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Cardiovascular Disease and Mortality in Prediabetes

Apr 21, 2018
 

Method to identify prediabetes found to impact risk of heart disease or death.

Individuals with prediabetes have higher risk of developing diabetes and are also associated with increased risk of cardiovascular disease (CVD) and mortality. Prediabetes can be defined using HbA1c, fasting plasma glucose (FPG) or 2-hr plasma glucose (2hPG). In this Whitehall II cohort study, 5,427 participants between the ages of 50-79 years with prediabetes were enrolled and followed for mean of 11.5 years. Participants were followed from the date of their 2002-2004 clinical exam until first cardiovascular event or June 30, 2015. According to World Health Organization (WHO)/ International Expert Committee (IEC), prediabetes is defined as FPG 6.1–6.9 mmol/L and/or HbA1c 6.0–6.4%. According to the American Diabetes Association (ADA), prediabetes is defined as FPG 5.6–6.9 mmol/L and/or HbA1c 5.7–6.4%. Out of 5,427 individuals, 628 (11.6%) had prediabetes that was defined by WHO/IEC criteria and 1,996 (36.8%) by the ADA criteria. A total of 663 (14.0%) individuals were defined to have prediabetes by 2hPG. This Whitehall II study compared the risk of fatal or nonfatal CVD or all-cause mortality in individuals with prediabetes identified by FPG, 2hPG or HbA1c. Incidence of CVD included coronary artery disease and stroke.

The results of this study show that during the follow-up period of 11.5 years, 134 individuals (21.3%) and 370 (18.5%) with prediabetes defined by WHO/IEC and ADA developed CVD or died, respectively. With ADA and WHO/IEC criteria, the incidence rate of CVD or mortality for prediabetes group was 18.9/1,000 person-years and 22.7/1,000 person-years, respectively. This means that the incidence rate of CVD and death was lower when prediabetes is defined using ADA. The incidence rate of CVD or death was 54% and 37% higher in individuals with prediabetes than individuals with normoglycemia using WHO/IEC and ADA criteria, respectively.

When individuals were defined to have prediabetes with only FPG levels (without taking HbA1c into consideration), the rate of an event was 19.4% and 16.5% using WHO and ADA criteria respectively. These incident rates were very similar as the normoglycemic group for both WHO and ADA. When individuals were defined to have prediabetes with only HbA1c (without taking FPG levels into consideration), the incidence rate of CVD or death was 29.5% and 26% using IEC and ADA criteria respectively. These incidence rates were almost twice that of the rate in the normoglycemic group for both WHO and ADA. These results show that prediabetes defined by HbA1c had twice as high incidence rate than for patients who had normoglycemia. However, prediabetes defined by FPG levels had comparable event rate with the normoglycemic group.

This large Whitehall II cohort study showed that prevalence of prediabetes defined by FPG and/or HbA1c was three times higher when ADA criteria were used compared to when WHO/IEC definitions were used. In addition, individuals with prediabetes defined by HbA1c had much higher risk of CVD and mortality than those defined by FPG or 2hPG. It was also found that risk of CVD and death reduced in HbA1c defined prediabetes compared to FPG and 2hPG defined prediabetes. According to ADA guidelines, it is recommended that individuals with prediabetes should try to prevent transition from prediabetes to diabetes by doing lifestyle modifications or using metformin.

In conclusion, this study showed that after comparing different definitions of prediabetes, it was found that prediabetes defined using the ADA criteria has lower risk of CVD or mortality than for individuals who were identified of prediabetes by WHO/IEC criteria. It was also found that HbA1c is more specific and accurate in predicting CVD and mortality risk in individuals with prediabetes than FPG or 2hPG concentrations. Because many patients with prediabetes have other CVD risk factors, the results of this study are questionable regarding whether prediabetes as an independent factor can be used to predict risk of CVD and mortality.

One of the major strengths of this study was that the measures of FPG, HbA1c, and 2hPG were obtained and were linked to CVD risk or mortality over a long follow-up period. Another strength of this study is that different definitions of prediabetes were studied and compared. One of the weaknesses of this study is that some individuals with prediabetes may have developed diabetes during the follow-up period and may have received treatment that could reduce their CVD risk. This can result in biased results.

Practice Pearls:·

  • Prediabetes defined by using the ADA criteria has lower risk of developing CVD or mortality than when prediabetes is defined using WHO/IEC criteria.
  • HbA1c is more accurate in predicting CVD and mortality risk in individuals with prediabetes than FPG or 2hPG concentration.
  • It is questionable to say whether prediabetes as an independent factor can be used to predict risk of CVD and/or mortality.

Reference:

Vistisen D, Witte RD, Brunner EJ, et al. Risk of Cardiovascular Disease and Death in Individuals with Prediabetes Defined by Different Criteria: The Whitehall II study. Diabetes Care. 2018

Vidhi Patel, Pharm. D. Candidate 2018, LECOM School of Pharmacy