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| ==Overview== | | ==Overview== |
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| ==Treatment==
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| {{main|Diabetes management}}
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| Type 1 is treated with insulin replacement therapy — usually by injection or [[insulin pump]], dietary control, typically including carbohydrate tracking, and careful monitoring of [[blood glucose]] levels using [[Glucose meter]]s.
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| Untreated Type 1 diabetes can lead to one form of diabetic coma, diabetic ketoacidosis, which can be fatal. At present, insulin treatment must be continued for a lifetime; this will change if better treatment, or a cure, is discovered. Continuous glucose monitors have been developed which alert to the presence of dangerously high or low blood sugar levels.
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| In some extreme cases, a pancreas transplant can help restore proper glucose regulation. However, the surgery and accompanying immunosuppression required is considered by many physicians to be more dangerous than continued insulin replacement therapy and is therefore often used only as a last resort (such as when a kidney must also be transplanted or in cases where the patient's blood glucose levels are extremely control resistant). Experimental replacement of beta cells (by transplant or from stem cells) is being investigated in several research programs and may become clinically available in the future. Thus far, beta cell replacement has only been performed on patients over age 18, and with tantalizing successes amidst nearly universal failure.
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| ===Pancreas transplantation===
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| {{main|Pancreas transplantation}}
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| Pancreas transplants are not generally recommended because introducing a new, functioning pancreas to a patient with diabetes can have negative effects on the patient's normally functioning [[kidney]].
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| ===Artificial Pancreas===
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| {{main|Artificial pancreas}}
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| ==Prevalence==
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| It is estimated that about 5%–10% of North American diabetes patients have type 1. The fraction of type 1 in other parts of the world differs; this is likely due to both differences in the rate of type 1 and differences in the rate of other types, most prominently type 2. Most of this difference is not currently understood. Variable criteria for categorizing diabetes types may play a part.
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| ==Research foundations==
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| The major charitable organization in the USA devoted to type 1 diabetes research is the [[Juvenile Diabetes Research Foundation]] (JDRF), whose mission is to cure type 1 diabetes and its complications through the support of research. Since its founding in 1970, JDRF has contributed more than $1 billion to diabetes research, including more than $137 million in FY 2007. In FY2007, the Foundation funded 700 centers, grants and fellowships in 20 countries.
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| The [[International Diabetes Federation]] is a worldwide alliance of over 160 countries to address diabetes research and treatment.
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| The [[American Diabetes Association]] funds some work on type 1 but devotes much of its resources to [[type 2 diabetes]] due to the increasing prevalence of the latter type.
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| Diabetes Australia is involved in promoting research and education in Australia on both type 1 and type 2 diabetes.
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| The [[Canadian Diabetes Association]] is also involved in educating, researching, and sustaining sufferers of Type 1 Diabetics in Canada.
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| ==Cure==
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| As of 2008, there is no known cure for diabetes mellitus type 1 used by modern medical insitutes or hospitals.<ref>Without the use of large doses of [[immunosuppressant]]s, that causes a multitude of other medical issues.</ref> There is ongoing [[biomedical research|research]] on various approaches to curing diabetes type 1.
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| Diabetes type 1 is caused by the non-existence of a sufficient number of [[beta cell]]s in the body; these cells, which are found in the [[Langerhans islets]] in the [[pancreas]], produce and secrete [[insulin]], the single hormone responsible for allowing [[glucose]] to enter from the [[blood]] into [[cell (biology)|cell]]s. Hence, the phrase "curing diabetes type 1" means "causing a maintenance or restoration of the [[endogenous]] ability of the body to produce insulin in response to the level of blood glucose". This section does not deal with approaches other than that (for instance, closed-loop integrated glucometer/insulin pump products), which may also greatly increase quality of life for those who have diabetes type 1, and may by some be termed "artificial pancreas". Instead, it only deals with such approaches for thoroughly curing the underlying condition of diabetes type 1, by enabling the body to endogenously, ''in vivo'', produce insulin in response to the level of blood glucose.
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| ===Reversion===
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| ====Encapsulation approach====
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| [[Image:Bio-artificial pancreas with Islet Sheet technology.JPG|thumb|left|300px|'''The Bio-artificial pancreas''': this diagram shows a cross section of [[tissue engineering|bio-engineered tissue]] with encapsulated [[islets of Langerhans|islet cells]] which deliver [[endocrine]] [[pancreas#function|hormones]] in response to [[glucose]].]]
