Type 1 diabetes
| Type 1 diabetes | |
|---|---|
| Specialty | Diabetology  |
Diabetes mellitus type 1 (Type 1 diabetes, Type I diabetes, T1D, IDDM) is a form of diabetes mellitus. Type 1 diabetes is an autoimmune disease that results in the permanent destruction of insulin producing beta cells of the pancreas. Type 1 is lethal unless treatment with exogenous insulin via injections replaces the missing hormone.
Type 1 diabetes (formerly known as "childhood," "juvenile," or "insulin-dependent" diabetes) is not primarily a childhood problem. The adult incidence of Type 1 is similar to that for children[1], which is why "Type 1" is the preferred term. Many adults who contract Type 1 diabetes are misdiagnosed with Type 2, due to the misconception of Type 1 as a disease of children.
It should be noted that there is no known preventative measure that can be taken against type 1 diabetes. Most people affected by type 1 diabetes are otherwise healthy and of a healthy weight when onset occurs. Diet and exercise cannot reverse or prevent type 1 diabetes.
The most useful laboratory test to distinguish Type 1 from Type 2 diabetes is the C-peptide assay, which is a measure of endogenous insulin production since external insulin (to date) has included no C-peptide. However, C-peptide is not absent in Type 1 diabetes until insulin production has fully ceased, which may take months[citation needed]. Lack of insulin resistance, determined by a glucose tolerance test, would also be suggestive of Type 1. Many Type 2 diabetics still produce some insulin internally, and all have some degree of insulin resistance.
Testing for GAD 65 antibodies has been proposed as an improved test for differentiating between Type 1 and Type 2 diabetes.
Pathophysiology
Type I diabetes is an autoimmune disorder in which the body's own immune system attacks the beta cells in the Islets of Langerhans of the pancreas, destroying them or damaging them sufficiently to reduce and eventually eliminate insulin production. The autoimmune attack may be triggered by reaction to an infection, for example by one of the viruses of the Coxsackie virus family, or German measles.
This vulnerability is not shared by everyone, for not everyone infected by these organisms develops Type 1 diabetes. This has suggested a genetic vulnerability and there is indeed an observed inherited tendency to develop Type 1. It has been traced to particular HLA phenotypes, though the connection between them and the triggering of an auto-immune reaction is poorly understood.
Some researchers believe that the autoimmune response is influenced by antibodies against cow's milk proteins. A large retrospective controlled study published in 2006 strongly suggests that infants who were never breast fed had twice the risk for developing Type 1 diabetes as infants who were breast fed for at least three months. The mechanism, if any, is not understood. No connection has been established between autoantibodies, antibodies to cow's milk proteins, and Type 1 diabetes. A subtype of Type 1 (identifiable by the presence of antibodies against beta cells) typically develops slowly and so is often confused with Type 2. In addition, a small proportion of Type 1 cases have the hereditary condition maturity onset diabetes of the young (MODY) which can also be confused with Type 2.
Vitamin D in doses of 2000 IU per day given during the first year of a child's life has been connected in one study in Northern Finland (where intrinsic production of Vitamin D is low due to low natural light levels) with a reduction in the risk of getting Type 1 diabetes later in life (by 80%). Some suggest that Vitamin D3 (one of several related chemicals with Vitamin D activity) may be an important pathogenic factor in Type 1 diabetes independent of geographical latitude.
Some chemicals and drugs specifically destroy pancreatic cells. Vacor (N-3-pyridylmethyl-N'-p-nitrophenyl urea), a rodenticide introduced in the United States in 1976, selectively destroys pancreatic beta cells, resulting in Type 1 diabetes after accidental or intentional ingestion. Vacor was withdrawn from the U.S. market in 1979. Zanosar is the trade name for streptozotocin, an antibiotic and antineoplastic agent used in chemotherapy for pancreatic cancer, that kills beta cells, resulting in loss of insulin production.
Other pancreatic problems, including trauma, pancreatitis or tumors (either malignant or benign), can also lead to loss of insulin production. The exact cause(s) of Type 1 diabetes are not yet fully understood, and research on those mentioned, and others, continues.
Treatment
Type 1 is treated with insulin replacement therapy — usually by injection or insulin pump — carbohydrate counting, and careful monitoring of blood glucose levels using Glucose meters.
Untreated diabetes can lead to one form of diabetic coma, diabetic ketoacidosis, or even death. Insulin treatment must be continued indefinitely. Continuous glucose monitors have been developed which alert to the presence of dangerously high or low blood sugar levels.
