Short summary

The optimal strategy to prevent cardiovascular disease (CVD) among persons with type 2 diabetes (T2D) remains uncertain. 

By combining CT imaging for the purpose to detect subclinical atherosclerosis and new medical treatment, we strongly believe that we can develop individualized treatment algorithms which significantly reduce CVD morbidity and mortality in persons with T2D.

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Rationale

The optimal strategy to prevent cardiovascular disease (CVD) among persons with type 2 diabetes (T2D) remains uncertain. Coronary artery calcification (CAC) is easily detected by cardiac non-contrast computed tomography (CT) and documented to significantly improve the risk classification. Indeed, CAC score measurements have been suggested to optimize CVD risk stratification in the general population.

By combining new technology and new medical treatment, we strongly believe that we can develop individualized treatment algorithms which significantly reduce CVD morbidity and mortality in persons with T2D.

Method:

Design: Randomized screening and intervention trial. No exclusions.

Participants: 33.000, 40-59 year old men and women are randomized (1:1) to a CVD screening (screening group) or to usual care without any screening (control group).

Screening: Non-contrast cardiac CT, brachial and ankle blood pressure and blood- and urine-analyzes to measure and detect: CAC, atrial fibrillations, aneurisms, peripheral arterial disease, hypertension, HbA1c, B-type natriuretic peptide, lipids and albuminuria. After the screening examination the participants are allocated to one of four risk groups.

Intervention: The intervention is depending on the risk group and the participants are treated with: statin, aspirin, rivaroxaban, GLP1 agonists, SGLT2 inhibitor, PSK9-inhibitor or nothing.

Outcome: Registry-based follow-up on all-cause mortality after 8 years. Secondary outcomes are CVD, potential harms, quality of life and costs.

Sample size: The all-cause mortality rate in the control group is estimate to be 9.2%. A reduction at 10% is expected. To prove this, we need to include 33,000 T2D patients with probability of a type 1 error=5% and type II error=80%.

Blinding: Because of the complexity, masking is not possible. However, the control group is not notified at any time about their role in the trial.

Statistical methods: Intention-to-treat principle for all analyses.

Discussion:

It positive effects are shown this study might be a paradigm shift in the prevention of CVD in persons with T2D.

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Description of the cohort

40-59 year old men and women with type 2 diabetes

Data and biological material

Medical interview

Blood and urine measurements: HbA1c, C-peptid, GAD antibodies, BNP, lipids, hemoglobin, creatinine, Natrium, Potassium, creatine kinase (CK), alanine aminotransferase (ALAT), C-reactive protein, and albuminuria are measured.

Imaging database including: non-contrast cardiac CT scan and a non-contrast CT scanning proximal from the mandibular bone and distally to the proximal third of the femur.

Biological material including blood samples is stored.

Collaborating researchers and departments

The Executive Committee consists of:

Department of Cardiology, OUH

• Professor Axel Diederichsen

Department of Cardiothoracic and Vascular Surgery, OUH

• Professor Jes Lindholt 

Department of Endocrinology, OUH

• Professor Jan Frystyk

The Steering Committee will consist of members of the executive committee and:

Representatives from the screening sites: 

Department of Cardiology, Rigshospitalet, Copenhagen

• Associated professor Klaus Fuglsang Kofoed

• Professor Michael Hecht Olsen (Holbæk)
• Consultant Marek Karon (Nykøbing Falster)
• Associated professor Jess Lambrechtsen (Svendborg)
• Consultant Flemming Hald (Vejle)
• Consultant Frank-Peter Elpert (Åbenrå)
• Consultant Allan Roholt (Esbjerg)
• Associated professor Lars Frost (Silkeborg)

Representatives from the STENO centers: 

STENO Diabetes Center Copenhagen

• Professor Peter Rossing

STENO Diabetes Centre Sjælland

• Professor Lise Tarnow

STENO Diabetes Centre Odense

• Professor Jan Erik Henriksen

STENO Diabetes Center Aarhus

• Professor Niels Jessen 

Identification of persons with T2D: 

Department of Clinical Pharmacology, OUH

• Professor Jesper Hallas

Department of Clinical Biochemistry, OUH

• Professor Lars Melholt Rasmussen

Steno Diabetes Center Aarhus

• Professor Niels Jessen

Aarhus University

• Health economics: Professor Rikke Søgaard

Database management and register-based research: 

Odense Patient data Explorative Network, OPEN - Odense Patient data Explorative Network

• Associate professor Katrine Hass Rubin, PhD, MHS

Department of Nuclear Medicine, OUH

• Biostatistician Oke Gerke, PhD