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IGF Binding Protein 1 Predicts Cardiovascular Morbidity and Mortality in Patients With Acute Myocardial Infarction and Type 2 Diabetes

¹ Medicine and Cardiology Unit, Karolinska Institutet, Stockholm, Sweden
² Department of Molecular Medicine and Surgery, Endocrine and Diabetes Unit, Karolinska Institutet, Stockholm, Sweden

Address correspondence and reprint requests to Märit Wallander, MD, Cardiology, N5:00, Karolinska University Hospital Solna, 171 76 Stockholm, Sweden. E-mail: marit.wallander{at}ki.se

OBJECTIVE—There are indications that the IGF system is related to both type 2 diabetes and cardiovascular disease (CVD). We tested the hypothesis that low IGF-I and high IGF-binding protein (IGFBP)-1 predict future cardiovascular mortality and morbidity in patients with acute myocardial infarction (AMI) and type 2 diabetes.

RESEARCH DESIGN AND METHODS—The Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 Trial recruited 1,253 patients with type 2 diabetes and AMI, of whom 575 were enrolled in a biochemical program with repeated blood sampling. Primary and secondary end points included adjudicated cardiovascular mortality and a composite of cardiovascular events (cardiovascular death, reinfarction, or stroke). Multiple Cox proportional hazard regression was used to study the relationship between the end points and the variables. Admission variables were used for the survival analysis and for blood glucose, and A1C updated mean values during follow-up were also available.

RESULTS—During a median follow-up period of 2.2 years, 131 (23%) patients died from all-cause mortality and 102 (18%) from CVD, whereas 175 patients (30%) suffered from at least one cardiovascular event. The independent predictors for cardiovascular death in the Cox regression model were (as hazard ratio [HR] [95% CI]): ln updated mean blood glucose (12.2 [5.8–25.7]), age (+5 years) (1.5 [1.4–1.7]), ln IGFBP-1 (1.4 [1.1–1.8]), and ln serum creatinine at admission (2.4 [1.3–4.2]). The model predicting cardiovascular events contained the same variables (ln IGFBP-1 at admission, 1.2 [1.0–1.4]).

CONCLUSIONS—High levels of IGFBP-1 at admission are associated with increased risk for cardiovascular mortality and morbidity in type 2 diabetes patients with AMI.

Abbreviations: AMI, acute myocardial infarction • CVD, cardiovascular disease • DIGAMI, Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction • IGFBP, IGF binding protein • RIA, radioimmunoassay

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