Individualized Lifestyle Intervention in Subjects With Prediabetes

Study Overview
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Brief Summary
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The purpose of this prospective randomized multicenter intervention study is to determine whether in the prevention of Diabetes an intensified lifestyle intervention is superior to a conventional lifestyle intervention in high risk non-Responder subjects. Further, the intensive phenotyping to determine subgroups with an increased risk for diabetes enables an individualized prevention and therapy of type 2 diabetes mellitus.

Detailed Description
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The study start with an intensive phenotyping at baseline (initial examination) to determine subjects with prediabetes. These high risk non-Responder are randomized in two arms (intensified vs normal lifestyle intervention)with equal number of subjects (n=250). The results are compared with each other at the end of the study. The low risk Responder are randomized in two arms (normal vs. once lifestyle intervention = control group) with equal number of subjects (n=250). After the screening at baseline the 12 month lifestyle intervention starts for lifestyle intervention groups. The different therapy groups are formed as described before. The subjects with intensified lifestyle intervention get 16 consultations, the subjects with normal lifestyle intervention get 8 consultations, the subjects of the control group get one consultation to learn more about a healthier lifestyle. During the whole study there is a continuous supervision from physician and nutritional advisers and the subjects have to document a nutrition and an exercise protocol as well as subjective measurements. At baseline, after 24 weeks and at follow up 1, 2 and 3 years later there is an elaborate metabolic characterization of all subjects (also the Responder groups) a 75 g venous oral glucose tolerance test (OGTT) as well as an analysis of the distribution of body fat confirmed by MR-Imaging and proton magnetic resonance spectroscopy by 3 T whole body imager.

Official Title
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Prediabetes Lifestyle Intervention Study

Conditions
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Diabetes Mellitus Type 2

Intervention / Treatment
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* Behavioral: intensified lifestyle intervention
* Behavioral: normal lifestyle intervention
* Behavioral: Single lifestyle advice


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: impaired fasting glucose (IFG) fasting blood glucose 99-126 mg/dl and/or impaired glucose tolerance (IGT) 75 g OGTT 120 minutes: 139-200 mg/dl Exclusion Criteria: current pregnancy or breastfeeding BMI > 45 kg/m² Diabetes mellitus Typ 1 or 2 serious disease e.g symptomatic coronary heart disease serious symptomatic malignant disease (weight loss > 10% within the last 6 month) severe liver or kidney disease ( an increase in transaminases > 3 times than the upper limit of the standardized range, GFR < 50 ml/min/1,73m²) systemic infection (CRP > 1 mg/dl) severe mental illness drug abuse treatment with steroids potentially incompliant subjects exclusion criteria for magnetic resonance tomography any kind of metal in or on the body: cardiac pacemakers prosthetic heart valves metal prosthesis magnetic implanted metallic parts contraceptive coil metal fragments/ grenade shrapnel fixed braces acupuncture needles insulin pump intraport etc. Field strength > 3 Tesla further tattoos, permanent make-up persons with limited thermosensory or heightened sensitivity to heating persons where cardiovascular disease cannot be ruled out by examination persons with heightened sensitivity to loud noise or diseases of the ear used closed whole body scanner: claustrophobia Additional for spirometry acute coronary syndrome higher cardiac arrhythmia decompensated heart failure acute carditis pulmonary embolism acute deep leg vein thrombosis ( phlebothrombosis) hyperthyroidism (TSH) hypokalemia

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: high risk non-responder, intensified lifestyle intervention<br>high risk non-responder: A) reduced Insulin secretion (disposition index: (IGI * ISI-Matsuda)< 760) B) insulin resistance (ISI-Matsuda < 9,2) C) elevated liver fat ( MRT > 5,56%) A+B or A+C or B+C or A+B+C | Behavioral: intensified lifestyle intervention<br>* physical activity 6 hours per week, 50% guided activity recorded by an accelerometer (Aipermotion 440) 16 sessions per year with a lifestyle advisor nutritional advice (target weight: 5% less, if BMI > 25kg/m², less than 30% fat per caloric intake, less than 10% fatty acids per caloric intake, more than 15 g fibre per 1000 kcl)<br>|
| Active Comparator: hight risk non responder, normal lifestyle intervention<br>high risk non-responder: A) reduced Insulin secretion (disposition index: (IGI * ISI-Matsuda)< 760) B) insulin resistance (ISI-Matsuda < 9,2) C) elevated liver fat ( MRT > 5,56%) A+B or A+C or B+C or A+B+C | Behavioral: normal lifestyle intervention<br>* physical activity 3 hours per week recorded by an accelerometer (Aipermotion 440) 8 sessions per year with a lifestyle advisor nutritional advice (target weight: 5% less, if BMI > 25kg/m², less than 30% fat per caloric intake, less than 10% fatty acids per caloric intake, more than 15 g fibre per 1000 kcl)<br>|
| Active Comparator: Responder, normal lifestyle intervention<br>Responder: A) reduced Insulin secretion (disposition index: (IGI * ISI-Matsuda)< 760) B) insulin resistance (ISI-Matsuda < 9,2) C) elevated liver fat ( MRT > 5,56%) No A, only B or C | Behavioral: normal lifestyle intervention<br>* physical activity 3 hours per week recorded by an accelerometer (Aipermotion 440) 8 sessions per year with a lifestyle advisor nutritional advice (target weight: 5% less, if BMI > 25kg/m², less than 30% fat per caloric intake, less than 10% fatty acids per caloric intake, more than 15 g fibre per 1000 kcl)<br>|
| Active Comparator: Responder, single lifestyle advice (control group)<br>Responder: A) reduced Insulin secretion (disposition index: (IGI * ISI-Matsuda)< 760) B) insulin resistance (ISI-Matsuda < 9,2) C) elevated liver fat ( MRT > 5,56%) No A, only B or C | Behavioral: Single lifestyle advice<br>* - Single Health care advice and lifestyle advice (30 minutes) at the beginning recommend the individual target weight (5% less, if BMI 25> kg/m²)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| postprandial glycaemia (2h plasma glucose level of the 75 g oral glucose tolerance test (OGTT)) |  | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| insulin sensitivity confirmed by 75 g oral glucose tolerance test (OGTT) | insulin resistance is calculated as follows: Insulinogenic index (IGI) = (I30 - I0) / (G30 - G0) ISIest= 10000/²√ ((G0 x I0) x ((G0+G30+G60+G90+G120)/5) x ((I0+I30+I60+I90+I120)/5)) | one year | 
| insulin secretion confirmed by 75 g oral glucose tolerance test (OGTT) | insulin resistance is calculated as follows: Insulinogenic index (IGI) = (I30 - I0) / (G30 - G0) ISIest= 10000/²√ ((G0 x I0) x ((G0+G30+G60+G90+G120)/5) x ((I0+I30+I60+I90+I120)/5)) | one year | 
| distribution of body fat confirmed by MR-Imaging and proton magnetic resonance spectroscopy by 3 T whole body imager |  | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes mellitus type 2, impaired glucose tolerance, lifestyle intervention, body fat distribution, prevention