Incident Myocardial Infarction is Four-fold Higher in Subjects at High Risk for Type 2 Diabetes M.P. McKenna 1 , M. Rowe 1 , J. Kolberg 1 , O. Pedersen 2 , K. Borch-Johnsen 3 , T. Jørgensen 2,4 1 Research, Tethys Bioscience, Emeryville, CA, United States, 2 Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark, 3 Steno Diabetes Center, Copenhagen, Denmark, 4 Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark Presented at the European Association for the Study of Diabetes (EASD) 46th Annual Meeting, September 20–24, 2010, Stockholm, Sweden Aim We and others have observed that subjects at high risk for developing type 2 diabetes mellitus (T2DM) have a higher incidence of primary cardiovascular disease. The aim of this study was to understand the differences between biomarkers of cardiovascular and diabetes risk. Introduction T2DM has been established as a major risk factor for cardiovascular disease, and a significant portion of this risk is known to occur in the prediabetic state 1 . The PreDx ® Diabetes Risk Score (DRS) is a simple and accurate test based on circulating biomarkers that provides a quantitative estimate of the 5-year risk of developing T2DM 2,3 . In this study, we applied a model utilizing the circulating biomarkers of the DRS to the Inter99 study population to assess the 5-year risk of primary cardiovascular events (CVE) for subjects at low, moderate and high risk for T2DM. We compared the cardiovascular risk factor status of high-risk individuals prior to the onset of clinical diabetes with the corresponding risk factor status of individuals who remained free of diabetes during a 5-year follow-up period. The data here show a greater incidence of primary cardiovascular events among high DRS subjects as compared to low DRS subjects, and that certain biomarkers in the DRS are strongly predictive of cardiovascular events. Careful management of cardiovascular risk for patients with a high DRS should therefore be considered. Methods Subjects. Subjects for this study were from the Inter99 cohort, a random population of subjects from the southwestern part of Copenhagen County, Denmark who were drawn from the Danish Civil Registration System to participate in a prevention study for cardiovascular disease 4 . Of the 6,784 subjects who participated at baseline assessment, serum samples were available for the present study from 5,764 subjects. Subjects were excluded from the present study if there was a prior history of cardiovascular disease, if necessary measures needed for the analyses were not available, or if assessment of diabetes outcomes was not available at five year follow-up. Diagnosis of T2DM was based upon criteria from the World Health Organization, defined as either a 2-h plasma glucose of ≥ 11.1 mmol/L [≥200 mg/dL] from an oral glucose tolerance test (OGTT) or fasting plasma glucose (FPG) of ≥7.0 mmol/L [≥ 126 mg/dL] 5 . After applying the exclusion criteria, there were 4,202 subjects in the study. Among these, 171 developed diabetes and 76 exhibited cardiovascular events (26 myocardial infarction, 30 stroke, 31 revascularization) during the follow-up period. Clinical measures and risk scores: At each visit, data were collected regarding lifestyle, anthropometric measures (e.g. blood pressure, waist circumference, height, weight), routine laboratory measures (e.g. HbA1c, FPG and lipids), and OGTT as described previously 4 . The multivariate algorithm for a general cardiovascular risk score (Framingham CVD) and the Reynolds Risk Score (Reynolds) was calculated as reported 6,7 . PreDx Diabetes Risk Score (DRS): The risk of developing T2DM within five years was expressed as the DRS, which was calculated from quantitative measures of seven circulating biomarkers in baseline samples 2 . Quantification of FPG, fasting serum insulin and HbA1c was determined at Steno Diabetes Center, Copenhagen, Denmark 4 . HbA1c concentrations were determined by ion exchange HPLC (BioRad, USA) with a coefficient of variation of 11%. Quantification of fasting serum adiponectin, C-reactive protein (CRP), ferritin and interleukin-2 receptor alpha (IL2-Ra) was carried out at the Tethys Clinical Laboratory, Emeryville, CA. Ferritin was