Prevalence of β-cell antibodies and associated autoimmune diseases in children and adolescents with type 1 diabetes (T1DM) versus type 2 diabetes (T2DM) in Qatar

Fawzia Alyafei, Ashraf Soliman, Fawziya Alkhalaf, Aml Sabt, Vincenzo De Sanctis, Nagwa Elsayed, Reem Waseef, Fawzia Alyafei, Ashraf Soliman, Fawziya Alkhalaf, Aml Sabt, Vincenzo De Sanctis, Nagwa Elsayed, Reem Waseef

Abstract

Introduction: Type 1 diabetes mellitus (T1DM) is an autoimmune disease with the development of abnormal immune responses to specific β-cell autoantigens in addition to other organ-specific autoimmunity. The most frequent associated disorders are thyroid dysfunctions and celiac disease. There are limited studies in the current literature on the prevalence of associated autoimmunity, especially multiple, in children and adolescents with T1DM and Type 2 diabetes mellitus (T2DM).

Objectives: The aim of the present study was to determine the prevalence of autoantibodies and thyroid dysfunctions in a cohort of children and adolescents (aged 0.5-16 years) with T1DM living in Qatar.

Research design and methods: The records of all children and adolescents attending the Pediatric Diabetes Center of Hamad Medical Center, for the past 5 years (from January 2012 to December 2016), were reviewed and all clinical and biochemical data, including β-cell autoimmunity [anti-glutamic acid decarboxylase (GAD) antibodies, anti-islet cell and anti-insulin antibodies (IAA)], thyroid function (Free thyroxine: FT4 and thyroid-stimulating hormone: TSH), anti-thyroid peroxidase antibodies (TPO) and anti-tissue transglutaminase (ATT) were collected at their first presentation (cross-sectional study). Data for patients with T1DM (n=431) and T2DM (n=59) were recorded analyzed and the prevalence calculated and compared with other studies.

Results: The prevalence of anti-GAD antibodies was 75.5 % in T1DM and 29.3% in T2DM. Anti β-islet antibodies (Ab) were detected in 53.4% of T1DM and 29.4% of T2DM. Anti-insulin Ab were detected in 40.4% of T1DM and 58.3% of T2DM. The three antibodies together were detected in 18.4 % of T1DM and none of T2DM. At presentation, hypothyroidism (FT4 <11.5 pmol/L) was detected in 10.6% of T1DM and 10% of T2DM. Subclinical hypothyroidism was diagnosed in 3.5% of T1DM and 8% of T2DM. High anti TPO was detected in 27.2% of T1DM and 34.6% of T2DM. High TPO with normal thyroid function were found in 22.7% of T1DM and 23.1% of T2DM. ATT IgA was high in 5% of T1DM and 8.7% of T2DM whereas ATT IgG was high in 4.4 % of T1DM and not detected in any patient with T2DM. Mucosal biopsy proved celiac disease in 9 out of 12 patients (75%) with positive ATT IgA and IgG antibodies.

Conclusions: Qatar has a relatively high incidence of T1DM compared to incidences reported worldwide. The incidence increased over the period 2012-2015. We report a high prevalence of associated autoimmune abnormalities in our patients with T1DM and T2DM. These data strengthen the argument for routine screening of all children and adolescents with T1DM and T2DM for other autoimmune disorders, particularly the thyroid gland.

Figures

Figure 1.
Figure 1.
Prevalence of autoantibodies in children and adolescents with T1DM and T2DM in Qatar and their family history of DM
Figure 2.
Figure 2.
Suggested clinical classification for DM types and subtypes in children and adolescents

