Diabetes mellitus type 1
Encyclopedia
Diabetes mellitus type 1 (Type 1 diabetes, T1DM, IDDM, or, formerly, juvenile diabetes) is a form of diabetes mellitus
that results from autoimmune destruction of insulin
-producing beta cells of the pancreas
. The subsequent lack of insulin leads to increased blood and urine glucose. The classical symptoms are polyuria
(frequent urination), polydipsia
(increased thirst), polyphagia
(increased hunger), and weight loss.
Incidence varies from 8-17/100,000 in Northern Europe and the U.S., with a high of about 35/100,000 in Scandinavia, to a low of 1/100,000 in Japan and China.
Eventually, type 1 diabetes is fatal unless treated with insulin
. Injection is the most common method of administering insulin; other methods are insulin pump
s and inhaled insulin. Pancreatic transplants have been used. Pancreatic islet cell transplantation is experimental, though growing.
Most people who develop type 1 are otherwise healthy. Although the cause of type 1 diabetes is still not fully understood, it is believed to be of immunological origin.
Type 1 can be distinguished from type 2 diabetes
via a C-peptide
assay, which measures endogenous insulin production.
Type 1 treatment must be continued indefinitely in all cases. Treatment is not intended to significantly impair normal activities, and can be done adequately if sufficient patient training, awareness, appropriate care, discipline in testing and dosing of insulin is taken. However, treatment remains quite burdensome for many people. Complications may be associated with both low blood sugar
and high blood sugar, both largely due to the non-physiological manner in which insulin is replaced. Low blood sugar may lead to seizures or episodes of unconsciousness and requires emergency treatment. High blood sugar may lead to increased fatigue and can also result in long term damage to organs.
-dependent diabetes characterized by dramatic and recurrent swings in glucose
levels, often occurring for no apparent reason. The result can be irregular and unpredictable hyperglycemia
s, frequently with ketosis
, and sometimes serious hypoglycemia
s. Brittle diabetes occurs no more frequently than in 1% to 2% of diabetics.
(frequent urination), polydipsia
(increased thirst), polyphagia
(increased hunger), fatigue, and weight loss.
.
region on chromosome 6, at staining region 6p21. Certain variants of this gene increases the risk for decreased histocompatibility
characteristic of type 1. Such variants include DRB1 0401, DRB1 0402, DRB1 0405, DQA 0301, DQB1 0302 and DQB1 0201, which are common in North Americans of European ancestry and in Europeans. There are also variants that appear to be protective.
The risk of a child developing type 1 diabetes is approximately 10% if the father has it, approximately 10% if a sibling has it, approximately 4% if the mother has type 1 diabetes and is/was aged 25 or younger when the child is/was born, and approximately 1% if the mother is/was over 25 years old when the child is/was born.
triggered autoimmune response in which the immune system attacks virus infected cells along with the beta cells in the pancreas. The Coxsackie virus
family or Rubella
is implicated, although the evidence is inconclusive. In type 1, pancreatic beta cells in the Islets of Langerhans
are destroyed decreasing endogenous insulin
production. This distinguishes type 1's origin from type 2 DM. 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.
, intestinal permeability, and immune function in the gut; wheat in particular has been shown to have a connection to the development of type 1 diabetes, although the relationship is poorly understood.
Some researchers believe that the autoimmune response is influenced by antibodies against cow's milk proteins. 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.
Short breast-feeding period and short attendance to day care is associated with the risk of type 1 diabetes in Czech children.
(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.
s in the pancreas, regardless of which risk factors or causative entities have been present.
Individual risk factors can have separate pathophysiological processes to, in turn, cause this beta cell destruction. Still, a process that appears to be common to most risk factors is an autoimmune response towards beta cell
s, involving an expansion of autoreactive CD4+ and CD8+ T helper cell
s, autoantibody
-producing B cell
s and activation of the innate immune system
.
About a quarter of people with new type 1 diabetes have developed some degree of diabetic ketoacidosis
(a type of metabolic acidosis which is caused by high concentrations of ketone bodies, formed by the breakdown of fatty acids and the deamination of amino acids) by the time the diabetes is recognized. The diagnosis of other types of diabetes is usually made in other ways. These include ordinary health screening, detection of hyperglycemia during other medical investigations, and secondary symptoms such as vision changes or unexplainable fatigue. Diabetes is often detected when a person suffers a problem that may be caused by diabetes, such as a heart attack, stroke, neuropathy, poor wound healing or a foot ulcer, certain eye problems, certain fungal infections, or delivering a baby with macrosomia or hypoglycemia.
A positive result, in the absence of unequivocal hyperglycemia, should be confirmed by a repeat of any of the above-listed methods on a different day. Most physicians prefer to measure a fasting glucose level because of the ease of measurement and the considerable time commitment of formal glucose tolerance testing, which takes two hours to complete and offers no prognostic advantage over the fasting test. According to the current definition, two fasting glucose measurements above 126 mg/dL (7.0 mmol/L) is considered diagnostic for diabetes mellitus.
Patients with fasting glucose levels from 100 to 125 mg/dL (5.6 to 6.9 mmol/L) are considered to have impaired fasting glucose. Patients with plasma glucose at or above 140 mg/dL (7.8 mmol/L), but not over 200 mg/dL (11.1 mmol/L), two hours after a 75 g oral glucose load are considered to have impaired glucose tolerance
. Of these two pre-diabetic states, the latter in particular is a major risk factor for progression to full-blown diabetes mellitus and cardiovascular disease.
isoform of glutamic acid decarboxylase (GAD) and autoantibodies targeting the phosphatase
-related IA-2 molecule. Per definition, the diagnosis of diabetes type 1 can be made first at the appearance of clinical symptoms and/or signs, but the emergence of autoantibodies may itself be termed latent autoimmune diabetes
. Not everyone with autoantibodies progress to diabetes type 1, but the risk increases with the number of antibody types, with three to four antibody types giving a risk of progressing to diabetes type 1 of 60%–100%. The time interval from emergence of autoantibodies to frank diabetes type 1 can be a few months in infants and young children, but in some people it may take years – in some cases more than 10 years. Islet cell autoantibodies are detected by conventional immunofluorescence
while the rest are measured with specific radiobinding assay
s.
stage, before it starts destroying beta cells.
and other side effects make it highly inappropriate for long-term use.
