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How is Cardiovascular Health Related to Duration of Diabetes and Prediabetes?

Mar 10, 2018
 

Study finds disease duration in middle age to be independently related to development of subclinical atherosclerosis and cardiac dysfunction later in life.

Owing to development of type 2 diabetes earlier in life than what was previously seen, adults are living with the disease for a greater number of years and are exposed to extended episodes of hypo and hyperglycemia. The longer time of exposure to glycemic episodes may lead to increased cardiovascular risks. Regardless of the previous studies researching the relationship, it is not clear whether longer duration of diabetes or prediabetes are to blame for to cardiovascular disease often seen in individuals with diabetes. One study conducted by Caroline Fox and colleagues reported the risks of coronary heart disease to be increased with longer duration of diabetes. On the other hand, Lynne Wagenknecht et al, refuted the association between length of the disease and effects on the cardiovascular health, but did determine that established diabetes is to blame for increased risk of atherosclerosis. To clarify the relationship between the length of diabetes or prediabetes on cardiovascular dysfunction and atherosclerosis, CARDIA study was conducted over a period of thirty years. Recently, its results were published in Diabetes Care journal.

Coronary Artery Risk Development in Young Adults (CARDIA) study is a multicenter, population-based cohort study that recruited patients from Birmingham, Chicago, Minneapolis, and Oakland between the ages of 18 and 30 in 1985 and 1986 in hopes of determining the development of clinical and subclinical CV disease due diabetes. Main exclusion criteria for enrollment included diagnosis of diabetes or prediabetes at baseline, and non-completion of CT scan or ECHO during follow-up. The study enrolled 3,628 subjects with similar baseline characteristics. Participants were examined at enrollment, then again at year 2, 5, 7, 10, 15, 20, 25, and 30. Diabetes and prediabetes were diagnosed based on values of fasting plasma glucose levels, percentage of HbA1c, self-report use of anti-diabetic medications, and the oral glucose tolerance test.  Number of years with prediabetes or diabetes was counted starting on year 7 of follow-up; for instance, if the patient developed diabetes 10 years after initial inclusion in the trial, that individual was thought to be living with diabetes for 3 years. Subjects were diagnosed with coronary artery calcified plaque (CAC) if they had calcification within their arteries that was corresponding to score greater than 0 in Agatston units.

Throughout the duration of study, 12.7% of patients developed diabetes, while 53.8% developed prediabetes. Subjects lived with diabetes for an average of 10.7 years compared to 9.5 years for prediabetes. Highest fasting plasma glucose and HbA1c levels were seen in those subjects who lived with prediabetes and diabetes longer than 15 years. Independent relationship was established for duration of diabetes and prediabetes and risk of CAC: every 5 years living with the disease increased the risk for CAC by hazard ratio of 1.15 and 1.07 for diabetes and prediabetes, respectively.  Subclinical systolic function was affected by duration of diabetes and prediabetes as well; greater number of years with both of the conditions led to worse systolic function, p-value <0.001. Other clinical manifestation that were seen with longer duration of diabetes and prediabetes included: lower ejection fraction, worse longitudinal strain, impaired left ventricular relaxation and diminished left ventricular filling pressure.

Although there are previous studies published that correlate diabetes to atherosclerosis and cardiovascular dysfunction, this study clarifies the impact seen on a population level. Furthermore, this comprehensive study is the only study available to date that shows implications of prediabetes in cardiovascular outcomes. As such, this knowledge may be used to improve cardiovascular health in affected individuals. The relationship between prediabetes and cardiovascular dysfunction was not as strong as it was with diabetes, however, taking into consideration that more and more people are being diagnosed with prediabetes, there could be a large number of individuals affected by subclinical cardiovascular disease.

Practice Pearls:

  • Out of 3,628 subjects enrolled in study, there were 12.7% and 53.8% of individuals who developed diabetes and prediabetes, respectively.
  • Independent relationship between prediabetes and CVD and diabetes and CVD was established, as shown with HR of 1.07 and 1.15, respectively.
  • Longer duration of prediabetes and diabetes correlated to worse systolic dysfunction, impaired ventricular relaxation and filling pressure, and lower ejection fraction.

References:

Jared Reis, Norrina Allen, Michael Bancks, et al. “Duration of Diabetes and Prediabetes During Adulthood and Subclinical Atherosclerosis and Cardiac Dysfunction in Middle Age: The CARDIA Study.” Diabetes Care. 2018.  http://care.diabetesjournals.org/content/early/2018/01/08/dc17-2233.  Accessed on Jan 2018.

Caroline Fox, Lisa Sullivan, Ralph D’Agostino, et al. “The significant effect of diabetes duration on coronary heart disease mortality: the Framingham Heart Study.” Diabetes Care. 2004. http://care.diabetesjournals.org/content/27/3/704.long. Accessed on Jan 2018.

Lynne Wagenknecht, Ralph D’Agostino, Peter Savage, et al. “The Insulin Resistance Atherosclerosis Study (IRAS). Duration of diabetes and carotid wall thickness.” Stroke 1997.  http://stroke.ahajournals.org/content/28/5/999.long. Accessed on Jan 2018.

 

Lamija Zimic, PharmD(c), University of South Florida, College of Pharmacy