Diabetes: New Strides and New Hurdles-Department of Biological Sciences - Carnegie Mellon University

Friday, October 31, 2008

Diabetes: New Strides and New Hurdles

According to current estimates by the National Information Diabetes clearinghouse, 7% of the population (20.8 million) people are currently suffering from diabetes. In terms of finances, the direct cost of the disease is $92 billion [1]. And this doesn't even include the costs associated with disability or work loss. As a result, the government and several research institutions have begun the search for new and innovative ways to treat those suffering from diabetes. And although there is a lot of interesting research out there, many of them now face serious difficulties, whether it is related to side-effects, political ideals, or social policy.

High glucose levels in your blood cause diabetes. Normally, after the foods you eat are broken down into glucose, a hormone (insulin) is released that helps your cells to take up the glucose from the environment. Glucose is essential in cells because it is the primary source of energy. There are two subtypes of the disease, both of which cause the glucose levels in your blood to skyrocket. With Type 1 Diabetes, your body is not able to synthesize insulin efficiently. With Type 2 Diabetes, your body is not back to use insulin in an efficient manner [4]. Type 1 is usually seen with younger children whereas Type 2 is more often seen with older children and adults. Another possible reasoning for Type 2 Diabetes is that the body has become immune to effects of insulin and is no longer triggered to take in glucose when the insulin is released. This reasoning has led to theories that it is our bad diets, rich in fats and processed carbohydrates, which have led to the high prevalence of Type 2 diabetes. Most of the current solutions being proposed for Diabetes revolve only around Type 1 [3]. Although many of the proposals could potentially lead to answers for Type 2 Diabetes, external factors that could be responsible for Type 2 (bad diet, lack of exercise, etc.) are forcing doctors to focus more on the reasons associated with the ability of the body to synthesize the hormone, as opposed to the malfunction of the hormone [3].

To completely understand the following research proposals, an in-depth understanding of Type 1 diabetes can help. Essentially, within the pancreas are cells that act as blood glucose detectors and as producers of insulin. With Type 1 Diabetes, a patient's immune system is triggered to attack and destroy these cells. As a result, the body is unable to synthesize insulin.

Oral Therapies

One possible solution involves the use of oral insulin to prevent or delay the onset of Type 1 diabetes in children. Led by the Children's Hospital of Pittsburgh's Division of Pediatric Diabetes & Endocrinology, an international clinical trial experimented with oral capsules of synthesized insulin (which has no known side effects) [1]. The research revolves around the hope that when insulin is introduced to the body through the digestive tract, the immune system's attack of itself will cease, and the cells wil be able to take up the available glucose. The trial is currently underway at 150 sites all over the globe [1]. An earlier trial by Children's Hospital (Diabetes Prevention Trial 1) similarly tested the effects of oral insulin in children [1]. This study found that the oral insulin was able to delay the onset of Type 1diabetes in some. The cells have transformed in the subjects over a period of four years, but this only occurred in those that already had auto-antibodies to insulin in their circulation.

Umbilical Cord Stem Cells

South of Pittsburgh, in Florida, another team of researchers has proposed their own solution to the problem of type 1 diabetes, and it lies in the promise of banked umbilical cord blood [3]. Here, the researcher, led by Dr. Michael Haller, have extracted stem cells from banked cord blood and stimulated them to differentiate into beta-like cells. They then began infecting children who were recently diagnosed with Type 1 diabetes with 2-7 of these stem cell infusions [3]. Because only two to seven infusions were used, it was imperative that only children that were recently diagnosed acted as test subjects because their insulin needs were still minimal. After delivering the infusions to the diagnosed children, evaluations were conducted over two years to assess blood sugar levels and cell function. It was found that the children required less medicinal insulin and also maintained better control of their blood sugar [3]. Additionally, they had higher levels of regulatory immune cells in their blood, indicating that the procedure was successful. However, Dr. Haller explains that the findings were not a "cure-all" [3]. Instead, the delivery of infusions should be regarded as a form of "immunotherapy" that will attempt to "protect what's left of their insulin production for an extended period of time."

