Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

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doi: 10.17219/acem/159800

Publication type: original article

Language: English

License: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

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Zawada AE, Naskręt D, Piłaciński S, et al. Helicobacter pylori infection is associated with increased accumulation of advanced glycation end products in the skin in patients with type 1 diabetes: A preliminary study [published online as ahead of print on March 7, 2023]. Adv Clin Exp Med. 2023. doi:10.17219/acem/159800

Helicobacter pylori infection is associated with increased accumulation of advanced glycation end products in the skin in patients with type 1 diabetes: A preliminary study

Agnieszka Ewa Zawada1,A,B,C,D,F, Dariusz Naskręt2,B,E, Stanisław Piłaciński2,C, Anna Adamska2,B,C, Marian Grzymisławski1,A,E, Piotr Eder3,D,E,F, Agata Grzelka-Woźniak2,C, Dorota Zozulińska-Ziółkiewicz2,C,E,F, Agnieszka Dobrowolska1,A,E,F

1 Department of Gastroenterology, Dietetics and Internal Disease, Poznan University of Medical Sciences, Poland

2 Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences, Poland

3 Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, Poland


Background. Helicobacter pylori infection (HPI) is more frequently diagnosed in patients with diabetes. Insulin resistance in patients with type 1 diabetes (DMT1) is associated with the accumulation of advanced glycation end products (AGEs) in the skin and progression of chronic complications.
Objectives. Assessment of the relationship between the incidence of HPI and skin AGEs in patients with DMT1.
Material and Methods. The study included 103 Caucasian patients with a DMT1 duration >5 years. A fast qualitative test was performed to detect the HP antigen in fecal samples (Hedrex). The content of AGEs in the skin was estimated using an AGE Reader device (DiagnOptics).
Results. The HP-positive (n = 31) and HP-negative (n = 72) groups did not differ in terms of age, gender, duration of diabetes, fat content, body mass index (BMI) and lipid profile, metabolic control, and inflammatory response markers. The studied groups differed in the amount of AGEs in the skin. The relationship between HPI and increased AGEs in the skin was confirmed in a multifactor regression model taking into account age, gender, DMT1 duration, glycated hemoglobin A1c (HbA1c), BMI, low-density lipoprotein cholesterol (LDL-C) and the presence of hypertension, and tobacco use. The studied groups also differed in serum levels of vitamin D.
Conclusion. Increased accumulation of AGEs in the skin of patients with DMT1 with coexisting HPI suggests that eradication of HP may significantly improve DMT1 outcomes.

Key words

vitamin D, H. pylori, advanced glycation end products, type 1 diabetes, diabetic complications

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References (49)

