Juvenile Diabetes

What is Type 1 Diabetes?

Diabetes mellitus type 1 (Type 1 diabetes, T1D, T1DM, IDDM, juvenile diabetes) is a form of diabetes mellitus. Type 1 diabetes is an autoimmune disease that results in destruction of insulin-producing beta cells of the pancreas. Lack of insulin causes an increase of fasting blood glucose (around 70-120 mg/dL in nondiabetic people) that begins to appear in the urine above the renal threshold (about 190-200 mg/dl in most people), thus connecting to the symptom by which the disease was identified in antiquity, sweet urine. Glycosuria or glucose in the urine causes the patients to urinate more frequently, and drink more than normal (polydipsia). Classically, these were the characteristic symptoms which prompted discovery of the disease.

Type 1 diabetes is fatal unless treated with exogenous insulin. Injection is the traditional and still most common method for administering insulin; jet injection, indwelling catheters, and inhaled insulin has also been available at various times, and there are several experimental methods as well. All replace the missing hormone formerly produced by the now non-functional beta cells in the pancreas. In recent years, pancreas transplants have also been used to treat type 1 diabetes. Islet cell transplant is also being investigated and has been achieved in mice and rats, and in experimental trials in humans as well. Use of stem cells to produce a new population of functioning beta cells seems to be a future possibility, but has yet to be demonstrated even in laboratories as of 2008.

Type 1 diabetes (formerly known as "childhood", "juvenile" or "insulin-dependent" diabetes) is not exclusively a childhood problem; the adult incidence of type 1 is noteworthy—in fact, many adults who contract type 1 diabetes are misdiagnosed with type 2 due to confusion at this point.

There is currently no clinically useful preventive measure against developing type 1 diabetes, though a vaccine has been proposed and anti-antibody approaches are also being tested. Most people who develop type 1 were otherwise healthy and of a healthy weight on onset, although some can be mildly overweight to slightly obese upon diagnosis of type one. Unfortunately, however, they can lose weight quickly and dangerously, if not promptly diagnosed. Although the cause of type 1 diabetes is still not fully understood, the immune system damage is characteristic of type 1.

The most definite 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 has not (to date) included C-peptide. The presence of anti-islet antibodies (to Glutamic Acid Decarboxylase, Insulinoma Associated Peptide-2 or insulin), or lack of insulin resistance, determined by a glucose tolerance test, would also be suggestive of type 1. Many type 2 diabetics continue to produce 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 as it appears that the immune system malfunction is connected with their presence. Further, injections with GAD65 has in clinical trials delayed the destruction of beta cells for at least 30 months, without serious adverse effects. Patients treated with the substance showed higher levels of regulatory cytokines, thought to protect the beta cells. Phase III trials are under way in the USA and in Europe, with most sites actively pursuing participants.

Type 1 treatment must be continued indefinitely in essentially all cases. Treatment need not significantly impair normal activities, if sufficient patient training, awareness, appropriate care, discipline in testing and dosing of insulin is taken. However, treatment is burdensome for patients; insulin is replaced in a non-physiological manner, and this approach is therefore far from ideal. The average glucose level for the type 1 patient should be as close to normal (80–120 mg/dl, 4–6 mmol/L) as is ''safely'' possible. Some physicians suggest up to 140–150 mg/dl (7-7.5 mmol/L) for those having trouble with lower values, such as frequent hypoglycemic events. Values above 400 mg/dl (20 mmol/L) are sometimes accompanied by discomfort and frequent urination leading to dehydration. Values above 600 mg/dl (30 mmol/L) usually require medical treatment and may lead to ketoacidosis, although they are not immediately life-threatening. However, low levels of blood glucose, called hypoglycemia, may lead to seizures or episodes of unconsciousness and absolutely must be treated immediately, via emergency high-glucose gel placed in the patient's mouth, intravenous administration of dextrose, or an injection of glucagon.

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. The longest surviving Type I diabetes patient is Gladys Dull, who has lived with the condition for over 83 years.

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Diabetes Mellitus Type 1 Pathophysiology

The cause of type 1 diabetes is still not fully understood. Some theorize that type 1 diabetes is generally a virally triggered autoimmune response in which the immune system's attack on virus infected cells is also directed against the beta cells in the pancreas. 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, although the evidence is inconclusive. In type 1, pancreatic beta cells in the Islets of Langerhans are destroyed or damaged sufficiently to effectively abolish endogenous insulin production. This etiology distinguishes type 1's origin from type 2. It should also be noted that the use of insulin in treating a patient does ''not'' mean that patient has type 1 diabetes; the type of diabetes a patient has is determined only by the cause—fundamentally by whether the patient is insulin resistant (type 2) or insulin deficient without insulin resistance (type 1).

This vulnerability is not shared by everyone, for not everyone infected by the suspected organisms develops type 1 diabetes. This has suggested presence of a genetic vulnerability and there is indeed an observed inherited tendency to develop type 1. It has been traced to particular HLA genotypes, though the connection between them and the triggering of an auto-immune reaction is still 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 breastfed had a risk for developing type 1 diabetes twice that of infants who were breastfed for at least three months. The mechanism is not fully 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 2 cases manifest a genetic form of the disease called maturity onset diabetes of the young (MODY).