Anti-CD3 antibodies, including teplizumab
and otelixizumab
, had suggested evidence of preserving insulin production (as evidenced by sustained C-peptide
production) in newly diagnosed type 1 diabetes patients. A probable mechanism of this effect was believed to be preservation of regulatory T cell
s that suppress activation of the immune system and thereby maintain immune system homeostasis and tolerance to self-antigens. The duration of the effect is still unknown, however. In 2011, Phase III studies with otelixizumab and teplizumab both failed to show clinical efficacy.
An anti-CD20
antibody, rituximab
, inhibits B cell
s and has been shown to provoke C-peptide
responses three months after diagnosis of type 1 diabetes, but long-term effects of this have not been reported.
decreased the risk in later life; various other nutritional risk factors are being studied, but no firm evidence has been found.
Giving children 2000 IU of Vitamin D
during their first year of life is associated with reduced risk of type 1 diabetes, though the causal relationship is obscure.
Children with antibodies to beta cell proteins (i.e. at early stages of an immune reaction to them) but no overt diabetes, and treated with vitamin B3 (niacin
), had less than half the diabetes onset incidence in a 7-year time span as did the general population, and an even lower incidence relative to those with antibodies as above, but who received no vitamin B3.
, along with attention to dietary management, typically including carbohydrate
tracking, and careful monitoring of blood glucose levels using glucose meter
s. 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 analog
s 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.
Treatment of diabetes focuses on lowering blood sugar or glucose (BG) to the near normal range, approximately 80–140 mg/dl (4.4–7.8 mmol/L). The ultimate goal of normalizing BG is to avoid long term complications that affect the nervous system (e.g. peripheral neuropathy leading to pain and/or loss of feeling in the extremities), and the cardiovascular system (e.g. heart attacks, vision loss). There are two primary types of diabetes, type 1 and type 2. People with type 1 diabetes always need to take insulin. Treatment with insulin can lead to low BG, or hypoglycemia
, i.e. BG less than 70 mg/dl (3.9 mmol/L). Hypoglycemia is a very common occurrence in people with diabetes, usually the result of a mismatch in the balance among insulin, food and physical activity, although the non-physiological method of delivery also plays a role.
required is considered by many physicians to be more dangerous than continued insulin replacement therapy, and is therefore generally only used 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 cyclosporine. 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.
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. Scientists in New Zealand with Living Cell Technologies are currently in human trials with Diabecell, placing pig islets within a protective capsule 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.
, diabetic neuropathy
, diabetic retinopathy
among others. However, there is some evidence that cardiovascular disease as well as neuropathy may, in fact, have an autoimmune basis as well.
(loss of peripheral vision or visual acuity), or peripheral neuropathy
(loss of feeling in the feet) can impair a driver’s ability to read street signs, control the speed of the vehicle, apply appropriate pressure to the brakes, etc.
Second, hypoglycemia can affect a person’s thinking process, coordination, and state of consciousness. This disruption in brain functioning is called neuroglycopenia. Studies have demonstrated that the effects of neuroglycopenia
impair driving ability. A study involving people with type 1 diabetes found that individuals reporting two or more hypoglycemia-related driving mishaps differ physiologically and behaviorally from their counterparts who report no such mishaps. For example, during hypoglycemia, drivers who had two or more mishaps reported fewer warning symptoms, their driving was more impaired, and their body released less epinephrine (a hormone that helps raise BG). Additionally, individuals with a history of hypoglycemia-related driving mishaps appear to use sugar at a faster rate and are relatively slower at processing information. These findings indicate that although anyone with type 1 diabetes may be at some risk of experiencing disruptive hypoglycemia while driving, there is a subgroup of type 1 drivers who are more vulnerable to such events.
Given the above research findings, it is recommended that drivers with type 1 diabetes with a history of driving mishaps should never drive when their BG is less than 70 mg/dl. Instead, these drivers are advised to treat hypoglycemia and delay driving until their BG is above 90 mg/dl. Such drivers should also learn as much as possible about what causes their hypoglycemia, and use this information to avoid future hypoglycemia while driving.
Studies funded by the National Institutes of Health (NIH) have demonstrated that face-to-face training programs designed to help individuals with type 1 diabetes better anticipate, detect, and prevent extreme BG can reduce the occurrence of future hypoglycemia-related driving mishaps. An internet-version of this training has also been shown to have significant beneficial results. Additional NIH funded research to develop internet interventions specifically to help improve driving safety in drivers with type 1 diabetes is currently underway.
Rates vary widely by country. In Finland, the incidence is a high of 35/100,000 per year, in Japan and China a low of 1–3/100,000 per year, and in Northern Europe and the U.S., an intermediate 8–17/100,000 per year.
Type 1 diabetes was previously known as juvenile diabetes to distinguish it from type 2 diabetes, which generally has a later onset; however, the majority of new-onset type 1 diabetes is seen in adults. Studies that use antibody testing (glutamic acid decarboxylase antibodies (GADA), islet cell antibodies (ICA), and insulinoma-associated autoantibodies (IA-2)) to distinguish between type 1 and type 2 diabetes demonstrate that most new-onset type 1 diabetes is seen in adults. Adult-onset type 1 autoimmune diabetes is two to three times more common than classic childhood-onset autoimmune diabetes.
(JDRF) is the leading charitable funder of research into type 1 diabetes in the world. It has offices in the UK, Denmark, USA, Canada, Australia, Israel, Mexico and India. JDRF's 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 $1.3 billion to diabetes research, including more than $156 million in FY 2008. In FY 2008, the Foundation funded 1,000 centers, grants and fellowships in 22 countries. In November 2008 JDRF launched an online social network for people with type 1 diabetes: Juvenation.
