Discussion
The present data show that community-based Australian adults with T1D were more than three times more likely to die compared with matched people without diabetes from the same population during an average of >20 years of follow-up. The age at death was approaching 7 years younger in the participants with T1D. CVD deaths were more frequent in the T1D group, accounting for approaching half of all-cause mortality versus one-third in the cohort without diabetes. Diagnosis of T1D in late adolescence/young adulthood in our participants carried a poor prognosis relative to other age groups, as did poor glycemic control and its consequences (albuminuria and retinopathy). In an analysis of age-matched and sex-matched groups of FDS1 participants with T1D or T2D, mortality was significantly greater in those with T1D driven primarily by their worse glycemic control and their higher retinopathy burden.
The mean 6.6 year loss of life expectancy in our participants with T1D is less than in previous reports (≥10 years)6 7 and likely reflects the older age at diagnosis of the FDS1 cohort relative to other studies. Indeed, the MRR was not significantly increased in FDS1 participants aged ≥75 years at study entry compared with a substantially higher and significant MRR (>20) in those aged <45 years. The fact that individuals in the FDS1 diagnosed with T1D between the ages of 18 years and 27 years were at significantly increased risk of death compared with participants both younger and older at diagnosis independently of other risk factors likely reflects the adverse impact of new-onset diabetes at a time of substantial life changes including reduced parental support and difficulties in transitioning to the adult healthcare system.29 30
Although interpretation is complicated by the low number of events, one in eight CVD deaths was in the FDS1 participants below the age of 55 years compared with none of the matched cohort without diabetes. In addition, late adolescence/early adulthood was an even stronger independent aetiological risk factor for CVD death compared with all-cause mortality in the Cox regression analysis. Clinical trial data supporting intensification of CVD risk factor management in young adults with T1D are lacking, but it is interesting that only around a quarter of the participants who died of CVD were taking lipid-lowering medication at baseline and that only half were on antihypertensive therapy. The latest American Diabetes Association guidelines recommend consideration of moderate-intensity statin therapy and a blood pressure target of <130/80 mm Hg in T1D,31 the latter level well below the baseline mean in the FDS1 participants who died of CVD (148/81 mm Hg).
Glycemic control at baseline in our participants with T1D in the form of HbA1c was significantly associated with both all-cause and CVD death in Cox models. These real-world findings add weight to the need for continued good glycemic control in T1D as exemplified by the durable benefits for CVD outcomes in the Diabetes Control and Complications Trial.32 Retinopathy and an increased uACR were also independent aetiological predictors of all-cause death, and uACR was prognostically significant in a competing risk model of CVD death in our T1D cohort. These observations are consistent with the well-recognized associations between both retinopathy33 and albuminuria34 and death in T1D. In addition, the association between ABSI (which, when elevated, indicates that the waist circumference is higher than expected for a given height and weight) and death in our cohort is consistent with findings from studies in the general population22 and of obesity in T1D.35
We explored comparative mortality in T1D versus T2D in our cohort using age-matched and sex-matched samples, with three-quarters of the FDS1 cohort successfully matched with a participant with T2D. Consistent with other population-based studies,12 our study showed that there was a higher risk of all-cause death in T1D. However, the detailed phenotypical data allowed an assessment of whether this was due to the type of diabetes per se or other independent risk factors. Age, HbA1c, uACR, retinopathy, IHD, and a CCI of ≥3 were independent predictors of all-cause mortality, but T1D was not. This questions whether, as has been postulated,17 there are factors specific to T1D that contribute to premature mortality and adds further to the evidence supporting intensive management of conventional modifiable cardiorenal risk factors including glycemic control, regardless of diabetes type.31
The non-CVD-related deaths in the T1D cohort were spread across a range of causes, with renal disease and malignancy the main subgroups although with small numbers of cases. There were no recorded cases of deaths due to acute metabolic complications. This is consistent with a declining rate of acute presentations with DKA and severe hypoglycemia over recent decades,19 but there is also evidence that such complications may be under-reported on death certificates.36
The present study had limitations. Given the relative prevalence of T1D versus T2D, the FDS1 T1D sample was small compared with some other longitudinal studies, with a limited number of deaths especially in the subgroup where this was due to CVD. In light of population differences in the epidemiology and management of T1D,11 the racial/ethnic backgrounds of our participants were considered for inclusion in multivariable models, but the majority (approximately 60%) were of Anglo-Celtic origin. We did not have data on interventions (such as statin initiation) during follow-up in either our participants with T1D or T2D that may have influenced the risk of death. We had relatively few paediatric participants but would likely have captured most people with T1D, given the peaks in incidence in adolescence and middle age.8 11 The strengths of the study are its representative, community-based sample,20 the availability of detailed phenotypical data including diabetes type, detailed death data which may be deficient in administrative database studies,1 2 7 37 and the long duration of follow-up over several decades.
We conclude that poor glycemic control and its associated tissue damage have implications for premature all-cause and CVD mortality in T1D. People diagnosed in late adolescence/young adulthood need careful assessment and management of CVD risk. Visceral obesity is a potential modifiable risk factor for CVD death in T1D, while people with T1D and a history of IHD should also have their CVD risk factor management optimized. Although the risk of death was higher in T1D versus T2D in the FDS1 cohort, we found no evidence that type of diabetes was independently associated with mortality.