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   Table of Contents      
ORIGINAL ARTICLE
Year : 2015  |  Volume : 3  |  Issue : 2  |  Page : 53-55

Ophthalmic disorder in patients with latent autoimmune diabetes in adult


1 Department of Microbiology, Unit of Immunology, Faculty of Medicine, Al Neelain Medical Research Centre, Al Neelain University, Khartoum, Sudan
2 Sudan Academy of Science, Council of Biological Science, New Technology and Environment, Khartoum, Sudan
3 Department of Microbiology, El Ribat University Hospital, Khartoum, Sudan

Date of Web Publication17-Dec-2015

Correspondence Address:
Ahmed Bolad
Department of Microbiology, Unit of Immunology, Faculty of Medicine, Al Neelain Medical Research Centre, Al Neelain University, Khartoum
Sudan
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DOI: 10.4103/1858-6538.172100

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  Abstract 

It is well known that about 90% of all cases of diabetes mellitus (DM) are type 2, which is characteristic for adults aged above 40 years. Ten percent is represented by type 1 DM, typical for children and young. Adult's onset diabetes represent a heterogeneous mixture of type 1 and type 2 DM, often difficult to differentiate between, those patients may have actually latent autoimmune diabetes in adults (LADAs), where beta-cell destruction is less aggressive, leading to a slower development of insulin dependency. Studies indicated that antibodies against glutamic acid decarboxylase 65 (GAD 65) are good marker for diagnosis of autoimmune diabetes in adults who are not responding to oral hypoglycemic and may be at risk for getting complications namely increased risk of diabetic retinopathy. GAD 65 is mainly expressed in beta-cells of Langerhans but also in nonbeta-cells. GAD is an enzyme required for gama-aminobutyric acid (GABA) synthesis that acts as neurotransmitter in neurons of central nervous system and in pancreatic islets. GABA is probably involved in controlling the release of insulin from secretary granules.

Keywords: Beta-cells of langerhans, DM, gama-aminobutyric acid, glutamic acid decarboxylase 65, LADA, neurotransmitter


How to cite this article:
Bolad A, Abdelmageed R, Manofaly A, Abdelrahim HM. Ophthalmic disorder in patients with latent autoimmune diabetes in adult. Albasar Int J Ophthalmol 2015;3:53-5

How to cite this URL:
Bolad A, Abdelmageed R, Manofaly A, Abdelrahim HM. Ophthalmic disorder in patients with latent autoimmune diabetes in adult. Albasar Int J Ophthalmol [serial online] 2015 [cited 2019 Dec 12];3:53-5. Available from: http://www.bijojournal.org/text.asp?2015/3/2/53/172100


  Latent Autoimmune Diabetes in Adult and Diabetic Retinopathy Top


The latent autoimmune diabetes in adult (LADA) is genetically linked, hereditary autoimmune disorder that develops in adults. Adults with LADA are frequently initially misdiagnosed as having type 2 diabetes mellitus (DM), based on age rather than etiology. LADA is distinguished from type 2 DM by the presence of islet autoantibodies.[1],[2] These autoantibodies include beta cell-specific autoantibodies (glutamic acid decarboxylase 65 [GAD 65] and insulinoma antigen 2 [IA-2A]); however, beta-cell destruction is less aggressive, leading to a slower development of insulin dependency.[3],[4],[5] In its early stages, LADA typically presents as type 2 diabetes and is often misdiagnosed as such. However, LADA more closely resembles type 1 diabetes and shares common physiological characteristics of type 1 for metabolic dysfunction, genetics, and autoimmune features, but it does not affect children and has classified distinctly as being separate from juvenile diabetes. It has been estimated that approximately 20% of all persons diagnosed with type 2 diabetes may actually cases of LADA and they are more rapidly fail to oral hypoglycemic therapy than beta cell-specific autoantibodies-negative type 2 patients.

The Immunology Diabetes Society has recently proposed the following criteria for diagnosis of patients with LADA: Patients should be at least 30 years of age, positive for at least one of the four antibodies commonly found in type 1 diabetic patients (ICAs and autoantibodies to GAD 65, IA-2, and insulin) and not treated with insulin within the first 6 months after diagnosis.

