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As we saw in Part 1, diabetes refers to a spectrum of long-lasting health disorders seen in individuals whose blood sugar levels remain high over a prolonged period, with adverse health consequences.
In the U.S., diabetes is responsible for more deaths every year than breast cancer and AIDS combined. Having diabetes raises the chance of having a heart attack by nearly two-fold and also increases the risk for stroke and cancer.
Both type 2 diabetes – which is the most common form of diabetes, accounting for 95% of all cases – and cancer are severe, chronic diseases that share many common risk factors and have a tremendous impact on health all over the world. Worldwide, cancer is the second and diabetes is the 12th leading cause of death. In the U.S., cancer is the second and diabetes is the seventh leading cause of death. However, it must be remembered that diabetes is not always mentioned as an existing condition on death certificates.
Unfortunately, population studies indicate that people with diabetes are at much greater risk for many forms of cancer.4 Population studies – also known as epidemiologic studies – reveal links and associations, but do not shed any light on cause and effect.
To explore this potential link between diabetes and cancer, the American Diabetes Association and the American Cancer Society convened a so-called “consensus development conference” in December 2009.
At the end of the conference, a consensus report was created in which various experts were asked to address the following questions:
- Is there a real link between diabetes and cancer incidence? If yes, the incidence of which types of cancer is influenced by diabetes?
- What risk factors are common to diabetes and cancer?
- What are the possible links between diabetes and cancer risk?
Further, the authors of the report were asked to address any existing gaps in the evidence and propose research strategies for developing more convincing data.
Let’s take an in-depth look at the answers to these questions.
Consensus Report: Overview
According to the report created at the consensus development conference in 2009, type 2 diabetes is indeed associated with a higher risk for liver, pancreas, endometrial, colorectal, breast, and bladder cancer.
Interestingly, type 2 diabetes is associated with a lower risk of prostate cancer. There appears to be no link between diabetes and other cancers, or else the evidence is simply not conclusive enough.
Of course, some of these associations between diabetes and cancer may be due to shared risk factors, such as aging, obesity, diet, and physical inactivity. However, hyperinsulinemia (high insulin), hyperglycemia (high blood glucose), and higher than normal levels of inflammation seen in diabetes might also be directly responsible for cancer formation.
Promisingly, consuming a healthy diet, regular physical activity, and weight management have been shown to reduce risk and improve outcomes of type 2 diabetes, as well as some forms of cancer.
The consensus report recommends that patients with diabetes be strongly encouraged to undergo cancer screenings as recommended for their age and gender category.
Evidence suggests that external insulin taken to control blood sugar levels may be associated with a higher risk of cancer. Further research is needed to clarify this link and to assess whether certain types of commercially available insulin are more strongly associated with cancer risk than others.
For those with diabetes who have been judged to have a very high risk for cancer occurrence or recurrence, these issues clearly require careful attention and follow up.
Known Associations Between Diabetes and Cancer
For more than 50 years, clinicians have been diagnosing some of their patients with concurrent diabetes and cancer. In the 1960s, a link between these two diseases was identified based on population studies.
A meta-analysis conducted in 2009 concluded that some cancers do develop more commonly in patients with type 2 diabetes and that “diabetes and cancer have a complex relationship that requires more clinical attention and better-designed studies”.
Specifically, having diabetes raised the risk of liver, pancreas, and endometrial cancer by about twofold or higher and cancers of the colon and rectum, breast, and bladder by about 1.2 to 1.5-fold. However, the risk of developing other cancers, for example lung cancer, does not appear to be associated with diabetes. The evidence for a connection between diabetes and kidney cancer, non-Hodgkin lymphoma and other cancers is inconclusive. So far, very few studies have explored potential links between cancer and type 1 diabetes.
A systematic review and meta-analysis comparing overall survival in cancer patients with and without preexisting diabetes was conducted in 2008, with the authors finally settling on 48 articles describing original investigations.
A meta-analysis is a statistical analysis that combines the results of multiple scientific studies, with the idea that there is a common truth behind all conceptually similar scientific studies that can be uncovered by such a comparison.
A meta-analysis of 23 of the 48 articles showed that diabetes was associated with a higher death rate in cancer patients, regardless of the type of cancer. Specifically, diabetes increased risk of death in patients with cancers of the endometrium, breast and, most of all, colon & rectum.
Another retrospective population study published in 2008 compared deaths between women with breast cancer aged 55-79 years with diabetes and without diabetes.
Women with diabetes were typically found to be slightly older, more likely to reside in a lower income neighborhood, and had a greater risk of dying from a combination of the 2 diseases, relative to women without diabetes.
The risk of dying following breast cancer was seen to be nearly 40% higher in women with diabetes relative to women without diabetes, within the first 5 years following breast cancer diagnosis. In other words, early survival following breast cancer is lower in women with diabetes, likely due to diabetes-related causes.
