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Published in: BMC Medicine 1/2011

Open Access 01-12-2011 | Research article

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

Authors: Ilaria Barchetta, Francesco Angelico, Maria Del Ben, Marco Giorgio Baroni, Paolo Pozzilli, Sergio Morini, Maria Gisella Cavallo

Published in: BMC Medicine | Issue 1/2011

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Abstract

Background

Hypovitaminosis D has been recently recognized as a worldwide epidemic. Since vitamin D exerts significant metabolic activities, comprising free fatty acids (FFA) flux regulation from the periphery to the liver, its deficiency may promote fat deposition into the hepatocytes. Aim of our study was to test the hypothesis of a direct association between hypovitaminosis D and the presence of NAFLD in subjects with various degree of insulin-resistance and related metabolic disorders.

Methods

We studied 262 consecutive subjects referred to the Diabetes and Metabolic Diseases clinics for metabolic evaluation. NAFLD (non-alcoholic fatty liver disease) was diagnosed by upper abdomen ultrasonography, metabolic syndrome was identified according to the Third Report of National Cholesterol Education Program/Adult Treatment Panel (NCEP/ATPIII) modified criteria. Insulin-resistance was evaluated by means of HOMA-IR. Fatty-Liver-Index, a recently identified correlate of NAFLD, was also estimated. Serum 25(OH)vitamin D was measured by colorimetric method.

Results

Patients with NAFLD (n = 162,61.8%) had reduced serum 25(OH) vitamin D levels compared to subjects without NAFLD (14.8 ± 9.2 vs 20.5 ± 9.7 ng/ml, p < 0.001, OR 0.95, IC 95% 0.92-0.98). The relationship between NAFLD and reduced 25(OH)vitamin D levels was independent from age, sex, triglycerides, high density lipoproteins (HDL) and glycaemia (p < 0.005) and Fatty Liver Index inversely correlated with low 25(OH) vitamin D regardless sex, age and HOMA-IR (p < 0.007).

