Type I Diabetes Mellitus among Children and Adolescent in Sulaimaniyah City, Iraq

Authors

  • Khelan Saeed Hama Amin Charmo Research Center, Charmo University, Chamchamal, Kurdistan Region, Iraq. Author
  • Karzan Jalal Salih Pharmaceutical Chemistry Department, College of Medical and Applied Science, University of Charmo, Chamchamal, Kurdistan Region, Iraq. Author
  • Dlzar Dlshad Ghafoor Medical Laboratory Science Department, Komar University of Science and Technology, Sulaimani, Kurdistan Region, Iraq. & Chemistry Department, College of Science, University of Sulaimani, Kurdistan Region, Iraq. Author

DOI:

https://doi.org/10.17656/jzs.10916

Keywords:

GADA, ICA, IA2A, IAA, risk factors, TIDM

Abstract

Diabetes mellitus type I is an autoimmune disorder in which pancreatic β cell autoantibodies are the most significant immunological markers. In this study, we investigated the prevalence of antibodies GADA, IAA, IA2A, and ICA. Seventy-seven patients were selected for the study and another 93 healthy controls were studied. Autoantibodies were measured in the serum samples obtained from both patients and the control group using enzyme-linked immunosorbent assay (ELISA). According to the results of this study, there was a significant difference in the level of GAD65 when the patient group was compared to the control. The mean value for the GAD in the control group was 2.095±0.89, while in patient groups it was 3.56±3.95 ng/ml, and they were significantly different (p<0.01). A qualitative measurement for both antibodies ICA and IA2A showed a positive result in more than 50% of the patients while ICA was positive in 12% of the control groups and IA2A was positive in 1.3% in the control group. Qualitative assessment of the IAA antibodies revealed that 32.8% were positive, while all healthy subjects were negative. Fasting C-peptide level in the patient group was 0.745±0.12 ng/ml while it was 2.12±0.48 ng/ml in healthy subjects. HbA1C level in patients was 10.46±2.27 while it was 5.38±0.24 in healthy subjects. The risk factors, maternal status, and children’s status effect on the development of diabetes were studied and it was found that a significant difference (p<0.05) when a family history of DM was compared with patient and control groups, while there was not significant difference found between both groups when a family history of other autoimmune diseases was compared. Neonatal diseases between both groups were compared and no significant difference was observed as well. From the result of this study, it can be concluded that environmental risk factors such as obesity, family history of DM may play a significant role in triggering the immune system and leading to beta cells destruction, while ethnic background, geography, maternal obesity, maternal diseases, infections during pregnancy, neonatal diseases such as jaundice, thyroid, vitiligo, and celiac are not regarded as a potential risk factor in developing the disease. More than 90% of T1D individuals tested positive for autoantibodies. The most often found autoantibodies were IA2A and GADA. Antibodies were much more prevalent in female children.

References

American Diabetes Association. (2009). Diagnosis and classification of diabetes mellitus. Diabetes Care. DOI: https://doi.org/10.2337/dc09-S062

(SUPPL. 1):62–7.

Cannon MJ, Masalovich S, Ng BP, Soler RE, Jabrah R, Ely EK, Smith BD. (2020). Retention Among

Participants in the National Diabetes Prevention Program Lifestyle Change Program, 2012–2017. Diabetes

Care.43(9):2042–9.

Vicki M. Aalborg Universitet. (2019). Diabetes mellitus and cardiovascular disease Identification of

prognostic factors for ischaemic stroke and myocardial infarction. PhD Dissertation, Department of Clinical

Medicine, Aalborg University, Denmark.

Hodge AM, Jenkins AJ, English DR, O’Dea K, Giles GG. (2009). NMR-determined lipoprotein subclass

profile predicts type 2 diabetes. Diabetes Research and Clinical Practice.83(1):132–9.

