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Journal of Endocrinological Investigation

, Volume 42, Issue 9, pp 1099–1107 | Cite as

Vitamin D status and non-alcoholic fatty liver disease in patients with type 1 diabetes

  • E. Cipponeri
  • N. Vitturi
  • V. Mariano
  • F. Boscari
  • S. Galasso
  • C. Crepaldi
  • G. P. Fadini
  • S. Vigili de Kreutzenberg
  • M. C. Marescotti
  • E. Iori
  • F. Cavallin
  • L. Sartori
  • A. Baritussio
  • A. Avogaro
  • D. BruttomessoEmail author
Original Article

Abstract

Purpose

In patients with type 1 diabetes (T1D), the prevalence of non-alcoholic fatty liver disease (NAFLD) ranges from 10 to 53% and contrasting evidence suggests that vitamin D deficiency may favor liver fat accumulation. Here, we investigated the association between vitamin D status and NAFLD in adults with T1D.

Methods

220 consecutive adult T1D patients on multiple daily injections or continuous subcutaneous insulin infusion and not taking calcium or vitamin D supplements were included. Patient characteristics, 25(OH)D serum levels, and metabolic parameters were analyzed. Vitamin D status was defined as sufficiency ( ≥ 75 nmol/L; 30 ng/ml), insufficiency (50–75 nmol/L; 20–30 ng/ml), or deficiency ( < 50 nmol/L; 20 ng/ml). NAFLD was diagnosed at ultrasound examination and graded 0–3.

Results

NAFLD was present in 57 patients (29.5%): 51 grade 1, 5 grade 2, and 1 grade 3. Median 25(OH)D levels were 53 nmol/L (IQR 38–70) in patients with NAFLD and 50 nmol/L (34–69) in patients without (p = 0.46). At multivariable analysis, NAFLD was not associated with 25(OH)D levels (p = 0.42) or vitamin D deficiency (p = 0.55), while BMI (OR 1.16, 95% CI 1.07–1.27) and serum triglycerides (OR 1.02, 95% CI 1.01–1.03) were independently associated with NAFLD.

Conclusions

Vitamin D status appears to have no link with low-grade NAFLD in patients with type 1 diabetes.

Keywords

Type 1 diabetes Non-alcoholic fatty liver disease (NAFLD) Vitamin D Ultrasound 

Notes

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Compliance with ethical standards

Conflict of interest

The authors declare no competing interests for this manuscript.

Ethical approval

All procedures in studies involving human participants were in accordance with the Ethical Standards of the institutional and /or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