Similarly, another 2008 study observed men who were participating in the Physicians’ Health Study and had been diagnosed with prostate cancer. Possible links were examined between body-mass index (BMI, a marker of overweight and obesity) and blood levels of C-peptide (a marker of insulin resistance, a condition that can lead on to diabetes) on prostate cancer-associated deaths.
A high BMI and higher than normal blood levels of C-peptide were both seen to predispose men with a subsequent diagnosis of prostate cancer to a greater likelihood of dying of their disease. Patients with both factors were seen to have the worst outcome.
A similar relationship was seen between C-peptide levels and colorectal cancer.
Is it direct – for example, is cancer triggered by high blood sugar?
Is diabetes simply a marker of underlying factors that raise cancer risk, such as insulin resistance and high blood levels of insulin?
Alternatively, is the link between diabetes and cancer indirect and a consequence of shared risk factors, such as obesity and levels of physical activity?
The authors of the consensus report state that these questions can only be answered by carrying out large-scale population studies with high-quality databases, so that the incidence of specific cancers between subjects with high circulating insulin levels with or without diabetes, relative to nondiabetic individuals with normal insulin sensitivity and low insulin levels can be objectively compared and clearly understood.
In these studies, including diabetes-related biomarkers and potentially common underlying factors along with a better characterization of diabetes duration, therapy, degree of glycemic control in relation to cancer risk would likely contribute valuable information on the precise nature of the link(s) between diabetes and cancer.
Risk Factors Common to Diabetes and Cancer
Potential risk factors common to both diabetes and cancer include age, obesity, gender, race/ethnicity, diet, levels of physical activity, alcohol consumption, and smoking.
The likelihood and incidence of most cancers increases with age. In economically developed countries, up to 78% of all newly diagnosed cancers happen in individuals aged 55 years and older.10 Similarly, diabetes also becomes increasingly common with age.
Also, an analysis of over 2000 subjects who were 50 years or older and had diabetes showed that roughly 1 percent of them developed pancreatic cancer within the first 3 years of meeting the criteria for diabetes.
Obesity is becoming increasingly prevalent worldwide and has been linked to an increased incidence and death from diabetes as well as many cancers. Specifically, overweight (BMI ≥25 and <30 kg/m2) or obese (BMI ≥30 kg/m2) individuals have a higher risk for many types of cancer compared with individuals with BMI in the normal range. These include breast (in postmenopausal women), colon/rectum, endometrium, pancreas, adenocarcinoma of the esophagus, kidney, gallbladder, and liver cancer.
Greater body fat is also a probable cause of cancers of the mouth, pharynx and larynx, stomach, gallbladder, ovary and prostate.12 Maintaining a healthy weight throughout life is one of the most important ways to protect against cancer, while also lowering risk for developing diabetes.
Promisingly, weight loss has been shown to lower diabetes risk, including gestational diabetes. However, the link between weight loss and cancer risk is less obvious, for various reasons. For example, the Nurses’ Health Study clearly showed that weight gain during adult life, specifically since menopause, increases risk of breast cancer in postmenopausal women. On the other hand, weight loss after menopause is associated with a decreased risk of breast cancer only when weight loss is maintained for 4 years.
As we saw earlier, having a high BMI – which increases risk for diabetes – also predisposed men with a subsequent diagnosis of prostate cancer to a greater likelihood of dying of their disease.
In parallel with the growing obesity epidemic, type 2 diabetes is becoming more frequent among adolescents and young adults, adding years of additional risk from diabetes and associated health problems – including raising their risk for various obesity-associated cancers – as they grow into adults.
While certain cancers happen only in men (testicular, prostate) or only in women (cervix, uterine), generally cancer tends to occur more frequently in men. Interestingly, men also have a slightly higher risk of developing diabetes relative to women.
The incidence of cancer and diabetes varies quite a bit between different races and ethnicities, likely due to differences in the prevalence of major risk factors, genetic factors, medical practices such as screening, completeness of reporting, as well as other economic and social factors.
Most studies looking at the effects of diet on cancer risk, regardless of their different designs and study populations, indicate the same thing. As recommended by the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR), a plant-based diet rich in whole grains, vegetables, fruits, and legumes like beans and lentils, with limited amounts of red or processed meat and a strong emphasis on eliminating all processed foods, sugar-sweetened drinks, and alcohol, is clearly associated with a lower risk for developing many types of cancer.
A study examining possible connections between dietary habits and health among almost 42,000 cancer-free people aged 40 and older over an eight-year period showed that people who most closely followed the WCRF/AICR diet had a 12% lower risk of cancer. Promisingly, this diet was especially protective against prostate and colon cancer. There is strong evidence that eating whole grains and other foods containing dietary fiber such as pulses, beans and lentils (at least 30 grams daily) protects against colorectal cancer.
