The study aims to assess the impact of the P4 approach on established markers of glucose metabolism in type 2 diabetics.

Secondary objectives are examination of the changes in physical characteristics, quality of life and the indices for beta cell function, hepatic insulin resistance and muscle insulin resistance .

This study will be a proof-of-principle exploratory study. Subjects in the P4 program will receive a personalized diagnosis and treatment. After investigation of the status of the different organs involved in diabetes (liver, muscle, pancreas), subjects in the P4 group are divided into 3 subgroups. Each subgroup receives a personalized lifestyle advice. This lifestyle advice may comprise different interventions, i.e. very low calorie diet, low calorie diet, strength training, endurance training. Dependent on the type of intervention, these interventions will be supervised by a dietitian or physiotherapist.

All subjects will visit a central study center 5 times during the study and 3 times during follow-up. During these visits physical measures will be taken and data will be collected by the general practitioner assistant.

After the three month intervention period the subjects will return to usual care via the general practitioner.

Inclusion Criteria:

1. Healthy as assessed by the

   • health and lifestyle questionnaire, (P9607 F02; in Dutch)
   • physical examination
   • results of the pre-study laboratory tests

2. Age 30-80 years

3. Stable BMI 25-35 kg/m2

4. Diagnosis diabetes type 2 based upon:

   Fasting glucose >6.9 mmol/l on two different days or one measurement of non-fasting glucose >11.0 mmol/l in combination with symptoms of hyperglycemia

5. Duration of diabetes maximally 1 year

6. Informed consent signed;

7. Willing to comply with the study procedures during the study;

8. Appropriate veins for blood sampling/ cannula insertion according to the general practitioner assistant (GPA);

9. Voluntary participation

10. Physically able to perform training activities

11. Willing to accept use of all nameless data, including publication, and the confidential use and storage of all data for at least 15 years.

Exclusion Criteria:

1. Use of insulin, corticosteroids (systemic), or beta-blockers in past month
2. Diabetes occurring after several attacks of pancreatitis known as pancreatic diabetes
3. Slow onset type 1 diabetes
4. Use of oral diabetes medication in past year
5. (Having a history of a) medical condition that might significantly affect the study outcome as judged by the medical investigator and health and life style questionnaire. This includes diabetes type 1, gastrointestinal dysfunction, diseases related to inflammation or allergy, or a psychiatric disorder.
6. Hypertension: systolic blood pressure >160 mmHg, diastolic blood pressure >90 mmHg
7. Kidney problems based upon proteinuria and creatinine >150 mmol/l
8. Insufficient beta cell function based on Disposition index < 1.5 as determined during the OGTT in study on day 01*
9. Physical activity higher than according to the Diabetes guidelines (moderate intensity one hour a day, seven days a week (overweight adults))
10. Alcohol consumption > 21 (women) - 28 (men) units/week
11. Reported unexplained weight loss or gain of > 2 kg in the month prior to the pre-study screening
12. Recent blood donation (<1 month prior to the start of the study)
13. Not willing to give up blood donation during the study
14. Personnel of TNO and their partner
15. Not having a general practitioner
16. Not willing to accept information-transfer concerning participation in the study, or information regarding his health, like laboratory results, findings at anamnesis or physical examination and eventual adverse events to and from his general practitioner.