GAD autoantibodies (GAD-Abs), which present in the cytoplasm of the human beta-cell, is an enzyme required for gamma-aminobutyric acid (GABA) synthesis that acts as neurotransmitter in neurons of central nervous system, in pancreatic islets [6] and probably involved in controlling the release of insulin from secretary granules. Autoantibodies to GAD 65 show no correlation with age at onset and is therefore a particularly attractive marker for autoimmune diabetes in the adult population.[7] Moreover, GAD 65 reactive antibodies can be detected years after the clinical onset of the disease, indicating that these autoantibodies may be permanent markers for the autoimmune response.[8] However, it has been suggested that antibodies to antigens other than GAD and IA-2 are more prevalent in LADA [9] and raises the intriguing possibility that some unidentified antigens are more commonly involved in LADA than type 1 diabetes.

Patients with type 1 DM retinopathy have shown inverse correlation to GAD 65-Abs.[10] GADA may have some effect on the development of diabetic retinopathy since GAD 65 is expressed in the neural retina as well as the pancreas and the central nervous system [6] and were associated with an increased risk of diabetic retinopathy 15 years later. The patients with type 1 DM depend on exogenous insulin to prevent metabolic derangement (e.g., ketoacidosis) and death.[11] The commonest long-term complications of type 1 DM are diabetic retinopathy (DR), diabetic nephropathy, and diabetic neuropathy. Retinopathy, on the other hand, has shown increased risk among human leukocyte antigen locus (DQB1*0201-A1*0501 and DBQ1*0302-A1*0301) individuals and inverse correlation to GAD 65-Abs.[1],[12] Neuropathy is highly controversial. It was reported that GAD 65-Ab may be present in type 1 diabetes patients with neuropathy, but numerous subsequent studies have failed to confirm this early demonstration.[13] However, a lower prevalence of retinopathy in patients with LADA is reported after 12 years of duration. Accordingly, the report advised a dilated eye examination in patients with LADA.[14] A higher proportion of subjects with LADA had evidence of microvascular complications of DM namely retinopathy and neuropathy.

One of the three criteria to define LADA is the absence of insulin requirement for at least 6 months after diagnosis. Therefore, early insulin treatment could be an inappropriate, but the justification for that treatment approach would allow beta-cell rest, at least in part by downregulating the beta-cell metabolism and/or by releasing them from the hyperglycemic stress.[15] Result of this is a decrease in the severity of “insulitis" and in the number of infiltrative antigen-presenting cells in and around the pancreatic islets.[16] This was clearly demonstrated by two studies carried out in Japan that revealed preservation of beta-cell function with insulin compared with sulfonylurea treatment in islets cells autoantibody-positive and GAD autoantibody-positive phenotypic type 2 diabetes subjects.[17],[18]

LADA Patients with insulin resistance could benefit from Metformin therapy, a drug that improves peripheral insulin action and indirectly protects beta cells from continuous hyperstimulation. Thiazolidinediones (TZDs)[19] or 'glitazones' are another class of oral Antidiabetic drugs that improve metabolic control in patients with type 2 diabetes through the improvement of insulin sensitivity. They have the capabilities to improve insulin content, insulin secretion, preserve beta cell mass and islet structure. TZDs also have anti-inflammatory effects that facilitate beta cell proliferation and protect them from oxidative stress and apoptosis.[19],[20]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

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Fasanmade OA, Odeniyi IA, Ogbera AO. Diabetic ketoacidosis: Diagnosis and management. Afr J Med Med Sci 2008;37:99-105.  Back to cited text no. 1
    
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Groop LC, Eriksson J, Ekstrand A, Franssila-Kallunki A, Saloranta C, Miettinen A. Metabolic characteristics of autoimmune diabetes mellitus in adults. Diabetologia 1991;34:46-51.  Back to cited text no. 3
    
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Tuomi T, Groop LC, Zimmet PZ, Rowley MJ, Knowles W, Mackay IR. Antibodies to glutamic acid decarboxylase reveal latent autoimmune diabetes mellitus in adults with a non-insulin-dependent onset of disease. Diabetes 1993;42:359-62.  Back to cited text no. 4
    
