Diet and Exercise Intervention in Type 2 Diabetes

Study Overview
=================
Brief Summary
-----------------
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.

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).

Official Title
-----------------
Diet and Exercise Intervention in Type 2 Diabetes

Conditions
-----------------
Type 2 Diabetes

Intervention / Treatment
-----------------
* Behavioral: Intensive Lifestyle Intervention
* Behavioral: Standard Care


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 25-68 yrs old BMI 27.0-50.0 kg/m² 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 HbA1C ≤9.5 %. 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: Any change in diabetes medication in previous 3 months Treated with >0.5 units of insulin/kg body weight per day Unstable weight (>2% change during the last 2 months before entering the study) 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). Evidence of serious cardiac abnormalities during exercise stress testing that increase cardiac risk of initiating an exercise program. Creatinine >1.5 mg/dL Microalbuminuria; spot urine albumin:creatinine ratio >50 (50 μg albumin/mg creatinine) Coagulation disorders Anemia (Hemoglobin <10.0 g/dL) Liver enzymes (ALT and AST) ≥3 times the upper limit of normal Uncontrolled proliferative diabetic retinopathy Severe peripheral neuropathy diagnosed by monofilament testing Severe organ dysfunction Pregnant or breastfeeding Participating in regular exercise (>1 h of structured exercise/week) Joint replacement within the last year Smokes tobacco Severe lactose intolerance Take any medication that might interfere with interpretation of the metabolic studies 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.

Ages Eligible for Study
-----------------
Minimum Age: 25 Years
Maximum Age: 68 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Standard Care<br>Participants randomized to this arm will receive dietary and physical activity instructions as recommended by the American Diabetes Association (ADA) guidelines. | Behavioral: Standard Care<br>* 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).<br>|
| Experimental: Intensive Lifestyle intervention<br>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<br>* 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.<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Type 2 diabetes, Exercise, Weight loss