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Sunday, June 3, 2018

Latent Autoimmune Diabetes in Adults With Low-Titer GAD Antibodies ...
src: care.diabetesjournals.org

Latent autoimmune diabetes of adults (LADA) is a form of diabetes mellitus type 1 that occurs in adulthood, often with a slower course of onset than type 1 diabetes diagnosed in juveniles. Adults with LADA may initially be diagnosed incorrectly as having type 2 diabetes based on their age, particularly if they have risk factors for type 2 diabetes such as a strong family history or obesity.

The diagnosis is typically based on the finding of hyperglycemia together with the clinical impression that islet failure rather than insulin resistance is the main cause; detection of a low C-peptide and raised antibodies against the islets of Langerhans support the diagnosis. It can only be treated with the usual oral treatments for type 2 diabetes for a certain period of time, after which insulin treatment is usually necessary, as well as long-term monitoring for complications.

The concept of LADA was first introduced in 1993, though The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus does not recognize the term, instead including it under the standard definition of diabetes mellitus type 1.


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Signs and symptoms

The symptoms of latent autoimmune diabetes of adults are similar to those of other forms of diabetes: polydipsia (excessive thirst and drinking), polyuria (excessive urination), and often blurred vision. Compared to juvenile type 1 diabetes, the symptoms develop comparatively slowly, over a period of at least six months.


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Diagnosis

It is estimated that more than 50% of persons diagnosed as having non-obesity-related type 2 diabetes may actually have LADA. Glutamic acid decarboxylase autoantibody (GADA), islet cell autoantibody (ICA), insulinoma-associated (IA-2) autoantibody, and zinc transporter autoantibody (ZnT8) testing should be performed on all adults who are not obese who are diagnosed with diabetes. However, some overweight patients are misdiagnosed with type 2 due to their weight. Moreover, 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.

Persons with LADA typically have low, although sometimes moderate, levels of C-peptide as the disease progresses. Those with insulin resistance or type 2 diabetes are more likely to have high levels of C-peptide due to an over production of insulin.

Autoantibodies

Glutamic acid decarboxylase autoantibodies (GADA), islet cell autoantibodies (ICA), insulinoma-associated (IA-2) autoantibodies, and zinc transporter autoantibodies (ZnT8) are all associated with LADA; GADAs are commonly found in cases of diabetes mellitus type 1.

The presence of Islet Cell Complement Fixing Autoantibodies also 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.

Persons with LADA usually test positive for Glutamic acid decarboxylase antibodies, whereas in type 1 diabetes these antibodies are more commonly seen in adults rather than in children. 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 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.

Classification

The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus does not recognize the term "latent autoimmune diabetes" (LADA); rather, it 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."


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Prevention

There are no known ways of preventing LADA type 1 diabetes, though some researchers believe it could be stopped at a very early stage if a diagnosis is made prior to the body's destruction of its beta cells.


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Management

About 80% of all LADA patients initially misdiagnosed with type 2 (and who have GAD antibodies) will become insulin-dependent within 3 to 15 years (according to differing LADA sources).

The treatment for Type 1 diabetes/LADA is exogenous insulin to control glucose levels, prevent further destruction of residual beta cells, reduce the possibility of diabetic complications, and prevent death from diabetic ketoacidosis (DKA). Although LADA may appear to initially respond to similar treatment (lifestyle and medications) 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. People with LADA have insulin resistance similar to long-term type 1 diabetes; some studies showed that people with LADA have less insulin resistance, compared with those with type 2 diabetes; however, others have not found a difference.


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Prevalence

It is estimated that between 6-50% of all persons, depending on population, 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. People with LADA typically have a normal BMI or may be underweight due to weight loss prior to diagnosis. Some people with LADA, however, may be overweight to mildly obese.

Contrary to popular belief, some people having LADA do carry a family history of type 2 diabetes.


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History

Although type 1 diabetes has been identified as an autoimmune disease since the 1970s, the concept of latent autoimmune diabetes mellitus was not noted until 1993, when it was used to describe slow-onset type 1 autoimmune diabetes occurring in adults. This followed the concept that GAD autoantibodies were a feature of type 1 diabetes and not type 2 diabetes.


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References

Notes

Sources

  • Eisenbarth, George S., ed. (2010). Immunoendocrinology: Scientific and Clinical Aspects. Contemporary Endocrinology. Humana Press. ISBN 978-1-603-27477-7. 
  • Flynn, John A.; Michael J. Choi; L. Dwight Wooster, eds. (2013). Oxford American Handbook of Clinical Medicine. Oxford American Handbooks in Medicine. Oxford University Press. ISBN 978-0-195-18849-3. 
  • Munden, Julie, ed. (2006). Diabetes Mellitus: A Guide to Patient Care. Lippincott Williams & Wilkins. ISBN 978-1-58255-732-8. 

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External links

  • Diabetes Research Centre, Melbourne, Australia LADA information, trials, resource links.

Source of article : Wikipedia