  1. Crowe SE. Helicobacter pylori infection. N Engl J Med. 2019;380(12):1158–1165. doi:10.1056/NEJMcp1710945
  2. Bravo D, Hoare A, Soto C, Valenzuela MA, Quest AF. Helicobacter pylori in human health and disease: Mechanisms for local gastric and systemic effects. World J Gastroenterol. 2018;24(28):3071–3089. doi:10.3748/wjg.v24.i28.3071
  3. Pellicano R, Ribaldone DG, Fagoonee S, Astegiano M, Saracco GM, Mégraud F. A 2016 panorama of Helicobacter pylori infection: Key messages for clinicians. Panminerva Med. 2016;58(4):304–317. PMID:27716738.
  4. Zhou X, Zhang C, Wu J, Zhang G. Association between Helicobacter pylori infection and diabetes mellitus: A meta-analysis of observational studies. Diabetes Res Clin Pract. 2013;99(2):200–208. doi:10.1016/j.diabres.2012.11.012
  5. Delitala AP, Pes GM, Malaty HM, Pisanu G, Delitala G, Dore MP. Implication of cytotoxic Helicobacter pylori infection in autoimmune diabetes. J Diabetes Res. 2016;2016:7347065. doi:10.1155/2016/7347065
  6. Williams KV, Erbey JR, Becker D, Arslanian S, Orchard TJ. Can clinical factors estimate insulin resistance in type 1 diabetes? Diabetes. 2000;49(4):626–632. doi:10.2337/diabetes.49.4.626
  7. Amato MC, Giordano C, Galia M, et al. Visceral adiposity index: A reliable indicator of visceral fat function associated with cardiometabolic risk. Diabetes Care. 2010;33(4):920–922. doi:10.2337/dc09-1825
  8. Gallagher D, Heymsfield SB, Heo M, Jebb SA, Murgatroyd PR, Sakamoto Y. Healthy percentage body fat ranges: An approach for developing guidelines based on body mass index. Am J Clin Nutr. 2000;72(3):694–701. doi:10.1093/ajcn/72.3.694
  9. de Luis DA, de la Calle H, Roy G, et al. Helicobacter pylori infection and insulin-dependent diabetes mellitus. Diabetes Res Clin Pract. 1998;39(2):143–146. doi:10.1016/S0168-8227(97)00127-7
  10. Mulder DJ, Water TVD, Lutgers HL, et al. Skin autofluorescence, a novel marker for glycemic and oxidative stress-derived advanced glycation endproducts: An overview of current clinical studies, evidence, and limitations. Diabetes Technol Ther. 2006;8(5):523–535. doi:10.1089/dia.2006.8.523
  11. Da Moura Semedo C, Webb M, Waller H, Khunti K, Davies M. Skin autofluorescence, a non-invasive marker of advanced glycation end products: Clinical relevance and limitations. Postgrad Med J. 2017;93(1099):289–294. doi:10.1136/postgradmedj-2016-134579
  12. Meerwaldt R, Graaff R, Oomen PHN, et al. Simple non-invasive assessment of advanced glycation endproduct accumulation. Diabetologia. 2004;47(7):1324–1330. doi:10.1007/s00125-004-1451-2
  13. Koetsier M, Lutgers HL, de Jonge C, Links TP, Smit AJ, Graaff R. Reference values of skin autofluorescence. Diabetes Technol Ther. 2010;12(5):399–403. doi:10.1089/dia.2009.0113
  14. Faria M, Pavin EJ, Parisi MCR, Nagasako CK, Mesquita MA. Dyspeptic symptoms in patients with type 1 diabetes: Endoscopic findings, Helicobacter pylori infection, and associations with metabolic control, mood disorders and nutritional factors. Arch Endocrinol Metab. 2015;59(2):129–136. doi:10.1590/2359-3997000000025
  15. Dai YN, Yu WL, Zhu HT, Ding JX, Yu CH, Li YM. Is Helicobacter pylori infection associated with glycemic control in diabetics? World J Gastroenterol. 2015;21(17):5407–5416. doi:10.3748/wjg.v21.i17.5407
  16. Demir M, Gokturk HS, Ozturk NA, Kulaksizoglu M, Serin E, Yilmaz U. Helicobacter pylori prevalence in diabetes mellitus patients with dyspeptic symptoms and its relationship to glycemic control and late complications. Dig Dis Sci. 2008;53(10):2646–2649. doi:10.1007/s10620-007-0185-7
