Incidence of Diabetes After Cancer Development: A Korean National Cohort Study

Abstract

Importance: Diabetes is an established risk factor for developing cancer. A limited body of evidence also suggests that cancer can increase the risk of developing new cases of diabetes, but the evidence is inconclusive.

Objective: To evaluate whether the development of cancer is associated with increasing risk of subsequent diabetes.

Design, setting, and participants: This cohort study included a nationally representative sample of the Korean general population observed for up to 10 years (January 1, 2003, to December 31, 2013). A total of 524 089 men and women 20 to 70 years of age without diabetes and with no history of cancer at baseline were included.

Exposures: Incident cancer (time-varying exposure).

Main outcomes and measures: Incident type 2 diabetes using insurance claim codes.

Results: During 3 492 935.6 person-years of follow-up (median follow-up, 7.0 years) in 494 189 individuals (50.0% female; mean [SD] age, 41.8 [12.5] years), 15 130 participants developed cancer and 26 610 participants developed diabetes. After adjustment for age, sex, precancer diabetes risk factors, metabolic factors, and comorbidities, the hazard ratio (HR) for diabetes associated with cancer development was 1.35 (95% CI, 1.26-1.45; P < .001). The excess risk for diabetes was highest in the first 2 years after cancer diagnosis, but it remained elevated throughout follow-up. By cancer type, development of pancreatic (HR, 5.15; 95% CI, 3.32-7.99), kidney (HR, 2.06; 95% CI, 1.34-3.16), liver (HR, 1.95; 95% CI, 1.50-2.54), gallbladder (HR, 1.79; 95% CI, 1.08-2.98), lung (HR, 1.74; 95% CI, 1.34-2.24), blood (HR, 1.61; 95% CI, 1.07-2.43), breast (HR, 1.60; 95% CI, 1.27-2.01), stomach (HR, 1.35; 95% CI, 1.16-1.58), and thyroid cancer (HR, 1.33; 95% CI, 1.12-1.59) was associated with a significantly increased risk of diabetes.

Conclusions and relevance: In this large Korean cohort, cancer development increased the risk of subsequent diabetes. These data provide evidence that cancer is associated with an increased risk of diabetes in cancer survivors independent of traditional diabetes risk factors. Physicians should remember that patients with cancer develop other clinical problems, such as diabetes, with higher frequency than individuals without cancer, and should consider routine diabetes screening in these patients.

Figure 1.. Cumulative Incidence of Diabetes by Cancer Status

Cumulative incidence was calculated using Kaplan-Meier curves. Participants who developed cancer contributed person-time to the exposed group from the time of cancer development. Unexposed person-time was contributed by participants who did not develop cancer and by participants who developed cancer prior to diabetes development. To reduce the potential impact of surveillance bias, we excluded from the analysis cases of diabetes that occurred in the first 31 days after cancer diagnosis (n = 72).

Figure 2.. Hazard Ratios for Incident Diabetes Associated With Cancer Development by Time Since Cancer Diagnosis

Adjusted for age (20-29, 30-39, 40-49, 50-59, and 60-69 years) and sex. Model 2 was further adjusted for body mass index (continuous), smoking (never, former, current, and missing), and frequency of alcohol intake (<1 time per month, 1-2 times per week, 3-4 per week, almost every day, and missing). Model 3 was further adjusted for hypertension (yes or no), hyperlipidemia (yes or no), Charlson comorbidity index (0, 1, 2, ≥3), systolic blood pressure (continuous), fasting glucose (continuous), and total cholesterol (continuous). Error bars indicate 95% confidence intervals.

Figure 3.. Hazard Ratios (HRs) for Incident Diabetes Associated With Cancer Development by Type of Cancer

Adjusted for age (20-29, 30-39, 40-49, 50-59, and 60-69 years) and sex. Model 2 was further adjusted for body mass index (continuous), smoking (never, former, current, and missing), and frequency of alcohol intake (<1 time per month, 1-2 times per week, 3-4 per week, almost every day, and missing). Model 3 was further adjusted for hypertension (yes or no), hyperlipidemia (yes or no), Charlson comorbidity index (0, 1, 2, ≥3), systolic blood pressure (continuous), fasting glucose (continuous), and total cholesterol (continuous). Error bars indicate 95% confidence intervals.