Why are cancer rates increasing in those with type 2 diabetes?
Cancer is overtaking cardiovascular disease as a leading cause of death in people with type 2 diabetes. A new paper in Diabetologia looks at trends in cancer mortality in England over a 20-year period and its findings suggest that cancer prevention should now play a larger role in diabetes management.
Rates of major cardiovascular complications and mortality have been decreasing in people with diabetes in the past two decades – at least, in some high-income countries. However, this welcome trend goes in parallel with increasing contributions of other diseases, such as cancer, to mortality.
Accumulating evidence suggests that there is a higher rate of both incidence and mortality for some types of cancer among people with diabetes. Prolonged exposure to hyperglycaemia, hyperinsulinaemia, insulin resistance and chronic inflammation are potential underlying mechanisms for cancer in diabetes. There is also robust evidence of a causal relationship between type 2 diabetes and pancreatic, liver and endometrial cancer. And, as is well known, both diabetes and cancer are linked to obesity and smoking.
Previous studies have looked at inequalities in vascular outcomes by socioeconomic status among people with type 2 diabetes. Far less is known about whether such inequalities exist in cancer mortality rates. A new study by Suping Ling and colleagues at the Leicester Diabetes Research Centre, UK, described long-term trends in cancer mortality rates in people with type 2 diabetes by sociodemographic characteristics and risk factors.
The Clinical Practice Research Datalink was used to extract data on 137,804 individuals diagnosed with type 2 diabetes between 1998 and 2018, linking it with other databases to extract information on ethnicity, hospitalisations, socioeconomic status and date and cause of death. The underlying cause of death was used to estimate the proportion of cancer deaths.
The researchers also collected information about the four most common cancers in the UK (lung, colorectal, breast and prostate) and the four that are causally linked to diabetes (pancreatic, liver, endometrial and gallbladder), according to a recent meta-analysis. During a median follow-up of 8.4 years, there were 39,212 deaths.
All-cancer mortality rates
All-cause mortality rates decreased at all ages between 1998 and 2018 among this cohort with type 2 diabetes. Trends in all-cancer mortality rates differed according to age, with reductions in younger age groups and increases in older age groups. The average annual percentage change (AAPC) for the whole study period showed a decrease of 1.4% and 0.2% for 55 and 65-year-olds, and an increase of 1.2% and 1.6% for 75 and 85-year-olds.
Looking at other subgroups, higher AAPCs were observed in women than in men (1.5% versus 0.5%), in the least deprived than in the most deprived (1.5% versus 1%) and higher AAPCs were also observed in those with morbid obesity than in those of normal weight (5.8% versus 0.7%). However, all three subgroups showed upward trends in all-cancer mortality. These results mean there are persistent disparities by gender and socioeconomic status.
Meanwhile, the AAPC increased by 3.4% and 0.6% in current and former smokers, while it decreased by 1.4% in non-smokers. This has led to widening disparities by smoking status. Finally, analysis by ethnicity showed an overall increase in AAPC among those of White ethnicity of 2.4% and a decrease of 3.4% among those of other ethnicities.
Cancer-specific mortality rates
When it comes to looking at specific cancers (the four most common in the UK population), there was an increase in breast cancer mortality at younger ages, prostate cancer mortality at older ages, colorectal cancer at most ages and lung cancer at all ages.
For the four cancers thought to have a causal link with type 2 diabetes, there were increases in pancreatic and liver cancer at all ages. In endometrial cancer, the increase was confined to older age groups. For gallbladder cancer, there weren’t enough cases to draw any conclusions. The important take-home message from the analysis of this data is that people with type 2 diabetes had a more than 1.5-fold increased risk of dying from colorectal, pancreatic, liver or endometrial cancer.
Focus on cancer prevention
Increases in the incidence of early-onset type 2 diabetes means that people are being exposed to hyperglycaemia for longer. At the same time, the advent of glucose-lowering treatments with cardioprotective effects has contributed – and will continue to do so – to a reduced risk of dying from cardiovascular disease among those who have type 2 diabetes. This increases the likelihood of being diagnosed with conditions other than cardiovascular disease, including cancer. Early cancer detection and treatment have improved over time. Taken together, these factors may account for the trends in cancer mortality seen in this new study.
This is the first study to look at cancer mortality by sociodemographic characteristics and risk factors in people with type 2 diabetes in England. The authors caution that their analysis does not prove a causal relationship between any of these characteristics or factors and cancer.
Turning to studies on cancer and diabetes from elsewhere for comparison, the pattern is mixed. Several studies show downward trends in cancer mortality rates, but there are upward trends in Sweden, Taiwan and Australia. Cancer death rates in the USA are stable.
Clearly there is much more to be learned about the factors affecting the cancer burden in people with type 2 diabetes. In the meantime, however, these new findings have significant clinical and public health implications. Prevention of cardiovascular disease has long been a priority in type 2 diabetes management, but it seems that cancer is now becoming a leading cause of death as cardiovascular mortality declines. Therefore, cancer-prevention strategies now deserve more attention when it comes to supporting people with type 2 diabetes in living a long and healthy life. This is particularly so for older people and for liver, colorectal, endometrial and pancreatic cancer. Tailored interventions might be considered for smokers with type 2 diabetes, who seem to be particularly at risk of death from cancer.
Maybe changes to existing cancer screening programmes or more in-depth investigation of symptoms would be a way forward in reducing avoidable cancer deaths. For instance, it could be helpful to extend breast cancer screening to young women with type 2 diabetes. However, given the cost of and longer exposure to screening procedures that this would entail, further investigation is needed to determine the timing and those individuals most likely to benefit. Finally, the number of people with concurrent cancer and type 2 diabetes is likely to increase going forward, highlighting the need for multidisciplinary management in such cases.
In conclusion, these findings highlight the growing cancer burden among people with type 2 diabetes and the need to prioritise cancer prevention, research, early detection and management in this population. This is particularly so when it comes to colorectal, pancreatic, liver and endometrial cancer, where rates are substantially higher than in the general population. And there are persistent inequalities in cancer mortality by sociodemographic factors and widening disparities by smoking status. This suggests that tailored cancer prevention and detection strategies are needed.
To read this paper, go to: Ling S, Zaccardi F, Issa E, Davies MJ, Khunti K, Brown K. Inequalities in cancer mortality trends in people with type 2 diabetes: 20 year population-based study in England. Diabetologia online 24 January 2023. https://doi.org/10.1007/s00125-022-05854-8
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Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.