In this population-based study using nationally representative mortality data from the USA, we demonstrate that the age-standardised all-cause mortality due to diabetes as the underlying or contributing cause of death and cause-specific mortality among individuals with diabetes listed on death certificates declined 0.7–1.4% annually during the 11 year study period. Rates in mortality due to diabetes as underlying or contributing cause of death and CVD or diabetes-related mortality among individuals with diabetes reported on death certificates tended to decline earlier in the study period and then stabilised. In terms of trends in mortality within the CVD subcategories, significant differences existed among individuals with diabetes listed on death certificates.
Our findings are consistent with previously reported trends in all-cause mortality due to diabetes and cause-specific mortality among individuals with diabetes [19, 24, 25]. Studies analysing diabetic cohorts from Framingham [26] and Minnesota [18] showed that diabetes-related mortality decreased during the 1990s. A study based on the US NHIS reported that death rates among subjects with diabetes declined between 1997 and 2006 [24]. A recently updated study using data from the NHIS reported age-specific mortality rates and proportional mortality from all causes, vascular causes, cancers, and non-vascular, non-cancer causes by diabetes status from 1985 to 2015 [27]. The mortality trends outlined in this study used cohorts with and without self-reported diabetes, which is the required study design for causes and trends in mortality regarding diabetes [27, 28]. Consistent with our results, all-cause mortality rates declined 20% every 10 years among adults with diabetes, while death from vascular (32%) and cancer-related (16%) causes declined at a discordant rate. However, the decline in mortality rates was significantly greater among individuals with diabetes than those without diabetes [27]. In another study using the NHIS data, relative changes in 10-year mortality were significant for major CVD and ischaemic heart disease, but not in the heart failure subset, consistent with our analysis [29]. However, because these studies followed mortality until December of 2015, they were unable to exclude the possibility that the recent decline in diabetes-related death may be associated with the relatively short follow-up period in 2005–2009 (17.6 death rate per 1000 person-years) and 2010–2015 (15.2) compared with 1995–1999 (23.6) and 2000–2004 (21.4) subcohorts [27]. Our study demonstrates the declining trend in mortality due to diabetes as the underlying or contributing cause of death and CVD/cancer-related mortality among individuals with diabetes listed on death certificates regardless of a distinct gap in follow-up.
The improvement in outcomes observed in our study most likely reflects the impact of medical advances in the prevention, treatment and monitoring of this chronic disease. The decline in CVD-related mortality rates has been attributed to improvement in the management of risk factors related to CVD such as dyslipidaemia and hypertension, as well as advances in revascularisation techniques leading to better outcomes [25, 30]. However, these findings have paradoxical implications for present and future burdens of diabetes in the USA. A declining mortality among individuals with diabetes in the past decade may have led to a substantial increase in the prevalence of diabetes and economic health burden related to diabetes [31, 32]. Interestingly, we found that all-cause mortality rates due to diabetes as the underlying or contributing cause of death and CVD-related mortality rates among individuals with diabetes listed on death certificates remained stable during the past 5 years. This may be partially explained by the excess mortality associated with diabetes being potentially spread among a considerably greater proportion of the population [24]. Additionally, reduction in mortality may lag behind improvement in the management and treatment of specific risk factors [24]. In real-life experience, such a lag time may result in the current plateau in mortality among individuals with diabetes [24]. One recent study suggests that individuals with diabetes in the USA had substantial improvements in control of risk factors between 1999 and 2010 [33]. However, 30–50% of individuals with diabetes still did not meet individual targets for glucose level, BP or lipid levels [33]. Another study demonstrated improvements in BP control and decline in the prevalence of smoking during the 2000s as compared with previous decades [34].