Conclusions

Low 25(OH)vitamin D levels are associated with the presence of NAFLD independently from metabolic syndrome, diabetes and insulin-resistance profile.
Literature
1.
go back to reference Bruyère O, Malaise O, Neuprez A, Collette J, Reginster JY: Prevalence of vitamin D inadequacy in European postmenopausal women. Curr Med Res Opin. 2007, 23: 1939-1944. 10.1185/030079907X219562.CrossRefPubMed Bruyère O, Malaise O, Neuprez A, Collette J, Reginster JY: Prevalence of vitamin D inadequacy in European postmenopausal women. Curr Med Res Opin. 2007, 23: 1939-1944. 10.1185/030079907X219562.CrossRefPubMed
2.
go back to reference Pinelli NR, Jaber LA, Brown MB, Herman WH: Serum 25-hydroxy vitamin d and insulin resistance, metabolic syndrome, and glucose intolerance among Arab Americans. Diabetes Care. 2010, 33: 1373-1375. 10.2337/dc09-2199.CrossRefPubMedPubMedCentral Pinelli NR, Jaber LA, Brown MB, Herman WH: Serum 25-hydroxy vitamin d and insulin resistance, metabolic syndrome, and glucose intolerance among Arab Americans. Diabetes Care. 2010, 33: 1373-1375. 10.2337/dc09-2199.CrossRefPubMedPubMedCentral
3.
go back to reference Anderson JL, May HT, Horne BD, Bair TL, Hall NL, Carlquist JF, Intermountain Heart Collaborative (IHC) Study Group, et al: Relation of vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population. Am J Cardiol. 2010, 106: 963-968. 10.1016/j.amjcard.2010.05.027.CrossRefPubMed Anderson JL, May HT, Horne BD, Bair TL, Hall NL, Carlquist JF, Intermountain Heart Collaborative (IHC) Study Group, et al: Relation of vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population. Am J Cardiol. 2010, 106: 963-968. 10.1016/j.amjcard.2010.05.027.CrossRefPubMed
4.
go back to reference Kendrick J, Targher G, Smits G, Chonchol M: 25-Hydroxyvitamin D deficiency is independently associated with cardiovascular disease in the Third National Health and Nutrition Examination Survey. Atherosclerosis. 2009, 205: 255-260. 10.1016/j.atherosclerosis.2008.10.033.CrossRefPubMed Kendrick J, Targher G, Smits G, Chonchol M: 25-Hydroxyvitamin D deficiency is independently associated with cardiovascular disease in the Third National Health and Nutrition Examination Survey. Atherosclerosis. 2009, 205: 255-260. 10.1016/j.atherosclerosis.2008.10.033.CrossRefPubMed
5.
go back to reference Pittas AG, Lau J, Hu FB, Dawson-Hughes B: The role of vitamin D and calcium in type 2 diabetes: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2007, 92: 2017-2029. 10.1210/jc.2007-0298.CrossRefPubMedPubMedCentral Pittas AG, Lau J, Hu FB, Dawson-Hughes B: The role of vitamin D and calcium in type 2 diabetes: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2007, 92: 2017-2029. 10.1210/jc.2007-0298.CrossRefPubMedPubMedCentral
6.
go back to reference Forouhi NG, Luan J, Cooper A, Boucher BJ, Wareham NJ: Baseline serum 25-hydroxy vitamin d is predictive of future glycemic status and insulin resistance: the Medical Research Council Ely Prospective Study 1990-2000. Diabetes. 2008, 57: 2619-25. 10.2337/db08-0593.CrossRefPubMedPubMedCentral Forouhi NG, Luan J, Cooper A, Boucher BJ, Wareham NJ: Baseline serum 25-hydroxy vitamin d is predictive of future glycemic status and insulin resistance: the Medical Research Council Ely Prospective Study 1990-2000. Diabetes. 2008, 57: 2619-25. 10.2337/db08-0593.CrossRefPubMedPubMedCentral
7.
go back to reference Hypponen E, Boucher BJ, Berry DJ, Power C: 25-hydroxyvitamin D, insulin-like growth factor 1 and metabolic syndrome at age 45y: a cross-sectional study in the 1958 British birth cohort. Diabetes. 2008, 57: 298-305.CrossRefPubMed Hypponen E, Boucher BJ, Berry DJ, Power C: 25-hydroxyvitamin D, insulin-like growth factor 1 and metabolic syndrome at age 45y: a cross-sectional study in the 1958 British birth cohort. Diabetes. 2008, 57: 298-305.CrossRefPubMed
8.
go back to reference Zhou QG, Hou FF, Guo ZJ, Liang M, Wang GB, Zhang X: 1,25-Dihydroxyvitamin D improved the free fatty-acid-induced insulin resistance in cultured C2C12 cells. Diabetes Metab Res Rev. 2004, 24: 459-464.CrossRef Zhou QG, Hou FF, Guo ZJ, Liang M, Wang GB, Zhang X: 1,25-Dihydroxyvitamin D improved the free fatty-acid-induced insulin resistance in cultured C2C12 cells. Diabetes Metab Res Rev. 2004, 24: 459-464.CrossRef
9.
go back to reference Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, et al: Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004, 40: 1387-1395. 10.1002/hep.20466.CrossRefPubMed Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, et al: Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004, 40: 1387-1395. 10.1002/hep.20466.CrossRefPubMed
10.
go back to reference Bedogni G, Miglioli L, Masutti F, Castiglione A, Crocè LS, Tiribelli C, et al: Incidence and natural course of fatty liver in the general population: the Dionysos study. Hepatology. 2007, 46: 1387-1391. 10.1002/hep.21827.CrossRefPubMed Bedogni G, Miglioli L, Masutti F, Castiglione A, Crocè LS, Tiribelli C, et al: Incidence and natural course of fatty liver in the general population: the Dionysos study. Hepatology. 2007, 46: 1387-1391. 10.1002/hep.21827.CrossRefPubMed
11.
go back to reference Gupte P, Amarapurkar D, Agal S, Baijal R, Kulshrestha P, Pramanik S, et al: Non-alcoholic steatohepatitis in type 2 diabetes mellitus. Journal of Gastroenterology and Hepatology. 2004, 19: 854-858. 10.1111/j.1440-1746.2004.03312.x.CrossRefPubMed Gupte P, Amarapurkar D, Agal S, Baijal R, Kulshrestha P, Pramanik S, et al: Non-alcoholic steatohepatitis in type 2 diabetes mellitus. Journal of Gastroenterology and Hepatology. 2004, 19: 854-858. 10.1111/j.1440-1746.2004.03312.x.CrossRefPubMed
