Latent autoimmune diabetes

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Latent autoimmune diabetes in adults (LADA) is a term coined by Tuomi et al in 1993 (Diabetes 42:359-362) to describe slow-onset Type 1 autoimmune diabetes in adults. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (Diabetes Care, Volume 30, Supplement 1, January 2007) does not recognize the term LADA; rather, the Expert Committee includes LADA in the definition of Type 1 autoimmune diabetes (“Type 1 diabetes results from a cellular-mediated autoimmune destruction of the beta-cells of the pancreas. In Type 1 diabetes, the rate of beta-cell destruction is quite variable, being rapid in some individuals (mainly infants and children) and slow in others (mainly adults).”) The National Institutes of Health (NIDDK) defines LADA as “a condition in which Type 1 diabetes develops in adults.” LADA is a genetically-linked, hereditary autoimmune disorder that results in the body mistaking the pancreas as foreign and responding by attacking and destroying the insulin-producing beta islet cells of the pancreas. Simply stated, autoimmune disorders, including LADA, are an "allergy to self.”

Adults with LADA are frequently initially misdiagnosed as having Type 2 diabetes, based on age not etiology. In a recent survey conducted by Australia’s Type 1 Diabetes Network, one third of all Australians with type 1 diabetes reported being initially misdiagnosed as having the more common type 2 diabetes.

Contents 1 Other names for LADA 2 Diagnosing latent autoimmune diabetes 2.1 C-peptide (also known as insulin C-peptide, connecting peptide) 2.2 Diabetes mellitus autoantibody panel 2.3 Islet Cell Antibodies (ICA) tests 2.4 Glutamic Acid Decarboxylase (GAD) Antibodies tests 2.5 Insulin Antibodies (IAA)tests 3 Prevalence 4 Treatment 4.1 Hypoglycemia 4.2 Hyperglycemia 5 Long-term complications 6 Prognosis 7 Comparison between LADA, type 1 diabetes and type 2 diabetes 8 See also 9 References 10 External links

[edit] Other names for LADA

LADA may be diagnosed using any of the following terms:

• latent autoimmune diabetes of adulthood
• late-onset autoimmune diabetes of adulthood
• slow onset type 1 diabetes, or
• type 1.5 (type one-and-a-half) diabetes

[edit] Diagnosing latent autoimmune diabetes

It is estimated that 20% of persons diagnosed as having non-obesity-related type 2 diabetes may actually have LADA. Islet cell, insulin, and GAD antibodies testing should be performed on all adults who are not obese that appear to present with type 2 diabetes.^[1] Not all people having LADA are thin or skinny, however—there are plus-sized individuals carrying LADA but not getting accurately diagnosed because of their weight. These individuals are more often denied insulin by their health care physicians, considering people who were diagnosed with or have type 2 diabetes are given those treatments by diabetes specialists or their physicians extremely often.^[2] Furthermore, it is now becoming evident that autoimmune diabetes may be highly underdiagnosed in many individuals who have diabetes, and that the body mass index levels may have rather limited use in connections with latent autoimmune diabetes.^[3]

Diagnostic tests include:

[edit] C-peptide (also known as insulin C-peptide, connecting peptide)

This test measures residual beta cell function by determining the level of insulin secretion (C-peptide). Persons with LADA typically have low, although sometimes moderate, levels of C-peptide as the disease progresses. Patients with insulin resistance or type 2 diabetes are more likely to, but will not always, have high levels of C-peptide due to an over production of insulin.^[4][5]

[edit] Diabetes mellitus autoantibody panel

Glutamic acid decarboxylase (GAD) autoantibodies, radioimmunoassay (RIA) and insulin antibodies, radioimmunoassay, RIA.

Glutamic acid decarboxylase antibodies are commonly found in diabetes mellitus type 1.

[edit] Islet Cell Antibodies (ICA) tests

Islet Cell IgG Cytoplasmic Autoantibodies, IFA; Islet Cell Complement Fixing Autoantibodies, Indirect Fluorescent Antibody (IFA); Islet Cell Autoantibodies Evaluation; Islet Cell Complement Fixing Autoantibodies - Aids in a differential diagnosis between LADA and type 2 diabetes. Persons with LADA often test positive for ICA, whereas type 2 diabetics only seldom do.^[4][6]

[edit] Glutamic Acid Decarboxylase (GAD) Antibodies tests

Microplate ELISA: Anti-GAD, Anti-IA2, Anti-GAD/IA2 Pool - In addition to being useful in making an early diagnosis for type 1 diabetes mellitus, GAD antibodies tests are used for differential diagnosis between LADA and type 2 diabetes^[4][7][8] and may also be used for differential diagnosis of gestational diabetes, risk prediction in immediate family members for type 1, as well as a tool to monitor prognosis of the clinical progression of type 1 diabetes.

