Vitamin D status and non-alcoholic fatty liver disease in patients with type 1 diabetes
- 82 Downloads
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 Google 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 Google 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 Google 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 Google 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 Google 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 Google 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 Google 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 Google 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 Google 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 Google 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 Google 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 Google 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 Google Scholar
- 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 146:1011–1015Google Scholar
- 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 43:26–31Google 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 Google Scholar
- 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 95:309–314Google Scholar
- 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 7:563–567Google Scholar
- 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):129–133Google Scholar
- 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):61–66Google Scholar
- 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 9:439–441Google Scholar
- 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):1515–1520Google 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 Google Scholar
- 35.Kotronen A, Yki-Järvinen H (2008) Fatty liver: a novel component of the metabolic syndrome. Arterioscler Thromb Vasc Biol 28(1):27–38Google Scholar
- 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):1–10Google Scholar
- 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):1286–1292Google Scholar
- 40.Garlanda C, Riva F, Bonavita E, Mantovani A (2013) Negative regulatory receptors of the IL_1 family. Semin Immunol 25:408–415Google 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) Google Scholar