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| A biological approach to the artificial pancreas is to implant [[tissue engineering|bioengineered tissue]] containing [[islets of Langerhans|islet cells]], which would secrete the amounts of insulin, [[amylin]] and [[glucagon]] needed in response to sensed glucose.
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| When islet cells have been transplanted via the [[Edmonton protocol]], insulin production (and glycemic control) was restored, but at the expense of [[immunosuppression]]. [[Micro-encapsulation|Encapsulation]] of the islet cells in a protective coating has been developed to block the immune response to transplanted cells, which relieves the burden of immunosuppression and benefits the longevity of the transplant.<ref>[http://www.isletmedical.com/pages/define_methods.htm Cerco Medical: Science: Methods<!-- Bot generated title -->]</ref>
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| One concept of the bio-artificial pancreas uses encapsulated islet cells to build an ''islet sheet'' which can be surgically implanted to function as an artificial pancreas.<ref>[http://www.isletmedical.com/pages/company_research.htm Cerco Medical: Company: Islet Sheet Research<!-- Bot generated title -->]</ref>
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| This islet sheet design consists of:
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| *an inner mesh of fibers to provide strength for the islet sheet;
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| *islet cells, encapsulated to avoid triggering a proliferating immune response, adhered to the mesh fibers;
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| *a [[semi-permeable membrane|semi-permeable]] protective layer around the sheet, to allow the [[diffusion]] of nutrients and secreted hormones;
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| *a protective coating, to prevent a foreign body response resulting in a fibrotic reaction which walls off the sheet and causes failure of the islet cells.
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| Islet sheet with encapsulation research is pressing forward with large animal studies at the present, with plans for human clinical trials within a few years.
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| ====Islet cell transplantation approach====
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| {{main|Islet cell transplantation}}
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| Less invasive than a pancreas transplant, islet cell transplantation is considered a very promising approach to curing type 1 diabetes.
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| In one variant of this procedure, islet cells are injected into the patient's [[liver]], where they take up residence and begin to produce insulin. The liver is expected to be the most reasonable choice because it is more accessible than the pancreas, and the islet cells seem to produce insulin well in that environment. The patient's body, however, will treat the new cells just as it would any other introduction of foreign tissue. The [[immune system]] will attack the cells as it would a bacterial infection or a skin graft. Thus, the patient also needs to undergo treatment involving [[immunosuppressants]], which reduce immune system activity.
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| Recent studies have shown that islet cell transplants have progressed to the point that 58% of the patients in one study were insulin independent one year after the operation.<ref>{{cite web|url=http://www.mayoclinic.com/health/islet-cell-transplant/DA00046|title=Islet cell transplant: Experimental treatment for type 1 diabetes - MayoClinic.com|accessdate=2007-06-04|format= |work=}}</ref> It would be best to use islet cells which will not provoke this immune reaction.
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| ====Islet cell regeneration approach====
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| Research undertaken at the Massachusetts General Hospital in Boston Masschusetts from 2001 and 2003 demonstrated a protocol to reverse type 1 diabetes in mice.<ref>{{cite web |url=http://www.massgeneral.org/news/releases/111303faustman.htm|title=November 13, 2003 Regeneration of insulin-producing islets may lead to diabetes cure|accessdate=2007-06-04|format= |work=}}</ref> Three other institutions have had similar results, published in the March 24, 2006 issue of [[Science (journal)|''Science'']]. A fourth study by the [[National Institutes of Health]] further confirmed the approach, and also sheds light on the biological mechanisms involved.<ref name="pmid17124308">{{cite journal |author=Faustman DL, Tran SD, Kodama S, ''et al'' |title=Comment on papers by Chong et al., Nishio et al., and Suri et al. on diabetes reversal in NOD mice |journal=Science |volume=314 |issue=5803 |pages=1243; author reply 1243 |year=2006 |pmid=17124308 |doi=10.1126/science.1129811}}</ref>
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| ====Stem cells approach====
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| Research is being done at several locations in which islet cells are developed from [[stem cell]]s.
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| In January 2006, a team of South Korean scientists has grown pancreatic beta cells, which can help treat diabetes, from stem cells taken from the umbilical cord blood of newborn babies.
