Diet and Exercise Intervention in Type 2 Diabetes (LID)

The purpose of this study is to determine the effect of a worksite-based intensive lifestyle therapy intervention (weight loss with exercise training) on blood sugar control in people with obesity and type 2 diabetics.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Behavioral: Standard Care; Behavioral: Intensive Lifestyle Intervention

Detailed Description

The purpose of this study is to conduct a randomized, controlled trial in people with obesity and type 2 diabetes to determine the therapeutic effects of intensive lifestyle therapy conducted at the worksite compared to standard care on: i) the major factors involved in the pathogenesis of type 2 diabetes (insulin sensitivity, β-cell function and the metabolic response to glucose ingestion), ii) body composition; iii) physical function (cardiorespiratory fitness and muscle strength); iv) and the potential cellular mechanisms that can affect insulin action in muscle and adipose tissue (fat).

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 25-68 yrs old
2. BMI 27.0-50.0 kg/m²
3. Diagnosis of type 2 diabetes based on HbA1C>6.5% or results of an oral glucose tolerance test or current use of anti-diabetic medications
4. HbA1C ≤9.5 %.
5. Work at Washington University in St. Louis, Barnes Jewish Hospital, St. Louis Children's Hospital, Shriners, St. Louis College of Pharmacy, Central Institute for the Deaf, Rehabilitation Institute of St. Louis, and/or any institutions affiliated with these.

Exclusion Criteria:

1. Any change in diabetes medication in previous 3 months
2. Treated with >0.5 units of insulin/kg body weight per day
3. Unstable weight (>2% change during the last 2 months before entering the study)
4. History or evidence of serious pulmonary or cardiovascular disease, including acute coronary syndrome, heart failure requiring medications, or New York Heart Association class III heart failure (patients with marked limitation of activity and who are comfortable only at rest) or IV heart failure (patients who should be at complete rest, confined to bed or chair and who have discomfort with any physical activity).
5. Evidence of serious cardiac abnormalities during exercise stress testing that increase cardiac risk of initiating an exercise program.
6. Creatinine >1.5 mg/dL
7. Microalbuminuria; spot urine albumin:creatinine ratio >50 (50 μg albumin/mg creatinine)
8. Coagulation disorders
9. Anemia (Hemoglobin <10.0 g/dL)
10. Liver enzymes (ALT and AST) ≥3 times the upper limit of normal
11. Uncontrolled proliferative diabetic retinopathy
12. Severe peripheral neuropathy diagnosed by monofilament testing
13. Severe organ dysfunction
14. Pregnant or breastfeeding
15. Participating in regular exercise (>1 h of structured exercise/week)
16. Joint replacement within the last year
17. Smokes tobacco
18. Severe lactose intolerance
19. Take any medication that might interfere with interpretation of the metabolic studies
20. Unable or unwilling to follow the study protocol or for any reason the research team believes the volunteer is not an appropriate candidate for this study, including non-compliance with screening appointments or previous medical visits.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Standard Care; Participants randomized to this arm will receive dietary and physical activity instructions as recommended by the American Diabetes Association (ADA) guidelines.	Behavioral: Standard Care; After receiving dietary and physical activity instructions as recommended by the American Diabetes Association (ADA) guidelines participants will meet approximately every month for about 7 months with a study team member to record body weight, review diet and physical activity behaviors, and document medication use. Participants will continue their routine medical management, including regular clinic visits with their personal physician and/or diabetes educator during their participation in this study. Any changes medications will made by the participants' personal physician(s).
Experimental: Intensive Lifestyle intervention; Participants randomized to this arm will be participate in weekly dietary and behavioral education session in addition to four 60-min supervised exercise training sessions per week for 8 months. All dietary and- behavioral education and exercise training sessions will be conducted at the worksite.	Behavioral: Intensive Lifestyle Intervention; Participants will be instructed to consume ~500 kcal/day less than their calculated estimated total daily energy requirements. The supervised exercise program will include both endurance and resistance exercise training sessions. The doses of diabetes medications will be adjusted by study physicians every 1-2 weeks, as needed to avoid hypoglycemia.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Skeletal muscle insulin sensitivity	Skeletal muscle insulin sensitivity will be calculated as the glucose disposal rate per kg fat-free mass divided by plasma insulin during a hyperinsulinemic-euglycemic clamp procedure.	7-8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver insulin sensitivity	Liver insulin sensitivity will be assessed by using the hepatic insulin sensitivity index.	7-8 months
Adipose tissue insulin sensitivity	Adipose tissue insulin sensitivity will be assessed by using the adipose tissue insulin sensitivity index.	7-8 months
β-cell function	β-cell function will be assessed from a modified oral glucose tolerance test	7-8 months
Insulin clearance	Insulin clearance will be assessed from a modified oral glucose tolerance test	7-8 months
Diabetes remission	Remission of type 2 diabetes will be defined as HbA1c <6.0% without the use of diabetes medications use of diabetes medications.	7-8 months
Cardiorespiratory fitness	Peak oxygen consumption will be assessed using indirect calorimetry during a graded exercise test to volitional exhaustion.	7-8 months
Muscle strength	Muscle strength will be assessed as the total maximal weight lifted during the 1 repetition maximum tests for leg press, knee flexion, seated row, and chest press exercises.	7-8 months
Whole-body fat mass	Total body fat mass will be assessed by dual-energy X-ray absorptiometry.	7-8 months
Whole-body fat-free mass	Fat-free mass will be assessed by dual-energy X-ray absorptiometry.	7-8 months
Appendicular lean mass	Appendicular lean mass will be assessed by dual-energy X-ray absorptiometry.	7-8 months
Intra-abdominal adipose tissue volume	Intra-abdominal adipose tissue volume will be determined by using magnetic resonance imaging.	7-8 months
Intrahepatic triglyceride content	Intrahepatic triglyceride content will be determined by using magnetic resonance spectroscopy.	7-8 months
Plasma adipokine concentrations	Plasma adiponectin and PAI-1 concentrations will be measured in the Washington University Clinical Core Laboratory.	7-8 months
Transcriptome in muscle and adipose tissue	The transcriptome (all RNA that are responsible for making proteins from DNA templates) will be evaluated by using RNA sequencing techniques.	7-8 months
Skeletal muscle mitochondrial metabolites	The content of muscle mitochondrial-related metabolites will be determined by liquid chromatography mass spectrometry.	7-8 months

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: National Dairy Council; American Egg Board

Publications and helpful links

General Publications

• Yoshino M, Yoshino J, Smith GI, Stein RI, Bittel AJ, Bittel DC, Reeds DN, Sinacore DR, Cade WT, Patterson BW, Cho K, Patti GJ, Mittendorfer B, Klein S. Worksite-based intensive lifestyle therapy has profound cardiometabolic benefits in people with obesity and type 2 diabetes. Cell Metab. 2022 Oct 4;34(10):1431-1441.e5. doi: 10.1016/j.cmet.2022.08.012. Epub 2022 Sep 8.
• Mittendorfer B, Patterson BW, Smith GI, Yoshino M, Klein S. beta Cell function and plasma insulin clearance in people with obesity and different glycemic status. J Clin Invest. 2022 Feb 1;132(3):e154068. doi: 10.1172/JCI154068.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2013
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: October 14, 2013
• First Submitted That Met QC Criteria: October 30, 2013
• First Posted (Estimate): November 6, 2013

Study Record Updates

• Last Update Posted (Actual): April 15, 2022
• Last Update Submitted That Met QC Criteria: April 13, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Exercise; Type 2 diabetes; Weight loss
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 201302095

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No