Simmons KM, Youngkin E, Alkanani A, Miao D, McDaniel K, Yu L & Michels AW. (2019). Screening

children for type 1 diabetes-associated antibodies at community health fairs’. Pediatric Diabetes. 20(7):909– DOI: https://doi.org/10.1111/pedi.12902

Davids SFG, Matsha TE, Peer N, Erasmus RT, Kengne AP. (2020). The 7-Year Change in the Prevalence DOI: https://doi.org/10.1155/2020/3781214

of Insulin Resistance, Inflammatory Biomarkers, and Their Determinants in an Urban South African

Population. Journal of Diabetes Research. (1) :1-11.

Jones AG, Hattersley AT. (2013). The clinical utility of C-peptide measurement in the care of patients with DOI: https://doi.org/10.1111/dme.12159

diabetes. Diabetic Medicine.30(7):803–17.

Dormoy Y, Candau S. (1991). Transient electric birefringence study of highly dilute agarose solutions. DOI: https://doi.org/10.1002/bip.360310110

Biopolymers, Original Research on Biomolecules.31(1):109-17.

Yosten GLC, Maric-Bilkan C, Luppi P, Wahren J. (2014). Physiological effects and therapeutic potential of DOI: https://doi.org/10.1152/ajpendo.00130.2014

proinsulin C-peptide. American Journal of Physiology-Endocrinology and Metabolism.307(11):955–68.

Polonsky KS, Licinio-Paixao J, Given BD, Pugh W, Rue P, Galloway J, Karrison T, Frank B. (1986). Use

of Biosynthetic Human C-peptide in the Measurement of Insulin Secretion Rates in Normal Volunteers and

Type I Diabetic Patients. The Journal of Clinical Investigation.77(1):98–105.

Awdeh ZL, Yunis EJ, Audeh MJ, Fici D, Pugliese A, Larsen CE, Alper CA. (2006). A genetic explanation

for the rising incidence of type 1 diabetes, a polygenic disease. Journal of Autoimmunity.27(3):174–81. DOI: https://doi.org/10.1016/j.jaut.2006.08.004

Borchers AT, Uibo R, Gershwin ME. (2010). The geoepidemiology of type 1 diabetes. Autoimmunity DOI: https://doi.org/10.1016/j.autrev.2009.12.003

reviews. 9(5):A355–65.

Boettler T, von Herrath M. (2011). Protection against or triggering of Type 1 diabetes? Different roles for DOI: https://doi.org/10.1586/eci.10.91

viral infections. Expert Review of Clinical Immunology. 7(1):45–53.

Luopajärvi K, Savilahti E, Virtanen SM, Ilonen J, Knip M, Akerblom HK, Vaarala O. (2008). Enhanced

levels of cow’s milk antibodies in infancy in children who develop type 1 diabetes later in childhood. Pediatric

Diabetes.9(5):434–41.

Ziegler AG, Bonifacio E. (2020). Why is the presence of autoantibodies against GAD associated with a

relatively slow progression to clinical diabetes? Diabetologia. 63(8):1665–6.

Stanworth DR, Jones VM, Lewin I V., Aayyar S. (1990). Allergy treatment with a peptide vaccine. The DOI: https://doi.org/10.1016/0140-6736(90)92963-I

Lancet. 336(8726):1279–81.

O’Sullivan-Murphy B, Urano F. (2012). ER stress as a trigger for b-cell dysfunction and autoimmunity in DOI: https://doi.org/10.2337/db12-0091

type 1 diabetes. Diabetes. 61(4):780–1.

Baekkeskov S, Aanstoot HJ, Christgau S, Reetz A, Solimena M, Cascalho M, Folli F, Richter-Olesen H,

Camilli PD. (1990). Identification of the 64K autoantigen in insulin-dependent diabetes as the GABA-

synthesizing enzyme glutamic acid decarboxylase. Nature. 347(6289):151–6.