References

    1. Soltesz G, Patterson CC, Dahlquist G. EURODIAB Study Group. Worldwide childhood type 1 diabetes incidence--what can we learn from epidemiology? Pediatr Diabetes. 2007;8(Suppl 6):6–14.
    1. EURODIAB ACE Study Group. Variation and trends in incidence of childhood diabetes in Europe. Lancet. 2000;355:873–6.
    1. Jahromi MM, Eisenbarth GS. Cellular and molecular pathogenesis of type 1A diabetes. Cell Mol Life Sci. 2007;64:865–72.
    1. The DIAMOND Project Group. Incidence and trends of childhood Type 1 diabetes worldwide 1990–1999. Diab Med. 2006;23:857–66.
    1. Burek CL, Rose NR, Guire KE, Hoffman WH. Thyroid autoantibodies in black and in white children and adolescents with type 1 diabetes mellitus and their first degree relatives. Autoimmunity. 1990;7:157–67.
    1. Roldan MB, Alonso M, Barrio R. Thyroid autoimmunity in children and adolescents with type 1 diabetes mellitus. Diab Nutr Metab. 1999;12:27–31.
    1. Radetti G, Paganini C, Gentili L, Bernasconi S, Betterle C, Borkenstein M, Cvijovic K, Kadrnka-Lovrencic M, Krzisnik C, Battelino T. Frequency of Hashimoto’s thyroiditis in children with type 1 diabetes mellitus. Acta Diabetol. 1995;32:121–4.
    1. Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE, Serum TSH. T4 and thyroid antibodies in the United States population (1988 to 1994): national health and nutrition examination survey. J Clin Endocrinol Metab. 2002;87:489–99.
    1. Tunbridge WM, Evered DC, Hall R, Appleton D, Brewis M, Clark F, Evans JG, Young E, Bird T, Smith PA. The spectrum of thyroid disease in a community: the Whickham survey. Clin Endocrinol. 1977;7:481–93.
    1. Witting V, Bergis D, Sadet D, Badenhoop K. Thyroid disease in insulin-treated patients with type 2 diabetes: a retrospective study. Thyroid Res. 2014 Mar 1;7(1):2.
    1. Pozzilli P, Buzzetti R. A new expression of diabetes: double diabetes. Trends Endocrinol Metab. 2007;18:52–7.
    1. Pozzilli P, Guglielmi C, Pronina E, Petraikina E. Double or hybrid diabetes associated with an increase in type 1 and type 2 diabetes in children and youths. Pediatr Diabetes. 2007;8(Suppl 9):88–95.
    1. Pozzilli P, Guglielmi C. Double diabetes: a mixture of type 1 and type 2 diabetes in youth. Endocr Dev. 2009;14:151–66.
    1. Sang-Youl R, Young-Seol Kim. Double Diabetes. Korean Diabetes J. 2009;33:1–8.
    1. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care. 2003;26(Suppl 1):S5–S20.
    1. Yoo EG, Shin HJ, Kim DH. The clinical types and characteristics of diabetes mellitus in Korean children. J Korean Pediatr Soc. 2000;43:1591–8.
    1. Atkinson MA, Eisenbarth GS, Michels AW. Type 1 diabetes. Lancet. 2014;383:69–82.
    1. Lee CW, Shin HJ, Kim DH. Prevalence of autoimmune antibodies in type i diabetic children and their siblings. J Korean Soc Pediatr Endocrinol. 1999;4:78–87.
    1. Betterle C, Lazzarotto F, Fusari A, Zanchetta R, Benedini S, Pedini B, Moscon A, Presotto F. Pancreatic autoantibodies in Italian patients with newly diagnosed type 1 diabetes mellitus over the age of 20 years. Acta Diabetol. 2006;43:79–83.
    1. Lee SH, Yoon JS, Eun MJ, Kim JH, Park YH, Won KC. Five year follow-up of ICA and GADA in childhood onset type 1 DM. J Korean Diabetes Assoc. 2003;27:395–404.
    1. Park YS. Prospective follow-up of autoantibody prevalences in patients with type 1 diabetes. J Korean Diabetes Assoc. 2003;27:391–4.
    1. Decochez K, Tits J, Coolens JL, Van Gaal L, Krzentowski G, Winnock F, Anckaert E, Weets I, Pipeleers DG, Gorus FK. High frequency of persisting or increasing islet-specific autoantibody levels after diagnosis of type 1 diabetes presenting before 40 years of age. The Belgian Diabetes Registry. Diabetes Care. 2000;23:838–44.
    1. D’Adamo E, Caprio S. Type 2 Diabetes in Youth: Epidemiology and Pathophysiology. Diabetes Care. 2011;34(Supplement 2):S161–S5.
    1. Defronzo RA. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009;58:773–95.
    1. Zimmet PZ, Tuomi T, Mackay IR, Rowley MJ, Knowles W, Cohen M, Lang DA. 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.