The Diabetes Research Institute Foundation is the only organization solely dedicated to curing diabetes. Founded by a group of parents of children with diabetes who wanted to put an end to type 1 diabetes, the Diabetes Research Institute Foundation has grown into an international coalition of business leaders, celebrities, research scientists, clinicians, families and other concerned individuals who have been a strong voice for cure-focused research. Supported by private philanthropy, the DRI Foundation has been and continues to be the organization of choice for those who are serious, passionate and committed to finding a cure for diabetes. Its mission is to provide the Diabetes Research Institute with the funding necessary to cure diabetes now.
The International Diabetes Federation
is a worldwide alliance of over 160 countries to address diabetes research and treatment. The American Diabetes Association
funds some type 1 research along with other a variety of diabetes-related research (not necessarily cure-specific) including type 2 diabetes, gestational diabetes
and others) that looks at treatments, prevention, as well as some cure-specific research. Diabetes Australia
is involved in promoting research and education in Australia on both type 1 and type 2 diabetes. The Canadian Diabetes Association
is involved in educating, researching, and sustaining type 1 diabetes patients in Canada. Pacific Northwest Diabetes Research Institute conducts clinical and basic research on type 1 and type 2 diabetes.
(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 T-cells. Instead of pro-inflammatory cytokines, the T-cells begin to release cytokines that inhibit inflammation. This phenomenon is commonly known as "acquired immune tolerance
".
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
that results from autoimmune destruction of insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
-producing beta cells of the pancreas
Pancreas
The pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...
. The subsequent lack of insulin leads to increased blood and urine glucose. The classical symptoms are polyuria
Polyuria
Polyuria is a condition usually defined as excessive or abnormally large production or passage of urine . Frequent urination is sometimes included by definition, but is nonetheless usually an accompanying symptom...
(frequent urination), polydipsia
Polydipsia
Polydipsia is a medical symptom in which the patient displays excessive thirst. The word derives from the Greek πολυδιψία, which is derived from πολύς + δίψα...
(increased thirst), polyphagia
Polyphagia
Polyphagia means "eating too much". It derives from the Greek words πολύς which means "very much", and φαγῶ , verb for "I eat"....
(increased hunger), and weight loss.
Incidence varies from 8-17/100,000 in Northern Europe and the U.S., with a high of about 35/100,000 in Scandinavia, to a low of 1/100,000 in Japan and China.
Eventually, type 1 diabetes is fatal unless treated with insulin
Insulin therapy
Insulin therapy is the treatment of diabetes by administration of exogenous insulin.Insulin is used medically to treat some forms of diabetes mellitus. Patients with Type 1 diabetes mellitus depend on external insulin for their survival because the hormone is no longer produced internally...
. Injection is the most common method of administering insulin; other methods are insulin pump
Insulin pump
The insulin pump is a medical device used for the administration of insulin in the treatment of diabetes mellitus, also known as continuous subcutaneous insulin infusion therapy.The device includes:...
s and inhaled insulin. Pancreatic transplants have been used. Pancreatic islet cell transplantation is experimental, though growing.
Most people who develop type 1 are otherwise healthy. Although the cause of type 1 diabetes is still not fully understood, it is believed to be of immunological origin.
Type 1 can be distinguished from type 2 diabetes
Diabetes mellitus type 2
Diabetes mellitus type 2formerly non-insulin-dependent diabetes mellitus or adult-onset diabetesis a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. Diabetes is often initially managed by increasing exercise and...
via a C-peptide
C-peptide
C-peptide is a protein that is produced in the body along with insulin. First preproinsulin is secreted with an A-chain, C-peptide, a B-chain, and a signal sequence. The signal sequence is cut off, leaving proinsulin...
assay, which measures endogenous insulin production.
Type 1 treatment must be continued indefinitely in all cases. Treatment is not intended to significantly impair normal activities, and can be done adequately if sufficient patient training, awareness, appropriate care, discipline in testing and dosing of insulin is taken. However, treatment remains quite burdensome for many people. Complications may be associated with both low blood sugar
Hypoglycemia
Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...
and high blood sugar, both largely due to the non-physiological manner in which insulin is replaced. Low blood sugar may lead to seizures or episodes of unconsciousness and requires emergency treatment. High blood sugar may lead to increased fatigue and can also result in long term damage to organs.
Classification
Brittle diabetes, also known as unstable diabetes or labile diabetes, refers to a type of insulinInsulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
-dependent diabetes characterized by dramatic and recurrent swings in glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
levels, often occurring for no apparent reason. The result can be irregular and unpredictable hyperglycemia
Hyperglycemia
Hyperglycemia or Hyperglycæmia, or high blood sugar, is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a glucose level higher than 13.5mmol/l , but symptoms may not start to become noticeable until even higher values such as 15-20 mmol/l...
s, frequently with ketosis
Ketosis
Ketosis is a state of elevated levels of ketone bodies in the body. It is almost always generalized throughout the body, with hyperketonemia, that is, an elevated level of ketone bodies in the blood. Ketone bodies are formed by ketogenesis when the liver glycogen stores are depleted...
, and sometimes serious hypoglycemia
Hypoglycemia
Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...
s. Brittle diabetes occurs no more frequently than in 1% to 2% of diabetics.
Signs and symptoms
The classical symptoms of type 1 diabetes include: polyuriaPolyuria
Polyuria is a condition usually defined as excessive or abnormally large production or passage of urine . Frequent urination is sometimes included by definition, but is nonetheless usually an accompanying symptom...
(frequent urination), polydipsia
Polydipsia
Polydipsia is a medical symptom in which the patient displays excessive thirst. The word derives from the Greek πολυδιψία, which is derived from πολύς + δίψα...
(increased thirst), polyphagia
Polyphagia
Polyphagia means "eating too much". It derives from the Greek words πολύς which means "very much", and φαγῶ , verb for "I eat"....
(increased hunger), fatigue, and weight loss.
Cause
Diabetes type I is induced by a combination of genetic susceptibility, a diabetogenic trigger and exposure to a driving antigenThe Environmental Determinants of Diabetes in the Young
The Environmental Determinants of Diabetes in the Young is a multiyear, multinational effort to determine some of the causes of type 1 diabetes , also known as juvenile diabetes, insulin-deppendent diabetes mellitus , or childhood diabetes....
.
