Using contemporary aggregate data on all-cause mortality in people with type 1 diabetes from six data sources in high-income countries, we obtained four key findings. First, all data sources showed a decline in the age- and sex-standardised all-cause mortality rates in people with type 1 diabetes aged 0–79 years from 2000 to 2016 (or a subset thereof), with an annual estimated change in mortality rates ranging from −2.1% (95% CI −2.8%, −1.3%) to −5.8% (95% CI −6.5%, −5.1%). Furthermore, annual mortality rates declined in most country- and sex-specific populations, although this decline was not statistically significant in the Latvian and Spanish female populations. Second, mortality declined at a wide range of ages for most data sources. Third, the SMR, reflecting excess mortality, fell in half of the six included data sources. Fourth, despite reductions in absolute all-cause mortality rates, and, in some countries, in the SMR, people with type 1 diabetes still had a two to five times higher risk of death compared with those without diabetes.
Our observation of the decline in the age-standardised mortality rates in most populations with type 1 diabetes is consistent with previous studies from these countries for other time periods, with mortality declines among male and female populations with type 1 diabetes being reported in Australia (2000–2011) [4], Denmark (2005–2016) [8] and Scotland (from 2006–2010 to 2011–2015) [7]. Cardiovascular diseases are a major cause of deaths in individuals with type 1 diabetes [11, 12], although other important contributors to excess mortality include renal diseases, cancer and infectious diseases. Decreasing mortality in people with type 1 diabetes may be attributable to the advances in treatment and interventions for type 1 diabetes, as well as improvement in cardiovascular disease prevention with widespread use of statins and anti-hypertensive medications over the last two decades.
Despite reductions in all-cause mortality rates in people with type 1 diabetes in most populations studied, the improvement in the excess risk of all-cause death among people with type 1 diabetes relative to the non-diabetic population was less evident, with SMR decreasing in only three of the six data sources over the study period. Previous data from Australia showed that there was a reduction in excess all-cause mortality among both male and female individuals with type 1 diabetes aged 0–75 years between 1997 and 2010 [14]. A recent analysis of the Danish Diabetes Register reported that the SMR declined by approximately 2% per year for both sexes in the entire population with type 1 diabetes between 2005 and 2016 [8]. However, a cohort study from Sweden showed a decreased mortality rate among adults with type 1 diabetes from 1998 to 2014, but they did not find a similar decline in the excess mortality relative to the general population [5].
Similar to other studies [3], absolute mortality rates in people with type 1 diabetes increased with increasing age, while the excess mortality for type 1 diabetes relative to those without diabetes decreased with increasing age. As has been reported previously [9, 16], we found that the SMR associated with type 1 diabetes was higher among female individuals than male individuals across all ages for most calendar years. We also noted that mortality declined over the study period across most ages for both male and female individuals, while SMR declined at all ages examined in only three out of six data sources. Studies of age-specific trends in all-cause mortality rates or excess mortality in people with type 1 diabetes are scarce, and most were restricted to younger individuals with type 1 diabetes [6, 9, 10, 14]. Previous work from our group indicated that age-specific SMRs in people with type 1 diabetes in Australia did not significantly change between 1997–2003 and 2004–2010 [14]. A cohort study of individuals diagnosed with type 1 diabetes before the age of 15 years from Northern Ireland did not find a significant change in either all-cause mortality rates or corresponding SMR associated with type 1 diabetes from 1989 to 2012 [10]. Studies in Uzbekistan (1998–2014) [6] and Scotland (2004–2017) [9] identified mortality reductions in children <15 years and in people aged below 50 years, respectively. However, there was no improvement in excess mortality for individuals with type 1 diabetes under age 50 years in Scotland from 2004 to 2017 [9].
