Investigation of the Frequency of Polyglandular Autoimmune Syndrome in Patients with Type 1 Diabetes Mellitus and Its Relationship with the Prognosis and Complications of Diabetes

Yıl 2023, , 102 - 111, 31.08.2023

Rabia Acar , Faruk Kilinc

https://doi.org/10.25048/tudod.1296972

Öz

Aim: One third of patients with type 1 diabetes mellitus (T1DM) have an autoimmune polyglandular syndrome (OPS). In this study, it
was aimed to investigate the frequency of OPS accompanying T1DM and the relationship of diabetes with prognosis and complications.
Material and Methods: Our study included 99 patients who applied to the endocrine outpatient clinic and were followed up with
the diagnosis of T1DM. Chi-square analysis (Pearson Chi-square), Kolmogorov-Smirnov test, Student’s t-test, Mann Whitney-U test,
Spearman Correlation test and Kruskal Wallis test were used in the analysis of the data. SPSS 22 package program was used in the
analysis of the data. The significance value was taken as p≤ 0.05.
Results: Of the patients included in the study, 25 (25.3%) had hypothyroidism and 8 (8.1%) had celiac disease. Anti-endomysium
antibodies in 9 (9.1%), islet antibodies in 50 (50.5%), anti-insulin antibodies in 22 (22.2%) patients, and anti-parietal antibodies in 26
(26.3%) patients’ antibody, tissue transglutaminase IG A in 8 (8.1%), ANA in 43 (43.4%), ASMA positivity in 4 (4.0%) and OPS in 25
(25.3%) detected. It was determined that the duration of the disease of the patients with retinopathy, neuropathy and nephropathy in
T1DM patients was significantly higher than the duration of the disease in those who did not. It was found that there was a positive
correlation between the patients’ disease year and BMI and waist circumference, and a negative correlation between the disease year and
HbA1c and C peptide. It was determined that there was no significant difference between the presence of OPS in terms of presence of
retinopathy, presence of neuropathy) and presence of nephropathy. In addition, there was no significant difference between the presence
of OPS in terms of HbA1c value.
Conclusion: The incidence of other autoimmune diseases has increased significantly over the years in patients with T1DM, and
autoimmune diseases should be considered both at the time of diagnosis and in the following years in terms of reducing the risk of
complications in the follow-up of diabetic patients, a good prognosis, good clinical development and early diagnosis.

Anahtar Kelimeler

Type 1 diabetes mellitus,, polyglandular syndrome,, prognosis

Tip 1 Diabetes Mellitus Tanılı Hastalarda Poliglandüler Otoimmün Sendrom Sıklığının Tespiti ve Diyabetin Prognoz ve Komplikasyonları ile İlişkisinin Araştırılması

Öz

Amaç: Tip 1 diabetes mellitus (T1DM) tanılı hastaların üçte birinde otoimmün poliglandüler sendrom (OPS) bulunmaktadır. Çalışmada
T1DM’ye eşlik eden OPS sıklığı ve diyabetin prognoz, komplikasyonları ile ilişkisinin araştırılması amaçlanmıştır.
Gereç ve Yöntemler: Çalışmaya Endokrinoloji polikliniğine başvuran ve T1DM tanısı ile takipli 99 hasta dahil edildi. Verilerin analizinde
Ki-Kare analizi (Pearson Chi-kare), Kolmogorov-Smirnov testi, Student t-testi, Mann Whitney-U testi, Spearman Korelasyon testi ve
Kruskal Wallis testi kulanılmıştır. Verilerin analizinde SPSS 22 paket programı kullanıldı. Anlamlılık değeri p≤ 0,05 olarak alındı.
Bulgular: Çalışmaya alınan hastaların 25’inde (%25,3) hipotiroidi ve 8’inde (%8,1) çölyak hastalığı saptandı. Hastaların 9’unda (%9,1)
anti endomisyum antikor, 50’sinde (%50,5) adacık antikoru, 22’sinde (%22,2) anti insülin antikor, 26’sında (%26,3) anti parietal antikor,
8’inde (%8,1) doku transglutaminaz IG A, 43’ünde (%43,4) ANA, 4’ünde (%4,0) ASMA pozitifliği ve 25’inde (%25,3) OPS varlığı tespit
edildi. T1DM tanılı hastalarda retinopati, nöropati ve nefropati gelişen hastaların hastalık süresi gelişmeyenlerin hastalık süresinden
anlamlı şekilde yüksek olduğu tespit edildi. Hastaların hastalık yılı ile VKİ ve bel çevresi arasında pozitif yönde, hastalık yılı ile HbA1c
ve c peptit arasında ise negatif yönde anlamlı bir korelasyon saptandı. OPS varlığı arasında retinopati varlığı, nöropati varlığı ve nefropati
varlığı açısından anlamlı farklılık olmadığı saptandı. Bunun yanında OPS varlığı arasında HbA1c değeri açısından da anlamlı farklılık
görülmedi.
Sonuç: T1DM tanılı hastalarda diğer otoimmün hastalıkların sıklığında yıllar geçtikçe ciddi bir artış gelişmekte olup, diyabetik hastaların
takiplerinde komplikasyon risklerinin azaltılması, iyi bir prognoz, iyi klinik gelişim ve erken tanı açısından otoimmün hastalıkların
diyabetin hem tanı anında hem de ilerleyen yıllarında dikkate alınması gerekmektedir

