Advertisement

Diabetologia

, Volume 57, Issue 7, pp 1339–1345 | Cite as

Risk of renal disease in patients with both type 1 diabetes and coeliac disease

  • Kaziwe MollazadeganEmail author
  • Michael Fored
  • Sigrid Lundberg
  • Johnny Ludvigsson
  • Anders Ekbom
  • Scott M. Montgomery
  • Jonas F. Ludvigsson
Article

Abstract

Aims/hypothesis

Our aim was to study the risk of renal disease in patients with type 1 diabetes (T1D) and coexisting coeliac disease (CD).

Methods

Individuals with T1D were defined as having a diagnosis of diabetes recorded at ≤30 years of age in the Swedish Patient Register between 1964 and 2009. Individuals with CD were identified through biopsy reports with villous atrophy (Marsh stage 3) from 28 pathology departments in Sweden between 1969 and 2008. We identified 954 patients with both T1D and CD. For each patient with T1D + CD, we selected five age- and sex-matched reference individuals with T1D only (n = 4,579). Cox regression was used to estimate the following risks: (1) chronic renal disease and (2) end-stage renal disease in patients with CD + T1D compared with T1D patients only.

Results

Forty-one (4.3%) patients with CD + T1D and 143 (3.1%) patients with T1D only developed chronic renal disease. This corresponded to an HR of 1.43 for chronic renal disease (95% CI 0.94, 2.17) in patients with CD + T1D compared with T1D only. In addition, for end-stage renal disease there was a positive (albeit statistically non-significant) HR of 2.54 (95% CI 0.45, 14.2). For chronic renal disease, the excess risk was more pronounced after >10 years of CD (HR 2.03, 95% CI 1.08, 3.79). Risk estimates were similar when we restricted our cohort to the following T1D patients: (1) those who had an inpatient diagnosis of T1D; (2) those who had never received oral glucose-lowering medication; and (3) those who had not received their first diabetes diagnosis during pregnancy.

Conclusions/interpretation

Overall this study found no excess risk of chronic renal disease in patients with T1D and CD. However, in a subanalysis we noted a positive association between longstanding CD and chronic renal disease in T1D.

Keywords

Coeliac disease Cohort studies Renal disease Type 1 diabetes 

Abbreviations

CD

Coeliac disease

ESRD

End-stage renal disease

GFD

Gluten-free diet

T1D

Type 1 diabetes

VA

Villous atrophy

Notes

Funding

This study was funded by the Swedish Research council and the Swedish Coeliac Society (JFL).

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Contribution statement

All authors made substantial contributions to the study’s conception and design, acquisition of data and analysis and interpretation of data. All authors were involved in drafting the article and revising it critically for important intellectual content and gave final approval of the version to be published. KM and JFL are responsible for the integrity of the work as a whole.

Supplementary material

125_2014_3223_MOESM1_ESM.pdf (32 kb)
ESM text (PDF 32 kb)
125_2014_3223_MOESM2_ESM.pdf (64 kb)
ESM Fig. 1 (PDF 64 kb)