References

  1. 1.
    Benedict M, Zhang X (2017) Non-alcoholic fatty liver disease: an expanded review. World J Hepatol 9(16):715–732.  https://doi.org/10.4254/wjh.v9.i16.715 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Bellentani S (2017) The epidemiology of non-alcoholic fatty liver disease. Liver Int 37(Suppl 1):81–84.  https://doi.org/10.1111/liv.13299 CrossRefPubMedGoogle Scholar
  3. 3.
    Lonardo A, Bellentani S, Argo CK, Ballestri S, Byrne CD, Caldwell SH, Cortez-Pinto H, Grieco A, Machado MV, Miele L, Targher G, Non-alcoholic Fatty Liver Disease Study Group (2015) Epidemiological modifiers of non-alcoholic fatty liver disease: focus on high-risk groups. Dig Liver Dis 47(12):997–1006.  https://doi.org/10.1016/j.dld.2015.08.004 CrossRefGoogle Scholar
  4. 4.
    Cusi K, Sanyal AJ, Zhang S, Hartman ML, Bue-Valleskey JM, Hoogwerf BJ, Haupt A (2017) Non-alcoholic fatty liver disease (NAFLD) prevalence and its metabolic associations in patients with type 1 diabetes and type 2 diabetes. Diabetes Obes Metab 19(11):1630–1634.  https://doi.org/10.1111/dom.12973 CrossRefPubMedGoogle Scholar
  5. 5.
    Targher G, Lonardo A, Byrne CD (2018) Nonalcoholic fatty liver disease and chronic vascular complications of diabetes mellitus. Nat Rev Endocrinol 14(2):99–114.  https://doi.org/10.1038/nrendo.2017.173 CrossRefPubMedGoogle Scholar
  6. 6.
    Mantovani A, Sani E, Fassio A, Colecchia A, Viapiana O, Gatti D, Idolazzi L, Rossini M, Salvagno G, Lippi G, Zoppini G, Byrne CD, Bonora E, Targher G (2018) Association between non-alcoholic fatty liver disease and bone turnover biomarkers in post-menopausal women with type 2 diabetes. Diabetes Metab S1262–S3636(18):30195–30202.  https://doi.org/10.1016/j.diabet.2018.10.001 CrossRefGoogle Scholar
  7. 7.
    Serra-Planas E, Aguilera E, Castro L, Rodríguez R, Salinas I, Lucas A, Joaquín C, Puig R, Mauricio D, Puig-Domingo M (2017) Low prevalence of non-alcoholic fatty liver disease in patients with type 1 diabetes is associated with decreased subclinical cardiovascular disease. J Diabetes 9(12):1065–1072.  https://doi.org/10.1111/1753-0407.12539 CrossRefPubMedGoogle Scholar
  8. 8.
    Targher G, Pichiri I, Zoppini G, Trombetta M, Bonora E (2012) Increased prevalence of chronic kidney disease in patients with Type 1 diabetes and non-alcoholic fatty liver. Diabet Med 29(2):220–226.  https://doi.org/10.1111/j.1464-5491.2011.03427.x CrossRefPubMedGoogle Scholar
  9. 9.
    Targher G, Mantovani A, Pichiri I, Mingolla L, Cavalieri V, Mantovani W, Pancheri S, Trombetta M, Zoppini G, Chonchol M, Byrne CD, Bonora E (2014) Nonalcoholic fatty liver disease is independently associated with an increased incidence of chronic kidney disease in patients with type 1 diabetes. Diabetes Care 37(6):1729–1736.  https://doi.org/10.2337/dc13-2704 CrossRefPubMedGoogle Scholar
  10. 10.
    Targher G, Bertolini L, Chonchol M, Rodella S, Zoppini G, Lippi G, Zenari L, Bonora E (2010) Non-alcoholic fatty liver disease is independently associated with an increased prevalence of chronic kidney disease and retinopathy in type 1 diabetic patients. Diabetologia 53(7):1341–1348.  https://doi.org/10.1007/s00125-010-1720-1 CrossRefPubMedGoogle Scholar
  11. 11.
    Barchetta I, Angelico F, Del Ben M, Baroni MG, Pozzilli P, Morini S, Cavallo MG (2011) Strong association between non alcoholic fatty liver disease (NAFLD) and low 25(oh) vitamin D levels in an adult population with normal serum liver enzymes. BMC Med 9:85.  https://doi.org/10.1186/1741-7015-9-85 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Chung GE, Kim D, Kwak MS, Yang JI, Yim JY, Lim SH, Itani M (2016) The serum vitamin D level is inversely correlated with nonalcoholic fatty liver disease. Clin Mol Hepatol 22(1):146–151.  https://doi.org/10.3350/cmh.2016.22.1.146 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Eliades M, Spyrou E, Agrawal N, Lazo M, Brancati FL, Potter JJ, Koteish AA, Clark JM, Guallar E, Hernaez R (2013) Meta-analysis: vitamin D and non-alcoholic fatty liver disease. Aliment Pharmacol Ther 38(3):246–254.  https://doi.org/10.1111/apt.12377 CrossRefPubMedGoogle Scholar
  14. 14.