Anahtar Kelimeler

Tip 1 diabetes mellitus,, Otoimmün poliglandüler sendrom,, Prognoz

Kaynakça

• 1. Alemzadeh R, Ali O. Diabetes Mellitus. In: Behrman RE, Kliegman RM, Jenson HB, et al. Nelson Textbook of Pediatrics. 19 th ed. Philadelphia: Elsevier Saunders, 2011: 1968-1990.
• 2. Saka N, Baş F. Diabetes Mellitus. Neyzi O, Ertuğrul T, editörler. Pediyatri’de. İstanbul: Nobel Matbaacılık, 2010; 1625-1641.
• 3. Winter WE. The use of islet autoantibody markers in the prediction of autoimmune type 1 diabetes. Clin Immunol Newslett 1999; 19: 25-39.
• 4. Bach JF. Infections and autoimmune diseases. J Autoimmun 2005; 25: 74-80.
• 5. Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor a-chains (CD25). Breakdown of a singlemechanism of self-tolerance causes various autoimmune diseases. J Immunol 1995; 155: 1151-1164.
• 6. Neufeld M, Maclaren N, Blizzard R. Autoimmune polyglandular syndromes. Pediatr Ann 1980; 9: 154-162.
• 7. Atkinson MA, Eisenbarth GS. Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet 2001; 358: 221- 229
• 8. Tuomilehto J. The emerging global epidemic of type 1 diabetes. Curr Diab Rep 2013; 13: 795-804.
• 9. Hansen MP, Kahaly GJ. Autoimmune polyglandularsyndromes. Dtsch Med Wochenschr 2013; 138: 319-326.
• 10. Chong V, Leong K, Wallymahmed M, Sturgess R, MacFarlane A. Is coeliac disease more prevalent in young adults with coexisting type 1 diabetes mellitus and autoimmune thyroid disease compared with those with type 1 diabetes mellitus alone? Diabet Med 2002; 19: 334-337.
• 11. Evertsen J, Alemzadeh R, Xujing W. Incidence of pediatric type 1 diabetes mellitus in Southeastern Wisconsin: Relationship with body weight at diagnosis. Plos One 2009; 4: 873-877.
• 12. Taşkın E, Yılmaz E, Kılıç M, Ertuğrul S. İnsüline bağımlı diabetes mellitusun epidemiyolojik özellikleri. FÜ Sağ Bil Dergisi 2007; 21: 75-79.
• 13. Şimşek E, Karabay M, Kocabay K. Batı Karadeniz Bölgesinde yaşayan çocuklarda insüline bağımlı diabetes mellitusun epidemiyolojik özellikleri. Türk Pediatri Arşivi 2003; 38: 216- 222.
• 14. Kandemir N, Açikgöz E, Yordam N. The epidemiology of juvenile-onset insulin-dependent diabetes mellitus in Turkish children. A retrospective analysis of 477 cases. Turk J Pediatr 1994; 36: 191-195.
• 15. Diabetes Control and Complication Trial Research Group, The Effect of Intensive Treatment pof Diabetes on the developement and progression of Long-Term Complications in Insulin- Diependet Diabetes Mellitus. New Eng J of Medicine 329: 977- 986
• 16. Mortensen HB, Hougaard P (1997) Comparison of metaboliccontrol in a cross-sectional study of 2,873 children and adolescents with IDDM from 18 countries. The Hvidore study group on childhood diabetes. Diabetes Care 20: 714-720
• 17. Daneman D, Wolfson DH, Becker DJ, Drash AL. Factors affecting glycosylated hemoglobin values in children with insulin-dependent diabetes. J Pediatr 1981; 99: 847-853.
• 18. Kaufman FR, Halvorson M, Carpenter S. Association between diabetes control and visits to a multidisciplinary pediatric diabetes clinic. Pediatrics 1999; 103: 948-951.
• 19. Gerstl EM, Rabl W, Rosenbauer J, Gröbe H, Hofer SE, Krause U, Holl RW. Metabolic control as reflected by HbA1c in children, adolescents and young adults with type-1 diabetes mellitus: combined longitudinal analysis including 27,035 patients from 207 centers in Germany and Austria during the last decade. Eur J Pediatr 2008; 167: 447-453.