Despite reductions in absolute all-cause mortality rates, and, in some countries, in the SMR, type 1 diabetes still confers a higher excess risk of death compared with individuals without diabetes. Suboptimal glycaemic control and the presence of acute and chronic complications are key contributors to excess risk of death in type 1 diabetes [3, 9, 15]. Even among people with type 1 diabetes who have an HbA1c below the target level of 53 mmol/mol (7.0%), the risk of all-cause mortality is still twice that of the general population [15]. Evidence shows that intensive insulin therapy is associated with a decreased all-cause mortality compared with conventional therapy, with a persistent benefit more than 30 years later [24, 25]. However, data from the USA T1D Exchange Clinic Network showed that there was an increase in mean HbA1c from 62 mmol/mol (7.8%) to 68 mmol/mol (8.4%) between 2010–2012 and 2016–2018 [26]. More recent Scottish data showed that, despite an overall declining trend in HbA1c level from 70 mmol/mol (8.6%) to 68 mmol/mol (8.4%) in people with type 1 diabetes (2012–2016), more than one-third of all those with type 1 diabetes still had poor glycaemic control with an HbA1c> 75 mmol/mol (>9%) in 2016 [27]. Poor glycaemic control in younger people with type 1 diabetes increases the risk of developing complications when they age [25], and increases the risk of death from any cause or from cardiovascular causes [15]. In addition to glycaemic management, data from the Swedish National Diabetes Register suggested a steep increase in the excess risk of all-cause death with decreasing number of cardiovascular risk factors (BP, LDL-cholesterol, smoking and albuminuria) meeting target levels among people with type 1 diabetes [28].
Strengths and weaknesses
A key strength of this work is that we have assembled six large population-based cohorts, with a sizeable number of people with type 1 diabetes and a long study period to enable us to provide estimates of time trends in all-cause mortality rates in six countries, and by sex and age categories. To the best of our knowledge, this work is the only study of this kind, and provides the most recent data on mortality trends in people with type 1 diabetes across a broader age range. Four out of six sources were national diabetes registries, which cover the entire population with type 1 diabetes in those countries.
Several potential limitations of our study should be considered. First, misclassification of diabetes type cannot be ruled out. Algorithms based on clinical criteria, medication use and laboratory measurements are commonly used in administrative databases and diabetes registries to assign diabetes type. However, the absence of some laboratory data from the database, such as autoantibody or C-peptide levels, may lead to misclassification of diabetes type. The use of algorithms to classify type 1 diabetes based on age at diagnosis in some data sources may exclude those with older-onset type 1 diabetes [29], which means that the mortality rates in type 1 diabetes may be underestimated. However, within each data source, the same approach was used to classify diabetes type across time periods, therefore mortality trends are less likely to be affected by the potential misclassification of older-onset type 1 diabetes. Second, we did not have access to individual clinical data. Therefore, we could not determine whether mortality trends in people with type 1 diabetes were due to changes in glycaemic control, changes in other risk factors, or differences in the prevalence of acute or chronic diabetes-related complications over time. Moreover, improved survival over time will increase diabetes duration, an important risk factor for mortality, which may have attenuated improvements in age-specific mortality rates. We did not have access to data on age at diagnosis of type 1 diabetes or diabetes duration, and thus could not examine the relationship of mortality with duration of diabetes. As data were not available for risk factors in people with and without diabetes, we were not able to investigate possible explanations for the excess risk of mortality among people with type 1 diabetes. Third, the sample size was variable between the six data sources, with a relatively small number of people with type 1 diabetes in the data sources from Spain (Catalonia), the USA (KPNW) and Latvia. Fourth, the six data sources only represent high-income countries; therefore, our results may not be generalisable to middle- and low-income countries where patterns of mortality trends in people with type 1 diabetes remain uncertain. Fifth, we did not have data on ethnicity, socioeconomic status or population immigration. Finally, our data are limited in terms of the time period covered by some data sources.
Conclusions
This is the first multicountry analysis of six large contemporary population-based studies, and shows that all-cause mortality in people with type 1 diabetes has declined in recent years in most studied populations. However, excess mortality relative to the population without diabetes remains high in people with type 1 diabetes. Considering the increasing incidence of type 1 diabetes observed in younger populations in recent years [8, 30, 31], it is critical to continuously improve the multidimensional management of type 1 diabetes, particularly among younger populations.