|Year : 2016 | Volume
| Issue : 2 | Page : 233-237
The seroprevalence of immunoglobulin A transglutaminase in type 1 diabetic patients of South Indian origin
Annie A Pulikkal1, Anish Kolly1, KM Prasanna Kumar2, C Shivaprasad1
1 Department of Endocrinology and Metabolism, Vydehi Institute of Medical Sciences, Bengaluru, Karnataka, India
2 Department of Endocrinology, BDH and CDEC, Bengaluru, Karnataka, India
|Date of Web Publication||15-Feb-2016|
Department of Endocrinology and Metabolism, Vydehi Institute of Medical Sciences and Research, No. 82, Nallurahalli, Near BMTC, 18th Depot, Whitefield, Bengaluru - 560 066, Karnataka
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Context: Celiac disease (CD) is a commonly encountered autoimmune condition in patients with type 1 diabetes (T1D). There is sparse data on the seroprevalence of immunoglobulin A (IgA) transglutaminase (tTG) in T1D patients of South Indian origin. Aims: To detect the prevalence of IgA tTG in T1D patients of South Indian origin. To evaluate the relation between the presence of autoimmunity and metabolic control and complications of diabetes. Materials and Methods: We conducted a cross-sectional study on 258 T1D patients. All the patients were subjected to biochemical tests and evaluated for microvascular complications. IgA tTG was estimated by ELISA. IgA tTG levels >40 AU/ml was considered positive. Results: Of the 258 participants, 12 (4.65%) were found to be positive for IgA tTG antibodies. Distribution of IgA positivity was equal in both sexes. There was a significant negative correlation of IgA tTG positivity with hemoglobin and glycated hemoglobin (HbA1c). Conclusions: The seropositivity of CD in South Indian patients with T1D has been observed to be 4.68%. This is much lower compared to studies from North India. This can be explained by both the genetic and dietary factors. The seropositivity correlated negatively with hemoglobin and HbA1c.
Keywords: Autoimmunity, celiac, gluten, malabsorption, type 1 diabetes
|How to cite this article:|
Pulikkal AA, Kolly A, Prasanna Kumar K M, Shivaprasad C. The seroprevalence of immunoglobulin A transglutaminase in type 1 diabetic patients of South Indian origin. Indian J Endocr Metab 2016;20:233-7
|How to cite this URL:|
Pulikkal AA, Kolly A, Prasanna Kumar K M, Shivaprasad C. The seroprevalence of immunoglobulin A transglutaminase in type 1 diabetic patients of South Indian origin. Indian J Endocr Metab [serial online] 2016 [cited 2020 May 30];20:233-7. Available from: http://www.ijem.in/text.asp?2016/20/2/233/176359
| Introduction|| |
Celiac disease (CD) is a commonly encountered autoimmune condition in patients with type 1 diabetes (T1D). The prevalence of CD in T1D in various study ranges from 3% to 16%.,,,, Nearly, 98% of the patients with CD express human leukocyte antigen (HLA)-DQ2 or DQ8 haplotype., Around 10–15% of patients with T1D express the highly specific serological markers of celiac CD including autoantibodies to endomysium or tissue transglutaminase (tTG). The majority of the patients are asymptomatic or do not have symptoms severe enough to seek medical attention. The co-occurrence of both diseases can be explained by a shared genetic background and similar trigger mechanisms for the autoimmune processes.,,,
The seropositivity of immunoglobulin A (IgA) tTG in T1D patients of North Indian origin has been reported to be 8–22%., However, there is sparse data on the seroprevalence of IgA tTG in T1D patients of South Indian origin. We have undertaken this study to detect the prevalence of IgA tTG in T1D patients of South Indian origin and to evaluate the relation between the presence of autoimmunity and metabolic control and complications of diabetes.
| Materials and Methods|| |
The present cross-sectional study was conducted at two centers - Vydehi Institute of Medical sciences and Research Centre, Bengaluru, and Bangalore Diabetes Hospital, Bengaluru. The study was conducted over a period of 2 years, from August 2013 to July 2015. A total of 258 consecutive patients who were diagnosed with diabetes before the age of 18 years, as per the American Diabetes Association criteria, and WHO were classified as T1D based on clinical grounds were recruited for the study.
- Patients with acute illnesses
- Patients with diabetic ketoacidosis
- History of alcohol abuse
- Evidence of pancreatic calcifications
- Patients with other known causes of malabsorption.