    Eliades M, Spyrou E (2015) Vitamin D: a new player in non-alcoholic fatty liver disease? World J Gastroenterol 21(6):1718–1727.  https://doi.org/10.3748/wjg.v21.i6.1718 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Nelson JE, Roth CL, Wilson LA, Yates KP, Aouizerat B, Morgan-Stevenson V, Whalen E, Hoofnagle A, Mason M, Gersuk V, Yeh MM, Kowdley KV (2016) Vitamin D deficiency is associated with increased risk of non-alcoholic steatohepatitis in adults with non-alcoholic fatty liver disease: Possible role for mapk and nf-kappab? Am J Gastroenterol 111(6):852–863.  https://doi.org/10.1038/ajg.2016.51 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Dasarathy J, Periyalwar P, Allampati S, Bhinder V, Hawkins C, Brandt P, Khiyami A, McCullough AJ, Dasarathy S (2014) Hypovitaminosis D is associated with increased whole body fat mass and greater severity of non-alcoholic fatty liver disease. Liver Int 34(6):e118–127.  https://doi.org/10.1111/liv.12312 CrossRefPubMedGoogle Scholar
  17. 17.
    Targher G, Scorletti E, Mantovani A, Byrne CD (2013) Nonalcoholic fatty liver disease and reduced serum vitamin D(3) levels. Metab Syndr Relat Disord 11(4):217–228.  https://doi.org/10.1089/met.2013.0044 CrossRefPubMedGoogle Scholar
  18. 18.
    Patel YA, Henao R, Moylan CA, Guy CD, Piercy DL, Diehl AM, Abdelmalek MF (2016) Vitamin D is not associated with severity in NAFLD: results of a paired clinical and gene expression profile analysis. Am J Gastroenterol 111(11):1591–1598.  https://doi.org/10.1038/ajg.2016.406 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Bril F, Maximos M, Portillo-Sanchez P, Biernacki D, Lomonaco R, Subbarayan S, Correa M, Lo M, Suman A, Cusi K (2015) Relationship of vitamin D with insulin resistance and disease severity in non-alcoholic steatohepatitis. J Hepatol 62(2):405–411.  https://doi.org/10.1016/j.jhep.2014.08.040 CrossRefPubMedGoogle Scholar
  20. 20.
    Grammatiki M, Rapti E, Karras S, Ajjan RA, Kotsa K (2017) Vitamin D and diabetes mellitus: causal or casual association? Rev Endocr Metab Disord 18(2):227–241.  https://doi.org/10.1007/s11154-016-9403-y CrossRefPubMedGoogle Scholar
  21. 21.
    Barchetta I, Del Ben M, Angelico F, Di Martino M, Fraioli A, La Torre G, Saulle R, Perri L, Morini S, Tiberti C, Bertoccini L, Cimini FA, Panimolle F, Catalano C, Baroni MG, Cavallo MG (2016) No effects of oral vitamin D supplementation on non-alcoholic fatty liver disease in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial. BMC Med 14:92.  https://doi.org/10.1186/s12916-016-0638-y CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM, Endocrine Society (2011) Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96(7):1911–1930.  https://doi.org/10.1210/jc.2011-0385 CrossRefGoogle Scholar
  23. 23.
    Expert Panel of Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (2019) Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 285(19):2486–2497.  https://doi.org/10.1001/jama.285.19.2486 CrossRefGoogle Scholar
  24. 24.
    Nedlman L, Kurtz AB, Rifkin MD, Cooper HS, Pasto ME, Goldberg BB (1986) Sonography of diffuse benign liver disease: accuracy of pattern recognition and grading. Am J Roentgenol 146:1011–1015CrossRefGoogle Scholar
  25. 25.
    Joseph AE, Saverymuttu SH, Al-Sam S, Cook MG, Maxwell JD (1991) Comparison of liver histology with ultrasonography in assessing diffuse parenchymal liver disease. Clin Radiol 43:26–31CrossRefGoogle Scholar
  26. 26.
    Parente DB, Oliveira Neto JA, Brasil PEAA, Paiva FF, Ravani JPR, Gomes MB, Lanzoni V, Campos CFF, Machado-Silva L, Perez RM, Rodrigues RS (2018) Preperitoneal fat as a non-invasive marker of increased risk of severe non-alcoholic fatty liver disease in patients with type 2 diabetes. J Gastroenterol Hepatol 33(2):511–517.  https://doi.org/10.1111/jgh.13903 CrossRefPubMedGoogle Scholar
  27. 27.
    Suzuki R, Watanabe S, Hirai Y, Akiyama K, Nishide T, Matsushima Y, Murayama H, Ohshima H, Shinomiya M, Shirai K (1993) Abdominal wall fat index, estimated by ultrasonography, for assessment of the ratio of visceral fat to subcutaneous fat in the abdomen. Am J Med 95:309–314CrossRefGoogle Scholar
  28. 28.
    Armellini F, Zamboni M, Rigo L, Todesco T, Bergamo-Andreis IA, Procacci C, Bosello O (1990) The contribution of sonography to the measurement of intra-abdominal fat. J Clin Ultrasound 7:563–567CrossRefGoogle Scholar
  29. 29.
    Kawasaki S, Aoki K, Hasegawa O, Numata K, Tanaka K, Shibata N, Shimada S, Okamura A, Terauchi Y (2008) Sonographic evaluation of visceral fat by measuring para- and perirenal fat. J Clin Ultrasound 36(3):129–133CrossRefGoogle Scholar