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| In April 2007, it was reported by the ''Times Online'' that 15 young Brazilian patients diagnosed with Type 1 diabetes were able to naturally produce insulin once again after undergoing mild chemotherapy to temporarily weaken their immune systems and then injection of their own stem cells. This allowed the pancreatic beta cells to produce insulin. Since white blood cells were blocking the pancreas from producing insulin, Dr. Voltarelli and colleagues killed the immune cells, allowing the pancreas to secrete insulin once more.
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| However, there were no control subjects, which means that all of the processes could have been completely or partially natural. Secondly, no theory for the mechanism of cure has been promoted. It is too early to say whether the results will be positive or negative in the long run.<ref name="pmid17426276">{{cite journal |author=Voltarelli JC, Couri CE, Stracieri AB, ''et al'' |title=Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus |journal=JAMA |volume=297 |issue=14 |pages=1568-76 |year=2007 |pmid=17426276 |doi=10.1001/jama.297.14.1568}}</ref>
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| ====Gene therapy approach====
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| [[Image:Gene therapy.jpg|left|thumb|300px|[[Gene therapy]]: Designing a [[viral vector]] to deliberately infect cells with [[DNA]] to carry on the viral production of [[insulin]] in response to the blood sugar level.]]
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| Technology for [[gene therapy]] is advancing rapidly such that there are multiple pathways possible to support endocrine function, with potential to practically cure diabetes.<ref>[http://www.niddk.nih.gov/fund/reports/gene_therapy_summ.htm Gene Therapy Approaches to Diabetes<!-- Bot generated title -->]</ref>
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| *Gene therapy can be used to '''manufacture insulin directly''': an oral medication, consisting of viral vectors containing the insulin sequence, is digested and delivers its genes to the upper intestines. Those intestinal cells will then behave like any viral infected cell, and will reproduce the insulin protein. The virus can be controlled to infect only the cells which respond to the presence of glucose, such that insulin is produced only in the presence of high glucose levels. Due to the limited numbers of vectors delivered, very few intestinal cells would actually be impacted and would die off naturally in a few days. Therefore by varying the amount of oral medication used, the amount of insulin created by gene therapy can be increased or decreased as needed. As the insulin producing intestinal cells die off, they are boosted by additional oral medications.<ref>[http://www.liebertonline.com/doi/pdf/10.1089/dia.2005.7.549?cookieSet=1 Mary Ann Liebert, Inc. - Cookie absent<!-- Bot generated title -->]</ref>
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| *Gene therapy might eventually be used to '''cure the cause of beta cell destruction''', thereby curing the new diabetes patient before the beta cell destruction is complete and irreversible.<ref>http://www.hopkinsbayview.org/healthcarenews06/060605diabetes.html</ref>
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| *Gene therapy can be used to '''turn duodenum cells and duodenum adult stem cells into beta cells''' which produce insulin and amylin naturally. By delivering beta cell DNA to the intestine cells in the duodenum, a few intestine cells will turn into beta cells, and subsequently adult stem cells will develop into beta cells. This makes the supply of beta cells in the duodenum self replenishing, and the beta cells will produce insulin in proportional response to carbohydrates consumed.<ref>[http://www.engeneinc.com/ Engene Inc<!-- Bot generated title -->]</ref>
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| =====Yonsei University study=====
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| Scientists in the South Korean university of Yonsei have, in 2000, succeeded in reversing diabetes in mice and rats. Using a viral vector, a DNA encoding the production of an insulin analog was injected to the animals, which remained non-diabetic for at least the eight months duration of the study.<ref>[http://www.sciam.com/article.cfm?articleID=00042B27-190C-1C68-B882809EC588ED9F Gene Therapy for Diabetes: Scientific American<!-- Bot generated title -->]</ref>
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| ====Nanotechnology approach====
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| Under the nanotechnological approach to curing diabetes type 1, many "nanobots" would be injected into the patient's [[bloodstream]]. These nanobots would be able to synthesize insulin, and to secrete it according to the level of glucose they would sense.<ref>http://ieeexplore.ieee.org/iel5/6/29742/1353792/13537927.html</ref>
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| =====Nano Mist=====
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| An American body called "Nano Mist" claims to be involved in a diabetes cure-related nanotechnology project. Their product is at least 10 years behind FDA approval.<ref>[http://dev.nsta.org/evwebs/1150/futuretech.htm The Nano Mist - Curing Diabetes<!-- Bot generated title -->]</ref>
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| ==Prevention== | | ==Prevention== |
| ===="Immunization" approach==== | | ===="Immunization" approach==== |
For patient information click here.