A detailed history was taken with emphasis on dietary habits, along with a comprehensive physical examination with emphasis on anthropometry. All patients were subjected to biothesiometry, fundus examination, and biochemical tests which included fasting plasma glucose, glycated hemoglobin (HbA1c), serum calcium, serum albumin, thyroid stimulating hormone, and urine microalbumin estimation. Written informed consent was taken from the parents or from the patient as deemed appropriate, based on the age of the patient. Institutional ethical committee clearance was taken from both the centers.
IgA tTG was estimated using commercially available ELISA kits from Diametra Diagnostics, Italy.
Principle of the test
Antitissue tTG IgA test is based on the binding of serum or plasma antibodies on the human recombinant tissue tTG coated into the microplates. An anti-human IgA horseradish peroxidase conjugate solution recognizes IgA class antibodies bound to the immobilized antigens. A chromogenic substrate solution containing 3,3', 5, 5'-tetramethylbenzidine is dispensed into the wells. The solution's color changes into yellow. The amount of color is directly proportional to the concentration of IgA antibodies present in the original sample. IgA tTG value >40 AU/ml was considered as positive.
Data were reported using mean and standard deviation for the continuous variables, number, and percentages for the categorical variables. Independent t-test or Mann-Whitney U-test was used to compare the mean values of various clinical parameters between IgA tTG positive and negative groups. Spearman's Rank correlation was performed to assess the relationship between variables. Logistic regression analysis was performed to assess the factors associated with IgA positivity. All the analysis were analyzed using SPSS Inc. Released 2009. PASW Statistics for Windows, Version 18.0. Chicago. P < 5% was considered statistically significant.
| Results|| |
The study was carried out from August 2013 to July 2015 and included a total of 258 patients of T1D. The male to female ratio was 1.13 (137 males and 121 females). The mean duration of diabetes was 4.88 years (range: 0.6–18 years). Diabetic retinopathy was present in seven participants and diabetic peripheral neuropathy in one participant. None of the patients had diabetic nephropathy. Concomitant primary hypothyroidism was present in 19 participants, and all of them were on replacement with thyroxine. A positive family history was seen in one participant, where the father had T1D. The baseline anthropometric and biochemical characteristics of the study cohort are shown in [Table 1].
Of the 258 participants, 12 (4.65%) were found to be positive for IgA tTG antibodies [Figure 1]. Distribution of IgA positivity was equal in both sexes with six positives in each group. None of the positives had symptoms suggestive of CD.
|Figure 1:Seropositivity of immunoglobulin A transglutaminase in the study group|
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There was a significant negative correlation of IgA tTG positivity with hemoglobin [Table 2]. A negative correlation was also seen with HbA1c levels. Comparison between the two groups of IgA positivity and negativity showed patients with positive IgA tTG levels had lower hemoglobin (−0.125) and HbA1c (−0.161) [Table 3]. In multistep regression analysis, the same two variables were found to have significant association with IgA tTG positivity [Table 4].
|Table 2: Correlation between immunoglobulin A tissue transglutaminase positivity and anthropometric and biochemical variables|
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|Table 3: Comparison of parameters between immunoglobulin A tissue transglutaminase positive (>40) group and negative (<40) group#|
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|Table 4: Multi step regression analysis indicating predictors of positive IgA tissue transglutaminase levels (>40)|
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| Discussion|| |
The present study is among the largest studies done on the prevalence of IgA tTG in patients with T1D in India. A seroprevalence of 4.68% has been seen in this study.
The global prevalence of CD in T1D, based on seroprevalence of IgA tTG, varies from 4.4% to 20.8%,,,,,,,,, with the highest positivity seen in a study from Turkey. In previous studies from India, the positive seroprevalence for IgA tTG in T1D varied from 8.0% to 22%.,,, Most of these studies have been reported from North India. A positive seroprevalence of 14.9% was seen in a study by Tandon et al. In a study by Bhadada et al., a positive seroprevalence of 11.1% was seen. In a more recent study done by Dayal et al., a positive seroprevalence of 22% was seen. In a study in west India by Joshi and Madvariya, a positive seroprevalence of 15.49% was noticed. In a previous South Indian study by Jacob and Kumar, a positive seroprevalence of 8% was seen using a low tTG cut-off of 7. A multi-center study by Kota et al. including patients from the Eastern and Southern parts of India showed a positive seroprevalence of 12%.
The low seroprevalence of IgA tTG in our study population compared to similar studies in other parts of India can be attributed to both genetic and environmental factors. The predominant HLA gene in T1D patients from North India is HLA-DR3, which is strongly associated with the DQ2 haplotype. The HLA DR3-DQ2 haplotype had a strong association with CD. Whereas, there is no significant difference in the prevalence of HLA DR3 in South Indians compared to North Indians, the prevalence of DR3-DQ2 haplotype was found to be significantly lesser in the South Indian population. The current study population comprised predominant ragi or rice eating population, as compared to the predominant wheat eating population in the previous studies from other parts of India. This can explain the lower prevalence of seropositivity for CD in our study. None of the participants in our study had any symptoms suggestive of CD. Routine screening for CD in patients with T1D has been recommended at the time of diagnosis and every 1–2 years thereafter by ISPAD. Considering the low seroprevalence of IgA tTG positivity in our study, the utility of the recommendation in South Indian T1D patients may need to be explored further.
