Association Between Diabetes and Cause-Specific Mortality in Rural and Urban Areas of China

Abstract

Importance: In China, diabetes prevalence has increased substantially in recent decades, but there are no reliable estimates of the excess mortality currently associated with diabetes.

Objectives: To assess the proportional excess mortality associated with diabetes and estimate the diabetes-related absolute excess mortality in rural and urban areas of China.

Design, setting, and participants: A 7-year nationwide prospective study of 512 869 adults aged 30 to 79 years from 10 (5 rural and 5 urban) regions in China, who were recruited between June 2004 and July 2008 and were followed up until January 2014.

Exposures: Diabetes (previously diagnosed or detected by screening) recorded at baseline.

Main outcomes and measures: All-cause and cause-specific mortality, collected through established death registries. Cox regression was used to estimate adjusted mortality rate ratio (RR) comparing individuals with diabetes vs those without diabetes at baseline.

Results: Among the 512 869 participants, the mean (SD) age was 51.5 (10.7) years, 59% (n = 302 618) were women, and 5.9% (n = 30 280) had diabetes (4.1% in rural areas, 8.1% in urban areas, 5.8% of men, 6.1% of women, 3.1% had been previously diagnosed, and 2.8% were detected by screening). During 3.64 million person-years of follow-up, there were 24 909 deaths, including 3384 among individuals with diabetes. Compared with adults without diabetes, individuals with diabetes had a significantly increased risk of all-cause mortality (1373 vs 646 deaths per 100 000; adjusted RR, 2.00 [95% CI, 1.93-2.08]), which was higher in rural areas than in urban areas (rural RR, 2.17 [95% CI, 2.07-2.29]; urban RR, 1.83 [95% CI, 1.73-1.94]). Presence of diabetes was associated with increased mortality from ischemic heart disease (3287 deaths; RR, 2.40 [95% CI, 2.19-2.63]), stroke (4444 deaths; RR, 1.98 [95% CI, 1.81-2.17]), chronic liver disease (481 deaths; RR, 2.32 [95% CI, 1.76-3.06]), infections (425 deaths; RR, 2.29 [95% CI, 1.76-2.99]), and cancer of the liver (1325 deaths; RR, 1.54 [95% CI, 1.28-1.86]), pancreas (357 deaths; RR, 1.84 [95% CI, 1.35-2.51]), female breast (217 deaths; RR, 1.84 [95% CI, 1.24-2.74]), and female reproductive system (210 deaths; RR, 1.81 [95% CI, 1.20-2.74]). For chronic kidney disease (365 deaths), the RR was higher in rural areas (18.69 [95% CI, 14.22-24.57]) than in urban areas (6.83 [95% CI, 4.73-9.88]). Among those with diabetes, 10% of all deaths (16% rural; 4% urban) were due to definite or probable diabetic ketoacidosis or coma (408 deaths).

Conclusions and relevance: Among adults in China, diabetes was associated with increased mortality from a range of cardiovascular and noncardiovascular diseases. Although diabetes was more common in urban areas, it was associated with greater excess mortality in rural areas.

Figure 1. Prevalence of total diabetes at baseline and adjusted all-cause mortality RRs by age and area

Left panel shows age-specific prevalence and the percentages in the key represent the overall age- and gender-adjusted prevalence for urban and rural regions. The size of each box is proportional to the number of participants with diabetes and the error bars indicate the 95%CI. Right panel shows adjusted all-cause mortality rate ratios (RRs) by age-at-risk in three groups (35-59, 60-69, 70-79) and area and the values in the key represent the overall, urban and rural RRs comparing those with versus without diabetes at baseline, adjusted for age, geographic area (5 within each of rural and urban region), sex, education, smoking, alcohol drinking, physical activity and BMI. Age at risk was calculated according to baseline age and length of follow-up, with censoring date by 1.1.2014 or age of death if earlier. Each RR has a CI that reflects the variance of the log risk in that one group, taking into account the variance of the log risk in the non-diabetic reference group (shown with a dotted line, with shading indicating 95% group-specific CI) and has a vertical solid line that represents the 95%CI. Mortality RRs are plotted on a floating absolute scale. Each box has an area inversely proportional to the effective variance of the log RR. The analyses were restricted to those who died at age-at-risk 35-79 years, excluding 5 deaths at age-at-risk <35 and 1014 deaths at age-at-risk ≥80 years. The point estimates on the x-axis for both panels represent the mean of each age groups, with number of individuals (left panel) and number of person-years (right panel) shown underneath the x-axis. To avoid overlap of 95%CI lines, the boxes and their 95% CIs for rural and urban areas in right panel were moved apart slightly from the actual positions.

Figure 2. Rural and urban mortality rates of diabetic ketoacidosis or coma (definite or probable) and chronic kidney disease among people with diabetes by age at risk

The death rates by four age-at-risk groups (35-49, 50-59, 60-69 and 70-79) were standardized for sex, using the total diabetic population in CKB as the standard. The age at risk was calculated according to baseline age and length of follow-up, with censoring date by 1.1.2014 or age of death if earlier. The analyses were restricted to those who died at age-at-risk 35-79 years, excluding 0 deaths at age-at-risk <35 and 5 and 8 deaths at age-at-risk ≥80 years for diabetic ketoacidosis or coma and chronic kidney disease, respectively. The point estimates on the x-axis for both panels represent the rates for each age category, with number of deaths and person-years shown underneath the x-axis. The size of each box is proportional to the number of deaths in each group and the error bars indicate the 95%CI. To avoid overlap of 95%CI lines, the boxes and their 95% CIs for rural and urban areas were moved apart slightly from the actual positions.

Figure 3. Adjusted rate ratios for all-cause mortality and selected disease-specific mortality by duration since diagnosis at baseline

a) Diabetic ketoacidosis or coma, b) Chronic kidney disease, c) Cardiovascular disease, d) All-cause mortality. The adjusted RRs are relative to screen-detected diabetes (for diabetic ketoacidosis or coma and chronic kidney disease) or to those without diabetes (for cardiovascular disease and all-cause mortality). The point estimates on the x-axis are placed by each equally-spaced diabetes duration category, with number of deaths and person-years shown underneath the x-axis for those with diabetes. The dotted line indicates the RR for the reference group with shading indicating 95% group-specific CI. Other conventions for symbols same as in Figure 1.