Hormone Manipulations

Another solution comes from New York City's Columbia University Medical Center. Here, the scientists stepped out of the realm of insulin-based solutions and instead examined manipulations of normal hormones released by the body as a possibility [4]. However, the interesting note is that it mainly targets Type 2 diabetes.

This innovative study theorizes that the skeleton functions similarly to an endocrine organ, meaning it produces hormones whose functions lie outside of the bones. Dr. Gerard Karsenty, the lease researcher of the study, recently found that leptin, a hormone synthesized by our body's fat, was involved in several regulatory functions of bone metabolism [4]. In examining diabetes, Dr. Karsenty began to think that the connection between fat and bone may also work in the reverse order (i.e. bone-produced hormones also regulate fat metabolism). Dr Karsenty first isolated a hormone called osteocalcin, a hormone synthesized by the bone. Originally known as a noncollagenous protein, osteocalcin was previously thought to only have a role in mineralization and calcium ion homeostasis [4]. However, using obese mice, Dr. Karsenty and his team found that osteocalcin could also act as a signaling protein that helps muscle and liver cells take up glucose [4]. This solution is directed towards the effects of Type 2 diabetes because it is in these patients where the cells have become insulin-resistant. As a result, glucose levels have increased greatly and insulin production has declined. Osteocalcin is able to target both of these problems as well as help the mice lose weight [4].

Dr. Karsenty's study holds a lot of promise for two reasons. The obvious reason is the potential use of osteocalcin as a new treatment for Type 2 Diabetes [4]. The other reason involves the prospective connection between osteocalcin deficiency and type 2 Diabetes. If this connection is established as fact, a new door to possible treatments has been opened for researchers across the country [4].

Conclusion

Although each of the recently proposed solutions could drastically alter the landscape of diabetes, there remain some important roadblocks standing in the way of finding a cure. With the Children's Hospital clinical trial, researchers are still trusting that there are no side effects from digesting insulin capsules [4]. One problem that some worry they will face down the line deals with the role of insulin as a potent growth factor. This could potentially lead to an increased risk of cancer development. Dr. Haller and his group from the University of Florida face another unique set of problems. For one, banked umbilical cord blood is still a relatively new technology. Furthermore, banking this blood is an expensive feat, usually only done by the wealthy. Additionally, the manipulation of stem cells so as to help with differentiation into beta-like cells could also stir up some political controversy, what with the current debate on Capitol Hill about the use of stem cells for research. Even Dr. Karsenty's finding about the role of osteocalcin isn't in the clear yet. If anything, his research has only raised more questions, especially with regards to the role of immune system in Type 2 Diabetes.

If questions, criticisms, or potential problems mean anything, it's that there is still a long way to go when it comes to finding a cure or effective treatment for diabetes. Sadly, this means that it will continue to be the nation's fifth leading cause of death and that families from coast to coast will continue to be affected by the disease. However, despite the situation, the proposed solutions have raised important questions and have truly broken down the walls of what we once knew about diabetes.

References

[1] Lukasiak, Marc. "Children's Hospital studying drug with the potential to prevent/delay the onset of type 1 diabetes." Children's Hospital of Pittsburgh Press Release. http://www.eurekalert.org/bysubject/biology.php
[2] "National Diabetes Statistics." National Diabetes Information Clearinghouse. http://diabetes.niddk.nih.gove/dm/pubs/statistics/#14
[3] Ross, Melanie Fridl. "Cord blood may preserve insulin levels in children with type 1 diabetes." University of Florida News. http://news.ufl.edu/2007/06/25/cord-blood/
[4] Schaffer, Amanda. "In Diabetes, a Comple of Causes." The New York Times. 16 October 2007. http://www.nytimes.com/2007/10/16/health/16diab.html

Graphics References:

http://www.nichd.nih.gov/research/supported/images/skd238517sdc.jpg

Written by: Rashi Venkataraman, Biological Sciences Undergraduate

From The International Journal of Science, Society, and Law, The Science in Society Review, A Production of The Triple Helix, Vol. 4 No. 2 | CMU

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