    1. Umpaichitra V, Banerji MA, Castells S. Autoantibodies in children with type 2 diabetes mellitus. J Pediatr Endocrinol Metab. 2002;15(Suppl 1):525–30.
    1. Kaufman F. ‘Double diabetes’ in young people and how to treat it. Diabetes Voice. 2006;51:19–22.
    1. Hathout EH, Thomas W, El-Shahawy M, Nahab F, Mace JW. Diabetic autoimmune markers in children and adolescents with type 2 diabetes. Pediatrics. 2001;107:E102.
    1. Evia-Viscarra ML, Guardado-Mendoza R, Rodea-Montero ER. Clinical and Metabolic Characteristics among Mexican Children with Different Types of Diabetes Mellitus. Pietropaolo M. PLoS ONE. 2016;11(12):e0168377.
    1. von Oettingen JE, Wolfsdorf JI, Feldman HA, Rhodes ET. Utility of diabetes-associated autoantibodies for classification of new onset diabetes in children and adolescents. Pediatr Diabetes. 2016;17:417–25.
    1. Libman IM, Becker DJ. Coexistence of type 1 and type 2 diabetes. mellitus: “double” diabetes? Pediatr Diabetes. 2003;4:110–3.
    1. Nwosu BU. Double Diabetes: The Evolving Treatment Paradigm in Children and Adolescents. Vitam Trace Elem. 2013;2:e118.
    1. Umpierrez GE, Latif KA, Murphy MB, Lambeth HC, Stentz F, Bush A, Kitabchi AE. Thyroid dysfunction in patients with type 1 diabetes: a longitudinal study. Diabetes Care. 2003;26:1181–5.
    1. Kordonouri O, Klinghammer A, Lang EB, Grüters-Kieslich A, Grabert M, Holl RW. Thyroid autoimmunity in children and adolescents with type 1 diabetes: a multicenter survey. Diabetes Care. 2002;25:1346–50.
    1. Mantovani RM, Mantovani LM, Dias VM. Thyroid autoimmunity in children and adolescents with type 1 diabetes mellitus: prevalence and risk factors. J Pediatr Endocrinol Metab. 2007;20:669–75.
    1. Hanukoglu A, Mizrachi A, Dalal I, Admoni O, Rakover Y, Bistritzer Z, Levine A, Somekh E, Lehmann D, Tuval M, Boaz M, Golander A. Extrapancreatic autoimmune manifestations in type 1 diabetes patients and their first-degree relatives: a multicenter study. Diabetes Care. 2003;26:1235–40.
    1. Ardestani SK, Keshteli AH, Khalili N, Hashemipour M, Barekatain R. Thyroid Disorders in Children and Adolescents with Type 1 Diabetes Mellitus in Isfahan, Iran. Iran J Pediatr. 2011;21:502–8.
    1. Mantovani RM, Mantovani LM, Dias VM. Thyroid autoimmunity in children and adolescents with type 1 diabetes mellitus: prevalence and risk factors. J Pediatr Endocrinol Metab. 2007;20:669–75.
    1. Kordonouri O, Klinghammer A, Lang EB, Grüters-Kieslich A, Grabert M, Holl RW. Thyroid Autoimmunity in Children and Adolescents With Type 1 Diabetes. Diabetes Care. 2002;25:1346–50.
    1. Jung ES, Han DK, Yang EM, Kim MS, Lee D-Y, Kim CJ. Thyroid autoimmunity in children and adolescents with newly diagnosed type 1 diabetes mellitus. Ann Pediatr Endocrinol Metab. 2014;19:76–9.
    1. Orzan A, Novac C, Mihu M, Tirgoviste CI, Balgradean M. Type 1 Diabetes and Thyroid Autoimmunity in Children. Mædica (Buchar) 2016;11:308–12.
    1. Kakleas K, Paschali E, Kefalas N, Fotinou A, Kanariou M, Karayianni C, Karavanaki K. Factors for thyroid autoimmunity in children and adolescents with type 1 diabetes mellitus. Ups J Med Sci. 2009;114:214–20.
    1. Perros P, McCrimmon RJ, Shaw G, Frier BM. Frequency of thyroid dysfunction in diabetic patients: value of annual screening. Diabet Med. 1995;12:622–7.
    1. Vanderpump MP, Tunbridge WM, French JM, Appleton D, Bates D, Clark F, Grimley Evans J, Hasan DM, Rodgers H, Tunbridge F. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol (Oxf) 1995;43:55–68.
    1. Severinski S, Banac S, Severinski NS, Ahel V, Cvijović K. Epidemiology and clinical characteristics of thyroid dysfunction in children and adolescents with type 1 diabetes. Coll Antropol. 2009;33:273–9.
    1. Rai S, Kumar J A K P, Shetty SK, Rai T, Shrinidhi, Begum M, Shashikala Thyroid function in type 2 diabetes mellitus and in diabetic nephropathy. J Clin Diagn Res. 2013;7:1583–5.
    1. Krzewska A, Ben-Skowronek I. Effect of Associated Autoimmune Diseases on Type 1 Diabetes Mellitus Incidence and Metabolic Control in Children and Adolescents. Biomed Res Int. 2016;2016:6219730.

Source: PubMed

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