[edit] Insulin Antibodies (IAA)tests

RIA: Anti-GAD, Anti-IA2, Anti-Insulin; Insulin Antibodies - These tests are also used in early diagnosis for type 1 diabetes mellitus, and for differential diagnosis between LADA and type 2 diabetes, as well as for differential diagnosis of gestational diabetes, risk prediction in immediate family members for type 1, and to monitor prognosis of the clinical progression of type 1 diabetes. Persons with LADA may test positive for insulin antibodies; persons with type 2, however, rarely do.^[4][6]

Other characteristics of LADA that may aid in differential diagnosis include:^[9]

• Onset usually at 25 years of age or older

• Initially mimics non-obese type 2 diabetes (patients are usually thin or of normal weight, although some may be overweight to minimally obese)^[2][10]

• Oftentimes, although not always, lack of family history for T2DM^{[11][12][13][14]}

• Persons with LADA are insulin resistant like, but at prevalence levels less than, Type 2^[15][16]

• Human leukocyte antigen (HLA) genes associated with type 1 diabetes are seen in LADA but not in type 2 diabetes^[6]

[edit] Prevalence

It is estimated that approximately 20% of all persons diagnosed with type 2 diabetes might actually have LADA. This number accounts for an estimated 5%-10% of the total diabetes population in the U.S. or, as many as 3.5 million persons with LADA.^[1][5] Actual numbers, however, may be unbelievably higher and more severe than estimates indicate.

[edit] Treatment

LADA often does not require insulin at the time of diagnosis and may even be managed with changes in lifestyle in its early stages such as exercise, eating right, and, if optional, weight loss. However, some clinicians believe that insulin should be started at onset or as soon as possible, rather than using sulfonylureas or other diabetes pills for initial treatment. Moreover, it is not clear whether early insulin therapy is of benefit to the remaining beta islet cells.^[9][17]

Initially, a person with LADA may respond to oral diabetes medications, eating right and lifestyle changes, although beta cells continue to be destroyed and LADA patients should be closely monitored. Some studies have demonstrated that the use of sulfonylureas and the insulin-sensitizing drug metformin, may increase the risk of severe metabolic disorder in persons with LADA. When blood glucose can no longer be managed through lifestyle and medications, daily insulin injections will be required.

80% of persons initially diagnosed with type 2 but test positive for GAD (an indication of LADA). progress to insulin dependency within 6 years (some sources say between 3-12 years after diagnosis).^[18] Those who test positive for both GAD and IA2, however, will progress more rapidly to insulin dependence.^[4][7][8]

Living with any chronic illness is stressful, and patients with diabetes, let alone LADA, may be more prone to depression and eating disorders as a result.^{[citation needed]} Counseling, therapy, and participation in support groups can play an important and positive role in the lives of persons with LADA.^{[citation needed]}

Part of diabetes therapy should include patient education about diet, exercise, stress management, and handling their diabetes on "sick" days. Patients need to understand how to manage their diabetes, as well as how to recognize, treat, and prevent hypoglycemia (low blood sugar) and hyperglycemia (high blood sugar) and how to give injections of insulin and glucagon. Blood glucose levels should be checked not less than 3-4 times per day when a patient is insulin dependent and, often, at least once during the night.

[edit] Hypoglycemia

Hypoglycemia (low blood sugar) presents an immediate and life-threatening danger. Any reading 70 mg/dL (3.9 mmol/L) or below, for a person with diabetes, classifies as "low."

When blood glucose falls too low a person can become disoriented and unable to swallow. Without being able to ingest a fast-acting sugar they may lose consciousness. Untreated, hypoglycemia can lead to seizures, diabetic coma and death. Onset of hypoglycemia is often rapid and may be attributed to many things including too much insulin (insulin shock), not eating enough, heavy exercise, excitement, certain medications, or a combination of factors.

Because of the potential danger associated with hypoglycemia, persons using insulin should carry a glucagon kit, fast-acting food sugars, and medical identification with them at all times. At least one family member or friend should be instructed on glucagon administration as the patient is likely to be unable to inject themselves.

[edit] Hyperglycemia

Hyperglycemia (high blood glucose levels) occurs when too much food is eaten for insulin that was taken, not enough insulin, stress, dehydration, or illness are present. Hyperglycemia, untreated, can lead to a deadly state called diabetic ketoacidosis (DKA). When insufficient insulin is present the body cannot use blood glucose as energy. A combination of things happen, one of which is the body turning to fat stores for energy. Burning of fat causes a ketonic state that may result in an excess of ketones. Persons with high blood glucose levels should use a test strip to check their urine for ketones anytime their glucose levels are 240 mg/dL (13.3 mmol/L) or higher. Patients should call their doctor if ketones measure in the moderate-to-high range as DKA may require hospitalization.

