Skip to main content
Top

10-06-2017 | Gastrointestinal disorders | Article

Screening for celiac disease in poorly controlled type 2 diabetes mellitus: worth it or not?

Journal: BMC Endocrine Disorders

Authors: Muhammed Kizilgul, Ozgur Ozcelik, Selvihan Beysel, Hakan Akinci, Seyfullah Kan, Bekir Ucan, Mahmut Apaydin, Erman Cakal

Publisher: BioMed Central

share
SHARE

Abstract

Background

Recent studies have demonstrated that immune factors might have a role in the pathophysiology of insulin resistance and type 2 diabetes mellitus (T2DM). Inappropriate glycemic control in patients with T2DM is an important risk factor for the occurrence of diabetes complications. The prevalence of celiac disease (CD) is high in type 1 diabetes mellitus however, there are scarce data about its prevalence in T2DM. Our aim was to investigate the prevalence of celiac disease among insulin-using type 2 diabetes patients with inappropriate glycemic control.

Methods

IgA tissue transglutaminase antibodies (tTGA IgA) test was performed as a screening test. A total of 135 patients with T2DM whose control of glycemia is inappropriate (HbAlc value >7%) in spite of using insulin treatment for at least 3-months (only insulin or insulin with oral antidiabetic drugs) and 115 healthy controls were enrolled in the study. Upper gastrointestinal endoscopy with duodenal biopsy was performed to all patients with raised tTGA IgA or selective lgA deficiency.

Results

Gender, age, body mass index (BMI) and tTGA IgA, kreatinin, calcium, LDL-cholesterol (LDL-C), total cholesterol, 25-OH vitamin D3 levels were similar between groups. Systolic and diastolic blood pressure, waist circumference, fasting plasma glucose, postprandial plasma glucose, urea, sodium, HbA1c, LDL-C, triglyceride, vitamin B12 levels were significantly higher in DM group (p < 0.0001). BMI, high-sensitive CRP, microalbuminuria, and AST, ALT, potassium, phosphorus levels were significantly higher in the T2DM group (p < 0.05). HDL-cholesterol and parathormone levels were significantly lower in the T2DM group (p < 0.05). Two of the 135 patients with T2DM were diagnosed with CD (1.45%).

