Introduction
The overall age-standardised mortality in general populations, primarily from cardiovascular disease [
1,
2], has been decreasing since the 1970s. In line with this, mortality in type 1 diabetes has also declined, primarily because of better diabetes care and prevention of complications [
3‐
9]. However, most of the studies on mortality trends in type 1 diabetes focus on children and young adults [
6,
9,
10], and there are few studies assessing mortality trends in type 1 diabetes across a broader age range [
3‐
5,
7,
8]. Deaths in younger individuals with type 1 diabetes are rare, and are predominantly caused by acute complications. Secular mortality trends in middle-aged and older adults, for whom chronic complications dominate the causes of death [
11,
12], and among whom the vast majority of deaths in type 1 diabetes occur, may differ markedly from those in younger adults. One earlier study reported the trends in cumulative mortality by calendar period of diagnosis in people with early and late onset of type 1 diabetes [
13], but studies of age-specific trends in all-cause mortality in type 1 diabetes are scarce [
4].
People with type 1 diabetes have a significantly higher risk of all-cause mortality than do people without diabetes [
3,
8‐
10,
14‐
16]. However, it is not clear how this excess risk of all-cause death in people with type 1 diabetes has changed over time, and whether this has varied by sex, age or country.
Large observational studies with long follow-up times are needed to monitor these trends and to understand whether improvements in treatment have not only reduced all-cause mortality rates but have also narrowed the mortality gap between those with type 1 diabetes and the general population. Elucidating these mortality trends can help identify sub-populations in need of targeted intervention. Therefore, the aim of this study was to assess the trends in the absolute all-cause mortality rates among people with type 1 diabetes and trends in excess mortality in type 1 diabetes relative to those without diabetes in six countries, and to investigate whether the changes in both absolute and relative mortality rates over time varied by country, age and sex.
Results
Table
1 shows details for the six included data sources. All were from high-income countries: four European populations (Denmark, Latvia, Scotland and Spain), Australia and the USA. Four studies included national data, one study included regional data from Spain (Catalonia), and another study included data from a US regional health insurance database (KPNW) (Table
1). Quality scores for the data sources ranged from 5 to 9, with a median of 7 (IQR 6–8) (ESM Table
2).
There were 18,105 deaths (11,355 deaths in male individuals and 6750 in female individuals) during 1.55 million person-years of follow-up in 179,514 individuals with type 1 diabetes aged 0–79 years (Table
1, ESM Table
3). Overall, the ratio of male to female individuals with type 1 diabetes was 1.28 in the six included data sources, and the crude all-cause mortality rate was 11.7 (95% CI 11.5, 11.9) per 1000 person-years for all individuals with type 1 diabetes. The crude mortality rate was 13.2 (95% CI 12.9, 13.4) per 1000 person-years in male individuals, and 9.9 (95% CI 9.6, 10.1) per 1000 person-years in female individuals (ESM Fig.
1).
Discussion
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 HbA
1c 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 HbA
1c 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 HbA
1c 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 HbA
1c> 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].
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