• 20. Davis AK, DuBose SN, Haller MJ, Miller KM, DiMeglio LA, Bethin KE, Goland RS, Greenberg EM, Liljenquist DR, Ahmann AJ, Marcovina SM, Peters AL, Beck RW, Greenbaum CJ; T1D Exchange Clinic Network. Prevalence of detectable C-Peptide according to age at diagnosis and duration of type 1 diabetes. Diabetes Care 2015; 38(3): 476-481.
• 21. Barker A, Lauria A, Schloot N, Hosszufalusi N, Ludvigsson J, Mathieu C, Mauricio D, Nordwall M, Van der Schueren B, Mandrup-Poulsen T, Scherbaum WA, Weets I, Gorus FK, Wareham N, Leslie RD, Pozzilli P. Age-dependent decline of β-cell function in type 1 diabetes after diagnosis: a multi-centre longitudinal study. Diabetes Obes Metab 2014; 16: 262-267.
• 22. Olsen BS, Johannesen J, Sjølie AK, Borch-Johnsen K, Hougarrdss P, Thorsteinsson B. Metabolic control and prevalence of microvascular complications in young Danish patients with Type 1 diabetes mellitus. Diabet Med 1999; 16: 79-85.
• 23. Salgado PP, Silva IN, Vieira EC, Simões e Silva AC J Pediatr Endocrinol Metab 2010; 23: 1311-1320.
• 24. Raile K, Galler A, Hofer S, Herbst A, Dunstheimer D, Busch P. Diabetic nephropathy in 27,805 children, adolescents, and adults with type 1 diabetes: effect of diabetes duration, A1C, hypertension, dyslipidemia, diabetes onset, and sex. Diabetes Care 2007; 30: 2523-2528.
• 25. Kong YH, Kim MS, Lee DY. Comparison of the prevalance of islet autoantibodies according to age disease duration in patients with type 1 diabetes mellitus. Ann Pediatr Endocrinol Metab 2013; 18: 65-70.
• 26. Demir F, Günöz H, Saka N, Darendeliler F, Bundak R, Baş F, Neyzi O. Epidemiologic features of type 1 diabetic patients between 0 and 18 years of age in Istanbul City. J Clin Res Pediatr Endocrinol 2015; 7: 49-56.
• 27. Kocabaş A, Aldemir Kocabaş B, Karagüzel G, Akçurin S. Tip 1 diabetes mellitus olgularımızın antropometrik ve metabolik izlem özelliklerinin değerlendirilmesi. Türkiye Çocuk Hastalıkları Dergisi 2013; 3: 113-118.
• 28. Lee, K. Factors associated with the development of anti-insulin antibody in diabetic children. J Korean Soc Pediat Endocrinol 2000, 5: 100-106.
• 29. Kordonouri O, Klinghammer A, Lang EB, Gruters-Keslich A, Grabert M, Holl RW. Thyroid autoimmunity in children and adolescents with type 1 diabetes. Diabetes Care 2002; 25: 1346- 1350.
• 30. Kim EY, Shin CH, Yang SW. Polymorphisms of HLA class II predispose children and adolescents with type 1 diabetes to autoimmune thyroid disease. Autoimmunity 2003; 36: 177- 181.
• 31. Rattarasarn C, Diosdado MA, Ortego J, Leelawattana R, Soonthornpun S, Setasuban W, Jaruratanasirikul S, Patarakijvanich N. Thyroid autoantibodies in Thai type 1 diabetic patients: clinical significance and their relationship with glutamic acid decarboxylase antibodies. Diabetes Res Clin Pract 2000; 49: 107-111.
• 32. Sara Derrou, Fayçal El Guendouz, Yousra Benabdelfedil, Imad Chakri, Hassan Ouleghzal, Somaya Safi. The profile of autoimmunity in Type 1 diabetes patients. Ann Afr Med 2021; 20: 19-23.
• 33. Kawasaki E. Type 1 diabetes and autoimmunity, department of diabetes and metabolisme, Nagasaki harbor medical center city hospital, Nagasaki Japon. Clin Pediate Endocrinol 2014; 23: 99-105.
