A correlation between the antirejection drug sirolimus and an increased risk of diabetes has been reported in a recent study. Sirolimus (rapamycin) is a relatively new immunosuppressant drug used to prevent rejection in organ transplantation, and is especially useful in kidney transplants. John Gill (University of British Columbia, BC, Canada) reports, “We demonstrated a robust association between sirolimus and diabetes after transplantation in a large group of kidney transplant recipients in the United States [and] the risk of diabetes was independent of other factors that are known to increase the risk of [the disease].”
Kidney, liver or heart transplant patients are at a high risk of developing diabetes. This can lead to cardiovascular disease and rejection of the transplant. Factors such as age, weight and family history can increase the risk of new-onset diabetes after transplantation, as well as immunosuppressant drugs. US Renal Data System (RDS) data was analyzed for approximately 20,000 Medicare beneficiaries undergoing kidney transplantation between 1995 and 2003, none of whom had diabetes prior to their kidney transplantation. Treatment with sirolimus was assessed as a potential contributor to the risk of developing diabetes, in conjunction with other known potential risk factors.
The results of this study suggest a higher rate of post-transplantational diabetes among patients treated with sirolimus compared with other antirejection drugs. Gill states that “Sirolimus is a newer type of antirejection drug that has not been associated with diabetes in transplant recipients. However, a number of animal studies and small clinical studies have suggested that sirolimus may increase the risk.”
Depending on which additional drugs were administered, patients receiving sirolimus had an increased risk of 33–66% of developing the disease. A separate analysis of patients who remained on the same antirejection drugs throughout the first year after transplantation revealed similar results. The increase in risk was found to be unrelated to any of the other drugs used in combination with sirolimus, or to other risk factors, such as age, ethnicity or obesity.
The US RDS database revealed that the development of diabetes is a strong independent predictor of graft failure and mortality, with a 63 and 87% increased risk, respectively. The increased risk in mortality is believed to be associated with the increased risk of infections and other complications observed in transplant recipients who develop diabetes. “Patients who develop diabetes after transplantation have roughly the same risk of transplant failure as patients who develop acute transplant rejection,” states Gill. This recent report is the first large-scale clinical study to suggest that sirolimus may also be a risk factor. Further studies are required to support this data. Gill notes that “Some important limitations of the study [include] the fact that it was based on a review of previous data and limited to Medicare patients.” However, this first line of convincing evidence clearly merits further investgation.
Source: Gill JS. J. Am. Soc. Nephrol. (2008) (In Press).
New link found between sleep duration and metabolic syndrome
A new study has revealed that short and long sleepers are at a higher risk of suffering from metabolic syndrome, or a combination of disorders that increase the risk of developing cardiovascular disease.
Metabolic syndrome is best defined as a clustering of closely related medical conditions that increase the risk of developing heart disease and diabetes. Features that comprise metabolic syndrome and also increase the risk of future adult diabetes and heart disease include: increased blood triglyceride levels, decreased high-density lipoprotein (HDL) cholesterol levels, overweight particularly around the abdomen, increased blood pressure and increased blood glucose level.
Psychiatrists at the University of Pittsburgh School of Medicine (PA, USA) led the sleep study, analyzing 1214 adults aged between 30 and 54 years.
Results showed that the risk of developing metabolic syndrome increased by more than 45% in both short and long sleepers, with short sleep duration being the most common (20% of the sample sleeping less than 6 h per night), in contrast to only 8% of the sample sleeping for more than 8 h per night.
Hall states that “This relationship was strongest in the group of men and women who slept less than 6 h per night. On average, the odds of having the metabolic syndrome were nearly doubled in men and women who slept less than 6 hours, compared to those who slept between 7 and 8 h per night.” In conclusion, experts recommend that the optimum amount of sleep for adults is 7–8 h per night.
Source: Hall MF, Muldoon MF, Jennings JR et al. Self-reported sleep duration is associated with the metabolic syndrome in midlife adults. Sleep 31(5), 635–643 (2008).
Exposure to endocrine disrupters can lead to obesity
New research presented at the European Congress on Obesity supported by the National Institute of Environmental Health Sciences (NIEHS) in the USA and the Swiss National Science Foundation has revealed that exposure during development, either in the womb or during infancy, to chemicals used to make products such as baby bottles, the lining of food tins and some plastic food wraps and containers may contribute to the development of obesity.
Overeating and a lack of physical exercise still remain the major causes of obesity. However, chemicals known as endocrine disrupters (sometimes also referred to as hormonally active agents), which are exogenous substances that act like hormones in the endocrine system and disrupt the physiologic function of endogenous hormones, may also be a strong contributing factor.
Researchers reported new evidence that mice exposed to endocrine-disrupting chemicals during pregnancy (at levels either comparable to or close to those that humans are exposed to) produced offspring that developed into obese adults, with altered gene and metabolic functions involved in weight regulation.