A positive seroprevalence of IgA tTG antibodies was associated with low levels of hemoglobin. Previous studies have reported a prevalence of anemia in 12–69% of cases of CD. It is mainly due to iron deficiency and is typically refractory to oral iron treatment. Other causes of anemia include folate and B12 deficiency.
The relationship between glycemic status and CD in T1D is complicated. On one hand, the erratic absorption of glucose can lead to periods of high glycemic variability. This can manifest as an increased HbA1c. On the other hand, patients are typically prone to recurrent hypoglycemic episodes caused by decreased absorption of carbohydrates. The finding of low HbA1c levels with seropositivity can be explained on this basis. Similar findings have been observed in previous studies which have shown increased prevalence of hypoglycemia in T1D patients with CD compared to those without CD.
The strengths of our study include the large sample size and a study population that had belonged to the same ethnic background having similar dietary habits. A higher cut-off for IgA tTG was taken in our study for improving the specificity. The absence of concomitant IgA measurements and the unwillingness of IgA tTG positive participants to undergo duodenal biopsy are the drawbacks of our study.
| Conclusion|| |
The seropositivity of CD in South Indian patients with T1D has been observed to be 4.68%. This is much lower compared to studies from North India. This can be explained by both genetic and dietary factors. The seropositivity correlated negatively with hemoglobin and HbA1c.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Fasano A, Berti I, Gerarduzzi T, Not T, Colletti RB, Drago S, et al.
Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: A large multicenter study. Arch Intern Med 2003;163:286-92.
Mäki M, Mustalahti K, Kokkonen J, Kulmala P, Haapalahti M, Karttunen T, et al.
Prevalence of celiac disease among children in Finland. N Engl J Med 2003;348:2517-24.
Dubé C, Rostom A, Sy R, Cranney A, Saloojee N, Garritty C, et al.
The prevalence of celiac disease in average-risk and at-risk Western European populations: A systematic review. Gastroenterology 2005;128 4 Suppl 1:S57-67.
Gillett PM, Gillett HR, Israel DM, Metzger DL, Stewart L, Chanoine JP, et al.
High prevalence of celiac disease in patients with type 1 diabetes detected by antibodies to endomysium and tissue transglutaminase. Can J Gastroenterol 2001;15:297-301.
Volta U, Tovoli F, Caio G. Clinical and immunological features of celiac disease in patients with Type 1 diabetes mellitus. Expert Rev Gastroenterol Hepatol 2011;5:479-87.
Sollid LM, Thorsby E. HLA susceptibility genes in celiac disease: Genetic mapping and role in pathogenesis. Gastroenterology 1993;105:910-22.
Rewers M, Eisenbarth GS. Autoimmunity: Celiac disease in T1DM-the need to look long term. Nat Rev Endocrinol 2011;8:7-8.
Liu E, Li M, Bao F, Miao D, Rewers MJ, Eisenbarth GS, et al.
Need for quantitative assessment of transglutaminase autoantibodies for celiac disease in screening-identified children. J Pediatr 2005;146:494-9.
Holmes GK. Coeliac disease and type 1 diabetes mellitus – The case for screening. Diabet Med 2001;18:169-77.
Hill ID, Dirks MH, Liptak GS, Colletti RB, Fasano A, Guandalini S, et al.
Guideline for the diagnosis and treatment of celiac disease in children: Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 2005;40:1-19.
Rami B, Sumnik Z, Schober E, Waldhör T, Battelino T, Bratanic N, et al.
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;41:317-21.
Bhadada SK, Kochhar R, Bhansali A, Dutta U, Kumar PR, Poornachandra KS, et al.
Prevalence and clinical profile of celiac disease in type 1 diabetes mellitus in North India. J Gastroenterol Hepatol 2011;26:378-81.
Dayal D, Samprati M, Kaur N, Minz RW, Jayaraman D. Prevalence of Beta-cell, Thyroid and Celiac Autoimmunity in North Indian Children with Recent Onset Type 1 Diabetes (T1D). J Clin Diagn Res 2015;9:SM01-2.
Ashabani A, Abushofa U, Abusrewill S, Abdelazez M, Tucková L, Tlaskalová-Hogenová H. The prevalence of coeliac disease in Libyan children with type 1 diabetes mellitus. Diabetes Metab Res Rev 2003;19:69-75.