  17. Bonetto S, Gruden G, Beccuti G, Ferro A, Saracco GM, Pellicano R. Management of dyspepsia and gastroparesis in patients with diabetes: A clinical point of view in the year 2021. J Clin Med. 2021;10(6):1313. doi:10.3390/jcm10061313
  18. Chung GE, Heo NJ, Park MJ, Chung SJ, Kang HY, Kang SJ. Helicobacter pylori seropositivity in diabetic patients is associated with microalbuminuria. World J Gastroenterol. 2013;19(1):97–102. doi:10.3748/wjg.v19.i1.97
  19. Zizzi CF, Pellicano R, Biancone L. The relationship between Helicobacter pylori and chronic kidney disease: Update 2020. Minerva Gastroenterol Dietol. 2021;66(4):343–349. doi:10.23736/S1121-421X.20.02729-4
  20. Bajaj S, Rekwal L, Misra S, Misra V, Yadav R, Srivastava A. Association of Helicobacter pylori infection with type 2 diabetes. Indian J Endocr Metab. 2014;18(5):694–699. doi:10.4103/2230-8210.139235
  21. Huang J. Analysis of the relationship between Helicobacter pylori infection and diabetic gastroparesis. Chin Med J (Engl). 2017;130(22):2680–2685. doi:10.4103/0366-6999.218012
  22. Agrawal RP, Sharma R, Garg D, Pokharna R, Kochar DK, Kothari RP. Role of Helicobacter pylori in causation of diabetic gastropathies and non-gastrointestinal complications in type 2 diabetes. J Indian Med Assoc. 2010;108(3):140–143. PMID:21043350.
  23. Noach LA, Bosma NB, Jansen J, Hoek FJ, Van Deventer SJH, Tytgat GNJ. Mucosal tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-8 production in patients with Helicobacter pylori infection. Scand J Gastroenterol. 1994;29(5):425–429. doi:10.3109/00365529409096833
  24. Hillenbrand A, Weiss M, Knippschild U, Wolf AM, Huber-Lang M. Sepsis-induced adipokine change with regard to insulin resistance. Int J Inflam. 2012;2012:972368. doi:10.1155/2012/972368
  25. Vafaeimanesh J, Parham M, Seyyedmajidi M, Bagherzadeh M. Helicobacter pylori infection and insulin resistance in diabetic and nondiabetic population. ScientificWorldJournal. 2014;2014:391250. doi:10.1155/2014/391250
  26. Talebi-Taher M, Mashayekhi M, Hashemi MH, Bahrani V. Helicobacter pylori in diabetic and non-diabetic patients with dyspepsia. Acta Med Iran. 2012;50(5):315–318. PMID:22837084.
  27. Kaneko H, Konagaya T, Kusugami K. Helicobacter pylori and gut hormones. J Gastroenterol. 2002;37(2):77–86. doi:10.1007/s005350200000
  28. Jeffery PL, McGuckin MA, Linden SK. Endocrine impact of Helicobacter pylori: Focus on ghrelin and ghrelin o-acyltransferase. World J Gastroenterol. 2011;17(10):1249–1260. doi:10.3748/wjg.v17.i10.1249
  29. Jia EZ, Zhao FJ, Hao B, et al. Helicobacter pylori infection is associated with decreased serum levels of high density lipoprotein, but not with the severity of coronary atherosclerosis. Lipids Health Dis. 2009;8:59. doi:10.1186/1476-511X-8-59
  30. Kim HL, Jeon HH, Park IY, Choi JM, Kang JS, Min KW. Helicobacter pylori infection is associated with elevated low density lipoprotein cholesterol levels in elderly Koreans. J Korean Med Sci. 2011;26(5):654–658. doi:10.3346/jkms.2011.26.5.654
  31. van der Heyden JC, Birnie E, Mul D, Bovenberg S, Veeze HJ, Aanstoot HJ. Increased skin autofluorescence of children and adolescents with type 1 diabetes despite a well-controlled HbA1c: Results from a cohort study. BMC Endocr Disord. 2016;16(1):49. doi:10.1186/s12902-016-0129-3
  32. Samborski P, Naskręt D, Araszkiewicz A, Niedźwiecki P, Zozulińska-Ziółkiewicz D, Wierusz-Wysocka B. Assessment of skin autofluorescence as a marker of advanced glycation end product accumulation in type 1 diabetes. Pol Arch Med Wewn. 2011;121(3):67–72. PMID:21430607.