Jerry Heindel of the NEIHS and an expert in the field not involved in the aforementioned study states that, “The findings from these studies suggest that susceptibility to obesity is developed in the womb or early in life and that exposure to a variety of common household chemicals can, probably along with fetal nutrition, play a role in increasing that susceptibility. This information has the potential to change how people view and treat obesity. If these findings are proven to be true in humans, then the focus must change from losing weight as adults to prevention of weight gain during development, through reducing exposure to such substances.”
Bisphenol A (BPA) is one of the chemicals under scrutiny. BPA is used in the production of epoxy resins and polycarbonate plastics. These plastics are used in the packaging of food and drink, while the resins are commonly used as lacquers to coat metal products such as food cans, bottle tops and water supply pipes. Previous research has revealed that BPA leaches from these products, and the chemical has been found in a large number of individuals examined in developed countries. BPA has been detected not only in urine and blood, but also in amniotic fluid, placenta, umbilical cord blood and breast milk. Interestingly, laboratory results have shown that BPA can increase the production of fat cells.
A study led by Beverly Rubin, a neuroendocrinologist at Tufts University in the USA, revealed that female mice whose mothers were exposed to BPA from early pregnancy through to day 16 of lactation showed increased weight in adulthood. Food intake and activity levels were identical between the mice that gained weight and those that did not. The study also identified a disturbance in insulin sensitivity and glucose balance and in the weight-regulating hormone leptin. “This study indicates that developmental exposure to this chemical prior to and just after birth can exert a long lasting influence on bodyweight regulation” stated Rubin.
Results of another study carried out by Suzanne Fenton, a biologist at the US Environmental Protection Agency, revealed that the chemical perfluorooctanoic acid (PFOA) also has a detrimental effect on weight regulation. PFOA is a greaseproofing agent used in a number of products from microwave popcorn bags to pizza box liners and other food containers. When administered to pregnant mice, their offspring were unusually small at birth, becoming overweight as adults. By contrast, mice whose mothers were not exposed to the chemical and mice that were not exposed until adulthood presented a normal growth pattern. Fenton stated, “Our mouse study involved the lowest doses we have investigated to date and it shows the weight effect does occur at fairly low doses.” The next stage in the investigation is to unveil the mechanism of action for PFOA to establish whether or not there is a corresponding health risk for the human population.
Bruce Blumberg, a developmental biologist at the University of California (CA, USA) presented findings of a third study, which revealed that when pregnant mice were exposed to the chemical tributylin (TBT) at a dose comparable to that found in humans, a genetic mechanism triggered their obesity in later life. TBT is used in boat paint, plastic food wrap and as a fungicide on crops, and has been found to leach into food. Blumberg states that “Developmental exposure is more serious than adult exposure because the data with other such exposures suggest that the pro-obesity reprogramming is irreversible.” More research is required in order to determine the magnitude of the risk on humans, and this will depend on the levels of the chemicals present.
Source: Adapted from materials provided by International Obesity Taskforce www.iotf.org
Bone fracture risk in men with prostate cancer
Researchers at the Garvan Institute for Medical Research have revealed a correlation between prostate cancer and an increased risk of bone fracture.
Data analysis from the Dubbo Osteoporosis Epidemiology Study at the institute suggests that men with prostate cancer face a 50% higher risk of fracture, which increases to almost double the risk if they are receiving treatment.
Tuan Nguyan, the Associate Professor who instigated the study after hearing speculation on the topic, stated that “This is a controversial area, which has been under discussion for at least 3 years. The results suggest a link between the two diseases, although we still do not understand the mechanisms.” Nguyan and colleagues analyzed 822 males from Dubbo for almost 20 years. All the males were aged 60 years or over in 1989 when the study began. In total, 43 of the 822 males subsequently developed prostate cancer. Of these, 22 received androgen-deprivation therapy (ADT) and 21 did not. Results revealed that, in comparison to the males without prostate cancer, those with the disease showed a 50% increase in the risk of fracture. For patients undergoing ADT, the risk was increased approximately twofold.
Nguyan commented that “The results have important implications in practice for several reasons. First, most of the men who developed prostate cancer started out with a higher than average bone mineral density (BMD). Second, developing prostate cancer clearly increased their risk of fracture. Third, ADT treatment doubled their risk of fracture.” It is evident that the increased BMD in males with prostate cancer did not offer them any more protection from fracture, and the mechanisms underlying this process are not yet understood. “Osteoporosis in men often remains untreated, even after a fracture. It is highly unlikely, therefore, that any of the men at higher risk will be receiving antifracture therapy,” Nguyan stated.
It can be deduced from this study that patients with prostate cancer (particularly those receiving ADT) should consider being tested for osteoporosis. Nguyan concluded: “More and more we are seeing ways in which diseases are connected. In treating one disease, we must be careful not to increase the risk of another. As we understand these connections, we learn how better to treat the whole person.”
Source: Ahlborg HG, Nguyen ND, Center JR, Eisman JA, Nguyen TV. Incidence and risk factors for low trauma fractures in men with prostate cancer. Bone (2008) (In Press).