A Trial Evaluating the Effects of a One-year Lifestyle Intervention in Obese Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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Diabetic patients with uncontrolled disease are often characterized by increased energy expenditure and could thus present a high resting metabolic rate (RMR). Lifestyle interventions aimed at improving glucose control in these patients may lead to reductions of futile pathways, resulting in lower rates of energy expenditure, and paradoxically to making it more difficult to lose weight. However, only few studies investigated how exercise could influence patients' RMR and results are still not unanimous. In this study, we aim to investigate the effects on metabolic health of a combined dietary intervention and 12-week exercise training in obese adults with type 2 diabetes.

Detailed Description
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Although a number of exercise training interventions have been proposed to type 2 diabetes patients, the current clinical practice demonstrates that most patients are still sedentary and with excess body weight. A negative balance between energy intake and energy expenditure is crucial to reduce excess body weight. However, diabetic patients with uncontrolled disease are often characterized by increased energy expenditure and could thus present a high resting metabolic rate (RMR). Lifestyle interventions aimed at improving glucose control in these patients may lead to reductions of futile pathways, resulting in lower rates of energy expenditure, and paradoxically to making it more difficult to lose weight. However, no robust evidence has been collected on this issue, and the few studies that investigated how exercise could influence patients' RMR have not shown unanimous results, especially concerning combined dietary and physical activity interventions. This open-label randomized trial in obese adults with type 2 diabetes aims to investigate the effects of a 1-year caloric restriction and 12-week exercise training intervention on metabolic health, RMR and VO2max. In particular, eligible type 2 diabetes patients of our clinic will be invited to participate in a short lifestyle intervention (LSI). LSI will consist of four weekly group-led lessons lasting 60-90 minutes in which specialized professionals will educate patients on specific dietary and physical activity recommendations for improving health and metabolic control. After this month, patients will be randomly assigned either to: 1) 1-year caloric restriction with an immediate start of 12-week supervised structured exercise training (SSET) (Early-SSET intervention), followed by no exercise at health centers for 3 months; or: 2) 1-year caloric restriction with no exercise at health centers for 3 months and then a 12-week SSET from month 4 to month 6 (Late-SSET intervention). During the last 6 months participants' activity will be unrestricted. Type 2 diabetic and obese adult volunteers will be recruited and screened through medical history, physical examination and biochemical analyses.

Official Title
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A Randomized Trial Evaluating the Effects of One-Year Caloric Restriction and 12-Week Exercise Training Intervention in Obese Adults With Type 2 Diabetes: Emphasis on Metabolic Control and Resting Metabolic Rate

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Behavioral: Caloric restriction
* Behavioral: Exercise training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent age 30 to 64 years less than 60 min aerobic exercise/week absence of acute diseases no current treatment with insulin or sulfonylureas Exclusion Criteria: Body mass index (BMI)<28 HbA1c<6% Recent acute diseases, severe infections, trauma or surgery Uncontrolled hypertension or hyperglycemia Evidence of advanced cardiovascular, renal or hepatic diseases Contraindication to exercise Body weight change of more than 3% within the last 6 months Medication changes within the last 3 months

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: After the baseline assessment, patients will be randomly assigned either to: 1) 1-year caloric restriction with an immediate start of 12-week supervised structured exercise training (SSET) (Early-SSET intervention), followed by no exercise at health centers for 3 months; or: 2) 1-year caloric restriction with no exercise at health centers for 3 months and then a 12-week SSET from month 4 to month 6 (Late-SSET intervention). During the last 6 months participants' activity will be unrestricted.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Caloric restriction and early SSET<br>Patients will participate to a short lifestyle intervention (LSI), consisting of four weekly group-led lessons lasting 60-90 minutes to educate them on specific dietary and physical activity recommendations for improving health and metabolic control. At the end of the 1-month LSI, participants will start a caloric restriction and early exercise training (SSET) during the first 12-week, followed by no exercise at health centers for 3 months. Between the 6- and the 12-month assessments, participants will continue caloric restriction and will be encouraged to freely exercise. | Behavioral: Caloric restriction<br>* A structured dietary training will be implemented to educate participants about recommended dietary habits.Patients will follow a caloric restriction (CR) diet, with an energy intake equal to the measured Resting Metabolic Rate (RMR) and with 45% carbohydrate, 20%protein, 35%fat, and 30 g/day fibers. At each follow-up, nutritionist will adjust CR to the latest measured RMR and assess the compliance to the diet.<br>* Other names: One-year caloric restriction;Behavioral: Exercise training<br>* Trainers will supervise participants during 12-weeks of structured exercise consisting of 150 min/week workouts, divided in three sessions of progressive mixed (aerobic and resistance) exercise. All aerobic exercise will be performed using treadmill and/or cycle ergo-meter.<br>* Other names: 12-week structured supervised exercise training (SSET);|
