Short or Poor Sleep Can Lead to More Eating and Risk of Diabetes

Studies continue to show that sleep curtailment or decreased sleep quality can disturb neuroendocrine control of appetite, leading to overeating, and can decrease insulin or increase insulin resistance, both steps on the road to Type 2 diabetes.

On April 22, at the Experimental Biology 2009 meeting in New Orleans, a panel of leading sleep researchers describes recent and new studies in this fast growing field. The session is part of the scientific program of the American Association of Anatomists (AAA).

Short sleep, poor sleep: novel risk factors for obesity and for type 2 diabetes.

Dr. Eve Van Cauter, University of Chicago, is a specialist in the effect of circadian rhythms on the endocrine system and has conducted several studies in which short-term sleep restriction damaged the body’s ability to regulate eating by lowering levels of leptin, the hormone that tells the body when it has had enough. In the AAA symposium, Dr. Van Cauter describes other recently published studies from her group, one showing that only three days sleep disruption is sufficient to increase insulin resistance in humans (thus causing the body to need higher levels of insulin) and a large epidemiological study showing that short sleep over a five year period causes an increase in systolic blood pressure.

Energy metabolism during chronic sleep deprivation: sleep less, eat more, don’t gain weight, yet show signs of progression toward diabetes.

Panel member Dr. Michael Koban, Morgan State University, reports a new study in which sleep restriction in rats led to glucose intolerance, a prediabetic state in which the blood glucose remains higher than normal after glucose challenge. Significantly, this is the first rodent study of sleep deprivation in which there was no association between glucose dysregulation and weight gain.

The researchers believe that extending sleep restriction will produce more pronounced glucose intolerance in which glucose levels do not return to normal levels for a longer period, thus providing more evidence that not sleeping enough could lead to diabetes in humans. The researchers also are looking for mechanisms to explain the change in metabolism related to sleep deprivation and the dissociation between weight gain and glucose dysregulation and insulin resistance.

Stress-related behaviors and hormone changes after prolonged sleep deprivation – and environmental factors that appear to modify them

Dr. Deborah Suchecki, Universidade Federal de Sao Paulo, describes how prolonged sleep deprivation activates the neuroendocrine stress response, as measured by increased blood levels of the stress-related hormones adrenaline, adrenocorticotropic hormone (ACTH), and corticosterone. Earlier studies have shown that sleep restriction in animals can gradually change brain and neuroendocrine systems in ways similar to those seen in stress-related disorders such as depression, while epidemiological studies suggest that sleep restriction may be an important risk factor for cardiovascular and other diseases linked to stress.

CNS changes after chronic sleep deprivation have role in both food intake and metabolism.

Dr. Gloria Hoffman, also of Morgan State University, presents studies that explain the role of the central nervous system pathways in stimulating feeding and causing metabolic changes associated with progression to diabetes. Specifically, increased production of the neurotransmitter neuropeptide Y and decreased production of proopiomelanocortiini products in the hypothalamus explain the hyperphagic response.

Although the CNS’s role in regulating metabolic rate is not well understood, she believes that histamine might be involved. Histamine neurons not only affect the maintenance of wakefulness but also are regulators of peripheral metabolism. In sleep deprived rats, elevations in the glucose to insulin ratio were positively correlated with an increase in histamine expression that raises the possibility that a dysregulation of histamine function during impaired sleep might serve to trigger metabolic and other changes leading to diabetes.

The scientists agree that as sleep curtailment becomes more common in industrialized countries it becomes increasingly important to understand how limited or poor quality sleep produces changes that can lead to obesity and diabetes, both epidemic in the developed world. More and more scientists are jumping on board with these lines of investigation, says Dr. Hoffman, and there is an increased demand for information on the part of health professionals and members of the general public, many of whom consider themselves sleep deprived.

Kids Like Fruits and Veggies When Given a Chance

The good nutrition news is that children in poor, rural parts of the Lower Mississippi Delta are a lot more willing to try fresh fruits and vegetables than generally believed, even by their parents or the kids themselves. The bad news is that such foods are often in short supply in an area where gas stations and convenience stores are the closest places to buy food and where growing family gardens has given way to long work commutes by parents – and that the situation is growing worse with a worsening economy.