References

  1. 1.
    Dube C, Rostom A, Sy R et al (2005) The prevalence of celiac disease in average-risk and at-risk Western European populations: a systematic review. Gastroenterology 128:S57–S67PubMedCrossRefGoogle Scholar
  2. 2.
    Hansen D, Brock-Jacobsen B, Lund E et al (2006) Clinical benefit of a gluten-free diet in type 1 diabetic children with screening-detected celiac disease: a population-based screening study with 2 years’ follow-up. Diabetes Care 29:2452–2456PubMedCrossRefGoogle Scholar
  3. 3.
    Murray JA (2005) Celiac disease in patients with an affected member, type 1 diabetes, iron-deficiency, or osteoporosis? Gastroenterology 128:S52–S56PubMedCrossRefGoogle Scholar
  4. 4.
    Cronin CC, Shanahan F (1997) Insulin-dependent diabetes mellitus and coeliac disease. Lancet 349:1096–1097PubMedCrossRefGoogle Scholar
  5. 5.
    Ludvigsson JF, Ludvigsson J, Ekbom A, Montgomery SM (2006) Celiac disease and risk of subsequent type 1 diabetes: a general population cohort study of children and adolescents. Diabetes Care 29:2483–2488PubMedCrossRefGoogle Scholar
  6. 6.
    Welander A, Prutz KG, Fored M, Ludvigsson JF (2011) Increased risk of end-stage renal disease in individuals with coeliac disease. Gut 61:64–68PubMedCrossRefGoogle Scholar
  7. 7.
    Ludvigsson JF, Montgomery SM, Olen O, Ekbom A, Ludvigsson J, Fored M (2006) Coeliac disease and risk of renal disease—a general population cohort study. Nephrol Dial Transplant 21:1809–1815PubMedCrossRefGoogle Scholar
  8. 8.
    Mollsten A, Svensson M, Waernbaum I et al (2010) Cumulative risk, age at onset, and sex-specific differences for developing end-stage renal disease in young patients with type 1 diabetes: a nationwide population-based cohort study. Diabetes 59:1803–1808PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Aanstoot HJ, Anderson BJ, Daneman D et al. (2007) The global burden of youth diabetes: perspectives and potential. Pediatr Diabetes 8(Suppl. 8):1–44Google Scholar
  10. 10.
    Karvonen M, Viik-Kajander M, Moltchanova E, Libman I, LaPorte R, Tuomilehto J (2000) Incidence of childhood type 1 diabetes worldwide. Diabetes Mondiale (DiaMond) Project Group. Diabetes Care 23:1516–1526PubMedCrossRefGoogle Scholar
  11. 11.
    Bojestig M, Arnqvist HJ, Hermansson G, Karlberg BE, Ludvigsson J (1994) Declining incidence of nephropathy in insulin-dependent diabetes mellitus. N Engl J Med 330:15–18PubMedCrossRefGoogle Scholar
  12. 12.
    Harvey JN, Rizvi K, Craney L, Messenger J, Shah R, Meadows PA (2001) Population-based survey and analysis of trends in the prevalence of diabetic nephropathy in type 1 diabetes. Diabet Med 18:998–1002PubMedCrossRefGoogle Scholar
  13. 13.
    Bakker SF, Tushuizen ME, von Blomberg ME, Mulder CJ, Simsek S (2013) Type 1 diabetes and celiac disease in adults: glycemic control and diabetic complications. Acta Diabetol 50:319–324PubMedCrossRefGoogle Scholar
  14. 14.
    Leeds JS, Hopper AD, Hadjivassiliou M, Tesfaye S, Sanders DS (2011) High prevalence of microvascular complications in adults with type 1 diabetes and newly diagnosed celiac disease. Diabetes Care 34:2158–2163PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Skovbjerg H, Tarnow L, Locht H, Parving HH (2005) The prevalence of coeliac disease in adult Danish patients with type 1 diabetes with and without nephropathy. Diabetologia 48:1416–1417PubMedCrossRefGoogle Scholar
  16. 16.
    Gopee E, van den Oever EL, Cameron F, Thomas MC (2013) Coeliac disease, gluten-free diet and the development and progression of albuminuria in children with type 1 diabetes. Pediatr Diabetes 14:455–458PubMedCrossRefGoogle Scholar
  17. 17.
    Collins AJ, Foley RN, Herzog C et al. (2013) US Renal Data System 2012 annual data report. Am J Kidney Dis 61(Suppl. 1):A7, e1-476Google Scholar
  18. 18.
    Ludvigsson JF, Andersson E, Ekbom A et al (2011) External review and validation of the Swedish national inpatient register. BMC Public Health 11:450PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Thunander M, Petersson C, Jonzon K et al (2008) Incidence of type 1 and type 2 diabetes in adults and children in Kronoberg, Sweden. Diabetes Res Clin Pract 82:247–255PubMedCrossRefGoogle Scholar
  20. 20.
    Ludvigsson J, Carlsson A, Forsander G et al (2012) C-peptide in the classification of diabetes in children and adolescents. Pediatr Diabetes 13:45–50PubMedCrossRefGoogle Scholar
  21. 21.
    Miao J, Brismar K, Nyren O, Ugarph-Morawski A, Ye W (2005) Elevated hip fracture risk in type 1 diabetic patients: a population-based cohort study in Sweden. Diabetes Care 28:2850–2855PubMedCrossRefGoogle Scholar
  22. 22.
    Ludvigsson JF, Montgomery SM, Ekbom A, Brandt L, Granath F (2009) Small-intestinal histopathology and mortality risk in celiac disease. JAMA 302:1171–1178PubMedCrossRefGoogle Scholar
  23. 23.
