The Role of Autoimmunity at Diagnosis of Type 1 Diabetes in the Development of Thyroid and Celiac Disease and Microvascular Complications

Cytokines play a pivotal role in the maintenance of intestinal homeostasis inducing pro- or anti-inflammatory response and mucosal barrier function in celiac disease (CD) and type 1 diabetes (T1D). We aimed to compare the levels of pro- and anti-inflammatory cytokines in CD patients without and with coexisting T1D, as well as to evaluate its association with the presence of enteroviruses (EV), regulatory T cells (Tregs), and dendritic cells (DCs) in small bowel mucosa. Altogether, 72 patients (median age 10.1 years) who had undergone small bowel biopsy were studied. The study group consisted of 24 patients with CD (median age 6.5 years), 9 patients with CD and concomitant T1D (median age 7.0 years), two patients with T1D (median age 8.5 years), and 37 patients (median age 14.0 years) with functional gastrointestinal disorders (FGD) and a normal small bowel mucosa as controls. The levels of 33 cytokines in serum were measured by multiple analysis using the Milliplex® MAP Magnetic Bead assay. The densities of FOXP3+ Tregs, CD11c+ DC, indoleamine 2,3-dioxygenase+ (IDO+) DC, langerin+ (CD207+) DCs, and EV were evaluated by immunohistochemistry as described in our previous studies. Circulating anti-EV IgA and IgG were evaluated using ELISA. The most important finding of the study is the significant increase of the serum levels of IL-5, IL-8, IL-13, IL-15, IL-17F, IL-22, IL-27, IP-10, MIP-1β, sIL-2Rα, sTNFRII, and TNFαin CD patients compared to controls and its correlation with the degree of small bowel mucosa damage graded according to the Marsh classification. The leptin level was higher in females in all study groups. The levels of IL-2, IL-6, IL-12 (P70), IL-15, IP-10, and IFNγcorrelated significantly with the density of FOXP3+ Tregs inlamina propriaof the small bowel mucosa, which supports the evidence about the signaling role of these cytokines in the peripheral maintenance of FOXP3+ Tregs. At the same time, a significant negative correlation occurred between the level of IL-4 and density of FOXP3+ Tregs in controls. Another important finding of our study was the correlation of IL-17F, IP-10, sTNFRII, MCP-1, and GM-CSF with the density of EV-positive cells in thelamina propriaof the small bowel mucosa. Correlation of MIP-1 (CCL-4) with CD103+ DC and langerin+ DC densities may point to their significance in the recruitment of immune cells into thelamina propriaand in driving the inflammatory response in CD patients. Our results suggest the predominance of Th1 and Th17 immune responses over EV VP1 protein in CD and T1D patients. The significant elevation of Th2 cytokines, like IL-5 and IL-13, but not IL-4, in CD patients and its correlation with the degree of small bowel mucosa damage could reflect the role of these cytokines in gut defense and inflammation.

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Role of HLA‐DQ typing and anti‐tissue transglutaminase antibody titers in diagnosing celiac disease without duodenal biopsy in type 1 diabetes: A study of the population‐based pediatric type 1 diabetes cohort of Western Australia

Pediatric Diabetes ◽

10.1111/pedi.12857 ◽

2019 ◽

Cited By ~ 2

Author(s):

Kiranjit K. Joshi ◽

Aveni Haynes ◽

Elizabeth A. Davis ◽

Lloyd D'Orsogna ◽

Andrew McLean‐Tooke

Keyword(s):

Type 1 Diabetes ◽

Celiac Disease ◽

Tissue Transglutaminase ◽

Population Based ◽

Duodenal Biopsy ◽

Hla Dq ◽

Antibody Titers ◽

Pediatric Type 1 Diabetes

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SAT-668 Liver Function Test in Type 1 Diabetes Mellitus and Prevalence of Other Autoimmune Disease in Type 1 Diabetes Mellitus

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1721 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Nadig Anusha ◽

sree divya ◽

alok sachan ◽

v s suresh ◽

Ashok Venkatanarasu

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Celiac Disease ◽

Autoimmune Disease ◽

Liver Function ◽

Microvascular Complications ◽

Function Test ◽

B12 Deficiency ◽

Type 1 Dm

Abstract Background Recent studies suggest that non-alcoholic fatty liver disease (NAFLD) may be more common in type 1 diabetes. The pathogenesis of NAFLD has been hypothesized that, hepatic fat accumulation may be due to hyperglycemia induced activation of the transcription factors. Type 1 DM inducing autoimmune process can also affect other organs. So screening for celiac disease, Hashimoto’s thyroiditis and other autoimmune disorders is necessary. Aims: 1. To evaluate the prevalence of NAFLD in type 1 DM. And to correlate glycosylated hemoglobin (HbA1c) with aspartate transaminase (AST) and alanine transaminase (ALT). 2. To determine the prevalence of autoimmune disease like hypothyroidism, celiac disease, vitamin B12 deficiency and Vitiligo in type 1 DM. 3. To study the prevalence of microvascular complications and correlate it with HBA1c. Study design Cross sectional study Methods: Eighty patients with type 1 DM were taken, liver function test, HbA1c and TSH was sent. BMI was calculated. We calculated prevalence of elevated AST and ALT in all patients and correlated with HbA1c. All patients were screened for other autoimmune disorders. Screening for celiac disease was done by celiac antibodies and antibodies positive patients underwent duodenal biopsy. Thyroid screening was done by TSH and anti TPO antibodies. Vitamin B12 levels were also measured. Patients also underwent screening for microvascular complications to see its prevalence. Statistical Analysis Categorical data was represented in the form of frequencies and proportions. Chi square test was used as test of significance for qualitative data. Continuous data was represented as mean and standard deviation. Pearson correlation or Spearman’s correlation was done to find the correlation between two quantitative variables and qualitative variables and quantitative variables respectively. Results: Mean age of subjects was 21.38 ± 6.16 years, 57.6% were females and 42.4% were males, mean HBA1c was 10.45 ± 2.54, mean AST was 24.71 ± 15.85 and mean ALT was 22.08 ± 15.13. In the study significant positive correlation was observed between HbA1c and ALT, i.e. With increase in HbA1c there was increase in ALT and vice versa. There was no significant correlation between HbA1c and AST. In the study 21.2% were hypothyroid, 29.4%had Celiac disease, 1.2% had Vitiligo and 23.5% had B12 deficiency. In the study there was no significant association between Micro vascular complications and HbA1c. In the study 3.5% had neuropathy, 7% had retinopathy, 4.7% had nephropathy. Conclusion: Elevated ALT can be associated with NAFLD related risk factors. Type 1 diabetics with elevated ALT should be evaluated. And patients with type 1 DM should undergo screening for other autoimmune disease.

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