| Active Comparator: Caloric restriction and late SSET<br>Patients will participate to a short lifestyle intervention (LSI), consisting of four weekly group-led lessons lasting 60-90 minutes to educate them on specific dietary and physical activity recommendations for improving health and metabolic control. At the end of the 1-month LSI, participants will start a one-year caloric restriction with no exercise at health centers for 3 months, and then a 12-week exercise training (SSET). Between the 6- and the 12-month assessments, participants will continue caloric restriction and will be encouraged to freely exercise. | Behavioral: Caloric restriction<br>* A structured dietary training will be implemented to educate participants about recommended dietary habits.Patients will follow a caloric restriction (CR) diet, with an energy intake equal to the measured Resting Metabolic Rate (RMR) and with 45% carbohydrate, 20%protein, 35%fat, and 30 g/day fibers. At each follow-up, nutritionist will adjust CR to the latest measured RMR and assess the compliance to the diet.<br>* Other names: One-year caloric restriction;Behavioral: Exercise training<br>* Trainers will supervise participants during 12-weeks of structured exercise consisting of 150 min/week workouts, divided in three sessions of progressive mixed (aerobic and resistance) exercise. All aerobic exercise will be performed using treadmill and/or cycle ergo-meter.<br>* Other names: 12-week structured supervised exercise training (SSET);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline Glycated Hemoglobin (HbA1c) at 6 months | Venous blood samples will be collected at morning between 7-9 a.m. for the analysis of Glycated Hemoglobin, performed following standard quality-control procedures. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline Resting Metabolic Rate at 3 months | Resting Metabolic Rate will be measured using an open-circuit indirect calorimeter (Sensor Medics VO2max -229 Metabolic System, CA) under standardized procedures | 3 months | 
| Change from baseline Resting Metabolic Rate at 6 months | Resting Metabolic Rate will be measured using an open-circuit indirect calorimeter (Sensor Medics VO2max -229 Metabolic System, CA) under standardized procedures | 6 months | 
| Change from baseline Resting Metabolic Rate at 12 months | Resting Metabolic Rate will be measured using an open-circuit indirect calorimeter (Sensor Medics VO2max -229 Metabolic System, CA) under standardized procedures | 12 months | 
| Change from baseline Body mass index at 3 months | Body weight will be measured to the nearest 0.1 kg and height to the nearest 1 cm using a standard balance and stadiometer (Seca, Germany), with subjects wearing light clothing and no shoes. Body mass index will be computed from the ratio between weight (kg) and height (m) squared. | 3 months | 
| Change from baseline Body mass index at 6 months | Body weight will be measured to the nearest 0.1 kg and height to the nearest 1 cm using a standard balance and stadiometer (Seca, Germany), with subjects wearing light clothing and no shoes. Body mass index will be computed from the ratio between weight (kg) and height (m) squared. | 6 months | 
| Change from baseline Body mass index at 12 months | Body weight will be measured to the nearest 0.1 kg and height to the nearest 1 cm using a standard balance and stadiometer (Seca, Germany), with subjects wearing light clothing and no shoes. Body mass index will be computed from the ratio between weight (kg) and height (m) squared. | 12 months | 
| Change from baseline Fat-free mass at 3 months | Fat-free mass will be estimated by Dual Energy X-ray Absorptiometry, with fan-beam technology (Hologic QDR 4500 W, Inc.). | 3 months | 
| Change from baseline Fat-free mass at 6 months | Fat-free mass will be estimated by Dual Energy X-ray Absorptiometry, with fan-beam technology (Hologic QDR 4500 W, Inc.). | 6 months | 
| Change from baseline Fat-free mass at 12 months | Fat mass will be estimated by Dual Energy X-ray Absorptiometry, with fan-beam technology (Hologic QDR 4500 W, Inc.). | 12 months | 
| Change from baseline android to gynoid percent fat ratio at 3 months | Android to gynoid percent fat ratio will be estimated by Dual Energy X-ray Absorptiometry, with fan-beam technology (Hologic QDR 4500 W, Inc.). | 3 months | 
| Change from baseline android to gynoid percent fat ratio at 6 months | Android to gynoid percent fat ratio will be estimated by Dual Energy X-ray Absorptiometry, with fan-beam technology (Hologic QDR 4500 W, Inc.). | 6 months | 