Genetics
Type 1 diabetes is a polygenic disease, meaning many different genes contribute to its onset. 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 IIMHC class II
MHC Class II molecules are found only on a few specialized cell types, including macrophages, dendritic cells and B cells, all of which are professional antigen-presenting cells ....
region on chromosome 6, at staining region 6p21. Certain variants of this gene increases the risk for decreased histocompatibility
Histocompatibility
Histocompatibility is the property of having the same, or mostly the same, alleles of a set of genes called the major histocompatibility complex. These genes are expressed in most tissues as antigens, to which the immune system makes antibodies...
characteristic of type 1. Such variants include DRB1 0401, DRB1 0402, DRB1 0405, DQA 0301, DQB1 0302 and DQB1 0201, which are common in North Americans of European ancestry and in Europeans. There are also variants that appear to be protective.
The risk of a child developing type 1 diabetes is approximately 10% if the father has it, approximately 10% if a sibling has it, approximately 4% if the mother has type 1 diabetes and is/was aged 25 or younger when the child is/was born, and approximately 1% if the mother is/was over 25 years old when the child is/was born.
Environmental
Environmental factors can 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 exactly the same genome, one twin had the disease, where the other did not; this suggests that environmental factors, in addition to genetic factors, can influence disease prevalence. Other indications of environmental influence include the presence of a 10-fold difference in difference among Caucasians living in different areas of Europe, and a tendency to acquire the incidence of the disease of the destination country for people who migrate.Virus
One theory, discussed by DeLisa Fairweather & Noel R. Rose, among others, proposes that type 1 diabetes is a virallyVirus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
triggered autoimmune response in which the immune system attacks virus infected cells along with the beta cells in the pancreas. The Coxsackie virus
Coxsackie B4 virus
Coxsackie B4 virus is a virus which can trigger an autoimmune reaction which results in destruction of the insulin-producing beta cells of the pancreas, which is one of several different etiologies of diabetes mellitus....
family or Rubella
Rubella
Rubella, commonly known as German measles, is a disease caused by the rubella virus. The name "rubella" is derived from the Latin, meaning little red. Rubella is also known as German measles because the disease was first described by German physicians in the mid-eighteenth century. This disease is...
is implicated, although the evidence is inconclusive. In type 1, pancreatic beta cells in the Islets of Langerhans
Islets of Langerhans
The islets of Langerhans are the regions of the pancreas that contain its endocrine cells. Discovered in 1869 by German pathological anatomist Paul Langerhans at the age of 22, the islets of Langerhans constitute approximately 1 to 2% of the mass of the pancreas...
are destroyed decreasing endogenous insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
production. This distinguishes type 1's origin from type 2 DM. 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
Human leukocyte antigen
The human leukocyte antigen system is the name of the major histocompatibility complex in humans. The super locus contains a large number of genes related to immune system function in humans. This group of genes resides on chromosome 6, and encodes cell-surface antigen-presenting proteins and...
genotypes, though the connection between them and the triggering of an auto-immune reaction is still poorly understood.
Diet
There is a growing body of evidence that diet may play a role in the development of type 1 diabetes, through influencing gut floraGut flora
Gut flora consists of microorganisms that live in the digestive tracts of animals and is the largest reservoir of human flora. In this context, gut is synonymous with intestinal, and flora with microbiota and microflora....
, intestinal permeability, and immune function in the gut; wheat in particular has been shown to have a connection to the development of type 1 diabetes, although the relationship is poorly understood.
Some researchers believe that the autoimmune response is influenced by antibodies against cow's milk proteins. No connection has been established between autoantibodies
Autoantibody
An autoantibody is an antibody manufactured by the immune system that is directed against one or more of the individual's own proteins. It is derived from the Greek "auto" which means "self", "anti" which means "against" and "body"...
, antibodies to cow's milk proteins, and type 1 diabetes. A subtype of type 1
Latent autoimmune diabetes
Latent Autoimmune Diabetes of Adults , also known as, Diabetes Type 1.5, is a term coined by Tuomi et al. in 1993 to describe slow-onset Type 1 autoimmune diabetes in adults...
(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
Maturity onset diabetes of the young
Maturity onset diabetes of the young refers to any of several hereditary forms of diabetes caused by mutations in an autosomal dominant gene disrupting insulin production...
(MODY).
Vitamin D
Vitamin D
Vitamin D is a group of fat-soluble secosteroids. In humans, vitamin D is unique both because it functions as a prohormone and because the body can synthesize it when sun exposure is adequate ....
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
Finland
Finland , officially the Republic of Finland, is a Nordic country situated in the Fennoscandian region of Northern Europe. It is bordered by Sweden in the west, Norway in the north and Russia in the east, while Estonia lies to its south across the Gulf of Finland.Around 5.4 million people reside...
(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.
Short breast-feeding period and short attendance to day care is associated with the risk of type 1 diabetes in Czech children.
Chemicals and drugs
Some chemicals and drugs preferentially destroy pancreatic cells. PyrinuronPyrinuron
Pyrinuron is a chemical compound used as a rodenticide....
(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
Streptozotocin
Streptozotocin is a naturally occurring chemical that is particularly toxic to the insulin-producing beta cells of the pancreas in mammals...
, an antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
and antineoplastic agent used in chemotherapy for pancreatic cancer
Pancreatic cancer
Pancreatic cancer refers to a malignant neoplasm of the pancreas. The most common type of pancreatic cancer, accounting for 95% of these tumors is adenocarcinoma, which arises within the exocrine component of the pancreas. A minority arises from the islet cells and is classified as a...
; it also kills beta cells, resulting in loss of insulin production. Other pancreatic problems, including trauma, pancreatitis
Pancreatitis
Pancreatitis is inflammation of the pancreas. It occurs when pancreatic enzymes that digest food are activated in the pancreas instead of the small intestine. It may be acute – beginning suddenly and lasting a few days, or chronic – occurring over many years...
or tumors (either malignant or benign), can also lead to loss of insulin production.
Pathophysiology
The pathophysiology in diabetes type I is basically a destruction of beta cellBeta cell
Beta cells are a type of cell in the pancreas located in the so-called islets of Langerhans. They make up 65-80% of the cells in the islets.-Function:...
s in the pancreas, regardless of which risk factors or causative entities have been present.
