A new retrospective Korean cohort study of more than half a million men and women followed for 10 years shows that a diagnosis of nine types of cancer was associated with a significantly increased risk of subsequent diabetes. The observational study, led by Juhee Cho, PhD, of Sungkyunkwan University in Seoul, Korea, was published online June 7 in JAMA Oncology. The risk of diabetes was highest in the 2 years following cancer diagnosis, but remained elevated during the entire follow-up period, from 2003 to 2013. "While multiple studies have established that diabetes is a risk factor for the development of several types of cancer and a prognostic factor for cancer-related mortality, a limited body of evidence suggests that cancer can increase the risk of developing new cases of diabetes, especially after pancreatic, colorectal, and breast cancer," the authors write. "These data provide evidence that cancer is associated with an increased risk of diabetes in cancer survivors independent of traditional diabetes risk factors." And given the increased frequency of clinical problems in patients with cancer, including diabetes, clinicians "should consider routine diabetes screening in these patients," they advise. Risk of Diabetes Raised Five-Fold After Pancreatic Cancer The researchers note that prior studies linking cancer to diabetes have been limited by small sample sizes or restriction to specific cancer types, and they have often lacked information on diabetes risk factors such as obesity, physical inactivity, and smoking status prior to the development of cancer. For the current study, insurance claims data from Korea's single-payer national health system was used to develop a nationally representative sample of 2.2% of the population. The National Health Insurance Service–National Sample Cohort (NHIS-NSC) consisted of 524,089 men and women 20 to 70 years of age with no diabetes and no history of cancer at baseline. Over a median follow-up of 7 years, 15,130 participants were diagnosed with cancer. Cancer survivors were older than those who did not develop cancer and more likely to be women, drink alcohol daily, and have a higher body mass index and more comorbidities. Of the 26,610 incident cases of diabetes observed during the 10-year follow-up, 834 cases occurred after the development of cancer. The hazard ratio (HR) for diabetes associated with cancer development overall was 1.35 (P < 0.001), after adjusting for pre-cancer diabetes risk factors as well as age, sex, metabolic factors, and comorbidities, the study showed. The risk of diabetes was increased five-fold in participants diagnosed with pancreatic cancer (HR, 5.15). A significantly elevated risk of new diabetes was also observed in those diagnosed with tumors of the kidney (HR, 2.06), liver (HR, 1.95), gallbladder (HR 1.79), lung (HR, 1.74), blood (HR, 1.61), breast (HR, 1.60), stomach (HR 1.35), and thyroid (HR, 1.33). Development of testicular and brain cancer was also associated with increased risk of diabetes. However, the number of cases was too small to achieve statistical significance, the researchers note. "A strength of our analysis was that we could adjust for precancer risk factors for diabetes...The increased risk in diabetes did not affect all obesity-related cancers because colorectal and endometrial cancer were not associated with an increased risk of subsequent diabetes," say the researchers. An increased risk of diabetes was also not observed after development of uterine, ovarian, head and neck, esophageal, or prostate cancers. Study limitations include the lack of information on cancer stage, incomplete information on cancer treatment and management, and the fact that outcomes were based on insurance claims data, Cho and colleagues say. Potential Explanations The researchers go on to discuss a number of potential explanations. Because the highest increased risk of diabetes was observed in the first 2 years after cancer diagnosis, it's possible that the toxicity of cancer treatments, such as corticosteroids or chemotherapy, may play a role. The direct effects of cancer may also increase diabetes risk, they suggest, noting that cancer cachexia is associated with insulin resistance, impaired glucose tolerance, and diabetes. And because "disease-specific and treatment-related factors may contribute to diabetes development in patients with cancer, it is possible that the clinical course and response to therapy in diabetes in patients with cancer may be different than in patients with type 2 diabetes who do not have cancer," they add. "Further research is needed to establish the specific causes, natural history, and optimal management strategy for diabetes that occurs in patients with cancer." Source