In our study, the mortality rate associated with hypertensive heart disease has increased among individuals with diabetes based on information listed on death certificates. Consistently, the mortality rate of heart failure has increased during recent years as well. This finding is somewhat unexpected because the rates of mortality for ischaemic heart disease have decreased during the study period. These observations suggest that other processes, perhaps less well-treated, which increase the risk of hypertensive heart disease and heart failure are not as affected by current clinical care best practices. Due to systemic inflammation, which anti-hypertensive medications do not alleviate, being normotensive on medication may not eliminate in its entirety the risks associated with hypertension among individuals with diabetes, especially insulin resistance or other comorbidities such as dyslipidaemia [35]. In our study, we noted that cancer-related mortality among individuals with diabetes listed on death certificates steadily declined between 2007 and 2017. A prospective cohort study, the Cancer Prevention Study-II, showed that diabetes was associated with a higher risk of certain malignancies including breast, liver and pancreas cancers [36]. In contrast to our results, a study from Australia reported that cancer-related mortality increased substantially between 1977 and 2010 [37]. In our study, the number of cancer-related deaths increased from 25,362 (age-standardised mortality rate: 12.3) in 2007 to 29,190 (age-standardised mortality: 11.0) in 2017; however, age-standardised mortality rates declined steadily during the study period. This discrepancy can be partly explained by the lack of age-standardised mortality rates in the Australian study. Consistent with our study, a recent study using the US NHIS data showed that deaths from cancers decreased 16% every 10 years from 1988–1994 to 2010–2015 [27].
Analyses of diabetes-related mortality, including current national reports from the NVSS, generally tend to include deaths for which diabetes was listed as the underlying cause of death. The availability of death-certificate-assigned diabetes as an underlying cause of death is not sufficient for estimating national mortality attributed to diabetes [11,12,13] because subjects with diabetes generally have other conditions that may directly contribute to death (such as CVD, cancer, renal disease, etc.). In our study, we analysed both age-standardised all-cause mortality due to diabetes as the underlying or contributing cause of death and cause-specific mortality rates among individuals with diabetes listed on death certificates. Mean age-standardised diabetes-related mortality rates compared between underlying cause of death and mortality due to diabetes as the underlying or contributing cause of death (all-cause mortality) were 32.2 vs 105.1 per 100,000 individuals (75.7 for contributing cause of death). In agreement with our study, a recent study using the NHIS dataset and the National Health and Nutrition Examination Survey demonstrated that the proportion of deaths attributable to diabetes (all-cause mortality) was estimated to be 11.5–11.8%, while the proportion of deaths attributable to diabetes as underlying cause of death (3.3–3.7%) underestimated the contribution of diabetes-related mortality in the USA [9]. Current annual estimates from the NVSS [38] are based on underlying cause of death, which may fail to capture diabetes-related mortality attributed to CVD, cancer and other causes of death.
The key strength of our nationally representative study is the reporting of longitudinal trends in aetiology-specific mortality rates for diabetes over an 11-year period. This allowed us to compare nationwide mortality data, thus gaining unique insight into mortality trends among individuals with diabetes listed on death certificates. We also used recently updated nationally representative mortality data, which enabled us to capture current trends for diabetes. Our main limitation is the definition of diabetes which is listed as the underlying or contributing cause of death on the death certificate. This study design and the dataset have the potential for underestimation and misclassification. Currently, robust data are lacking to validate the death certificate as a monitoring modality for death in diabetes. The Framingham Heart Study reported that death certificates were least accurate in individuals over 85 years and that there was no significant change in coding accuracy over time [39]. Coding method has been constant over time, so it is unlikely to account for the presented temporal trends in diabetes-related mortality rates. Furthermore, ICD-10 codes for diabetes and diabetes-related mortality grossly underestimate the true prevalence. A plausible explanation for the low rates of diabetes-related mortality is the significant underreporting on death certificates leading to underestimation of the true prevalence of diabetes by using ICD-10 codes. This is an inherent limitation of the NVSS database. Such problems can be mitigated when analysing trends in which underestimation has been assumed to be relatively constant over the study period. Finally, age-standardised mortality rates may not represent actual mortality rates, but these rates were appropriate for comparisons during the study period as population distributions change over time.
In conclusion, age-standardised mortality due to diabetes as the underlying or contributing cause of death and cause-specific mortality among individuals with diabetes listed on death certificates declined annually during recent decades. However, trends in all-cause mortality due to diabetes as the underlying or contributing cause of death and cause-specific CVD or diabetes-related mortality among individuals with diabetes listed on death certificates were noted to reach a plateau in 2010 and have remained stable thereafter. Our results suggest that greater efforts are needed to prevent mortality from CVD and complications associated with diabetes in the future.