Individual risk factors can have separate pathophysiological processes to, in turn, cause this beta cell destruction. Still, a process that appears to be common to most risk factors is an autoimmune response towards beta cell
Beta cell
Beta cells are a type of cell in the pancreas located in the so-called islets of Langerhans. They make up 65-80% of the cells in the islets.-Function:...
s, involving an expansion of autoreactive CD4+ and CD8+ T helper cell
T helper cell
T helper cells are a sub-group of lymphocytes, a type of white blood cell, that play an important role in the immune system, particularly in the adaptive immune system. These cells have no cytotoxic or phagocytic activity; they cannot kill infected host cells or pathogens. Rather, they help other...
s, autoantibody
Autoantibody
An autoantibody is an antibody manufactured by the immune system that is directed against one or more of the individual's own proteins. It is derived from the Greek "auto" which means "self", "anti" which means "against" and "body"...
-producing B cell
B cell
B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...
s and activation of the innate immune system
Innate immune system
The innate immune system, also known as non-specific immune system and secondary line of defence, comprises the cells and mechanisms that defend the host from infection by other organisms in a non-specific manner...
.
Diagnosis
Diabetes mellitus is characterized by recurrent or persistent hyperglycemia, and is diagnosed by demonstrating any one of the following:- Fasting plasma glucose level at or above 7.0 mmol/L (126 mg/dL).
- Plasma glucose at or above 11.1 mmol/L (200 mg/dL) two hours after a 75 g oral glucose load as in a glucose tolerance testGlucose tolerance testA glucose tolerance test is a medical test in which glucose is given and blood samples taken afterward to determine how quickly it is cleared from the blood. The test is usually used to test for diabetes, insulin resistance, and sometimes reactive hypoglycemia and acromegaly, or rarer disorders of...
. - Symptoms of hyperglycemia and casual plasma glucose at or above 11.1 mmol/L (200 mg/dL).
- Glycated hemoglobin (hemoglobin A1C) at or above 6.5. (This criterion was recommended by the American Diabetes AssociationAmerican Diabetes AssociationThe American Diabetes Association is a United States-based association working to fight the consequences of diabetes, and to help those affected by diabetes...
in 2010, although it has yet to be adopted by the WHOWhoWho may refer to:* Who , an English-language pronoun* who , a Unix command* Who?, one of the Five Ws in journalism- Art and entertainment :* Who? , a 1958 novel by Algis Budrys...
.)
About a quarter of people with new type 1 diabetes have developed some degree of diabetic ketoacidosis
Ketoacidosis
Ketoacidosis is a metabolic state associated with high concentrations of ketone bodies, formed by the breakdown of fatty acids and the deamination of amino acids. The two common ketones produced in humans are acetoacetic acid and β-hydroxybutyrate....
(a type of metabolic acidosis which is caused by high concentrations of ketone bodies, formed by the breakdown of fatty acids and the deamination of amino acids) by the time the diabetes is recognized. The diagnosis of other types of diabetes is usually made in other ways. These include ordinary health screening, detection of hyperglycemia during other medical investigations, and secondary symptoms such as vision changes or unexplainable fatigue. Diabetes is often detected when a person suffers a problem that may be caused by diabetes, such as a heart attack, stroke, neuropathy, poor wound healing or a foot ulcer, certain eye problems, certain fungal infections, or delivering a baby with macrosomia or hypoglycemia.
A positive result, in the absence of unequivocal hyperglycemia, should be confirmed by a repeat of any of the above-listed methods on a different day. Most physicians prefer to measure a fasting glucose level because of the ease of measurement and the considerable time commitment of formal glucose tolerance testing, which takes two hours to complete and offers no prognostic advantage over the fasting test. According to the current definition, two fasting glucose measurements above 126 mg/dL (7.0 mmol/L) is considered diagnostic for diabetes mellitus.
Patients with fasting glucose levels from 100 to 125 mg/dL (5.6 to 6.9 mmol/L) are considered to have impaired fasting glucose. Patients with plasma glucose at or above 140 mg/dL (7.8 mmol/L), but not over 200 mg/dL (11.1 mmol/L), two hours after a 75 g oral glucose load are considered to have impaired glucose tolerance
Impaired glucose tolerance
Impaired glucose tolerance is a pre-diabetic state of dysglycemia that is associated with insulin resistance and increased risk of cardiovascular pathology. IGT may precede type 2 diabetes mellitus by many years...
. Of these two pre-diabetic states, the latter in particular is a major risk factor for progression to full-blown diabetes mellitus and cardiovascular disease.
Autoantibodies
The appearance of diabetes-related autoantibodies has been shown to be able to predict the appearance of diabetes type 1 before any hyperglycemia arises, the main ones being islet cell autoantibodies, insulin autoantibodies, autoantibodies targeting the 65 kDaAtomic mass unit
The unified atomic mass unit or dalton is a unit that is used for indicating mass on an atomic or molecular scale. It is defined as one twelfth of the rest mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state, and has a value of...
isoform of glutamic acid decarboxylase (GAD) and autoantibodies targeting the phosphatase
Phosphatase
A phosphatase is an enzyme that removes a phosphate group from its substrate by hydrolysing phosphoric acid monoesters into a phosphate ion and a molecule with a free hydroxyl group . This action is directly opposite to that of phosphorylases and kinases, which attach phosphate groups to their...
-related IA-2 molecule. Per definition, the diagnosis of diabetes type 1 can be made first at the appearance of clinical symptoms and/or signs, but the emergence of autoantibodies may itself be termed latent autoimmune diabetes
Latent autoimmune diabetes
Latent Autoimmune Diabetes of Adults , also known as, Diabetes Type 1.5, is a term coined by Tuomi et al. in 1993 to describe slow-onset Type 1 autoimmune diabetes in adults...