Conclusions

The prevalence of celiac disease among patients with type 2 diabetes, with poor glycemic control despite insulin therapy, is slightly higher than the actual CD prevalence in general population. Type 2 diabetic patients with inappropriate control of glycemia in spite of insulin treatment might be additionally tested for Celiac disease especially if they have low C-peptide levels.
Literature
1.
Guariguata L. By the numbers: new estimates from the IDF Diabetes Atlas Update for 2012. Diabetes Res Clin Pract. 2012;98:524–5. CrossRefPubMed
2.
Green PH, Jabri B. Coeliac disease. Lancet. 2003;362:383–91. CrossRefPubMed
3.
Dube 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. CrossRefPubMed
4.
Elfström P, Sundström J, Ludvigsson JF. Systematic review with meta-analysis: associations between coeliac disease and type 1 diabetes. Aliment Pharmacol Ther. 2014;40:1123–32. CrossRefPubMed
5.
Volta U, Fabbri A, Parisi C, Piscaglia M, Caio G, Tovoli F, et al. Old and new serological tests for celiac disease screening. Expert Rev Gastroenterol Hepatol. 2010;4:31–5. CrossRefPubMed
6.
Ashcroft FM, Rorsman P. Diabetes mellitus and the beta cell: the last ten years. Cell. 2012;148:1160–71. CrossRefPubMed
7.
Velloso LA, Eizirik DL, Cnop M. Type 2 diabetes mellitus—an autoimmune disease? Nat Rev Endocrinol. 2013;9:750–5. CrossRefPubMed
8.
Kahn SE. The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes. Diabetologia. 2003;46:3–19. CrossRefPubMed
9.
Spranger J, Kroke A, Möhlig M, Hoffmann K, Bergmann MM, Ristow M, et al. Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European prospective investigation into cancer and nutrition (EPIC)-potsdam study. Diabetes. 2003;52:812–7. CrossRefPubMed
10.
Tsukumo DM, Carvalho-Filho MA, Carvalheira JB, Prada PO, Hirabara SM, Schenka AA, et al. Loss of function mutation in Toll-like receptor 4 prevents diet-induced obesity and insulin resistance. Diabetes. 2007;56:1986–98. CrossRefPubMed
11.
Ozcan U, Cao Q, Yilmaz E, Lee AH, Iwakoshi NN, Ozdelen E, et al. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science. 2004;306:457–61. CrossRefPubMed
12.
Milanski M, Degasperi G, Coope A, Morari J, Denis R, Cintra DE, et al. Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: implications for the pathogenesis of obesity. J Neurosci. 2009;29:359–70. CrossRefPubMed
13.
Masters SL, Dunne A, Subramanian SL, Hull RL, Tannahill GM, Sharp FA, et al. Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1β in type 2 diabetes. Nature Immunol. 2010;11:897–904. CrossRef
14.
Araujo EP, De Souza CT, Ueno M, Cintra DE, Bertolo MB, Carvalheira JB, et al. Infliximab restores glucose homeostasis in an animal model of diet-induced obesity and diabetes. Endocrinology. 2007;148:991–7. CrossRef
15.
Winer DA, Winer S, Shen L, Wadia PP, Yantha J, Paltser G, et al. B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nat Med. 2011;17:610–7. CrossRefPubMedPubMedCentral
16.
Cohen NR, Garg S, Brenner MB. Antigen presentation by CD1 lipids, T cells, and NKT cells in microbial immunity. Adv Immunol. 2009;102:1–94. CrossRefPubMed
17.
Geddes K, Rubino SJ, Magalhaes JG, Streutker C, Le Bourhis L, Cho JH, et al. Identification of an innate T helper type 17 response to intestinal bacterial pathogens. Nat Med. 2011;17:837–44. CrossRefPubMed
18.
Sjöberg K, Eriksson KF, Bredberg A, Wassmuth R, Eriksson S. Screening for coeliac disease in adult insulin-dependent diabetes mellitus. J Intern Med. 1998;243:133–40. CrossRefPubMed
19.
Page SR, Lloyd CA, Hill PG, Peacock I, Holmes GK. The prevalence of coeliac disease in adult diabetes mellitus. QJM. 1994;87:631–7. PubMed
20.
Tourniaire J, Guichard-Rode S, Monier JC. Circulating antigliadin antibodies. Prevalence in a diabetic (type 1 or 2) and nondiabetic adult population. Presse Med. 1995;24:1425–7. PubMed
21.
Kanungo A, Shtauvere-Brameus A, Samal KC, Sanjeevi CB. Autoantibodies to tissue transglutaminase in patients from eastern India with malnutrition-modulated diabetes mellitus, insulin-dependent diabetes mellitus, and non-insulin-dependent diabetes mellitus. Ann N Y Acad Sci. 2002;958:232–4. CrossRefPubMed
22.
Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, et al. Association of glycemia with macrovascular and microvascular complications of Type 2 diabetes (UKPDS 35): Prospective observational study. BMJ. 2000;321:405–12. CrossRefPubMedPubMedCentral
23.
Karter AJ, Moffet HH, Liu J, Parker MM, Ahmed AT, Ferrara A, et al. Achieving good glycemic control: Initiation of new antihyperglycemic therapies in the patient with Type 2 diabetes from the Kaiser Permanente Northern California diabetes registry. Am J Manag Care. 2005;11:262–70. PubMedPubMedCentral
24.
Koro CE, Bowlin SJ, Bourgeois N, Fedder DO. Glycemic control from 1988 to 2000 among US adults diagnosed with type2 diabetes: A preliminary report. Diabetes Care. 2004;27:17–20. CrossRefPubMed
25.
Wallace TM, Matthews DR. Poor glycemic control in Type 2 diabetes, conspiracy of disease, suboptimal therapy and attitude. Q J M. 2000;93:369–74. CrossRef
26.
Marsh MN. Gluten, major histocompatibility complex, and the small intestine. Gastroenterology. 1992;102:330–54. CrossRefPubMed
27.
Pietropaolo M, Barinas-Mitchell E, Pietropaolo SL, Kuller LH, Trucco M. Evidence of islet cell autoimmunity in elderly patients with type 2 diabetes. Diabetes. 2000;49:32–8. CrossRefPubMed
28.
Maedler K, Sergeev P, Ris F, Oberholzer J, Joller-Jemelka HI, Spinas GA, et al. Glucose-induced β-cell production of interleukin-1β contributes to glucotoxicity in human pancreatic islets. J Clin Invest. 2002;110:851–60. CrossRefPubMedPubMedCentral
29.
Eldor R, Yeffet A, Baum K, Doviner V, Amar D, Ben-Neriah Y, et al. Conditional and specific NF-κB blockade protects pancreatic β cells from diabetogenic agents. Proc Natl Acad Sci USA. 2006;103:5072–7. CrossRefPubMedPubMedCentral
30.
Jagannathan M, McDonnell M, Liang Y, Hasturk H, Hetzel J. Rubin Det al.: Toll-like receptors regulate B-cell cytokine production in patients with diabetes. Diabetologia. 2010;53:1461–71. CrossRefPubMedPubMedCentral
31.
Van Exel E, Gussekloo J, de Craen AJ, Frölich M. Bootsma-Van Der Wiel A, Westendorp RG; Leiden 85 Plus Study. Low production capacity of interleukin-10 associates with the metabolic syndrome and type 2 diabetes: the Leiden 85-Plus Study. Diabetes. 2002;51:1088–92. CrossRefPubMed
32.
Folk JE, Finlaynson JS. The e-(g-glutamyl) lysine cross-link and the catalytic role of transglutaminases. Adv Protein Chem. 1997;31:1–133.
33.
Dvorcakova M, Macejova D, Pallet V, Higueret P, Vasson MP, Rock E, et al. Transglutaminase and endocrine system (minireview). Endocr Regul. 2002;36:31–6.
34.
Sener A, Dunlop ME, Gomis R, Matias PC, Malaisse-Lagae F, Malaisse WJ. The role of transglutaminase in insulin release. Study with glycine and sarcosine methylesters. Endocrinology. 1985;117:237–42. CrossRefPubMed
35.
Gomis R, Sener A, Malaisse-Lagae F, Malaisse WJ. Transglutaminase activity in pancreatic islets. Biochim Biophys Acta. 1983;8:384–8. CrossRef
36.
Rubio-Tapia A, Hill ID, Kelly CP, Calderwood AH, Murray JA. American College of G. ACG clinical guidelines: diagnosis and management of celiac disease. Am J Gastroenterol. 2013;108:656–76. CrossRefPubMedPubMedCentral
37.
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. CrossRefPubMed
38.
Usai P, Cherchi MV, Boi MF, Cirillo R, Santa Cruz G, Solinas MP, et al. Celiac disease in insulin-dependent diabetes mellitus and insulin-independent diabetes mellitus. Recenti Prog Med. 1989;80:56–8. PubMed
39.
Sánchez JC, Cabrera-Rode E, Sorell L, Galvan JA, Hernandez A, Molina G, et al. Celiac disease-associated antibodies in persons with latent autoimmune diabetes of adult and type 2 diabetes. Autoimmunity. 2007;40:103–7. CrossRefPubMed