Diabetes+Obesity, Together, Responsible for Nearly 800,000 Cancers Worldwide
The study, led by Imperial College London, found that nearly 6% of new worldwide cancer cases in 2012 were caused by the combined effects of diabetes and being overweight (BMI of over 25 kg/m2) or obese (BMI of over 30 kg/m2). For the 12 cancers types studied, diabetes and high BMI combined were responsible for nearly 800,000 new cancer cases.
As individual risk factors, being overweight was responsible for twice as many cancers as diabetes, 544,300 cases of cases were attributable to high BMI (equivalent to 3.9 per cent of all cancers), and 280,100 were attributable to diabetes (equivalent to two per cent).
One in four diabetes-related cancer cases in 2012 (77,000 cases) were attributable to the worldwide rise in diabetes between 1980 and 2002. Just under a third of weight-related cancer cases in 2012 (174,000) were attributable to the worldwide rise in the number of overweight and obese people over the same period.
Cancers caused by diabetes and being overweight or obese were almost twice as common in women as men, accounting for 496,700 and 295,900 overall cancer cases respectively.
The authors say that if global rates of diabetes and overweight continue to rise, the share of cancers attributable to the combined factors will increase by over 30 per cent in women and by 20 per cent in men by 2035.
The research is published today in The Lancet Diabetes & Endocrinology.
To conduct the study, the researchers gathered data on cases of 12 types of cancer from 175 countries in 2012. They combined this with data on high BMI and on diabetes. They matched the data sets by age group and gender.
The two factors accounted for a quarter of liver cancers and more than a third of all endometrial cancers worldwide. In men, liver cancer was the commonest cancer caused by diabetes and high BMI, accounting for 126,700 cases, or 42.8 per cent of all cancers caused by diabetes and high BMI. Colorectal cancer was the second commonest, accounting for 63,200 new cancer cases or 21.4 per cent.
In women, breast cancer was the commonest cancer caused by diabetes and high BMI, accounting for 147,400 cases or 29.7 per cent of such cancers. Endometrial cancer was the second commonest, accounting for 121,700 new cancer cases or 24.5 per cent.
The most cancer cases were seen in high-income western countries (38.2 per cent, 303,000 of 792,600 cases), however the largest increases from 1980 to 2002 were seen in low and middle-income countries. The leading cancer due to diabetes and high BMI in high-income western countries was breast cancer, accounting for 23.8 per cent of all cancers attributable to these risks. In East and South-East Asia, liver cancer accounted for 53.8 per cent of cancers attributable to diabetes and high BMI.
The new figures highlight the substantial role of diabetes in cancer worldwide, particularly in lower income countries where rates of people being overweight, diabetes and cancer cases are soaring.
Dr. Jonathan Pearson-Stuttard, lead author of the study from Imperial’s School of Public Health, said: “While obesity has been associated with cancer for some time, the link between diabetes and cancer has only been established quite recently. Our study shows that diabetes, either on its own or combined with being overweight, is responsible for hundreds of thousands of cancer cases each year across the world.”
The authors say that although the reason for the link between diabetes and cancer is still being investigated, high insulin or glucose levels, chronic inflammation, and sex hormone disruption are potential factors.
They say the figures highlight the need for effective food policies to tackle overweight and diabetes, and for clinicians to be aware of the high cancer risk carried by people of all ages who are overweight, have diabetes, or both.
Dr. Pearson-Stuttard added: “Both clinical and public health efforts should focus on identifying effective preventive, control and screening measures to structurally alter our environment, such as increasing the availability and affordability of healthy foods, and reducing the consumption of unhealthy foods. It is vital that coordinated polices are implemented to tackle the shared risk factors and complications of chronic diseases such as obesity and diabetes.
“The distinct features of cancer patients are evolving throughout the world. In the past, smoking was by far the major risk factor for cancer, but now healthcare professionals should also be aware that patients who have diabetes or are overweight also have an increased risk of cancer.
Type 2 Diabetes, It All Starts in the Liver
By deciphering how the protein PTPR-γ, which is increased in the context of obesity, inhibits insulin receptors located at the surface of liver cells, the scientists open the door to potential news therapeutic strategies. These results can be read in Nature Communications.
The bottom line: No diabetes without PTPR-γ.
“Mice totally lacking PTPR-γ, when put on a high-calorie diet, did develop obesity. But they did not show any sign of insulin resistance and seemed to be entirely protected from diet-induced diabetes”, explains Xavier Brenachot, a researcher at UNIGE Faculty of Medicine in Geneva and first author of this study. The scientists also administered lipopolysaccharide, a toxin pertaining to certain bacteria of the gut microbiota associated with obesity and insulin resistance. Once again, the animals lacking PTPR-γ did not develop insulin resistance.