| Change from baseline android to gynoid percent fat ratio at 12 months | Android to gynoid percent fat ratio will be estimated by Dual Energy X-ray Absorptiometry, with fan-beam technology (Hologic QDR 4500 W, Inc.). | 12 months | 
| Change from baseline fasting plasma glucose at 3 months | Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and plasma glucose will be assessed following standard quality-control procedures. | 3 months | 
| Change from baseline fasting plasma glucose at 6 months | Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and plasma glucose will be assessed following standard quality-control procedures. | 6 months | 
| Change from baseline fasting plasma glucose at 12 months | Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and plasma glucose will be assessed following standard quality-control procedures. | 12 months | 
| Change from baseline HDL cholesterol at 3 months | Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and HDL cholesterol will be assessed following standard quality-control procedures. | 3 months | 
| Change from baseline HDL cholesterol at 6 months | Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and HDL cholesterol will be assessed following standard quality-control procedures. | 6 months | 
| Change from baseline HDL cholesterol at 12 months | Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and HDL cholesterol will be assessed following standard quality-control procedures. | 12 months | 
| Change from baseline total cholesterol at 3 months | Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and total cholesterol levels will be assessed following standard quality-control procedures. | 3 months | 
| Change from baseline total cholesterol at 6 months | Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and total cholesterol levels will be assessed following standard quality-control procedures. | 6 months | 
| Change from baseline total cholesterol at 12 months | Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and total cholesterol levels will be assessed following standard quality-control procedures. | 12 months | 
| Change from baseline triglycerides levels at 3 months | Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and plasma triglycerides levels will be assessed following standard quality-control procedures. | 3 months | 
| Change from baseline triglycerides levels at 6 months | Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and plasma triglycerides levels will be assessed following standard quality-control procedures. | 6 months | 
| Change from baseline triglycerides levels at 12 months | Venous blood samples will be collected in the morning between 7-9 a.m. after 12 hours of fasting and plasma triglycerides levels will be assessed following standard quality-control procedures. | 12 months | 
| Change from baseline serum creatinine at 3 months | Serum creatinine will be assessed from venous blood samples following standard quality-control procedures. | 3 months | 
| Change from baseline serum creatinine at 6 months | Serum creatinine will be assessed from venous blood samples following standard quality-control procedures. | 6 months | 
| Change from baseline serum creatinine at 12 months | Serum creatinine will be assessed from venous blood samples following standard quality-control procedures. | 12 months | 
| Change from baseline urinary albumin-to-creatinine ratio at 3 months | Urine samples will be collected for the assessment of urinary albumin-to-creatinine ratio (ACR) following standard quality-control procedures. | 3 months | 
| Change from baseline urinary albumin-to-creatinine ratio at 6 months | Urine samples will be collected for the assessment of urinary albumin-to-creatinine ratio (ACR) following standard quality-control procedures. | 6 months | 
| Change from baseline urinary albumin-to-creatinine ratio at 12 months | Urine samples will be collected for the assessment of urinary albumin-to-creatinine ratio (ACR) following standard quality-control procedures. | 12 months | 
| Change from baseline maximal aerobic power at 3 months | VO2max will be measured by the Sensor Medics VO2max -229 Metabolic System using a continuous incremental treadmill protocol (Runner MTC Climb, Italy) according to the modified Naughton protocol. | 3 months | 
| Change from baseline maximal aerobic power at 6 months | VO2max will be measured by the Sensor Medics VO2max -229 Metabolic System using a continuous incremental treadmill protocol (Runner MTC Climb, Italy) according to the modified Naughton protocol. | 6 months | 
| Change from baseline maximal aerobic power at 12 months | VO2max will be measured by the Sensor Medics VO2max -229 Metabolic System using a continuous incremental treadmill protocol (Runner MTC Climb, Italy) according to the modified Naughton protocol. | 12 months | 
| Change from baseline Glycated Hemoglobin (HbA1c) at 3 months | Venous blood samples will be collected at morning between 7-9 a.m. for the analysis of Glycated Hemoglobin, performed following standard quality-control procedures. | 3 months | 
| Change from baseline Glycated Hemoglobin (HbA1c) at 12 months | Venous blood samples will be collected at morning between 7-9 a.m. for the analysis of Glycated Hemoglobin, performed following standard quality-control procedures. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Lifestyle intervention