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Zimmet PZ, Tuomi T, Mackay IR, Rowley MJ, Knowles W, Cohen M, et al. Latent autoimmune diabetes mellitus in adults (LADA): The role of antibodies to glutamic acid decarboxylase in diagnosis and prediction of insulin dependency. Diabet Med 1994;11:299-303.  Back to cited text no. 5
    
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Dotta F, Di Mario U. Antigenic determinants in type 1 diabetes mellitus. Review article. APMIS 1996;104:769-74.  Back to cited text no. 6
    
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Falorni A, Brozzetti A. Diabetes-related antibodies in adult diabetic patients. Best Pract Res Clin Endocrinol Metab 2005;19:119-33.  Back to cited text no. 7
    
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Borg H, Gottsäter A, Fernlund P, Sundkvist G. A 12-year prospective study of the relationship between islet antibodies and beta-cell function at and after the diagnosis in patients with adult-onset diabetes. Diabetes 2002;51:1754-62.  Back to cited text no. 8
    
9.
Seissler J, de Sonnaville JJ, Morgenthaler NG, Steinbrenner H, Glawe D, Khoo-Morgenthaler UY, et al. Immunological heterogeneity in type I diabetes: Presence of distinct autoantibody patterns in patients with acute onset and slowly progressive disease. Diabetologia 1998;41:891-7.  Back to cited text no. 9
    
10.
Agardh D, Agardh E, Landin-Olsson M, Gaur LK, Agardh CD, Lernmark A. Inverse relationship between GAD65 antibody levels and severe retinopathy in younger type 1 diabetic patients. Diabetes Res Clin Pract 1998;40:9-14.  Back to cited text no. 10
    
11.
Sherwin RS. Diabetes mellitus. In: Benntte JC, Plum F, editors. Cecil Text Book of Medicine. 20th ed. Philadelphia: WB. Saunders Company; 1996. p. 1258-77.  Back to cited text no. 11
    
12.
Frier BM, Fisher BM. Diabetes mellitus. In: Haslett S, Chilvers ER, Boon NA, College NR, Hunter JA, editors. Davidson's Principles and Practice of Medicine. 19th ed. London: Churchill Livingstone; 2002. p. 624-82.  Back to cited text no. 12
    
13.
Hoeldtke RD, Bryner KD, Horvath GG, Byerly MR, Hobbs GR, Marcovina SM, et al. Antibodies to GAD and glycemic control in recent-onset IDDM. Diabetes Care 1997;20:1900-3.  Back to cited text no. 13
    
14.
Isomaa B, Almgren P, Henricsson M, Taskinen MR, Tuomi T, Groop L, et al. Chronic complications in patients with slowly progressing autoimmune type 1 diabetes (LADA). Diabetes Care 1999;22:1347-53.  Back to cited text no. 14
    
15.
Argoud GM, Schade DS, Eaton RP. Insulin suppresses its own secretion in vivo. Diabetes 1987;36:959-62.  Back to cited text no. 15
[PUBMED]    
16.
Jansen A, Rosmalen JG, Homo-Delarche F, Dardenne M, Drexhage HA. Effect of prophylactic insulin treatment on the number of ER-MP23 macrophages in the pancreas of NOD mice. Is the prevention of diabetes based on beta-cell rest? J Autoimmun 1996;9:341-8.  Back to cited text no. 16
    
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Kobayashi T. Multicenter prevention trial of slowly progressive IDDM with small dose of insulin (The Tokyo study). Diabetes Metab Res Rev 2001;17:S29.  Back to cited text no. 17
    
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Kobayashi T, Maruyama T, Shimada A, Kasuga A, Kanatsuka A, Takei I, et al. Insulin intervention to preserve beta cells in slowly progressive insulin-dependent (type 1) diabetes mellitus. Ann N Y Acad Sci 2002;958:117-30.  Back to cited text no. 18
    
19.
Diani AR, Sawada G, Wyse B, Murray FT, Khan M. Pioglitazone preserves pancreatic islet structure and insulin secretory function in three murine models of type 2 diabetes. Am J Physiol Endocrinol Metab 2004;286:E116-22.  Back to cited text no. 19
    
20.
Hanefeld M. Pioglitazone and sulfonylureas: Effectively treating type 2 diabetes. Int J Clin Pract Suppl 2007;61(Suppl 153):20-7.  Back to cited text no. 20
    




 

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