To fine-tune their analysis, Roberto Coppari and his colleagues reconstituted the expression of PTPR-γ at normal levels, but only in hepatocytes (liver cells). The mice were again prone to insulin resistance, indicating the pivotal role of the liver. Moreover, a two-fold overexpression in the liver (mimicking the natural pathophysiology of obesity) was sufficient to cause insulin resistance.
The metabolic functions of this protein were never characterized; this discovery therefore opens the door for potential new therapies. Previous studies had already studied PTP proteins in search for diabetes treatments, unfortunately to no avail. However, contrary to some of its family members that are intracellular, the protein identified in Geneva is located on the cell membrane. It is therefore of much easier access for therapeutic molecules.
Interestingly, the very form of this protein allows for potential inhibition strategies: when two independent PTPR-γ molecules are brought together by a ligand, they cannot act any more. The researchers are now working on identifying the endogenous ligand produced by the body, or on developing molecules that could mimic its function.
It’s Not Fat, But Where the Fat Is That Determines Cardiovascular Disease Risk
It’s not the amount of fat in your body but where it’s stored that may increase your risk for heart attack, stroke and diabetes, according to a new study presented today at the annual meeting of the Radiological Society of North America (RSNA). The study looked at the differences in fat distribution patterns among overweight and obese men and women and their associated cardiometabolic risk.
According to the National Center for Health Statistics, more than 70 percent of Americans are considered overweight or obese. Obesity puts individuals at risk for a variety of health problems, and is the second leading cause of preventable death in the U.S.
However, people of the same weight or body mass index (BMI) may have very different risk profiles, based on genetics, lifestyle and diet. In addition, body composition differs between men and women, with women having proportionately more fat and men having more muscle mass.
Fat distribution is an important determinant of cardiometabolic risk. Most people have heard the phrases “apple-shaped” and “pear-shaped.” These are common descriptors of human body shapes, based on where fat tends to be stored in the body. In apple-shaped bodies, fat is distributed largely around the midsection, while in pear-shaped bodies, fat is distributed lower around the hips and thighs. The type of fat stored also plays a role in cardiometabolic risk. One type of fat–ectopic fat–is particularly dangerous. It may be found in places such as the abdominal region, muscles, liver and other organs.
“We hypothesized that there are gender-based differences in body composition and ectopic fat depots and that these could be associated with gender-specific risk profiles for diseases like diabetes, heart disease and stroke,” said lead author Miriam A. Bredella, M.D., radiologist at Massachusetts General Hospital and associate professor of radiology at Harvard Medical School in Boston.
For the study, Dr. Bredella and colleagues recruited 200 young (mean age 37), overweight and obese individuals who were otherwise healthy. Of the 200, 109 were women and 91 were men. Women and men were of a similar age and BMI.
After fasting overnight, the study participants underwent dual-energy x-ray absorptiometry (DXA) and CT scans to determine body composition, as well as magnetic resonance spectroscopy (MRS) for fat quantification and analysis.
The results showed that the women had a higher percentage of fat and more subcutaneous (below-the-skin) fat but lower lean mass, compared to men. However, men had more visceral adipose tissue (VAT), or ectopic fat depots located in the abdomen around the internal organs (commonly known as a “beer belly”), and more ectopic fat in the muscles and liver.
“Obese men have relatively higher visceral fat, fat within muscle cells and liver fat, which are all risk factors for cardiometabolic disease, compared to women with the same BMI,” Dr Bredella said. “However, men have higher muscle and lean mass, which are protective for cardiometabolic health. Women have a higher relative amount of total body fat and higher superficial thigh fat, which is protective for cardiometabolic health.”
Compared to women, men had higher measures of cardiometabolic risk overall, but ectopic fat was not significantly associated with cardiometabolic risk in men. Ectopic fat in women, however, was strongly associated with cardiometabolic risk measures.
“The detrimental fat depots deep in the belly, muscles and liver are more damaging for cardiometabolic health in women compared to men,” Dr. Bredella said.
In a related study presented by Dr. Bredella today at RSNA 2017, the researchers looked at the relationship between sarcopenic obesity–or the loss of skeletal lean muscle mass in the presence of obesity–and its relationship to cardiometabolic risk.
Many factors can lead to sarcopenic obesity in young adults, particularly obesity and lack of exercise.
“But there are also hormonal abnormalities,” Dr. Bredella said, “such as low growth hormone secretion in individuals with abdominal obesity. Growth hormone helps to build muscle mass. Nutrition also plays an important role, and too little intake of protein can lead to muscle loss.”
The researchers studied 188 young, overweight and obese adults who were otherwise healthy. Participants underwent DXA and CT scans and various metabolic tests. Results showed that having a lower lean muscle mass to BMI ratio was associated with cardiometabolic risk, and these effects were stronger in women than in men.
“Sarcopenic obesity may be an under-appreciated mechanism linking obesity to cardiometabolic disease,” Dr. Bredella said. “That stresses the importance of building up muscle mass in the setting of obesity.”