Two presentations drawing from a multi-year nutrition research program in Delta summer camps and schools were presented on April 19 at the Experimental Biology 2009 meeting in New Orleans as part of the scientific program of the American Society for Nutrition. The ongoing research program is being conducted under the direction of research nutritionist Dr. Beverly McCabe-Sellers, US Department of Agriculture/Agricultural Research Service, Little Rock, Arkansas, and is part of the Delta Obesity Prevention Research Unit (OPRU) headed by Executive Director Dr. Margaret Bogle.

The research arm of the Delta OPRU works with local communities to understand obstacles to better nutrition in the Lower Delta (including rural parts of Arkansas, Louisiana and Mississippi), which leads the nation in the rising prevalence of obesity in both adults and children.

The challenge to having more fruits and vegetables in the diets of youngsters is not their unwillingness, she says, nor is it necessarily the admittedly low income in the area. Potato chips are not inexpensive, but the children often had small bags of them for every meal. The largest challenge, she believes from her experience, is the difficulty in obtaining quality fresh produce at a reasonable cost in these rural areas far away from distribution centers.

Epidermal Growth Factor Receptor Found for Pancreatic Cancers

Finally some promising news about pancreatic cancer, one of the most fatal cancers, due to the difficulties of early detection and the lack of effective therapies: Johns Hopkins University pathologist Akhilesh Pandey has identified an epidermal growth factor receptor aberrantly active in approximately a third of the 250 human pancreatic cancers studied.

In a presentation April 18, at Experimental Biology 2009 in New Orleans, Dr. Pandey explained why this finding and related work in his Hopkins laboratory is promising in terms of both a new treatment for a large subset of pancreatic cancers and a potential blood or urine screening tool that might eventually do for pancreatic cancer detection what biomarkers like prostate-specific antigen levels have done for prostate cancer. His presentation was part of the scientific program of the American Society for Investigative Pathology.

Personalized treatment. Phosophorylated epidermal growth factor receptor (pEGFR), the receptor identified by Dr. Pandey, is closely related to HER-2, a growth factor receptor found and used as a drug target in a subset of breast cancers. After he found and profiled the pEGFR activated in the pancreatic cancers, Dr. Pandey realized the same receptor had been found by other researchers to be activated in a subset of lung cancers. And, most promising, an EGFR inhibitor named erlotinib already has been through the long and complex Food and Drug Administration approval process and is in use for treatment of these specific lung cancers.

But would the drug work in pancreatic cancers? Dr. Pandey’s group moved from studies of human cell lines to studies in mice in which human pancreatic tumor cells with activated EGFT had been placed. The tumors began growing. But when treated with erlotinib, they began to shrink. Other tumors without activated pECFR showed no response.

The promise – and the challenge – of using pEGFR is that of personalized medicine, says Dr. Pandey. Obviously a growth factor receptor that is activated only in a subset of all pancreatic cancers cannot be a one-size-fits-all target for treatment. Earlier studies in other laboratories and clinical trials already had tried EGF inhibitors as a treatment for pancreatic cancer and concluded that they did not work. When Dr. Pandey’s collaborators allowed them to re-examine their samples, they found that the only case in 12 cases that had responded to the EGF inhibitor was the only case with an activated EGF receptor. Dr. Pandey would like to see other researchers go back and re-analyze their data, separating patients with and without the activated receptor, and then determining the success rate. He believes it would tell a different, more hopeful story.

Screening for pancreatic cancer. Dr. Pandey’s other goal in his research is to use mass spectrometry to find additional markers of pancreatic cancer in the tumors themselves but also in blood and urine, which would avoid the problems of invasive biopsies. As a first step, his team has gone through the scientific literature to create a compendium of several hundred proteins and genes reported to be overexpressed in pancreatic cancers, making them excellent candidates for further study. The compendium already is being used by a consortium of investigators who are developing antibodies against the 60 most promising targets.