  33. Genuth S, Sun W, Cleary P, et al. Glycation and carboxymethyllysine levels in skin collagen predict the risk of future 10-year progression of diabetic retinopathy and nephropathy in the diabetes control and complications trial and epidemiology of diabetes interventions and complications participants with type 1 diabetes. Diabetes. 2005;54(11):3103–3111. doi:10.2337/diabetes.54.11.3103
  34. Gerrits EG, Lutgers HL, Kleefstra N, et al. Skin autofluorescence: A tool to identify type 2 diabetic patients at risk for developing microvascular complications. Diabetes Care. 2008;31(3):517–521. doi:10.2337/dc07-1755
  35. Meerwaldt R, Lutgers HL, Links TP, et al. Skin autofluorescence is a strong predictor of cardiac mortality in diabetes. Diabetes Care. 2007;30(1):107–112. doi:10.2337/dc06-1391
  36. Smit AJ, Smit JM, Botterblom GJ, Mulder DJ. Skin autofluorescence based decision tree in detection of impaired glucose tolerance and diabetes. PLoS One. 2013;8(6):e65592. doi:10.1371/journal.pone.0065592
  37. Lin HJ, Hsu FY, Chen WW, et al. Helicobacter pylori activates HMGB1 expression and recruits RAGE into lipid rafts to promote inflammation in gastric epithelial cells. Front Immunol. 2016;7:341. doi:10.3389/fimmu.2016.00341
  38. Radin JN, González-Rivera C, Ivie SE, McClain MS, Cover TL. Helicobacter pylori VacA induces programmed necrosis in gastric epithelial cells. Infect Immun. 2011;79(7):2535–2543. doi:10.1128/IAI.01370-10
  39. Yang H, Wang H, Czura C, Tracey K. The cytokine activity of HMGB1. J Leukoc Biol. 2005;78(1):1–8. doi:10.1189/jlb.1104648
  40. Morales EM, Rojas AR, Monasterio VA , et al. Expression of RAGE in Helicobacter pylori infested gastric biopsies [in Spanish]. Rev Med Chil. 2013;141(10):1240–1248. doi:10.4067/S0034-98872013001000002
  41. Kountouras J, Polyzos SA, Doulberis M, et al. Potential impact of Helicobacter pylori-related metabolic syndrome on upper and lower gastrointestinal tract oncogenesis. Metabolism. 2018;87:18–24. doi:10.1016/j.metabol.2018.06.008
  42. Rojas A, González I, Rodríguez B, et al. Evidence of involvement of the receptor for advanced glycation end-products (RAGE) in the adhesion of Helicobacter pylori to gastric epithelial cells. Microbes Infect. 2011;13(10):818–823. doi:10.1016/j.micinf.2011.04.005
  43. Savastio S, Cadario F, Genoni G, et al. Vitamin D deficiency and glycemic status in children and adolescents with type 1 diabetes mellitus. PLoS One. 2016;11(9):e0162554. doi:10.1371/journal.pone.0162554
  44. Mut Surmeli D, Surmeli ZG, Bahsi R, et al. Vitamin D deficiency and risk of Helicobacter pylori infection in older adults: A cross-sectional study. Aging Clin Exp Res. 2019;31(7):985–991. doi:10.1007/s40520-018-1039-1
  45. Yildirim O, Yildirim T, Seckin Y, Osanmaz P, Bilgic Y, Mete R. The influence of vitamin D deficiency on eradication rates of Helicobacter pylori. Adv Clin Exp Med. 2017;26(9):1377–1381. doi:10.17219/acem/65430
  46. El Shahawy MS, Hemida MH, El Metwaly I, Shady ZM. The effect of vitamin D deficiency on eradication rates of Helicobacter pylori infection. JGH Open. 2018;2(6):270–275. doi:10.1002/jgh3.12081
  47. Yang L, He X, Li L, Lu C. Effect of vitamin D on Helicobacter pylori infection and eradication: A meta-analysis. Helicobacter. 2019;24(5):e12655. doi:10.1111/hel.12655
  48. Xue Y, Zhou LY, Lu HP, Liu JZ. Recurrence of Helicobacter pylori infection: Incidence and influential factors. Chin Med J (Engl). 2019;132(7):765–771. doi:10.1097/CM9.0000000000000146
  49. Imai J, Yamada T, Saito T, et al. Eradication of insulin resistance. Lancet. 2009;374(9685):264. doi:10.1016/S0140-6736(09)60872-2