. Not everyone with autoantibodies progress to diabetes type 1, but the risk increases with the number of antibody types, with three to four antibody types giving a risk of progressing to diabetes type 1 of 60%–100%. The time interval from emergence of autoantibodies to frank diabetes type 1 can be a few months in infants and young children, but in some people it may take years – in some cases more than 10 years. Islet cell autoantibodies are detected by conventional immunofluorescence
Immunofluorescence
Immunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on biological samples. This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to specific biomolecule targets within a cell, and therefore allows...
while the rest are measured with specific radiobinding assay
Radiobinding assay
A radiobinding assay is a method of detecting and quantifying antibodies targeted towards a specific antigen. As such, it can be seen as the inverse of radioimmunoassay, which quantifies an antigen by use of corresponding antibodies.-Technique:...
s.
Prevention
Type 1 diabetes is not currently preventable. Some researchers believe that diabetes type 1 might be prevented at the latent autoimmuneLatent autoimmune diabetes
Latent Autoimmune Diabetes of Adults , also known as, Diabetes Type 1.5, is a term coined by Tuomi et al. in 1993 to describe slow-onset Type 1 autoimmune diabetes in adults...
stage, before it starts destroying beta cells.
Immunosuppressive drugs
Cyclosporine A, an immunosuppressive agent, has apparently halted destruction of beta cells (on the basis of reduced insulin usage), but its nephrotoxicityNephrotoxicity
Nephrotoxicity is a poisonous effect of some substances, both toxic chemicals and medication, on the kidneys. There are various forms of toxicity. Nephrotoxicity should not be confused with the fact that some medications have a predominantly renal excretion and need their dose adjusted for the...
and other side effects make it highly inappropriate for long-term use.
Anti-CD3 antibodies, including teplizumab
Teplizumab
Teplizumab is a monoclonal antibody which is used as an immunosuppressive drug.Teplizumab is a humanized Fc-engineered monoclonal antibody also known as MGA031 and hOKT3γ1....
and otelixizumab
Otelixizumab
Otelixizumab, also known as TRX4, is a monoclonal antibody, which is being developed for the treatment of type 1 diabetes and other autoimmune diseases. The antibody is being developed by Tolerx, Inc...
, had suggested evidence of preserving insulin production (as evidenced by sustained C-peptide
C-peptide
C-peptide is a protein that is produced in the body along with insulin. First preproinsulin is secreted with an A-chain, C-peptide, a B-chain, and a signal sequence. The signal sequence is cut off, leaving proinsulin...
production) in newly diagnosed type 1 diabetes patients. A probable mechanism of this effect was believed to be preservation of regulatory T cell
Regulatory T cell
Regulatory T cells , sometimes known as suppressor T cells, are a specialized subpopulation of T cells which suppresses activation of the immune system and thereby maintains tolerance to self-antigens. The existence of regulatory T cells was the subject of significant controversy among...
s that suppress activation of the immune system and thereby maintain immune system homeostasis and tolerance to self-antigens. The duration of the effect is still unknown, however. In 2011, Phase III studies with otelixizumab and teplizumab both failed to show clinical efficacy.
An anti-CD20
CD20
B-lymphocyte antigen CD20 or CD20 is an activated-glycosylated phosphoprotein expressed on the surface of all B-cells beginning at the pro-B phase and progressively increasing in concentration until maturity....
antibody, rituximab
Rituximab
Rituximab, sold under the trade names Rituxan and MabThera, is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of B cells...
, inhibits B cell
B cell
B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...
s and has been shown to provoke C-peptide
C-peptide
C-peptide is a protein that is produced in the body along with insulin. First preproinsulin is secreted with an A-chain, C-peptide, a B-chain, and a signal sequence. The signal sequence is cut off, leaving proinsulin...
responses three months after diagnosis of type 1 diabetes, but long-term effects of this have not been reported.
Diet
Some research has suggested that breastfeedingBreastfeeding
Breastfeeding is the feeding of an infant or young child with breast milk directly from female human breasts rather than from a baby bottle or other container. Babies have a sucking reflex that enables them to suck and swallow milk. It is recommended that mothers breastfeed for six months or...
decreased the risk in later life; various other nutritional risk factors are being studied, but no firm evidence has been found.
Giving children 2000 IU of Vitamin D
Vitamin D
Vitamin D is a group of fat-soluble secosteroids. In humans, vitamin D is unique both because it functions as a prohormone and because the body can synthesize it when sun exposure is adequate ....
during their first year of life is associated with reduced risk of type 1 diabetes, though the causal relationship is obscure.
Children with antibodies to beta cell proteins (i.e. at early stages of an immune reaction to them) but no overt diabetes, and treated with vitamin B3 (niacin
Niacin
"Niacin" redirects here. For the neo-fusion band, see Niacin .Niacin is an organic compound with the formula and, depending on the definition used, one of the forty to eighty essential human nutrients.Niacin is one of five vitamins associated with a pandemic deficiency disease: niacin deficiency...
), had less than half the diabetes onset incidence in a 7-year time span as did the general population, and an even lower incidence relative to those with antibodies as above, but who received no vitamin B3.
Insulin therapy
Type 1 is treated with insulin replacement therapy—either via subcutaneous injection or insulin pumpInsulin pump
The insulin pump is a medical device used for the administration of insulin in the treatment of diabetes mellitus, also known as continuous subcutaneous insulin infusion therapy.The device includes:...
, along with attention to dietary management, typically including carbohydrate
Carbohydrate
A carbohydrate is an organic compound with the empirical formula ; that is, consists only of carbon, hydrogen, and oxygen, with a hydrogen:oxygen atom ratio of 2:1 . However, there are exceptions to this. One common example would be deoxyribose, a component of DNA, which has the empirical...
tracking, and careful monitoring of blood glucose levels using glucose meter
Glucose meter
A glucose meter is a medical device for determining the approximate concentration of glucose in the blood. It is a key element of home blood glucose monitoring by people with diabetes mellitus or hypoglycemia...
s. 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
Eli Lilly and Company
Eli Lilly and Company is a global pharmaceutical company. Eli Lilly's global headquarters is located in Indianapolis, Indiana, in the United States...
, Novo Nordisk
Novo Nordisk
Novo Nordisk manufactures and markets pharmaceutical products and services. Created in 1989 through a merger of two Danish companies dating back to the 1920s, it has become one of the world's leading companies in diabetes care, where Novo Nordisk pursues research into pulmonary delivery systems;...