Al-Hussaini A, Sulaiman N, Al-Zahrani M, Alenizi A, El Haj I. High prevalence of celiac disease among Saudi children with type 1 diabetes: A prospective cross-sectional study. BMC Gastroenterol 2012;12:180.
Poulain C, Johanet C, Delcroix C, Lévy-Marchal C, Tubiana-Rufi N. Prevalence and clinical features of celiac disease in 950 children with type 1 diabetes in France. Diabetes Metab 2007;33:453-8.
Djuric Z, Stamenkovic H, Stankovic T, Milicevic R, Brankovic L, Ciric V, et al.
Celiac disease prevalence in children and adolescents with type 1 diabetes from Serbia. Pediatr Int 2010;52:579-83.
Sari S, Yesilkaya E, Egritas O, Bideci A, Cinaz P, Dalgiç B. Prevalence of Celiac disease in Turkish children with type 1 diabetes mellitus and their non-diabetic first-degree relatives. Turk J Gastroenterol 2010;21:34-8.
Goh C, Banerjee K. Prevalence of coeliac disease in children and adolescents with type 1 diabetes mellitus in a clinic based population. Postgrad Med J 2007;83:132-6.
Gabriel S, Mihaela I, Angela B, Mariana A, Doru D. Prevalence of IgA antitissue transglutaminase antibodies in children with type 1 diabetes mellitus. J Clin Lab Anal 2011;25:156-61.
Karavanaki K, Kakleas K, Paschali E, Kefalas N, Konstantopoulos I, Petrou V, et al.
Screening for associated autoimmunity in children and adolescents with type 1 diabetes mellitus (T1DM). Horm Res 2009;71:201-6.
Kordonouri O, Dieterich W, Schuppan D, Webert G, Mullr C, Danne T, et al
. Autoantibodies to tissue transglutaminase are sensitive serological parameters for detecting silent coeliac disease in patients with type 1 diabetes mellitus. Diabetes Med 2000;17:441-4.
Tandon N, Shtauvere-Brameus A, Hagopian WA, Sanjeevi CB. Prevalence of ICA-12 and other autoantibodies in North Indian patients with early-onset diabetes. Ann N
Y Acad Sci 2002;958:214-7.
Agrawal RP, Rathore A, Joshi A, Changal H, Kochar DK. Prevalence of celiac disease in type 1 diabetes mellitus in North West Rajasthan, India. Diabetes Res Clin Pract 2008;79:e15-6.
Joshi R, Madvariya M. Prevalence and clinical profile of celiac disease in children with type 1 diabetes mellitus. Indian J Endocr Metab 2015;19:797-803.
Jacob A, Kumar S. Celiac disease in patients with type-1 diabetes mellitus screened by tissue transglutaminase antibodies in Southern Kerala, India. Int J Nutr Wellness 2008;8:1-5.
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;6:70-6.
Tandon N. Understanding type 1 diabetes through genetics: Advances and prospects. Indian J Endocrinol Metab 2015;19 Suppl 1:S39-43.
Liu E, Lee HS, Aronsson CA, Hagopian WA, Koletzko S, Rewers MJ, et al.
Risk of pediatric celiac disease according to HLA haplotype and country. N Engl J Med 2014;371:42-9.
Shanmugalakshmi S, Balakrishnan K, Manoharan K, Pitchappan RM. HLA-DRB1*, -DQB1* in Piramalai Kallars and Yadhavas, two Dravidian-speaking castes of Tamil Nadu, South India. Tissue Antigens 2003;61:451-64.
Kordonouri O, Klingensmith G, Knip M, Holi R, Aanstoot H, Menon P, et al
. Other complications and diabetes-associated conditions in children and adolescents. Pediatr Diabetes 2014;15 Suppl 20:270-8.
Halfdanarson TR, Litzow MR, Murray JA. Hematologic manifestations of celiac disease. Blood 2007;109:412-21.
Hershko C, Patz J. Ironing out the mechanism of anemia in celiac disease. Haematologica 2008;93:1761-5.
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;25:1117-22.
Iafusco D, Rea F, Prisco F. Hypoglycemia and reduction of the insulin requirement as a sign of celiac disease in children with IDDM. Diabetes Care 1998;21:1379-81.
Mohn A, Cerruto M, Iafusco D, Prisco F, Tumini S, Stoppoloni O, et al.
Celiac disease in children and adolescents with type I diabetes: Importance of hypoglycemia. J Pediatr Gastroenterol Nutr 2001;32:37-40.
[Table 1], [Table 2], [Table 3], [Table 4]