Elevated Risk of Cardiovascular Disease Prior to Clinical Diagnosis of Type 2 Diabetes

Frank B. Hu, MD, Meir J. Stampfer, MD, Steven M. Haffner, MD, Caren G. Solomon, MD, Walter C. Willett, MD, and JoAnn E. Manson, MD


Diabetes Care. 2002;25(7) 

In This Article

Abstract and Introduction

Objective: To examine whether the risk of cardiovascular disease (CVD) is elevated before clinical diagnosis of type 2 diabetes in women.
Research Design and Methods: A total of 117,629 female nurses aged 30-55 years who were free of diagnosed CVD at baseline were recruited in 1976 and followed for 20 years.
Results: A total of 1,508 women had diagnosed type 2 diabetes at baseline in 1976. During 20 years of follow-up, 110,227 women remained free of diabetes diagnosis and 5,894 women developed type 2 diabetes. During 2.2 million person-years of follow-up, we documented 1,556 new cases of myocardial infarction (MI), 1,405 strokes, 815 fatal coronary heart disease (CHD), and 300 fatal strokes. Among women who developed type 2 diabetes during follow-up, the age-adjusted RRs of MI were 3.75 (95% CI 3.10-4.53) for the period before the diagnosis and 4.57 (3.87-5.39) for the period after the diagnosis, compared with women who remained free of diabetes diagnosis. The multivariate RRs further adjusting for BMI, smoking, and other cardiovascular risk factors were 3.17 (2.61-3.85) and 3.97 (3.35-4.71). The risk of stroke was also significantly elevated before diagnosis of diabetes (multivariate RR = 2.30 [1.76-2.99]). Further adjustment for history of hypertension or hypercholesterolemia did not appreciably alter the results.
Conclusions: Our data indicate a substantially elevated risk of CVD before clinical diagnosis of type 2 diabetes in women. These findings suggest that aggressive management of cardiovascular risk factors is warranted in individuals at increased risk for diabetes.

Cardiovascular disease (CVD) is the leading cause of death in individuals with type 2 diabetes, which affects some 15 million Americans.[1] Among diabetic individuals, CHD accounts for >50% of all deaths, and stroke accounts for an additional 15%.[2] Diabetic women are at particularly high risk of CVD; diabetes eliminates the usual female advantage for coronary disease mortality.[3]

There is some evidence that the risk for CVD starts to increase long before the onset of clinical diabetes, which has led to the "ticking clock" hypothesis.[4] In an 8-year follow-up of the San Antonio Heart Study,[4] subjects who converted to diabetes during the follow-up had higher baseline levels of total and LDL cholesterol, triglycerides, and blood pressure and lower levels of HDL than those who remained nondiabetic, even after adjustment for obesity. The enhanced atherogenic risk profile in the prediabetic state may contribute to the subsequent increased risk of CVD. To our knowledge, no long-term prospective data exist on incidence of cardiovascular end points in prediabetic subjects. The Nurses' Health Study (NHS) cohort afforded a unique opportunity to address this issue because of its large size and 20-year follow-up period. Therefore, we examined prospectively the risk of myocardial infarction (MI) or stroke among women who developed type 2 diabetes during follow-up as compared with those in the NHS cohort who remained nondiabetic. In particular, we estimated the risk of developing CVD according to the time from baseline to clinical diagnosis of diabetes (period before diagnosis).


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