, and Sanofi-Aventis
Sanofi-Aventis
Sanofi S.A. is a multinational pharmaceutical company headquartered in Paris, France, the world's fourth-largest by prescription sales. Sanofi engages in the research and development, manufacturing and marketing of pharmaceutical products for sale principally in the prescription market, but the...
. A more recent trend, from several suppliers, is insulin analog
Insulin analog
An insulin analog is an altered form of insulin, different from any occurring in nature, but still available to the human body for performing the same action as human insulin in terms of glycemic control...
s 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
Diabetic ketoacidosis
Diabetic ketoacidosis is a potentially life-threatening complication in patients with diabetes mellitus. It happens predominantly in those with type 1 diabetes, but it can occur in those with type 2 diabetes under certain circumstances...
, 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.
Treatment of diabetes focuses on lowering blood sugar or glucose (BG) to the near normal range, approximately 80–140 mg/dl (4.4–7.8 mmol/L). The ultimate goal of normalizing BG is to avoid long term complications that affect the nervous system (e.g. peripheral neuropathy leading to pain and/or loss of feeling in the extremities), and the cardiovascular system (e.g. heart attacks, vision loss). There are two primary types of diabetes, type 1 and type 2. People with type 1 diabetes always need to take insulin. Treatment with insulin can lead to low BG, or hypoglycemia
Hypoglycemia
Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...
, i.e. BG less than 70 mg/dl (3.9 mmol/L). Hypoglycemia is a very common occurrence in people with diabetes, usually the result of a mismatch in the balance among insulin, food and physical activity, although the non-physiological method of delivery also plays a role.
Pancreas transplantation
In more extreme cases, a pancreas transplant can restore proper glucose regulation. However, the surgery and accompanying immunosuppressionImmunosuppression
Immunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other...
required is considered by many physicians to be more dangerous than continued insulin replacement therapy, and is therefore generally only used together with or some time after a kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
transplant. One reason for this is that introducing a new kidney requires taking immunosuppressive drugs such as cyclosporine. 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.
Islet cell transplantation
Experimental replacement of beta cells (by transplant or from stem cells) is being investigated in several research programs. Islet cell transplantation is 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
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, 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
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
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. Scientists in New Zealand with Living Cell Technologies are currently in human trials with Diabecell, placing pig islets within a protective capsule 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.
Complications
Complications of poorly-managed type 1 diabetes mellitus may include cardiovascular diseaseCardiovascular disease
Heart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...
, diabetic neuropathy
Diabetic neuropathy
Diabetic neuropathies are neuropathic disorders that are associated with diabetes mellitus. These conditions are thought to result from diabetic microvascular injury involving small blood vessels that supply nerves in addition to macrovascular conditions that can culminate in diabetic neuropathy...
, diabetic retinopathy
Diabetic retinopathy
Diabetic retinopathy is retinopathy caused by complications of diabetes mellitus, which can eventually lead to blindness....
among others. However, there is some evidence that cardiovascular disease as well as neuropathy may, in fact, have an autoimmune basis as well.
Driving
Studies conducted in the United States and Europe showed that drivers with type 1 diabetes had twice as many collisions as their non-diabetic spouses, demonstrating the increased risk of driving collisions in the type 1 diabetes population. Diabetes can compromise driving safety in several ways. First, long-term complications of diabetes can interfere with the safe operation of a vehicle. For example, diabetic retinopathyDiabetic retinopathy
Diabetic retinopathy is retinopathy caused by complications of diabetes mellitus, which can eventually lead to blindness....
(loss of peripheral vision or visual acuity), or peripheral neuropathy
Peripheral neuropathy
Peripheral neuropathy is the term for damage to nerves of the peripheral nervous system, which may be caused either by diseases of or trauma to the nerve or the side-effects of systemic illness....
(loss of feeling in the feet) can impair a driver’s ability to read street signs, control the speed of the vehicle, apply appropriate pressure to the brakes, etc.
Second, hypoglycemia can affect a person’s thinking process, coordination, and state of consciousness. This disruption in brain functioning is called neuroglycopenia. Studies have demonstrated that the effects of neuroglycopenia
Neuroglycopenia
Neuroglycopenia is a medical term that refers to a shortage of glucose in the brain, usually due to hypoglycemia. Glycopenia affects the function of neurons, and alters brain function and behavior...
impair driving ability. A study involving people with type 1 diabetes found that individuals reporting two or more hypoglycemia-related driving mishaps differ physiologically and behaviorally from their counterparts who report no such mishaps. For example, during hypoglycemia, drivers who had two or more mishaps reported fewer warning symptoms, their driving was more impaired, and their body released less epinephrine (a hormone that helps raise BG). Additionally, individuals with a history of hypoglycemia-related driving mishaps appear to use sugar at a faster rate and are relatively slower at processing information. These findings indicate that although anyone with type 1 diabetes may be at some risk of experiencing disruptive hypoglycemia while driving, there is a subgroup of type 1 drivers who are more vulnerable to such events.
Given the above research findings, it is recommended that drivers with type 1 diabetes with a history of driving mishaps should never drive when their BG is less than 70 mg/dl. Instead, these drivers are advised to treat hypoglycemia and delay driving until their BG is above 90 mg/dl. Such drivers should also learn as much as possible about what causes their hypoglycemia, and use this information to avoid future hypoglycemia while driving.
Studies funded by the National Institutes of Health (NIH) have demonstrated that face-to-face training programs designed to help individuals with type 1 diabetes better anticipate, detect, and prevent extreme BG can reduce the occurrence of future hypoglycemia-related driving mishaps. An internet-version of this training has also been shown to have significant beneficial results. Additional NIH funded research to develop internet interventions specifically to help improve driving safety in drivers with type 1 diabetes is currently underway.
