (RaT) and rate of appearance of exogenous glucose (RaE), as well as the rates of disappearance (RdT and RdE) from the percentage of [6,6-2H2]glucose6 and of 13C-glucose in plasma glucose61. Endogenous glucose production (EGP) will be computed as RaT-RaE. Nonoxidative glucose disposal (NOGD) will be calculated by subtracting total carbohydrate oxidation from (RdT + RdE). Plasma glucose utilization will be assumed to be equivalent to RdT as has been confirmed previously. Muscle glycogen utilization during the active period will be calculated as total carbohydrate utilization during exercise minus plasma glucose utilization during exercise.	Before and after 1 month of intervention
Secondary	Fasting and postprandial glucose	Fasting and postprandial glucose in mg/dl measured in response to standard lunch	Before and after 1 month of intervention
Secondary	Fasting and postprandial insulin	Fasting and postprandial insulin in ml/iu measured in response to standard lunch	Before and after 1 month of intervention
Secondary	Fasting and postprandial C-Peptide	Fasting and postprandial C-peptide nmol/mL measured in response to standard lunch	Before and after 1 month of intervention
Secondary	Fasting and postprandial glucagon	Fasting and postprandial glucagon in pg/mL measured in response to standard lunch	Before and after 1 month of intervention
Secondary	Fasting and postprandial catecholamines	Fasting and postprandial catecholamines in pg/mL measured in response to standard lunch	Before and after 1 month of intervention
Secondary	Skeletal muscle content of protein kinase B (Akt) (Aktser473/total)	Vastus lateralis skeletal muscle biopsies will be collected from fasting participants by the Bergstrom technique. Biopsies will be used to measure protein kinase B (Akt) (Aktser473/total) using western blotting.	Before and after 1 month of intervention
Secondary	Skeletal muscle content of ACC (ACCS79/ total)	Vastus lateralis skeletal muscle biopsies will be collected from fasting participants by the Bergstrom technique. Biopsies will be used to measure ACC (ACCS79/ total) using western blotting.	Before and after 1 month of intervention
Secondary	Skeletal muscle content of TBC1D4 (AS160/ total)	Vastus lateralis skeletal muscle biopsies will be collected from fasting participants by the Bergstrom technique. Biopsies will be used to measure TBC1D4 (AS160/ total) using western blotting.	Before and after 1 month of intervention
Secondary	Skeletal muscle content of COX4	Vastus lateralis skeletal muscle biopsies will be collected from fasting participants by the Bergstrom technique. Biopsies will be used to measure citrate synthase (COX4) using western blotting.	Before and after 1 month of intervention