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 an 80% reduction in the risk of getting type 1 diabetes later in life. The causal connection, if any, is obscure.

Type 1 diabetes was previously known as juvenile diabetes because it is one of the most frequent chronic diseases in children; however, the majority of new-onset type 1 diabetes is seen in adults. Scientific studies that use antibody testing (glutamic acid decarboxylase antibodies (GADA), islet cell antibodies (ICA), and insulinoma-associated (IA-2) autoantibodies) to distinguish between type 1 and type 2 diabetes demonstrate that most new-onset type 1 diabetes is seen in adults. A 2008 book, “Type 1 Diabetes in Adults: Principles and Practice” (Informa Healthcare, 2008) says that adult-onset type 1 autoimmune diabetes is two to three times more common than classic childhood-onset autoimmune diabetes (p. 27). In type 1 diabetes, the body does not produce insulin. Insulin is a hormone that is needed to convert sugar (glucose), starches and other food into energy needed for daily life.

Some suggest that deficiency of 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, and so of available sun intensity.

Some chemicals and drugs preferentially destroy pancreatic cells. Pyrinuron (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, but is still used in some countries. Zanosar is the trade name for streptozotocin, an antibiotic and antineoplastic agent used in chemotherapy for pancreatic cancer; it also 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.

In December 2006, researchers from Toronto Hospital for Sick Children published 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. It's being suggested that faulty nerves in the pancreas could be a cause of type 1 diabetes.

This article is licensed under the Creative Commons Attribution-ShareAlike License. It uses material from the Wikipedia article on "Diabetes mellitus type 1" All material adapted used from Wikipedia is available under the terms of the Creative Commons Attribution-ShareAlike License. Wikipedia® itself is a registered trademark of the Wikimedia Foundation, Inc.

Diabetes Mellitus Type 1 Inheritance

Type 1 diabetes is a polygenic disease, meaning many different genes contribute to its expression. Depending on locus or combination of loci, it can be dominant, recessive, or somewhere in between. The strongest gene, IDDM1, is located in the MHC Class II region on chromosome 6, at staining region 6p21. This is believed to be responsible for the histocompatibility disorder characteristic of type 1: Insulin-producing pancreas cells (beta cells) display improper antigens to T cells. This eventually leads to the production of antibodies that attack these beta cells. Weaker genes are also located on chromosomes 11 and 18.

Environmental factors can strongly influence expression of type 1. A study showed that for identical twins, when one twin had type 1 diabetes, the other twin only had type 1 30%–50% of the time. Despite having the exact same genome, one twin had the disease, where the other did not; this shows that environmental factors, in addition to genetic factors, can influence disease prevalence.

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Type 1 Diabetes Treatment

Type 1 is treated with insulin replacement therapy—usually by insulin injection or insulin pump, along with attention to dietary management, typically including carbohydrate tracking, and careful monitoring of blood glucose levels using glucose meters. Today the most common insulins are biosynthetic products produced using genetic recombination techniques; formerly, cattle or pig insulins were used, and even sometimes insulin from fish. Major global suppliers include Eli Lilly and Company, Novo Nordisk, and Sanofi-Aventis. A more recent trend, from several suppliers, is insulin analogs which are slightly modified insulins which have different onset of action times or duration of action times.

Untreated type 1 diabetes commonly leads to coma, often from diabetic ketoacidosis, which is fatal if untreated. Continuous glucose monitors have been developed and marketed which can alert patients to the presence of dangerously high or low blood sugar levels, but technical limitations have limited the impact these devices have had on clinical practice so far.

In more extreme cases, a pancreas transplant can 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 volatile). Experimental replacement of beta cells (by transplant or from stem cells) is being investigated in several research programs. Thus far, beta cell replacement has only been performed on patients over age 18, and with tantalizing successes amidst nearly universal failure.

Pancreas transplantation

Pancreas transplants are generally performed together with or some time after a kidney transplant. One reason for this is that introducing a new kidney requires taking immunosuppressive drugs such as cyclosporin. Nevertheless this allows the introduction of a new, functioning pancreas to a patient with diabetes without any additional immunosuppressive therapy. However, pancreas transplants alone can be wise in patients with extremely labile type 1 diabetes mellitus. Scientists have found another alternative mode of pancreas transplantation through the use of xenografts especially from animals such as pigs. This alternative mode of transplantation from animals provides an alternative therapy for the treatment of Type 1 diabetes.

Islet cell transplantation

Islet cell transplantation is expected to be less invasive than a pancreas transplant which is currently the most commonly used approach in humans.

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 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, unless a method is developed to produce them from the patient's own stem cells or there is an identical twin available who can donate stem cells. The immune system will attack the cells as it would a bacterial infection or a skin graft. Thus, patients now also need 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 islet cell transplant. Ideally, it would be best to use islet cells which will not provoke this immune reaction, but scientists in New Zealand are also looking into placing them within a protective housing derived of seaweed which enables insulin to flow out and nutrients to flow in while protecting the islets from immune system attack via white blood cells.

This article is licensed under the Creative Commons Attribution-ShareAlike License. It uses material from the Wikipedia article on "Diabetes mellitus type 1" All material adapted used from Wikipedia is available under the terms of the Creative Commons Attribution-ShareAlike License. Wikipedia® itself is a registered trademark of the Wikimedia Foundation, Inc.