  30. 30.
    Lirussi F, Vitturi N, Azzalini L, Orando S, Orlando R, Plebani M, Realdi G (2009) Perihepatic adipose tissue thickness: a new non-invasive marker of NAFLD? J Gastrointestin Liver Dis 18(1):61–66PubMedGoogle Scholar
  31. 31.
    Riley TR, Bruno MA (2005) Sonographic measurement of the thickness of subcutaneous tissue in non-alcoholic fatty liver disease versus other chronic liver disease. J Clin Ultrasound 9:439–441CrossRefGoogle Scholar
  32. 32.
    Moghazi S, Jones E, Schroepple J, Arya K, McClellan W, Hennigar RA, O'Neill WC (2005) Correlation of renal histopathology with sonographic findings. Kidney Int 67(4):1515–1520CrossRefGoogle Scholar
  33. 33.
    Core Team R (2016) R: a language and environment for statistical computing. R Foundation for Statistical Computing, ViennaGoogle Scholar
  34. 34.
    Targher G, Bertolini L, Padovani R, Rodella S, Zoppini G, Pichiri I, Sorgato C, Zenari L, Bonora E (2010) Prevalence of non-alcoholic fatty liver disease and its association with cardiovascular disease in patients with type 1 diabetes. J Hepatol 53(4):713–718.  https://doi.org/10.1016/j.jhep.2010.04.030 CrossRefPubMedGoogle Scholar
  35. 35.
    Kotronen A, Yki-Järvinen H (2008) Fatty liver: a novel component of the metabolic syndrome. Arterioscler Thromb Vasc Biol 28(1):27–38CrossRefGoogle Scholar
  36. 36.
    Prati D, Taioli E, Zanella A, Della Torre E, Butelli S, Del Vecchio E, Vianello L, Zanuso F, Mozzi F, Milani S, Conte D, Colombo M, Sirchia G (2002) Updated definitions of healthy ranges for serum alanine aminotransferase levels. Ann Intern Med 137(1):1–10CrossRefGoogle Scholar
  37. 37.
    Leeds JS, Forman EM, Morley S, Scott AR, Tesfaye S, Sanders DS (2009) Abnormal liver function tests in patients with Type 1 diabetes mellitus: prevalence, clinical correlations and underlying pathologies. Diabet Med 26(12):1235–1241.  https://doi.org/10.1111/j.1464-5491.2009.02839.x CrossRefPubMedGoogle Scholar
  38. 38.
    Mofrad P, Contos MJ, Haque M, Sargeant C, Fisher RA, Luketic VA, Sterling RK, Shiffman ML, Stravitz RT, Sanyal AJ (2003) Clinical and histological spectrum of nonalcoholic fatty liver disease associated with normal ALT values. Hepatology 37(6):1286–1292CrossRefGoogle Scholar
  39. 39.
    Vivier E, Artis D, Colonna M, Diefenbach A, Di Santo JP, Eberl G, Koyasu S, Locksley RM, McKenzie ANJ, Mebius RE, Powrie F, Spits H (2018) Innate lymphoid cells: 10 years on. Cell 174(5):1054–1066.  https://doi.org/10.1016/j.cell.2018.07.017 CrossRefPubMedGoogle Scholar
  40. 40.
    Garlanda C, Riva F, Bonavita E, Mantovani A (2013) Negative regulatory receptors of the IL_1 family. Semin Immunol 25:408–415CrossRefGoogle Scholar
  41. 41.
    Lamendola CA, Ariel D, Feldman D, Reaven GM (2012) Relations between obesity, insulin resistance, and 25-hydroxyvitamin D. Am J Clin Nutr 95(5):1055–1059.  https://doi.org/10.3945/ajcn.111.032060 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Byrne CD, Patel J, Scorletti E, Targher G (2018) Tests for diagnosing and monitoring non-alcoholic fatty liver disease in adults. BMJ 362:k2734.  https://doi.org/10.1136/bmj.k2734 CrossRefPubMedGoogle Scholar
  43. 43.
    European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO) (2016) EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol 64(6):1388–1402.  https://doi.org/10.1016/j.jhep.2015.11.004 (Epub 2016 Apr 7) CrossRefGoogle Scholar
  44. 44.
    Barchetta I, Cimini FA, Cavallo MG (2017) Vitamin D supplementation and non-alcoholic fatty liver disease: present and future. Nutrients 9(9):1015. (review).  https://doi.org/10.3390/nu9091015 CrossRefPubMedCentralGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2019

Authors and Affiliations

  • E. Cipponeri
    • 1
  • N. Vitturi
    • 1
  • V. Mariano
    • 1
  • F. Boscari
    • 1
  • S. Galasso
    • 1
  • C. Crepaldi
    • 1
  • G. P. Fadini
    • 1
  • S. Vigili de Kreutzenberg
    • 1
  • M. C. Marescotti
    • 1
  • E. Iori
    • 1
  • F. Cavallin
    • 2
  • L. Sartori
    • 3
  • A. Baritussio
    • 3
  • A. Avogaro
    • 1
  • D. Bruttomesso
    • 1
    Email author
  1. 1.Division of Metabolic Diseases, Department of MedicineUniversity of PadovaPadovaItaly
  2. 2.SolagnaItaly
  3. 3.Department of Medicine, Clinica Medica 1University of PadovaPadovaItaly

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