    Mn M (1992) Gluten, major histocompatibility complex, and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity (‘celiac sprue’). Gastroenterology 102:330–354Google Scholar
  24. 24.
    Ludvigsson JF, Brandt L, Montgomery SM, Granath F, Ekbom A (2009) Validation study of villous atrophy and small intestinal inflammation in Swedish biopsy registers. BMC Gastroenterol 9:19PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Taranger J, Hagg U (1980) The timing and duration of adolescent growth. Acta Odontol Scand 38:57–67PubMedCrossRefGoogle Scholar
  26. 26.
    Ji J, Ludvigsson JF, Sundquist K, Sundquist J, Hemminki K (2011) Incidence of celiac disease among second-generation immigrants and adoptees from abroad in Sweden: evidence for ethnic differences in susceptibility. Scand J Gastroenterol 46:844–848PubMedCrossRefGoogle Scholar
  27. 27.
    Soderstrom U, Aman J, Hjern A (2012) Being born in Sweden increases the risk for type 1 diabetes—a study of migration of children to Sweden as a natural experiment. Acta Paediatr 101:73–77PubMedCrossRefGoogle Scholar
  28. 28.
    Nilsson AC, Spetz CL, Carsjo K, Nightingale R, Smedby B (1994) Reliability of the hospital registry. The diagnostic data are better than their reputation. Lakartidningen 91(598):603–605 [article in Swedish]Google Scholar
  29. 29.
    Ludvigsson JF, Rubio-Tapia A, van Dyke CT et al (2013) Increasing incidence of celiac disease in a North American population. Am J Gastroenterol 108:818–824PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Walker MM, Murray JA, Ronkainen J et al (2010) Detection of celiac disease and lymphocytic enteropathy by parallel serology and histopathology in a population-based study. Gastroenterology 139:112–119PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Malalasekera V, Cameron F, Grixti E, Thomas MC (2009) Potential reno-protective effects of a gluten-free diet in type 1 diabetes. Diabetologia 52:798–800PubMedCrossRefGoogle Scholar
  32. 32.
    Sanchez-Albisua I, Wolf J, Neu A, Geiger H, Wascher I, Stern M (2005) Coeliac disease in children with type 1 diabetes mellitus: the effect of the gluten-free diet. Diabet Med 22:1079–1082PubMedCrossRefGoogle Scholar
  33. 33.
    Sun S, Puttha R, Ghezaiel S, Skae M, Cooper C, Amin R (2009) The effect of biopsy-positive silent coeliac disease and treatment with a gluten-free diet on growth and glycaemic control in children with type 1 diabetes. Diabet Med 26:1250–1254PubMedCrossRefGoogle Scholar
  34. 34.
    Saadah OI, Zacharin M, O’Callaghan A, Oliver MR, Catto-Smith AG (2004) Effect of gluten-free diet and adherence on growth and diabetic control in diabetics with coeliac disease. Arch Dis Child 89:871–876PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Westman E, Ambler GR, Royle M, Peat J, Chan A (1999) Children with coeliac disease and insulin dependent diabetes mellitus—growth, diabetes control and dietary intake. J Pediatr Endocrinol Metab 12:433–442PubMedCrossRefGoogle Scholar
  36. 36.
    Tuire I, Marja-Leena L, Teea S et al (2012) Persistent duodenal intraepithelial lymphocytosis despite a long-term strict gluten-free diet in celiac disease. Am J Gastroenterol 107:1563–1569PubMedCrossRefGoogle Scholar
  37. 37.
    Lee SK, Lo W, Memeo L, Rotterdam H, Green PH (2003) Duodenal histology in patients with celiac disease after treatment with a gluten-free diet. Gastrointest Endosc 57:187–191PubMedCrossRefGoogle Scholar
  38. 38.
    Hansen TK, Forsblom C, Saraheimo M et al (2010) Association between mannose-binding lectin, high-sensitivity C-reactive protein and the progression of diabetic nephropathy in type 1 diabetes. Diabetologia 53:1517–1524PubMedCrossRefGoogle Scholar
  39. 39.
    Saraheimo M, Teppo AM, Forsblom C, Fagerudd J, Groop PH (2003) Diabetic nephropathy is associated with low-grade inflammation in type 1 diabetic patients. Diabetologia 46:1402–1407PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Kaziwe Mollazadegan
    • 1
    • 2
    Email author
  • Michael Fored
    • 1
  • Sigrid Lundberg
    • 3
  • Johnny Ludvigsson
    • 4
  • Anders Ekbom
    • 1
  • Scott M. Montgomery
    • 1
    • 5
    • 6
  • Jonas F. Ludvigsson
    • 1
    • 7
  1. 1.Clinical Epidemiology Unit, Department of MedicineKarolinska InstitutetStockholmSweden
  2. 2.St Erik Eye Hospital, Department of Clinical NeuroscienceKarolinska InstitutetStockholmSweden
  3. 3.Department of MedicineKarolinska InstitutetStockholmSweden
  4. 4.Div. of Pediatrics, Linköping University, and University Hospital, Östergötland County CouncilLinköpingSweden
  5. 5.Clinical Epidemiology and BiostatisticsÖrebro University Hospital and Örebro UniversityÖrebroSweden
  6. 6.Department of Epidemiology and Public HealthUniversity College LondonLondonUK
  7. 7.Department of PediatricsÖrebro University HospitalÖrebroSweden

Personalised recommendations