July 1st, 2018, Dr Chee L Khoo
With early diagnosis and improved treatment, many of our cancer patients have increased survival. You may already have noticed that many of our patients being managed in the multi-disciplinary oncology units are routinely promoting healthy lifestyles. Chronic co-morbidities including diabetes and cardiovascular diseases not only affect quality of life in these survivors but are the major cause of non-cancerous mortality in cancer patients. Diabetes is associated with a number of common cancers (e.g. breast, endometrial, ovarian, bowel) but a limited body of evidence suggest that patients with cancers are more prone to developing diabetes.
524 089 men and women between 20-70 years old who did not have a diagnosis of cancer or diabetes were followed up for up to 10 years in a large national cohort study in South Korea. They explored whether the risk of developing diabetes increased after the development of cancers. The study end-point was the development of diabetes. Patients who developed cancer after diabetes were not included.
During 3 492 935 person-years of follow-up (median follow-up was 7.0 years), 15 130 participants developed cancer. Compared with participants who did not develop cancer, those who did were older, more likely to be female, to drink alcohol every day, to have a higher body mass index and to have more comorbidities. 26 610 incident cases of diabetes were observed during follow up.
17.4 cases of diabetes per 1000 person years occurred after development of cancers compared with 7.5 cases per 1000 person years in those who either did not develop cancers or who developed diabetes before cancer diagnosis. The age- and sex-adjusted hazard ratio (HR) for diabetes associated with the development of cancer was 1.36 (95% CI, 1.27-1.46). The association did not materially change after adjustment for precancer diabetes risk factors, comorbidities or metabolic factors.
The excess risk for diabetes were highest in the first two years of diagnosis of cancer. Diabetes risk were worse in some cancers than others. The HR for pancreatic cancers, kidney and liver were 5.15, 2.06 and 1.95 respectively. Other cancers also associated with increased diabetes risk were gallbladder, lung, blood, breast stomach and thyroid. Cancers of the uterus, ovarian, colorectal, head and neck, oesophageal and prostate were NOT associated with increased risk of diabetes. The numbers for testicular and brain cancers were too small to be statistically significant.
Obesity, physical inactivity and smoking are common to the development of both cancers and diabetes. It may be that many of these patients are brewing both cancers and diabetes by harbouring these risk factors and either the diabetes or cancer surfaces first. Further, the increased risk of diabetes may relate to cancer treatment including corticosteroids2.
Chemotherapy agents may also directly cause hyperglycaemia. L-asparaginase, an agent often used in haematological cancers directly inhibits insulin release3. It is an established cause of hyperglycemia. Total body irradiation and immunosuppressive agents such as calcineurin inhibitors (cyclosporine and tacrilimus), often used in organ transplantation, may also increase the risk of diabetes4. Tamoxifen, an anti-estrogen, was also associated with an increased risk of diabetes in breast cancer5. Furthermore, the combined use of chemotherapy agents and corticosteroids may have a synergistic effect on diabetes risk.
Patients with advanced cancer experience substantial weight loss, muscle wasting and loss of appetite, a syndrome we call cancer cachexia. While weight loss is sometimes helpful in reducing the risk of type 2 diabees (T2D), the muscle loss is associated with increased insulin resistance and less favourable lipid profile. Further, reduction in physical activity from pain, loss of function and fatigue contributes to the risk of developing diabetes. Hyperglycaemia resulting from an acute illness is also a risk factor for subsequent development of diabetes.
It is important to recognise which cancers are more likely to be associated with the developing of diabetes. This study should remind us that patients with cancer develop diabetes at higher frequency than individuals without cancer and should consider routine diabetes screening in these patients. Further research is needed to establish the specific causes, natural history and optimal management strategy for diabetes that occurs in patients with cancer.
Access the abstract here
Reference
- Yul Hwangbo,MD, MSc; Danbee Kang, PhD; Minwoong Kang, Incidence of Diabetes After Cancer Development A Korean National Cohort Study. JAMA Oncol. Published online June 7, 2018. doi:10.1001/jamaoncol.2018.1684
- Clore JN, Thurby-Hay L. Glucocorticoid-induced hyperglycemia. Endocr Pract. 2009;15(5):469-474.
- Yoshida H, Imamura T, Saito AM, et al; Japan Association of Childhood Leukemia Study. Protracted administration of L-asparaginase in maintenance phase is the risk factor for hyperglycemia in older patients with pediatric acute lymphoblastic leukemia.
- Davidson J, Wilkinson A, Dantal J, et al; International Expert Panel. New-onset diabetes after transplantation: 2003 international consensus guidelines. proceedings of an international expert panel meeting. Barcelona, Spain, 19 February 2003. Transplantation. 2003;75(10) (suppl):SS3-SS24.
- Lipscombe LL, Fischer HD, Yun L, et al. Association between tamoxifen treatment and diabetes: a population-based study. Cancer. 2012; 118(10):2615-2622