• 34. Kahaly GJ, Hansen MP. Type 1 diabetes associated autoimmunity. Autoimmun Rev 2016; 15: 644-648.
• 35. Porandalaa S, Chitturia S, Sethia BK. Autoimmune thyroid disease in type 1 diabetes mellitus. Diabetes Res Clin Pract 2000; 50: 97-101.
• 36. Sharifi F, Ghasemi L, Mousavinasab N. Thyroid function and anti-thyroid antibodies in Iranian patients with type 1 diabetes mellitus: influences of age and sex. Iran J Allergy Immunol 2008; 7: 31-6.
• 37. Castaner M, Molina A, Jimenez-Lopez L, Gomez J, Soler J. Clinical presentation and early course of type 1 diabetes in patients with and without thyroid autoimmunity. Diabetes Care 1999; 22: 377-81.
• 38. Ardestani S, Keshteli A, Khalili N, Hashemipour M, Barekatain R. Thyroid disorders in children and adolescents with type 1 diabetes mellitus in Isfahan, Iran. Iran J Pediatr 2011; 21: 502- 508.
• 39. Prinz N, Tittel SR, Bachran R, Birnbacher R, Brückel J, Dunstheimer D, Haberland H, Hess M, Karges W, Oeverink R, Veigel A, Holl RW. Characteristics of Patients with Type 1 Diabetes and Additional Autoimmune Disease in the DPV Registry. J Clin Endocrinol Metab. 2021 Aug 18;106(9):e3381-e3389.
• 40. Barker JM, Yu J, Yu L, Wang J, Miao D, Bao F, Hoffenberg E, Nelson JC, Gottlieb PA, Rewers M, Eisenbarth GS. Autoantibody “subspecificity” in type 1 diabetes: risk for organ-specific autoimmunity clusters in distinct groups. Diabetes Care 2005; 28: 850-855.
• 41. Peretti N, Bienvenu F, Bouvet C, Fabien N, Tixier F, Thivolet C, Levy E, Chatelain PG, Lachaux A, Nicolino M. The temporal relationship betweenthe onset of type 1 diabetes and celiac disease: a study based on immunoglobulin A antitransglutaminase screening. Pediatrics 2004; 113: 418-422.
• 42. Karavanaki K, Kakleas K, Paschali E, Kefalas N, Konstantopoulos I, Petrou V, Kanariou M, Karayianni C. Screening for associated autoimmunity inchildren and adolescents with type 1 diabetes mellitus (T1DM). Horm Res 2009; 71: 201-206.
• 43. Djurić Z, Stamenković H, Stanković T, Milićević R, Branković L, Cirić V, Katić V. Celiac disease prevalence in children and adolescents with type1 diabetes from Serbia. Pediatr Int 2010; 52: 579-583.
• 44. Bhadada SK, Kochhar R, Bhansali A, Dutta U, Kumar PR, Poornachandra KS, Vaiphei K, Nain CK, Singh K. Prevalence and clinical profile of celiac disease in type 1 diabetes mellitus in north India. J Gastroenterol Hepatol 2011; 2: 378-381.
• 45. Gabriel S, Mihaela I, Angela B, Mariana A, Doru D. Prevalence of IgAantitissue transglutaminase antibodies in children with type 1 diabetesmellitus. J Clin Lab Anal 2011; 25: 156-161.
• 46. Rami B, Sumnik Z, Schober E, Waldhör T, Battelino T, Bratanic N, Kürti K, Lebl J, Limbert C, Madacsy L, Odink RJ, Paskova M, Soltesz G. Screening detected celiac disease in children with type 1 diabetes mellitus: effect on the clinical course (a case control study). J Pediatr Gastroenterol Nutr 2005; 41(3): 317- 321.
• 47. Picarelli A, Di Tola M, Sabbatella L, Mercuri V, Pietrobono D, Bassotti G, D’Amico T, Donato G, Picarelli G, Marino M, Borghini R, Centanni M, Gargiulo P. Type 1 diabetes mellitus and celiac disease: endothelial dysfunction. Acta Diabetol 2013; 50(4): 497-503.
• 48. Bakker SF, Tushuizen ME, von Blomberg ME, Mulder CJ, Simsek S. Type 1 diabetes and celiac disease in adults: glycemic control and diabetic complications. Acta Diabetol. 2013; 50: 319-324.