In some extreme cases, a pancreas transplant can help regulate glucose levels. However, this surgery is very dangerous and is often used as a last resort. Experimental replacement of beta cells (by transplant) 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 mixed with nearly universal failure.
Prevalence
About 5%–10% of North American diabetics 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.
Research foundations
The major charitable organization in the USA devoted to type I diabetes research is the Juvenile Diabetes Research Foundation, whose title is misleading as type I diabetes is not exclusively a disease of juveniles.
The International Diabetes Federation is a worldwide alliance of over 160 countries to address diabetes research and treatment.
The American Diabetes Association funds some work on type I but devotes much of its resources to type II diabetes.
Curing Type 1 Diabetes
Although type 1 diabetes is not currently curable, there are several approaches being researched:
Pancreas transplantation
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. For patients with kidney failure, however, a pancreas transplant is a viable option and is generally done simultaneously. Such patients, like all transplant patients, must take immunosuppresive drugs to prevent rejection.
Islet cell transplantation
Less invasive than a pancreas transplant, islet cell transplantation is considered a very promising approach to curing type 1 diabetes.
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.
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.[1] It would be best to use islet cells which will not provoke this immune reaction.
Islet cell regeneration
Research undertaken at the Massachusetts General Hospital in Boston Masschusetts from 2001 and 2003 demonstrated a protocol to reverse type 1 diabetes in mice.[2] Three other institutions have had similar results, published in the March 24, 2006 issue of Science. A fourth study by the National Institutes of Health further confirmed the approach, and also sheds light on the biological mechanisms involved.[3]
Artificial Pancreas
Genetic engineering
Fat or muscle cells that do not normally make insulin might possibly have a human insulin gene inserted by genetic engineering. These "pseudo" islet cells would then be transplanted into people with type 1 diabetes.
Immune modification
Shutting down the autoreactive T cells that attack beta islet cells, allowing the islet cells to regenerate. Denise Faustman is investigating this hypothesis at Mass General Hospital, in Boston, and has reported some success.
Stem cells
Research is being done at several locations in which islet cells are developed from stem cells.
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.
In April 2007, it was reported by the Times Online that fifteen 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.
However, there was 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 [4]
Relationship with nervous and immune systems
In December 2006 researchers from Toronto Hospital for Sick Children revealed research that shows a link between type 1 diabetes and the immune and nervous system. Using mice, the researchers discovered that a control circuit exists between insulin-producing cells and their associated sensory (pain-related) nerves.[5] It's being suggested that faulty nerves in the pancreas could be a cause of type 1 diabetes.
Obsolete treatments
Aspirin
In about 1988, a Russian doctor named B. I. Bleskin experimented with aspirin on young patients with emerging diabetes. He gave the patients aspirin and treated them with electrophoresis to deliver the aspirin to the patients´ pancreas. After 15-20 treatments of 10 minutes each the patients´ insulin production came back and their blood glucosed dropped[6].
Further reading
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) - Diabetes in America Textbook (PDFs)
References
- ^ "Islet cell transplant: Experimental treatment for type 1 diabetes - MayoClinic.com". Retrieved 2007-06-04.
- ^ "November 13, 2003 Regeneration of insulin-producing islets may lead to diabetes cure". Retrieved 2007-06-04.
- ^ Faustman DL, Tran SD, Kodama S; et al. (2006). "Comment on papers by Chong et al., Nishio et al., and Suri et al. on diabetes reversal in NOD mice". Science. 314 (5803): 1243, author reply 1243. doi:10.1126/science.1129811. PMID 17124308.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - ^ Voltarelli JC, Couri CE, Stracieri AB; et al. (2007). "Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus". JAMA. 297 (14): 1568–76. doi:10.1001/jama.297.14.1568. PMID 17426276.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - ^ "Canadian scientists reverse diabetes in mice". Retrieved 2007-06-04.
- ^
Mikhaĭlova EV, Lobanova AM, Romanovskaia GA, Mankeev SM (1990). "The expediency of using B. I. Bleskin's method in treating diabetics". Problemy endokrinologii (in Russian). 36 (3): 46–7. PMID 2395835.
{{cite journal}}: CS1 maint: multiple names: authors list (link)
External links
- [http://www.hormone.org/public/diabetes.cfm/ Diabetes Section of The Hormone Foundation
- Children with Diabetes
- Type 1 Diabetes TrialNet
- Type 1 Diabetes at the American Diabetes Association
- Sugar Sofa - Website for kids with type 1 diabetes
- National Diabetes Information Clearinghouse
- Diabetes Happens
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