Increased levels of NT-proBNP are known to increase the risk of cardiac events in diabetic patients. The other way around, patients with normal values have an excellent prognosis on short-term. We intend in our study to proof the hypothesis, whether it is possible to decrease NT-proBNP levels by intensified cardiac prevention care We aim those patients, who already have elevated levels, although no history of a cardiac disease. This decrease in NT-proBNP should be translated consequently in a decrease in cardiac events

Patients with diabetes mellitus have a several-fold increased risk for cardiovascular disease (1-3, 16). Early diagnosis of theses diseases might prevent or at least postpone occurence of clinical manifest CAD and CHF. Multifactorial intervention, with a special interest on cardiac disease are proven to be beneficial for diabetic patients (4). Whether all patients benefit from a multi-drug supply including lipid lowering agents or antihypertensive drugs is not known. Thus, special population have to be defined, who profit most. E.g. the STENO- study population (4) consisted of patients with microalbuminuria. Microalbuminuria is known to be a good marker for outcome in this population (5). Consistently to the fact that microalbuminuria is a good marker for long-term outcome, the STENO-Investigators found a long-term benefit (average 7.8 years) for multi-factorial intervention in this special population. We recently found, that Nt-proBNP (Roche) is an excellent short-term predictor of cardiovascular events and death (10 months on average) in diabetics without a history of cardiac disease (6), which is already known for long-term (7-10). Patients above the normal range have a 10 % risk of first occurrence of a cardiac disease or death within short time. The advantage of Nt-BNP as a marker of risk is based on the fact, that it is increased in all cardiac disease dependent on the severity. Our data reveal that Nt-proBNP is superior to most known markers. The limitations of traditional surrogate marker of risk in diabetic patients was recently discussed in a joint statement of the American Heart and Diabetic Associations ( Diabetes Care 2007 Januar).Whether lowering blood pressure or cholesterol is the optimal surrogate for therapeutic success is questionable. The Jikei Heart study (11) nicely shows a comparable decrease in blood pressure in several treatment groups, but a tremendous difference in outcome. The heart failure paradoxon demonstrates, that in this population patients with low blood pressure (12) or low cholesterol (13) are those with worse prognosis. And heart failure is immanent in diabetes. On the other hand a decrease in Nt-proBNP under therapy is known to be an excellent marker of outcome (14). We hypothesize, that including diabetic patients without a history of cardiac disease but increased levels of Nt-BNP will be an excellent short-term risk-population for prevention therapy. And, decreasing Nt-proBNP levels by optimized therapy will be a good marker for success to decrease the risk for future imminent events

Patients will be randomized into two groups:

Group A: Patients will be cared by a cardiologic unit. In accordance to the guidelines investigations will be performed to proof the existence of a manifest cardiac disease. Further on treatment will be tailored to minimize the individual risk profile in accordance to the guidelines (15). The main therapeutic focus will be a decrease in Nt-proBNP to 50% of the value at index time or below normal values. Secondly, a special focus will be set on optimizing anti-hyperglycemic therapy by a diabetologist (treatment to target). Further guideline-recommended medical treatment will be initiated if not yet started (if no contraindication exists all patients will receive oral anti-platelet therapy and lipid lowering medication). After obtained informed consent, patients will be investigated as clinical appropriate.

Performance of echocardiography is mandatory to exclude aortic stenosis and to proof the existence of heart failure- as recommended by the guidelines. Group A:patients will receive scheduled visits monthly to optimize pharmacologic treatment.

After optimization visits will be performed as clinical appropriate. In between patients have the opportunity to contact a responsible person and will be contacted additionally by telephone to proof therapeutic success. As clinical appropriate every visit laboratory sample will be drawn, demographic data, data about diabetic complications, pulse and blood pressure will be taken, to test, whether treating goals are reached (see CRF for details). After one year a scheduled visit is mandatory to obtain laboratory samples, pulse and blood pressure to proof final therapeutic success based on the goal parameter, cholesterol, Nt-pro-BNP, heart rate, blood pressure, HBA1c. Group B patients will be cared by the treating physicians as before. The patient and the physicians will be informed about the results of the investigations. After 1 year the patients receive a scheduled visit, where demographic data, data about diabetic complications, lab samples, ECG, and blood pressure will be taken. Anamnesis about hospitalization and drug prescription will be obtained. If a patient prematurely dies, data will be obtained by the treating physician or other responsible institutions. After two years only data about hospitalization and death will be obtained by telephone contact with the patient or the Melderegister in Group A and B. Observation period: 1 year Cohort: 150 patients in each group

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Inclusion Criteria:

• Age > 18 years
• Known Diabetes mellitus > 6 months
• Increased Nt-proBNP above 125pg/ml
• Given informed consent

Exclusion Criteria:

• Disease other than diabetes, with a life expectancy below 1 year
• patients who suffer from chronic infection or malignant disease
• Women in childbearing age without contraceptive
• History of cardiac disease
• systemic cortisone treatment
• patients who are on chronic or acute hemodialysis, ultra filtration or peritoneal dialysis