Patient reported outcomes among patients with diabetes and cancer: an overview and research agenda

Due to the increased aging of the population, early detection and better treatment of diseases, the number of people who suffer from both diabetes and cancer is increasing. Depending on cancer type, gender and age at cancer diagnosis, approximately up to one in four cancer patients also suffers from concurrent diabetes. Previous studies mainly focused on the impact of one disease on the incidence and mortality of the other disease. However, limited attention has been paid to the consequences of the combination of having both diabetes and cancer on Patient Reported Outcomes (PROs) such as symptoms, health status, quality of life, anxiety and depression. PROs are important outcome measures as they inform us on the effect of treatment on outcomes that are important to patients. We can use this information to tailor treatment and care for elderly living with both diseases.

Association between cancer and diabetes

Cancer and diabetes often occur together, recent meta-analyses indicate that some cancers more commonly develop among diabetes patients. For example, diabetes strongly increases the risk of developing primary liver cancer and pancreatic cancer, although there is still some discussion on reverse-causality. In addition, the risk of developing endometrial cancer among women with diabetes is almost doubled compared to women without diabetes. In contrast, diabetes patients have a reduced risk of developing prostate cancer (Diabetes-associated cancers). It was previously shown that diabetes prevalence at cancer diagnosis varied between 5%-25%, depending on cancer type, age and gender. Again, the highest prevalence of diabetes was found among endometrial and pancreatic cancer patients, with a prevalence of up to 25% among those aged 80 years or older[1].

Treatment related toxicity and complications

Having diabetes at cancer diagnosis not only results in less-aggressive cancer treatment, but it also results in a higher risk of treatment related toxicity and complications among cancer patients. Diabetes was found to be associated with an increased risk of toxicity after radiotherapy[2] or chemotherapy[3]. Breast cancer patients with diabetes were also more likely to be hospitalized for infection or fever, neutropenia, anemia or any other cause compared to those without diabetes[3]. Moreover, diabetes may accentuate other symptoms and side-effects of chemotherapy, such as peripheral neuropathy: Chemotherapy-induced neuropathy is an important symptom which receives increasing attention[4] and is estimated to be prevalent in 20% of cancer patients[5]. Neuropathy is also common among diabetes patients with a prevalence ranging between 10% and 20%[6]. It can therefore be hypothesized that patients with both cancer and diabetes are more likely to experience symptoms of neuropathy after chemotherapy than cancer patients without diabetes, although this has not been studied yet. The higher incidence of treatment related toxicity and complications among cancer patients with diabetes will probably result in more patient reported symptoms, subsequently resulting in worse health status or Health-Related Quality of Life (HRQoL).

Health-related Quality of life among patients with both diabetes and cancer

Previously conducted studies that investigated PROs among patients with both diabetes and cancer focused on HRQoL as outcome measure. Three cross-sectional[7][8][9] and two longitudinal studies[10][11] on HRQoL among cancer and diabetes patients were conducted. Most studies[9][10][11] focused on prostate cancer patients and found a lower urinary function [10] and lower general health and vitality[9][11] among patients with concurrent diabetes versus those without. A large study including patients with different types of cancer observed significantly lower HRQoL scores among cancer patients with diabetes compared to patients with either one or none of both diseases[7]. Finally, cancer patients with diabetes reported lower physical functioning compared to cancer patients without diabetes[8].

These previous studies often compared cancer patients with and without diabetes but did not include patients without cancer and diabetes or patients with only diabetes[8][9][10][11]. Including these patient groups might be insightful to study the contribution of either cancer or diabetes and a potential interaction effect of both diseases on PROs. Therefore, future studies should assess whether the combined effect of diabetes and cancer on PROs is larger than the sum of the individual effects of both diseases (i.e. biological or additive interaction).

Research agenda

Although, previous studies indicate that patients with both diabetes and cancer have a deteriorated HRQoL compared to those with either one of the diseases, many questions remain and deserve further investigation in order to improve quality of life of the growing group of patients who have both diabetes and cancer. Longitudinal studies on PROs among men and women with both diabetes and cancer are lacking, making it difficult to draw conclusion about the differences in disease course between patients with both diabetes and cancer compared to those with either one of the diseases. Moreover, current research only addresses HRQoL and does not focus on other PROs. Depression, for example, is a major issue among both diabetes and cancer patients and is known to be a prognostic factor among patients with either diabetes or cancer. Other important issues like diabetes self-management, health care utilization, symptoms such as neuropathy, sexual problems, fatigue and treatment-related complications should also be addressed among patients with both diabetes and cancer in future research. Moreover, different cancer types should be included, since previous studies mainly focused on prostate cancer.