• 49. Amin R, Murphy N, Edge J, Ahmed ML, Acerini CL, Dunger DB. A longitudinal study of the effects of a gluten-free diet on glycemic control and weight gain in subjects with type 1 diabetes and celiac disease. Diabetes Care 2002; 25: 1117-1122.
• 50. Kota SK, Meher LK, Jammula S, Kota SK, Modi KD. Clinical profile of coexisting conditions in type 1 diabetes mellitus patients. Diabetes Metab Syndr 2012; 6: 70-76.
• 51. Kaspers S, Kordonouri O, Schober E. Anthropometric parameters, metabolic control and thyroid autoimmunity in 127 biopsy-positive children and adolescents with Type 1 diabetes and celiac disease compared to 18,470 diabetic subjects without celiac disease. A multicenter survey. Diabetologia 2003; 44: 232-233.
• 52. Strickland RG, Mackay I. A reappraisal of the nature and significance of chronic atrophic gastritis. Am J Dig Dis 1973; 18: 426-440.
• 53. Magzoub MM, Abdel-Hameed AA, Bottazzo GF. Prevalence of islet cell and thyrogastric autoantibodies in Sudanese patients with type 1 diabetes. Diabet Med 1994; 11: 188-192.
• 54. akleas K, Kostaki M, Critselis E, Karayianni C, Giannaki M, Anyfantakis K, Haramaras I, Fotinou A, Papathanasiou A, Karavanaki K. Gastric Autoimmunity in Children and Adolescents with Type 1 Diabetes: A Prospective Study. Horm Res Paediatr 2012; 77: 121-126.
• 55. Muhsen K, Barak M, Henig C, Alpert G, Ornoy A, Cohen D. Is the association between Helicobacter pylori infection and anemia age dependent? Helicobacter 2010; 15: 467-472.
• 56. Barker JM: Clinical review: type 1 diabetes associated autoimmunity: natural history, genetic association, and screening. J Clin Endocrinol Metab 2006; 9: 1210-1217.
• 57. Maggiore G, Bernard O, Homberg JC, Hadchouel M, Alvarez F, Hadchouel P, Odièvre M, Alagille D: Liver disease associated with anti-liver kidney microsome antibody in children. J Pediatr 1986; 108: 399-404.
• 58. Allen S, Huber J, Devendrac D: Prevalence of organ-specific autoantibodies in childhood- and adult-onset type 1 diabetes. Ann N Y Acad Sci 2008; 1150: 260-262.
• 59. Heras P, Mantzioros M, Mendrinos D, Heras V, Hatzopoulos A, Xourafas V, Kritikos K, Karagiannis S. Autoantibodies in type 1 diabetes. Diabetes Res Clin Pract 2010; 90: 40-42.
• 60. Al-Hussaını, Abdulrahman A. Autoimmune hepatitis related autoantibodies in children with type 1 diabetes. Diabetology & Metabolic Syndrome 2014; 6: 1-5.
• 61. Kahaly GJ. Polyglandular autoimmune syndromes. Eur J Endocrinol 2009; 161: 11-20.
• 62. Kakleas K, Soldatou A, Karachaliou F, Karavanaki K. Associated autoimmune diseases in children and adolescents with type 1 diabetes mellitus (T1DM). Autoimmun Rev 2015; 14: 781-797.
• 63. Förster G, Krummenauer F, Kühn I, Beyer J, Kahaly G. Polyglandular autoimmune syndrome type II: epidemiologyand forms of manifestation. Dtsch Med Wochenschr 1999; 124: 1476-1481.
• 64. Ben-Skowronek I, Michalczyk A, Piekarski R, WysockaŁukasik B, Banecka B. Type III Polyglandular Autoimmune Syndromes in children with type 1 diabetes mellitus. Ann Agric Environ Med 2013; 20: 140-146.
• 65. Prinz N, Tittel SR, Bachran R, Birnbacher R, Brückel J, Dunstheimer D, Haberland H, Hess M, Karges W, Oeverink R, Veigel A, Holl RW. Characteristics of Patients with Type 1 Diabetes and Additional utoimmune Disease in the DPV Registry. J Clin Endocrinol Metab 2021;10.