A person in DKA requires immediate medical attention and should not attempt to simply administer more insulin independent of a physician's recommendation. Doing so (self-treating) could lead to serious health risks, even death. DKA can lead to heart failure, cerebral edema, coma, and death.

[edit] Long-term complications

The long-term complications of LADA are the same as for those with type one (formerly juvenile diabetes) and with type two. According to one major study, the Diabetes control and complications trial (DCCT), the risk of long-term problems are directly related to how well the blood glucose levels are managed. The American Diabetes Association recommends LADA patients strive for a HbA1c test of 7.0 or lower.

Uncontrolled diabetes of all types results in high blood glucose levels (hyperglycemia) which over time may cause diabetic neuropathy, diabetic retinopathy, eye trouble, kidney failure, heart disease, high blood pressure, stroke, peripheral arterial disease (PAD), chronic infections and wounds that may not heal, erectile and other urological dysfunction, gastroparesis (delayed emptying of stomach contents), gangrene, blindness, amputation, lactic acidosis, diabetic ketoacidosis (DKA).

[edit] Prognosis

According to one study—"Similar as in prediabetic relatives of type 1 diabetic patients the risk for beta cell failure in adult 'type 2 diabetic' patients increases with the number of antibodies positive."^[19]

Eventually, the latent autoimmune diabetic adult will become dependent upon injecting insulin in order to maintain glucose control. They will require daily injection of insulin and need to be diligent in following their diabetes care plan provided by their physician.

Diabetes, including latent autoimmune diabetes is a chronic illness that can have devastating complications. However, it is possible for most persons with diabetes to actively participate in their daily health care needs and dramatically reduce the risk of diabetes complications.

Patient education, motivation, and state of mental health all play an important role in how well a person with LADA will be able to manage their disease.

[edit] Comparison between LADA, type 1 diabetes and type 2 diabetes

LADA is neither classified as type 2 diabetes or type 1 diabetes but considered somewhere in between, although some are considering it as a form of type 1 diabetes that has similarities and differences to both type 1 and type 2 diabetes.^[4]

• Onset: Type 1 diabetes onsets rapidly and at a younger age than does LADA. Both LADA and type 2 onsets are slow, happening over many months or years.

• Family history: There is often although not always an absence of family history of type 2 diabetes in a LADA patient's family. (in other words—individuals having LADA will sometimes have family histories of T2DM involving parents, siblings, sisters, brothers, uncles, aunts, nephews, etc.)^[20][21][14] In addition, TCF7L2 genes associated with type 2 and genetic markers of HLA genes found in type 1 and LADA are present. LADA does not affect children or adolescents. It is most often diagnosed after age 35, although LADA does sometimes develop around 24-29 years of age.

• Antibodies: Persons with type 1 diabetes and LADA usually test positive for certain (same) antibodies that are not present in type 2 diabetes.

• GAD antibodies: Persons with LADA usually test positive for GAD antibodies, whereas in type 1 diabetes these antibodies are more commonly seen in adults rather than in children.^[4][22]

• Insulin resisting: Persons with LADA are insulin resistant like, but with prevalence levels less than, type two.^{[23][15][24][25][26]}

• Lifestyle and excess weight: Type 2 diabetes onsets as a result of substandard diets, a sedentary lifestyle and excess body weight (especially when excess weight is carried about the center, or in those with an "apple" shaped body). These factors are not thought of as contributing factors to the onset of type 1 diabetes or LADA. People with latent autoimmune diabetes of adults often have normal body weight or are skinny, although not always: people who have LADA sometimes carry body weight around the center or are overweight to somewhat obese.^[26][27] However individuals with T2DM are often, although not always, overweight. Developing type 2 is especially likely for individuals who are morbidly obese.

• Prognosis: About 80% of all persons initially diagnosed with type 2, who also have GAD antibodies, will become insulin dependent within 3 to 12 years (according to differing LADA sources).^[28] Those with both GAD and IA2 antibodies, however, will become insulin dependent sooner. LADA occurs slowly, but progresses towards insulin dependency.^[7]

• Treatment: Although LADA may appear to initially respond to similar treatment (lifestyle and medications, sometimes weight loss (if needed) as type 2 diabetes, it will not halt or slow the progression of beta cell destruction, and people with LADA will eventually become insulin dependent.

[edit] See also

• Diabetes type 1.5

[edit] References

[edit] External links

• Diabetes Research Centre, Melbourne, Australia LADA information, trials, resource links.
• Action Lada, The National Public Health Institute/Kansanterveyslaitos (KTL) in Helsinki, Finland acts as the Action LADA co-ordination centre for Finland. -