These results expand on previously published reports from the Allegheny County Type 1 Diabetes Registry cohort with an additional 9 years of follow-up (7
). Of note, now with a range of 28–43 years of type 1 diabetes duration, the risk of dying is 7 times higher than that of the local general population, with significant improvements in SMR for those with diabetes diagnosed most recently in this cohort. This SMR (7.4 [95% CI 6.4–8.4]) is higher than that reported by Nishimura et al. (7
) for this cohort for the 1999 follow-up (SMR 5.2 [4.4–6.0]), perhaps reflecting an increasing effect of long-term complications, which are keeping mortality rates much higher in individuals with type 1 diabetes compared with the general population.
This is the largest population-based type 1 diabetes cohort with at least 25 years of follow-up in the U.S. A recent population-based 20-year follow-up study in New Zealand showed the highest SMRs in individuals with type 1 diabetes diagnosed at age <30 (3.3 for men and 4.3 for women) (14
). A nationwide Norwegian cohort with childhood-onset (age <15 years) type 1 diabetes recently reported SMRs of 3.9 (male) and 4.0 (female) after 20 years of follow-up (6
). Similar results were seen by sex in the Diabetes U.K. Cohort Study with a mean 13.4 years of follow-up (male SMR 2.7; female SMR 4.0) (15
). Other recent reports of all-cause mortality in population-based cohorts of type 1 diabetes exist, with SMRs ranging from 1.8 to 4.2, but their follow-up is limited (<10 years), which is the most likely reason for their lower SMRs (16
The markedly higher mortality seen in our U.S. type 1 diabetes cohort is clearly limited to women, for the men have SMRs that are very comparable to those reported in other long-term follow-up studies (New Zealand, Norway, and the U.K.) (6
). However, directly comparing SMRs across countries is not appropriate because SMR differences may result from either methodological or cohort differences among these studies. To what extent these differences reflect our different health care system and a potential lack of access in the U.S. is difficult to determine. National measures of health care performance and other national economic measures have been shown to contribute to complications in individuals with type 1 diabetes (19
Compared with their respective general populations, women with type 1 diabetes had an SMR nearly 3 times higher than that of men with type 1 diabetes. This finding is partially reflective of the much lower mortality rates for young women in the general population. Long-term mortality rates do not differ by sex in type 1 diabetes, consistent with our previous findings (7
), but are markedly different from the findings in New Zealand, Norway, and the U.K. The respective male-to-female mortality RRs for these studies are 1.23 in New Zealand, 2.26 in Norway, and 1.29 in the U.K compared with 0.80 for our study. The reason for this discrepancy is unclear, but it appears that female sex completely lost its general survival advantage in our diabetes population.
Despite race being a significant predictor of mortality within the Allegheny County cohort (hazard ratio 3.2), no differences in SMR were seen by race, the African American SMR tending to be lower than the Caucasian SMR during follow-up (C
). This seemingly contradictory result can be explained by the extremely high mortality rates seen in young African-Americans in the general population, particularly resulting from violent deaths (20
). Thus, although mortality rates in type 1 diabetes are 2–3 times higher in African Americans, this excess can be attributed to the background African American mortality rates and not to their diabetes. In a 3-year follow-up of 725 African Americans with a mean 9-year duration of type 1 diabetes, SMRs for men and women were 7.0 and 10.5, respectively, compared with those for the local general African American population (21
Temporal improvements in mortality have been reported in other type 1 diabetes studies. A report from the U.K. on individuals in whom type 1 diabetes was diagnosed (age <17 years) between 1940 and 1989 (n
= 845) showed a fourfold decrease in SMRs between the 1940s cohort and the 1980s cohort (9.4 vs. 2.4, respectively) (22
). A large Danish study of mortality reported an increase of 15 years to the life expectancy of type 1 diabetic patients diagnosed over a 40-year period between 1933 and 1972 (23
). The reasons for temporal improvements in our cohort remain unclear, but an examination of cause-specific mortality is currently underway to determine whether chronic diabetes complications are being delayed or prevented in the youngest cohort (1975–1979) because of advances in care and to help explain the dramatic differences in SMRs by sex.
Onset mortality (death within the 1st year of diagnosis) improved in this cohort. The 1975–1979 diagnosis cohort had only one onset death compared with four and five in the 1965–1969 and 1970–1974 cohorts, respectively. These results are consistent with other studies and correspond to improvement in diagnosis and care at onset (24
Finally, this cohort is part of the DERI Study group with Finland (n
= 5,148) and Japan (n
= 1,410), exploring mortality differences in childhood-onset (age <18 years) type 1 diabetes in three countries (all diagnosed between 1965 and 1979). The most recent report compared mortalities in Japan and Finland after at least 15 years of follow-up (5
). The SMR for Japan was significantly higher (12.9) than that of Finland (3.7). The comparable SMR for our population was 5.8, which remains consistent with previous reports from DERI showing U.S. mortality rates sandwiched between Japanese and Finnish mortality rates (9
A few key limitations with this follow-up study must be addressed. First, these population-based data reflect the type 1 diabetes experience of individuals in Southwestern Pennsylvania with diabetes diagnosed between 1965 and 1979 and may not be representative of the entire U.S., of individuals not of African American or Caucasian ethnicity, or of those with diabetes diagnosed earlier or later than this cohort. In addition, 3% of the Allegheny County type 1 diabetes registry cohort was lost to follow-up, and vital status could not be determined for these individuals. Thus, the mortality rates might be slightly inflated. Thorough searches of both the SSDI and the NDI give us confidence that most (if not all) of these 32 individuals are still living. In addition, the analysis is limited to only a few key demographic variables (age at onset, race, and sex), as other key socioeconomic and clinical were not ascertained for all participants at study inception (8
). Finally, because diabetes in all individuals in this cohort was diagnosed before major modern-day advances in type 1 diabetes treatment (self-monitoring of blood glucose, A1C testing, and ACE inhibitors), the specific effect of these advances cannot be properly examined here.
Key strengths of this study include the size of this population-based cohort (n
= 1,075) and the 97% ascertainment rate after ≥25 years of follow-up. In addition, we now have sufficient follow-up data for temporal trend and other analyses in African Americans, providing important information for this understudied type 1 diabetes population (21
In summary, these results are encouraging and provide contemporary, population-based mortality figures for individuals with long-standing type 1 diabetes. Women in our cohort die at a rate similar to that of men, a result warranting further exploration, as younger women die much less frequently than younger men in the general U.S. population. These data illustrate that mortality rates are clearly decreasing in those in whom type 1 diabetes was diagnosed more recently; however, those with diabetes diagnosed most recently (1975–79) still die at rates 5 times higher than that of the general population. Thus, continuing improvements in treatment and care are essential, particularly in women and African Americans with type 1 diabetes.