Another study that followed over 90,000 premenopausal women from the Nurses’ Health Study II for 22 years found that those who ate the most fruit during adolescence compared with those who ate the least had a 25% lower risk of developing breast cancer. Specifically, women who had eaten a lot of apples, bananas, and grapes during adolescence, and oranges and kale during early adulthood had a lower risk of developing breast cancer.
Women from the same Nurses’ Health Study II with the highest fruit fiber intake had a 12% reduced risk of breast cancer, while those with the highest vegetable fiber intake had an 11% reduced risk.
Similarly, diets that are low in processed meat but high in monounsaturated fatty acids, fruits, vegetables, whole grain cereals, and dietary fiber also protect against the risk of developing type 2 diabetes. Indeed, most diets that are protective against both diabetes and cancer tend to be rich in plant foods.
The American Cancer Society, the World Cancer Research Fund, and the American Institute for Cancer Research have all recommended limiting or completely eliminating the consumption of energy-dense and sugary foods and sugar-sweetened drinks that contribute to overweight and obesity.
Fast foods or readily available convenience foods tend to be energy dense and include burgers, fried chicken pieces, French fries, and high-calorie drinks containing excess sugar, such as cola and even many commercially available fruit juices.
The more highly processed foods are, the higher in energy and lower in critical micronutrients they tend to be. Potato chips and crisps, white flour bread, pasta, and pizza, cakes, pastries, biscuits and cookies, and confectionery are all typical examples.
Minimizing or cutting out consumption of processed and sugary foods and sugar-sweetened drinks has been shown to protect against weight gain, overweight, and obesity and is therefore likely to protect against both diabetes and obesity-related cancers.
Further, diets containing low glycemic foods have been shown to offer protection from many chronic diseases, including diabetes, comparable with that seen for whole grain and high fiber consumption.
Level of physical activity
Published epidemiologic studies show that physically active men and women have about a 30 to 40% reduction in the risk of developing colon cancer, compared with inactive people. Similarly, physically active women have about a 20 to 30% reduction in risk of developing breast cancer, compared with inactive women. In both instances, it appears that 30-60 minutes of moderate to vigorous activity is required daily to reduce risk.
Similarly, scientific evidence indicates that increased physical activity probably reduces prostate and endometrial cancer risk and possibly lowers lung cancer risk as well. Weight control may be partly responsible for the protective effect of physical activity against these cancers – links between excess weight, central body fat, and greater cancer risk are well established.
Based on this evidence, some public health organizations recommend at least 30 minutes of moderate-to-vigorous intensity physical activity on at least 5 days every week to lower cancer risk. Evidence suggests that exercise also influences other aspects associated with cancer diagnosis, such as cancer detection, coping, rehabilitation, and survival after diagnosis.
There is a lot of convincing evidence that physical activity protects against weight gain, overweight, and obesity, and therefore, against diabetic outcomes as well. Indeed, 30 minutes of moderate-intensity exercise, such as walking, at least 5 days per week reduces the risk of developing type 2 diabetes by 25 to 36%.
Analyses of the intensive lifestyle intervention in the Diabetes Prevention Program indicates that subjects who did not reach weight loss goals still significantly reduced their risk of diabetes if they reached the exercise goals. However, weight loss was still the most effective predictor for reduced diabetes incidence. For every kilogram of weight loss, a 16% reduction in risk was seen.
Abstaining from alcohol may play a larger role in cancer prevention than previously thought.12 Even small amounts of alcoholic drinks can increase the risk of several cancers. There is no threshold of alcohol consumption below which cancer risk does not increase, at least for some cancers.
Simply put, the more alcohol we drink, the higher our cancer risk – specifically for cancer of the mouth, pharynx and larynx, esophagus, liver, colorectum, breast (both pre- and post-menopause), and stomach.
Alcoholic drinks of all types have a similar impact on cancer risk. The important factor is the amount of alcohol or ethanol consumed.
A systematic review was carried out in 2004 that examined the effects of alcohol use on incidence, management, and complications of diabetes in adults as determined by 32 different studies. Surprisingly, moderate alcohol consumption (one to three drinks daily) was seen to be associated with a 33 to 56% lower incidence of diabetes. Compared with moderate consumption, heavy alcohol consumption (more than 3 drinks daily) was associated with up to a 43% increased incidence of diabetes.
Tobacco smoking is estimated to be the cause of more than 70% of all trachea, bronchus, and lung cancer deaths. Other cancers that have been strongly linked with smoking include larynx, upper digestive, bladder, kidney, pancreas, leukemia, liver, stomach, and uterine cervical cancers.
Smoking has also been shown to nearly double the incidence of diabetes within 5 years. Specifically, the risk of diabetes has been shown to be greater for heavy smokers than for lighter smokers and lower for former smokers compared with active smokers.
Clearly, active smoking is associated with an increased diabetes risk. Not only that, smoking also increases the risk of developing cardiovascular disease, retinopathy, and other complications that are normally associated with diabetes.
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