Vitamin D status and non-alcoholic fatty liver disease in patients with type 1 diabetes
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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.
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.
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.
Vitamin D status appears to have no link with low-grade NAFLD in patients with type 1 diabetes.
KeywordsType 1 diabetes Non-alcoholic fatty liver disease (NAFLD) Vitamin D Ultrasound
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.
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 was obtained from all individual participants included in the study.
- 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.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
- 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.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
- 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.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.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
- 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.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
- 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.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
- 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.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.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
- 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
- 33.Core Team R (2016) R: a language and environment for statistical computing. R Foundation for Statistical Computing, ViennaGoogle Scholar
- 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
- 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
- 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