Epidemiology
Type 1 diabetes causes an estimated 5–10% of all diabetes cases or 11–22 million worldwide. In 2006 it affected 440 thousand children under 14 years of age and was the primary cause of diabetes in those less than 10 years of age. The incidence of type 1 diabetes has been increasing by about 3% per year.Rates vary widely by country. In Finland, the incidence is a high of 35/100,000 per year, in Japan and China a low of 1–3/100,000 per year, and in Northern Europe and the U.S., an intermediate 8–17/100,000 per year.
Type 1 diabetes was previously known as juvenile diabetes to distinguish it from type 2 diabetes, which generally has a later onset; however, the majority of new-onset type 1 diabetes is seen in adults. Studies that use antibody testing (glutamic acid decarboxylase antibodies (GADA), islet cell antibodies (ICA), and insulinoma-associated autoantibodies (IA-2)) to distinguish between type 1 and type 2 diabetes demonstrate that most new-onset type 1 diabetes is seen in adults. Adult-onset type 1 autoimmune diabetes is two to three times more common than classic childhood-onset autoimmune diabetes.
Economics
In the US in 2008, there were about one million people diagnosed with type 1 diabetes. The disease was estimated to cause $10.5 billion in annual medical costs ($875 per month per diabetic) and an additional $4.4 billion in indirect costs ($366 per month per diabetic).Foundations
The Juvenile Diabetes Research FoundationJuvenile Diabetes Research Foundation
JDRF is the leading global organization focused on type 1 diabetes research. Driven by volunteers connected to children, adolescents, and adults with this disease, JDRF is the largest charitable supporter of T1D research...
(JDRF) is the leading charitable funder of research into type 1 diabetes in the world. It has offices in the UK, Denmark, USA, Canada, Australia, Israel, Mexico and India. JDRF's 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 $1.3 billion to diabetes research, including more than $156 million in FY 2008. In FY 2008, the Foundation funded 1,000 centers, grants and fellowships in 22 countries. In November 2008 JDRF launched an online social network for people with type 1 diabetes: Juvenation.
The Diabetes Research Institute Foundation is the only organization solely dedicated to curing diabetes. Founded by a group of parents of children with diabetes who wanted to put an end to type 1 diabetes, the Diabetes Research Institute Foundation has grown into an international coalition of business leaders, celebrities, research scientists, clinicians, families and other concerned individuals who have been a strong voice for cure-focused research. Supported by private philanthropy, the DRI Foundation has been and continues to be the organization of choice for those who are serious, passionate and committed to finding a cure for diabetes. Its mission is to provide the Diabetes Research Institute with the funding necessary to cure diabetes now.
The International Diabetes Federation
International Diabetes Federation
The International Diabetes Federation is a worldwide alliance of some 200 diabetes associations in more than 160 countries, who have come together to enhance the lives of people with diabetes everywhere. For over 50 years, IDF has been at the vanguard of global diabetes advocacy...
is a worldwide alliance of over 160 countries to address diabetes research and treatment. The American Diabetes Association
American Diabetes Association
The American Diabetes Association is a United States-based association working to fight the consequences of diabetes, and to help those affected by diabetes...
funds some type 1 research along with other a variety of diabetes-related research (not necessarily cure-specific) including type 2 diabetes, gestational diabetes
Gestational diabetes
Gestational diabetes is a condition in which women without previously diagnosed diabetes exhibit high blood glucose levels during pregnancy . It is widely accepted as a disease only in the United States, there is some question whether the condition is natural during pregnancy...
and others) that looks at treatments, prevention, as well as some cure-specific research. Diabetes Australia
Diabetes Australia
Diabetes Australia is the third oldest diabetes association in the world, after the United Kingdom and Portugal. Originally established in the state of New South Wales in 1937, the organisation's head office is now in the nation's capital, Canberra...
is involved in promoting research and education in Australia on both type 1 and type 2 diabetes. The Canadian Diabetes Association
Canadian Diabetes Association
The Canadian Diabetes Association is an organization based in Toronto, Ontario, Canada. Its mission is to lead the fight against diabetes mellitus by helping Canadians with diabetes live healthy lives while work is continued to find a cure...
is involved in educating, researching, and sustaining type 1 diabetes patients in Canada. Pacific Northwest Diabetes Research Institute conducts clinical and basic research on type 1 and type 2 diabetes.
GAD65 vaccine
Injections with a vaccine containing GAD65, an autoantigen involved in type 1 diabetes, has in clinical trials delayed the destruction of beta cells when treated within six months of diagnosis. 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. Two prevention studies, where the vaccine is given to persons who have not yet developed diabetes are underway.T helper cell shift
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. Several groups are trying to achieve this by causing the activation state of the immune system to change from type 1 T helper cellT helper cell
T helper cells are a sub-group of lymphocytes, a type of white blood cell, that play an important role in the immune system, particularly in the adaptive immune system. These cells have no cytotoxic or phagocytic activity; they cannot kill infected host cells or pathogens. Rather, they help other...
(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
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
signaling molecules being released by T-cells. Instead of pro-inflammatory cytokines, the T-cells begin to release cytokines that inhibit inflammation. This phenomenon is commonly known as "acquired immune tolerance
Immune tolerance
Immune tolerance or immunological tolerance is the process by which the immune system does not attack an antigen. It can be either 'natural' or 'self tolerance', in which the body does not mount an immune response to self antigens, or 'induced tolerance', in which tolerance to external antigens can...
".
See also
- Kara Neumann caseKara Neumann caseThe Kara Neumann case was an incident in which parents of a sick child refused to treat her with anything other than prayer, resulting in the child's death...
– "treatment" by prayers case resulting in death - List of people with diabetes mellitus type 1
- Type 1 Diabetes AssociationType 1 Diabetes AssociationThe Type 1 Diabetes Association is a US nonprofit charity providing type 1 diabetes information, advocacy, and resources.The Type 1 Diabetes Association was founded in 2007 by Jon Strishak, a Type 1 diabetic marathon runner....
External links
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) – Diabetes in America Textbook (PDFs)
- IDF Diabetes Atlas
- International Diabetes Federation
- type 1 Diabetes at the American Diabetes AssociationAmerican Diabetes AssociationThe American Diabetes Association is a United States-based association working to fight the consequences of diabetes, and to help those affected by diabetes...
- National Diabetes Information Clearinghouse