Risk Factors, Mortality, and Cardiovascular Outcomes in Patients with Type 2 Diabetes

As physicians, we have all encountered a patient like Brian, a 62-year-old man who has never required hospital admission for an acute illness, and therefore considers himself “healthy.” However, his medical history includes a range of chronic conditions, including type 2 diabetes, hypertension, and dyslipidemia. Further, he was previously a smoker. The type 2 diabetes was diagnosed 4 years ago, at which point blood glucose levels were well-controlled with diet and exercise. However, he now requires metformin in addition to perindopril and atorvastatin.

Due to osteoarthritis in his knees, Brian no longer gets much exercise. His weight is 98 kg and his height is182 cm (body mass index, 29.6 kg/m²). Brian doesn’t like going to the doctor; he’d rather be fishing. When asked, he can’t remember the last time he had laboratory tests done.

Brian is just one of an estimated 30 million Americans who live with type 2 diabetes. Previous studies indicate that the risk for cardiovascular disease in patients with type 2 diabetes is two-to-fourfold higher than in the general population. Currently, an ever-increasing armamentarium of lifestyle and pharmacological interventions aimed at reducing cardiovascular and mortality risk in this patient group are available. However, the extent to which cardiovascular and mortality risks can be reduced by interventions such as smoking cessation and achieving glycemic targets is unclear.

In a Swedish study, Rawshani and colleagues compared the risk of death, myocardial infarction, stroke, and heart failure hospitalizations in a large cohort of patients with type 2 diabetes to that in age- and sex-matched controls. Specifically, the authors assessed risk according to the presence of five well-known predisposing risk factors —  elevated glycated hemoglobin, elevated low-density lipoprotein cholesterol level, elevated blood pressure, albuminuria, and smoking.   

The results showed a stepwise increase in risk of cardiovascular events and mortality for each additional risk factor that did not fall within target range.  Estimated overall mortality risk in patients with type 2 diabetes and no risk factors outside of the target range was only marginally higher than in control patients without diabetes (hazard ratio, 1.06; 95% CI, 1.00–1.12). Patients with diabetes also had marginal increases in risk for cardiovascular outcomes such as stroke, acute myocardial infarction and heart failure hospitalizations. In contrast, patients younger than 55 years with five risk factors outside of the target range had almost five times the mortality risk as controls (HR, 4.99; 95% CI, 3.43–7.27).

The authors also analyzed the relative importance of individual risk factors in predicting outcome. Of the five risk factors, smoking was the strongest predictor of all-cause mortality risk, followed by physical activity, glycated hemoglobin level, and use of statin medication.

Although Brian may see himself as seemingly “healthy,” this study supports the value of ongoing active management of modifiable risk factors in patients such as Brian with type 2 diabetes. Much can be done to reduce his cardiovascular and mortality risk. The importance of actively addressing risk factors such as smoking, physical activity, glycated hemoglobin, and low-density lipoprotein levels above the target range should continue to be emphasized in the care of patients with type 2 diabetes.

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Angela is a 2018-2019 NEJM editorial fellow. She is an endocrine fellow who trained at Flinders Medical Centre and the Royal Adelaide Hospital. Angela recieved her medical degree from the University of Adelaide, and masters of public health from the University of Sydney. Her clinical and research interests are in the areas of glucocorticoid and cardiovascular endocrinology and diabetes medicine.