Furthermore, it will be of great interest to investigate how diabetes and cancer therapy not only impact on survival but also on PROs. Recently, metformin, an oral glucose lowering drug, is being investigated for its potential anti-cancer effect. Metformin may suppress tumor growth directly by activating the AMP kinase pathway which inhibits a central cell growth controller, mTOR, resulting in the inhibition of cell proliferation and cell growth. In addition, metformin may act indirectly by reducing hyperinsulinemia and insulin resistance (Metformin and cancer risk). Also, a less extensively studied pathway that might be involved in the association between metformin and cancer risk is the inflammatory response[12]. Metformin might inhibit the inflammatory response and thereby delaying or blocking tumor growth. Inflammation is also thought to be related to symptoms such as fatigue[13], depression[14] and cognitive function[15]. Therefore, future research should address the effect of metformin on symptoms such as fatigue and patient reported depression and cognitive function and its impact on HRQoL.

References

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  2. ^ Chon BH, Loeffler JS. The Effect of Nonmalignant Systemic Disease on Tolerance to Radiation Therapy. The Oncologist 2002; 7: 136-143

  3. ^ Srokowski TP, Fang S, Hortobagyi GN, Giordano SH. Impact of diabetes mellitus on complications and outcomes of adjuvant chemotherapy in older patients with breast cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2009; 27: 2170-2176.

  4. ^ Mols F, Beijers T, Lemmens V, et al: Chemotherapy-Induced Neuropathy and Its Association With Quality of Life Among 2- to 11-Year Colorectal Cancer Survivors: Results From the Population-Based PROFILES Registry. Journal of clinical oncology. June, 2013 [Epub ahead of print]

  5. ^ Bennett MI, Rayment C, Hjermstad M et al. Prevalence and aetiology of neuropathic pain in cancer patients: a systematic review. Pain 2012; 153: 359-365.

  6. ^ Veves A, Backonja M, Malik RA. Painful diabetic neuropathy: epidemiology, natural history, early diagnosis, and treatment options. Pain medicine 2008; 9: 660-674.

  7. ^ Bowker SL, Pohar SL, Johnson JA. A cross-sectional study of health-related quality of life deficits in individuals with comorbid diabetes and cancer. Health and quality of life outcomes 2006; 4: 17.

  8. ^ Hershey DS, Given B, Given C et al. Diabetes and cancer: impact on health-related quality of life. Oncology Nursing Forum 2012; 39: 449-457.

  9. ^ Mols F, Aquarius AE, Essink-Bot ML et al. Does diabetes mellitus as a comorbid condition affect the health-related quality of life in prostate cancer survivors? Results of a population-based observational study. BJU international 2008; 1594-1600.

  10. ^ Latini DM, Chan JM, Cowan JE et al. Health-related quality of life for men with prostate cancer and diabetes: a longitudinal analysis from CaPSURE. Urology 2006; 68: 1242-1247.

  11. ^ Thong MS, van de Poll-Franse LV, Hoffman RM et al. Diabetes mellitus and health-related quality of life in prostate cancer: 5-year results from the Prostate Cancer Outcomes Study. BJU international 2011; 107: 1223-1231.

  12. ^ Mahmood K, Naeem M, Rahimnajjad NA. Metformin: The hidden chronicles of a magic drug. European Journal of Internal Medicine 2013; 24: 20-26.

  13. ^ Bower JE. Cancer-related fatigue: Links with inflammation in cancer patients and survivors. Brain, Behavior, and Immunity 2007; 21: 863-871.

  14. ^ Miller AH, Maletic V, Raison CL. Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression. Biological Psychiatry 2009; 65: 732-741.

  15. ^ Sartori AC, Vance DE, Slater LZ, Crowe M. The Impact of Inflammation on Cognitive Function in Older Adults: Implications for Healthcare Practice and Research. Journal of Neuroscience Nursing 2012; 44: 206-217.

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