Latent autoimmune diabetes of adults

Latent autoimmune diabetes of adults (LADA), often also late-onset autoimmune diabetes of adulthood or aging,^[1] slow onset type 1 diabetes or diabetes type 1.5 is a form of diabetes mellitus type 1 that occurs in adults, often with a slower course of onset. 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 based on the finding of high blood sugar 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,^[2][3] after which insulin treatment is usually necessary, as well as long-term monitoring for complications. The concept of LADA was first introduced in 1993.

Signs and symptoms

The symptoms of latent autoimmune diabetes of adults are similar to those of other forms of diabetes: excessive thirst and drinking, excessive urination, and often blurry vision.

Compared to childhood type 1 diabetes, the symptoms develop comparatively slowly.

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.^[4] Not all people having LADA are thin or skinny, however—there are overweight individuals with LADA who are misdiagnosed because of 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.^[4]

C-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, though will not always, have high levels of C-peptide due to an over production of insulin.^[5][6]

Autoantibody panel

Glutamic acid decarboxylase autoantibodies (GADA), islet cell autoantibodies (ICA), insulinoma-associated (IA-2) autoantibodies, and zinc transporter autoantibodies (ZnT8). Glutamic acid decarboxylase antibodies are commonly found in diabetes mellitus type 1.

Islet cell antibodies

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.^[5]

Glutamic acid decarboxylase antibodies

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^[5][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.

Insulin antibodies

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 autoantibodies (GAD, ICA, IA-2, ZnT8); autoantibodies are not present in persons with type 2 diabetes.^[5]

Classification

The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus does not recognize the term 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).” ^[9] The National Institutes of Health (NIDDK) defines LADA as "a condition in which Type 1 diabetes develops in adults".

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.^[4][6]

Prognosis

Diabetes, including latent autoimmune diabetes of adults, 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 diabetic 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.

Comparison

LADA is slow-onset Type 1 autoimmune diabetes in adulthood (NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases ).

• Onset: Type 1 diabetes onsets rapidly and at a younger age than does LADA.
• Family history: There is often a family history of autoimmune conditions (for example, Hashimoto's Disease (autoimmune hypothyroidism) and Celiac Disease, etc.). Contrary to popular belief, some people with latent autoimmune diabetes of adults do carry a family history for Type 2 diabetes.^[10][11]
• Autoantibodies: Persons with type 1 diabetes and LADA usually test positive for certain (same) autoantibodies (GAD, ICA, IA-2, ZnT8 ) that are not present in type 2 diabetes. Studies have reported an association of Type 1 diabetes/LADA with high risk genes, HLA-DR3, HLA-DR4. There are also TCF7L2 genes associated with Type 2 diabetes with latent autoimmune diabetes of adults.^[12]
• GAD autoantibodies: 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.^[5][13]
• Insulin resistance: 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.^[3]
• Lifestyle and weight: 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.^[14] LADA (Type 1 diabetes) is an autoimmune disease that cannot be prevented.
• Prognosis: About 80% of all persons initially misdiagnosed with type 2, who have GAD antibodies, will become insulin dependent within 3 to 15 years (according to differing LADA sources).^[15][16] Those with both GAD and IA2 antibodies, however, will become insulin dependent sooner. LADA occurs more slowly than classic rapid-onset Type 1 diabetes, though it progresses towards insulin dependency.^[7]
• Treatment: 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 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.

History

The concept of latent autoimmune diabetes mellitus was first described in 1993 to describe slow-onset type 1 autoimmune diabetes in adults.^[17] This followed the concept that GAD autoantibodies were a feature of type 1 diabetes and not type 2 diabetes.^[18]

References

1. "Diabetes mellitus: a guide to patient care"; page 20; Lippincott Williams & Wilkins; August 1, 2006; ISBN 978-1-58255-732-8
2. "Latent autoimmune diabetes". Mayo Clinic. Retrieved May 26, 2014.
3. "Latent autoimmune diabetes: a little known type of diabetes". Pharmacy Times. Retrieved May 26, 2014.
4. Landin-Olsson M (April 2002). "Latent autoimmune diabetes in adults". Annals of the New York Academy of Sciences. 958: 112–116. doi:10.1111/j.1749-6632.2002.tb02953.x. PMID 12021090.
5. Comparison of clinical features between (juvenile)type 1 diabetes, type 2 diabetes and LADA; Islets of Hope (2006)
6. C-peptide test; Labtestsoline.org
7. Latent Autoimmune Diabetes in Adults; David Leslie, Cristina Valerie DiabetesVoice.org; 2003
8. Unnikrishnan AG, Singh SK, Sanjeevi CB (December 2004). "Prevalence of GAD65 antibodies in lean subjects with type 2 diabetes". Annals of the New York Academy of Sciences. 1037: 118–21. doi:10.1196/annals.1337.018. PMID 15699503.
9. American Diabetes, Association (January 2007). "Diagnosis and classification of diabetes mellitus". Diabetes Care. 30 Suppl 1: S42–7. doi:10.2337/dc07-S042. PMID 17192378.
10. "Family History of Diabetes Involving LADA" (PDF). DiabetesJournals.org. Retrieved May 30, 2014.
11. "Latent Autoimmune Diabetes of Adults". JCEM. Retrieved Mar 23, 2016.
12. "Latent Autoimmune Diabetes of Adults and TCF7L2 Genes". PubMed. Retrieved May 26, 2014.
13. Diabetes Mellitus, Type 1: A Review; eMedicine.com; updated 07/02/2006
14. Insulin resistance leads to LADA (Report). Diabetes Health. Retrieved April 10, 2010.
15. "Prediction of Type I Diabetes". UCDenver.edu. Retrieved Mar 23, 2016.
16. "Type 1.5 Diabetes". Bottom Line Health. Retrieved Mar 23, 2016.
17. Tuomi T, Groop LC, Zimmet PZ, Rowley MJ, Knowles W, Mackay IR (February 1993). "Antibodies to glutamic acid decarboxylase reveal latent autoimmune diabetes mellitus in adults with a non-insulin-dependent onset of disease". Diabetes. 42 (2): 359–62. doi:10.2337/diab.42.2.359. PMID 8425674.
18. Hagopian, W A; Karlsen, A E; Gottsäter, A; Landin-olsson, M; Grubin, C E; Sundkvist, G; Petersen, J S; Boel, E; Dyrberg, T; Lernmark, A (January 1993). "Quantitative assay using recombinant human islet glutamic acid decarboxylase (GAD65) shows that 64K autoantibody positivity at onset predicts diabetes type Hagopian, W A ; Karlsen, A E ; Gottsäter, A ; Landin-olsson, M ; Grubin, C E ; Sundkvist, G ; Petersen, J S ; Boel, E ; Dyrberg, T ; Lernmark, A". The Journal of Clinical Investigation. 91 (1): 368–74. doi:10.1172/JCI116195. PMC 330036. PMID 8423232.

External links

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