Overall And Cause-Specific Mortality In Patients With Type 1 Diabetes Mellitus: A Population-Based Cohort Study In Taiwan From 1998 Through 2014 Ⅱ

RESULTS 

The study cohort included 7,696 prevalent (44.74%) and 9,507 incident (55.26%) cases of type 1 diabetes, with slight female dominance. The mean age at cohort enrollment was 33.05 (standard deviation [SD], 21.41; median, 28) years. In up to 17 years of follow-up, 4,916 patients died from causes at a mean age of 62.37 (SD, 16.68) years. Among the deceased individuals, 65 (1.32%) died at ages <20 years and 2,556 (51.99%) died at 65 years or older (table 2). Cumulative survival risk were significantly different between males and females (P < 0.001, log-rank test) (Figure 1) and across ages at enrollment (P < 0.001, log-rank test) (Figure 2).

Figure 1. Sex-specific survival curves in patients with type 1 diabetes

Figure 2. Age-specific survival curves in patients with type 1 diabetes

Diabetes was the leading UCOD (n = 1,482), which accounted for 30.15% of the total deaths, followed by cancer (n = 1,007, 20.48%), circulatory diseases (n = 646, 13.14%) and renal diseases (n = 563, 11.45%). The distributions of UCODs varied with age at death, in which the proportion of deaths from violence or accidents (including suicide) and diabetes were considerably higher in children (0–14 years) than in patients of older age groups. The proportions of deaths from circulatory diseases, renal diseases, infectious diseases, and pneumonia were higher among patients aged ≥45 years; the proportion of deaths from circulatory diseases increased with age (figure 1)

Distributions of UCOD were essentially similar between male and female subjects, with a slightly greater proportion of deaths from cancer noted in males and diabetes noted in females (eFigure 2). The proportions of deaths from circulatory diseases and infection increased over the study period, but the proportions of diabetes and chronic liver disease decreased (eFigure 3).

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The mortality rate of patients with type 1 diabetes was 26.93 per 1,000 person-years for the entire patient group, 29.25 per 1,000 person-years for males, and 24.90 per 1,000 person-years for females (Table 1). The UCOD with higher mortality rates in patients with type 1 diabetes were diabetes, cancer, and circulatory disease (8.12, 5.52, and 3.54 per 1,000 person-years, respectively). The leading causes of death with higher mortality rate were similar between males and females. Cancer in liver and intrahepatic bile ducts was the most frequent UCOD among listed site-specific cancers in both males and females. 

Compared with the general population, patients with type 1 diabetes were at a significantly increased risk of all-cause mortality (SMR 4.16; 95% CI, 4.04–4.28). Cause-specific analysis indicated that the most increased SMR was observed for diabetes (SMR, 16.45), followed by renal disease (SMR, 14.48), chronic hepatitis and liver cirrhosis (SMR, 4.91), infection (SMR, 4.59), and pneumonia (SMR, 3.00). Cancer and circulatory diseases also exhibited an increased SMR (SMR, 2.94 and 2.52, respectively). Significantly increased SMRs were observed for specific circulatory diseases, including heart disease, cerebrovascular disease, and hypertension without heart disease, as well as for listed site-specific cancers except kidney neoplasm. Among the cancer site-specific SMRs, SMR for the pancreas was mostly increased at 4.95. Type 1 diabetes was also associated with a significantly increased SMR for violence and accidents (SMR, 1.35) and COPD (SMR, 1.51) (Table 1).

Sex-specific SMRs are also shown in Table 1. Male and female type 1 diabetes were significantly associated with elevated all-cause mortality with SMR of 3.79 and 4.62, respectively. Both male and female patients had significantly increased SMRs for diabetes, renal diseases, and cancer. Although male and female genders were associated with significantly increased SMRs of circulatory diseases, infection, pneumonia, and chronic hepatitis and liver cirrhosis, female patients had greater SMRs of the above causes than males.

The absolute mortality rate and all-cause SMRs were also significantly increased for all ages at enrollment (Table 2). The most increased SMR was observed for patients aged 15–29 years (SMR, 8.46), followed by ages of 30–44 years (SMR, 8.08) and 0–14 years (SMR, 5.37); SMR was the least for those enrolled at ≥45 years (SMR, 3.57). Significantly increased SMRs were noted for circulatory disease, cancer, diabetes, and pneumonia in all age groups. A substantial increase in SMR of renal diseases was observed among patients aged 15–29 years (SMR, 98.86), 30–44 years (SMR, 48.73), and ≥45 years (SMR, 12.50). SMRs of infection and chronic hepatitis and liver cirrhosis were also significantly increased in the three order age groups and were similarly decreased among patients aged ≥45 years. SMR of diabetes was highest in the youngest group aged 0–14 years and decreased with age. SMR of violence and accidents was significantly increased only for ages 15–29 years (SMR, 1.68), and SMR of suicide significantly increased only for ages 30–44 years (SMR, 2.35). SMR of COPD was only significantly elevated for ages ≥45 years (Table 2).