Our findings from an analysis of mortality trends among participants with and without diabetes in the Framingham Heart Study are three-fold. First, contrary to recent NHANES findings, we observed a decline in all-cause mortality rates among both men and women with and without diabetes when comparing the earlier to the later time period. We also observed a decline in CVD mortality between the earlier and later time periods. Second, there was no change in non-CVD mortality rates among women or men with diabetes over time, and women with diabetes had approximately a two-fold higher risk of death from non-CVD causes than women without diabetes in both the earlier and later time periods. Lastly, we observed that men and women with diabetes continue to remain at a higher risk of all-cause and CVD mortality than their counterparts without diabetes.
There are several factors that may explain the decrease in mortality rates over time among those with and without diabetes. In recent decades there have been improvements in major CVD risk factors, including reductions in smoking prevalence, total cholesterol, and systolic blood pressure levels.6
Additionally, recent advances in secondary prevention therapies have also occurred which may have contributed to the decline.6
Decreases in incidence rates of CVD events have been observed among individuals both with and without diabetes.3
These substantial declines in mortality rates among individuals with diabetes over time are especially important to consider in light of the recent clinical trials which failed to find benefit of intensive as compared to standard glucose-lowering regimens,17, 18
and emphasize the continued importance of primary and secondary prevention in the overall reduction of mortality in individuals with diabetes over time.
We observed that non-CVD mortality was higher in both time periods in women with diabetes compared to women without diabetes, although the number of events was small. Nonetheless, these findings are supported by a prior examination of trends in non-CVD mortality among people with diabetes, which noted a significant increase in cancer mortality in the period from 1970 to 1994.9
In the Context of the Current Literature
A recent analysis of mortality trends among people with diabetes conducted using NHANES data showed that men with and without diabetes had a significant decline in all-cause mortality when comparing the time periods 1971-1986 to 1988-2000.4
However, women with and without diabetes did not have similar declines in the rates of all-cause mortality over the same time period. Among women, the absolute difference in all-cause mortality rates between those with and without diabetes more than doubled between 1971-1986 and 1988-2000. Both women and men without diabetes had significant declines in CVD mortality, but significant declines were not observed in either men or women with diabetes. In contrast, in our primary analysis, we observed strong and significant declines in all-cause and CVD mortality among both men and women with and without diabetes. However, in our analysis that was restructured to match the NHANES analysis, we did not observe a statistically significant decline in all-cause mortality among either men or women with diabetes, although substantial declines were observed among individuals with diabetes for CVD mortality. Importantly, we did not observe an increase in all-cause mortality among women in any of our analyses, as was observed in the prior analysis of NHANES data.
Potential differences in study design may explain the discrepancy in our results. Most likely, the breadth of the time period examined in the Framingham Heart Study as compared to the NHANES data could explain the disparate findings for all-cause mortality. The NHANES study period covered a narrower and more contemporary time period (1971-2000) than our primary analysis (1950-2005). For CVD mortality, additional methodologic factors may explain our disparate findings. First, NHANES relied on self-reported diabetes status while in the Framingham Heart Study, diabetes was routinely screened for using glucose measurements and medication use. A study using NHANES data revealed that the percentage of individuals with undiagnosed diabetes was 38% in 1976-1980, 36% in 1988-1994, and 29% in 1999-2000.19
A recent study showed that the sensitivity of self-reported diabetes was only 49.3% for women and 67.1% for men.20
If women are less likely to report their diabetes status correctly, it is possible that only the most severe cases of diabetes are identified through self-report. Additionally, the NHANES analysis ascertained mortality using death certificates, an approach that has been shown to overestimate CVD as a cause of death,21
whereas all deaths in FHS were adjudicated by a panel of three physicians. Therefore, misclassification of both exposure and outcome could have occurred within the NHANES analysis. Lastly, it is possible that the NHANES results differed from ours due to either the geographic variability or to the high proportion (~20%) of non-white participants in their study sample. The Framingham Heart Study is predominantly white and may not be as representative of the general US population as is the NHANES population.
In contrast to the NHANES study, the majority of studies of mortality trends among people with diabetes have shown decreases in mortality rates over time. Three studies have been conducted in predominantly white populations, similar to the racial composition of the Framingham Heart Study. In a population-based study in Rochester, MN, where diagnosis of diabetes was based on hospital records and cause of death information was obtained from death certificates, all-cause mortality decreased by 13.8% among those with diabetes and by 21.4% in those without diabetes between 1970 and 1994.9
Similarly, an examination of North Dakota death certificate data showed that the mortality rate among persons with diabetes (as identified on the death certificate) declined by 35% between 1997 and 2002 and sex-specific rates showed a similar trend to those for the total population.10
In a study of nearly 75,000 individuals from Norway, where diabetes status was self-reported and cause of death was identified from a national death registry, statistically significant declines in CHD mortality were observed in both men and women with diabetes from 1984-1997.11
Trends in mortality rates among people with diabetes have also been conducted among in multiethnic study samples. For example, a recent study from Ontario, Canada reported a 25% decline in all-cause mortality in both women and men with diabetes from 1995 to 2005.8
Therefore, differences in the ethnic composition of our study sample as compared to NHANES are unlikely to fully account for differences in the findings.
Strengths and Limitations
Strengths of this analysis include the routine screening for diabetes using glucose measurements to define diabetes status in our study sample, instead of relying on either self-reported diabetes status or on diabetes status from hospital admission records. Self-reported diabetes status can result in misclassification, as nearly one third of total diabetes cases are undiagnosed.22
Further, self-reported diabetes status would have only identified the most severe cases in the earlier years while in the later years there are fewer undiagnosed cases. Reliance on using hospital admission records to define diabetes status only confirms a positive diabetes diagnosis among those who have been admitted to the hospital. Therefore, the use of blood glucose measurements in our study is a more sensitive and specific way of defining those with and without diabetes. Another strength of our study is the broad time period of observation, which enabled us to elucidate long-term trends.
The results of this analysis should be interpreted in light of its limitations. Our study sample is predominantly white, thus the results may not be generalizable to other ethnic or racial groups where disparities in health care may exist. Additionally, we had a small number of deaths among the diabetes group in the sex-specific analyses, and therefore power to detect a modest effect may be limited. We used a differing diabetes definition in the Original and Offspring cohorts. However, a sensitivity analysis revealed that this is unlikely to account for our findings.
We observed a decline in all-cause and CVD mortality rates among both men and women with and without diabetes over the period 1950-2005. Both men and women with diabetes continue to remain at a higher risk of all-cause and CVD mortality than those without diabetes. Whether the lack of decrease in non-CVD mortality rates over time among individuals with diabetes is observed in other studies warrants further investigation.