The RISC Study

Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC)

Overview 

The RISC study was launched to investigate whether insulin resistance predicts cardiovascular disease (CVD) independently of traditional risk factors. Conducted in 19 European centers, it became the largest European study to directly measure insulin sensitivity in healthy individuals using the hyperinsulinemic–euglycemic clamp technique.

2002–2004 | Study Design and Recruitment

Between 2002 and November 2004, RISC recruited 1,504 healthy men and women (aged 30–60 years) across 14 European countries. Of these, 1,340 participants underwent full metabolic assessment, including the insulin clamp. These individuals formed the core RISC cohort. The study also included carotid ultrasound imaging to assess intima-media thickness (IMT) as an early marker of atherosclerosis.

Baseline Assessments

Participants underwent extensive testing, including:

• Hyperinsulinemic–euglycemic clamp (gold standard for insulin sensitivity)
• Carotid artery ultrasound (IMT and arterial stiffness)
• Oral and intravenous glucose testing
• Lipid profile and metabolic measurements
• Genetic sampling
• Physical activity monitoring (Actigraph and IPAQ)
• Lifestyle and medical history questionnaires

2007–2008 | 3-Year Follow-up

The 3-year follow-up was completed with 1,081+ participants returning for reassessment (data update as of October 30, 2008).

Participants repeated most baseline tests (excluding the clamp procedure and accelerometer monitoring). Annual phone contacts were maintained, and health status was updated again at year 4.

2015–2020 | 10-Year Follow-up

A long-term follow-up of 10–16 years has been completed in approximately 500 participants.

Publications arising from the RISC project are ongoing and can be found on PubMed. This extended follow-up phase strengthens the longitudinal evaluation of insulin resistance as a predictor of cardiometabolic outcomes.

Key Scientific Findings

Major findings from RISC analyses include:

• Insulin sensitivity was not cross-sectionally associated with carotid IMT.
• Increased IMT frequently reflected normal vascular aging, rather than early atherosclerosis.
• A substantial proportion of otherwise healthy participants met criteria for metabolic syndrome, particularly those with higher insulin resistance measured by the clamp.
• Higher levels of vigorous physical activity were associated with better arterial elasticity and attenuation of age-related arterial stiffening.
• Scientific Impact

RISC data has generated numerous peer-reviewed publications and scientific communications; the study remains a major European reference cohort for understanding the early metabolic determinants of cardiovascular disease.

Scientific Steering Committee

RISC is managed by a Project Management Board (PMB), responsible for:

• Developing and submitting the original proposal to the European Union
• Conducting the study according to the approved protocol and EU contract
• Overseeing scientific strategy and study coordination
• Each PMB member leads a specific work package, reflecting the operational structure of the project.

The committee meets regularly to review progress, coordinate analyses, and evaluate proposals for RISC subprojects.