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Priyamvada Singh, M.B.B.S. [2]; Cafer Zorkun, M.D., Ph.D. [3]
Diagnosis
History and Symptoms | Physical Examination | Laboratory Tests | Electrocardiogram | Chest X Ray | MRI | CT | Echocardiography | Other Imaging Findings | Other Diagnostic Studies
Treatment
Medical: Medical Therapy
Surgical: Surgery
Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies|Social issues
See also
References
Data from the Report of the Expert Committee on the diagnosis and classification of diabetes mellitus
External links
References
Template:WH
Template:WS
Overview
Prevention
"Immunization" approach
If a biochemical mechanism can be found that prevents the immune system from attacking beta cells, it may be administered to prevent commencement of diabetes type 1. The way several groups are trying to achieve this is by causing the activation state of the immune system to change from Th1 state (“attack” by killer T Cells) to Th2 state (development of new antibodies). This Th1-Th2 shift occurs via a change in the type of cytokine signaling molecules being released by regulatory T-cells. Instead of pro-inflammatory cytokines, the regulatory T-cells begin to release cytokines that inhibit inflammation.[4] This phenomenon is commonly known as "acquired immune tolerance".
DiaPep277
A substance designed to cause lymphocyte cells to cease attacking beta cells, DiaPep277 is a peptide fragment of a larger protein called HSP60. Given as a subcutaneous injection, its mechanism of action involves a Th1-Th2 shift. Clinical success has been demonstrated in prolonging the "honeymoon" period for people who already have type 1 diabetes [5]. The product is currently being tested in people with latent autoimmune diabetes of adults (LADA). Ownership of the drug has changed hands several times over the last decade. In 2007, Clal Biotechnology Industries (CBI) Ltd., an Israeli investment group in the field of life sciences, announced that Andromeda Biotech Ltd., a wholly owned subsidiary of CBI, signed a Term Sheet with Teva Pharmaceutical Industries Ltd. to develop and commercialize DiaPep277[6].
Intra-nasal insulin
There is pre-clinical evidence that a Th1-Th2 shift can be induced by administration of insulin directly onto the immune tissue in the nasal cavity. This observation has led to a clinical trial, called INIT II, which began in late 2006, based in Australia and New Zealand.
Tumor necrosis factor-alpha, or TNF-a, is part of the immune system. It helps the immune system discern between self and non-self. Type one diabetics are deficient in this substance. Dr. Faustman discovered that giving BCG, an inexpensive drug, to diabetic mice, stimulates TNF-a production. TNF-a kills the white blood cells responsible for destroying beta cells, and thus prevents, or reverses diabetes[1]. She has reversed diabetes in laboratory mice with this techniqe, but was only able to receive funding for subsequent research from Lee Iaccoca. Human trials began in 2007, and are still underway.
Entities involved in research
This section is a complete list of mainly commercial companies but also other entities, namely governmental institutions and individual persons, actively involved in research towards finding a cure to diabetes type 1.
It does not list research funds, hospitals in which research is undertaken, etc., but only the industrious, actual developers of such products.
Entities are listed along with their status of research in that field, so that also entities which ceased research into finding a cure to diabetes type 1 may be listed.
Entities are alphabetically listed.
- Cerco Medical [7] – Present status: Unknown
- Denise Faustman [8] – Present status: Working on immune modification
- DeveloGen [9] – Present status: Developing DiaPep 277
- Diamyd Medical [10] – Present status: Developing GAD65-based vaccine (phase III application submitted to the FDA)
- Encelle [11] – Present status: On hold; awaiting decision on whether to move forward into encapsulated beta cell transplantation.
Further reading
References
- ↑ Shinichiro Ryu, Shohta Kodama, Kazuko Ryu, David A. Schoenfeld & Denise L. Faustman. 2001. Reversal of established autoimmune diabetes by restoration of endogenous β cell function. J. Clin. Invest. 108(1): 63-72.
External links