Baekkeskov S, Landin M, Kristensen JK, Srikanta S, Bruining GJ, Mandrup-Poulsen T& De Beaufort C,

Soeldner JS, Eisenbarth G, Lindgren F. (1987). Antibodies to a 64,000 M(r) human islet cell antigen precede

the clinical onset of insulin-dependent diabetes. The Journal of Clinical Investigation. 79(3):926–34.

Solimena M, Butler MH, De Camilli P. (1994). GAD, diabetes, and Stiff-Man syndrome: Some progress DOI: https://doi.org/10.1007/BF03347745

and more questions. Journal of Endocrinological Investigation.17(7):509–20.

Kass I, Hoke DE, Costa MGS, Reboul CF, Porebski BT, Cowieson NP, Leh H, Pennacchietti E, McCoey

J, Kleifeld O, Borri Voltattorni C. (2014). Cofactor-dependent conformational heterogeneity of GAD65 and

its role in autoimmunity and neurotransmitter homeostasis. Proceedings of the National Academy of

Science.111(25):2524–29.

Mally MI, Cirulli V, Otonkoski T, Soto G, Hayek A. (1996). Ontogeny and tissue distribution of human DOI: https://doi.org/10.2337/diab.45.4.496

GAD expression. Diabetes.45(4):496–501.

Palmer JP, Asplin CM, Clemons P, Lyen K, Tatpati O, Raghu PK, Paquette TL. (1983). Insulin antibodies

in insulin-dependent diabetics before insulin treatment. Science .222(4630):1337–39. DOI: https://doi.org/10.1126/science.6362005

Ziegler AG, Vardi P, Gross DJ, Villa-komaroff L, Halban PA, Ikegami H & Soeldner JS, Eisenbarth GS.

(1989). Production of Insulin Antibodies by Mice Rejecting Insulin Transfected Cells. Journal of

Autoimmunity.2(3):219–27.

Pugliese A, Bugawan T, Moromisato R, Awdeh ZL, Alper CA, Jackson RA& Erlich HA, Eisenbarth GS.

(1994). Two Subsets of HLA-DQA1 Alleles Mark Phenotypic Variation in Levels of Insulin Autoantibodies

in First Degree Relatives at Risk for Insulin-dependent Diabetes. The Journal of Clinical Investigation.;

(6):2447–52.

Achenbach P, Koczwara K, Knopff A, Naserke H, Ziegler AG, Bonifacio E. (2004). Mature high-affinity

immune responses to (pro)insulin anticipate the autoimmune cascade that leads to type 1 diabetes. The Journal

of Clinical Investigation.114(4):589–97.

Solimena M, Dirkx R, Hermel JM, Pleasic-Williams S, Shapiro JA, Caron L& Rabin DU. (1996). ICA

, an autoantigen of type I diabetes, is an intrinsic membrane protein of neurosecretory granules. The

European Molecular Biology Organization Journal.15(9):2102–14.

Wijesekara N, Chimienti F, Wheeler MB. (2009). Zinc, a regulator of islet function and glucose DOI: https://doi.org/10.1111/j.1463-1326.2009.01110.x

homeostasis. Diabetes, Obesity and Metabolism.11(SUPPL. 4):202–14.

Bingley PJ, Christie MR, Bonifacio E, Bonfanti R, Shattock M, Fonte MT& Bottazzo GF, Gale EA. (1994).

Combined analysis of autoantibodies improves prediction of IDDM in islet cell antibody-positive relatives.

Diabetes.43(11):1304–10.

Notkins AL, Lernmark Å. (2001). Autoimmune type 1 diabetes: Resolved and unresolved issues. The DOI: https://doi.org/10.1172/JCI14257

Journal of Clinical Investigation.108(9):1247–52.

Atkinson MA, Maclaren NK. (1994). The Pathogenesis of Insulin-Dependent Diabetes Mellitus. New

England Journal of Medicine. 331(21), 1428–36

Chmiel R, Beyerlein A, Knopff A, Hummel S, Ziegler AG, Winkler C. (2015). Early infant feeding and

risk of developing islet autoimmunity and type 1 diabetes. Acta Diabetologica.52(3):621–4.

Weenink SM, Lo J, Stephenson CR, McKinney PA, Ananieva-Jordanova R, Rees Smith B& Furmaniak J,

Tremble JM, Bodansky HJ, Christie MR. (2009). Autoantibodies and associated T-cell responses to

determinants within the 831-860 region of the autoantigen IA-2 in Type 1 diabetes. Journal of

Autoimmunity.33(2):147–54.

Korneva KG, Strongin LG, Kolbasina E V., Budylina M V., Makeeva N V., Zagainov VE. (2020).

Diagnostic capabilities of islet autoantibodies in children with new-onset type 1 diabetes mellitus and healthy

siblings. Sovremennye Tehnologii v Medicine.12(6):29–35.

Kotani T, Umeki K, Matsunaga S, Kato E, Ohtaki S. (1986). Detection of autoantibodies to thyroid

peroxidase in autoimmune thyroid diseases by micro-ELISA and immunoblotting. The Journal of Clinical

Endocrinology & Metabolism.;62(5):928–33.

Al-Mendalawi MD. (2017). Challenges facing optimum care of diabetic children in Iraq. Indian Journal DOI: https://doi.org/10.4103/ijem.IJEM_122_17

of Endocrinology and Metabolism.21(4):642–3.

Cheng BW, Lo FS, Wang AM, Hung CM, Huang CY, Ting WH & Yang MO, Lin CH, Chen CC, Lin CL,

Wu YL. (2018). Autoantibodies against islet cell antigens in children with type 1 diabetes mellitus.

Oncotarget.;9(23):16275–83.

Crowe A, Lemaire M. Invitro and in situ absorption of SDZ-RAD using a human intestinal cell line

(Caco-2) and a single pass perfusion model in rats: comparison with rapamycin. Pharmaceutical

Research. 15(11):1666–72.

Knip M, Korhonen S, Kulmala P, Veijola R, Reunanen A, Raitakari OT & Viikari J, Åkerblom HK. (2010).

Prediction of type 1 diabetes in the general population. Diabetes Care.33(6):1206–12. DOI: https://doi.org/10.2337/dc09-1040

Winter WE, Schatz DA. (2011). Autoimmune markers in diabetes. Clinical chemistry.57(2):168–75. DOI: https://doi.org/10.1373/clinchem.2010.148205

Plagnol V, Howson JM, Smyth DJ, Walker N, Hafler JP, Wallace C & Stevens H, Jackson L, Simmonds

MJ, Type 1 Diabetes Genetics Consortium, Bingley PJ. (2011). Genome-wide association analysis of

autoantibody positivity in type 1 diabetes cases. PLoS Genetics.7(8):1002216. DOI: https://doi.org/10.1371/journal.pgen.1002216

Rubtsov A V., Rubtsova K, Kappler JW, Marrack P. (2010). Genetic and hormonal factors in femalebiased autoimmunity. Autoimmunity reviews. 9(7):494–8. DOI: https://doi.org/10.1016/j.autrev.2010.02.008

Libman IM, Pietropaolo M, Arslanian SA, LaPorte RE, Becker DJ. (2003). Changing prevalence of

overweight children and adolescents at onset of insulin-treated diabetes. Diabetes Care.26(10):2871–5. DOI: https://doi.org/10.2337/diacare.26.10.2871

Bonifacio E, Hummel M, Walter M, Schmid S, Ziegler AG. (2004). IDDM1 and multiple family history

of type 1 diabetes combine to identify neonates at high risk for type 1 diabetes. Diabetes Care.;27(11):2695– DOI: https://doi.org/10.2337/diacare.27.11.2695

Published

2023-12-20

How to Cite

Type I Diabetes Mellitus among Children and Adolescent in Sulaimaniyah City, Iraq. (2023). Journal of Zankoy Sulaimani - Part A, 25(2), 14. https://doi.org/10.17656/jzs.10916