12.
go back to reference Leite NC, Salles GF, Araujo AL, Villela-Nogueira CA, Cardoso CR: Prevalence and associated factors of non-alcoholic fatty liver disease in patients with type-2 diabetes mellitus. Liver Int. 2009, 29: 113-119. 10.1111/j.1478-3231.2008.01718.x.CrossRefPubMed Leite NC, Salles GF, Araujo AL, Villela-Nogueira CA, Cardoso CR: Prevalence and associated factors of non-alcoholic fatty liver disease in patients with type-2 diabetes mellitus. Liver Int. 2009, 29: 113-119. 10.1111/j.1478-3231.2008.01718.x.CrossRefPubMed
13.
go back to reference Powell EE, Jonsson JR, Clouston AD: Dangerous liaisons: the metabolic syndrome and nonalcoholic fatty liver disease. Ann Intern Med. 2005, 143: 753-754.CrossRefPubMed Powell EE, Jonsson JR, Clouston AD: Dangerous liaisons: the metabolic syndrome and nonalcoholic fatty liver disease. Ann Intern Med. 2005, 143: 753-754.CrossRefPubMed
14.
go back to reference McCullough AJ: The clinical features, diagnosis and natural history of nonalcoholic fatty liver disease. Clin Liver Dis. 2004, 8: 521-533. 10.1016/j.cld.2004.04.004.CrossRefPubMed McCullough AJ: The clinical features, diagnosis and natural history of nonalcoholic fatty liver disease. Clin Liver Dis. 2004, 8: 521-533. 10.1016/j.cld.2004.04.004.CrossRefPubMed
15.
go back to reference Farrell GC, Larter CZ: Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology. 2006, 4: S99-S112.CrossRef Farrell GC, Larter CZ: Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology. 2006, 4: S99-S112.CrossRef
16.
go back to reference Caldwell SH, Crespo DM: The spectrum expanded: cryptogenic cirrhosis and the natural history of non-alcoholic fatty liver disease. Journal of Hepatology. 2004, 40: 578-584. 10.1016/j.jhep.2004.02.013.CrossRefPubMed Caldwell SH, Crespo DM: The spectrum expanded: cryptogenic cirrhosis and the natural history of non-alcoholic fatty liver disease. Journal of Hepatology. 2004, 40: 578-584. 10.1016/j.jhep.2004.02.013.CrossRefPubMed
17.
go back to reference Targher G, Day CP, Bonora E: Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med. 2010, 363: 1341-1350. 10.1056/NEJMra0912063.CrossRefPubMed Targher G, Day CP, Bonora E: Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med. 2010, 363: 1341-1350. 10.1056/NEJMra0912063.CrossRefPubMed
18.
go back to reference Angelico F, Del Ben M, Conti R, Francioso S, Feole K, Fiorello S, Cavallo MG, et al: Insulin resistance, the metabolic syndrome, and nonalcoholic fatty liver disease. J Clin Endocrinol Metab. 2004, 90: 1578-1582. 10.1210/jc.2004-1024.CrossRefPubMed Angelico F, Del Ben M, Conti R, Francioso S, Feole K, Fiorello S, Cavallo MG, et al: Insulin resistance, the metabolic syndrome, and nonalcoholic fatty liver disease. J Clin Endocrinol Metab. 2004, 90: 1578-1582. 10.1210/jc.2004-1024.CrossRefPubMed
19.
go back to reference Fujita K, Nozaki Y, Wada K, Yoneda M, Fujimoto Y, Fujitake M, et al: Dysfunctional very-low-density lipoprotein synthesis and release is a key factor in nonalcoholic steatohepatitis pathogenesis. Hepatology. 2009, 50: 772-780. 10.1002/hep.23094.CrossRefPubMed Fujita K, Nozaki Y, Wada K, Yoneda M, Fujimoto Y, Fujitake M, et al: Dysfunctional very-low-density lipoprotein synthesis and release is a key factor in nonalcoholic steatohepatitis pathogenesis. Hepatology. 2009, 50: 772-780. 10.1002/hep.23094.CrossRefPubMed
20.
go back to reference Kotronen A, Westerbacka J, Bergholm R, Pietiläinen KH, Yki-Järvinen H: Liver fat in the metabolic syndrome. J Clin Endocrinol Metab. 2007, 92: 3490-3497. 10.1210/jc.2007-0482.CrossRefPubMed Kotronen A, Westerbacka J, Bergholm R, Pietiläinen KH, Yki-Järvinen H: Liver fat in the metabolic syndrome. J Clin Endocrinol Metab. 2007, 92: 3490-3497. 10.1210/jc.2007-0482.CrossRefPubMed
21.
go back to reference Matsuda M, DeFronzo RA: Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care. 1999, 22: 1462-1470. 10.2337/diacare.22.9.1462.CrossRefPubMed Matsuda M, DeFronzo RA: Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care. 1999, 22: 1462-1470. 10.2337/diacare.22.9.1462.CrossRefPubMed
22.
go back to reference Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al: Diagnosis and management of the metabolic syndrome. An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Executive Summary. Circulation. 2005, 112: e285-e290. 10.1161/CIRCULATIONAHA.105.169405.CrossRef Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al: Diagnosis and management of the metabolic syndrome. An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Executive Summary. Circulation. 2005, 112: e285-e290. 10.1161/CIRCULATIONAHA.105.169405.CrossRef
24.
go back to reference Saverymuttu SH, Joseph AE, Maxwell JD: Ultrasound scanning in the detection of hepatic fibrosis and steatosis. Br Med J (Clin Res Ed). 1986, 292: 13-15. 10.1136/bmj.292.6512.13.CrossRef Saverymuttu SH, Joseph AE, Maxwell JD: Ultrasound scanning in the detection of hepatic fibrosis and steatosis. Br Med J (Clin Res Ed). 1986, 292: 13-15. 10.1136/bmj.292.6512.13.CrossRef
25.
go back to reference Bedogni G, Bellentani S, Miglioli L, Masutti F, Passalacqua M, Castiglione A, et al: The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gatroenterology. 2006, 6: 33-10.1186/1471-230X-6-33.CrossRef Bedogni G, Bellentani S, Miglioli L, Masutti F, Passalacqua M, Castiglione A, et al: The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gatroenterology. 2006, 6: 33-10.1186/1471-230X-6-33.CrossRef
26.
27.
go back to reference DeLuca HF: Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr. 2004, 80: 1689S-1696S.PubMed DeLuca HF: Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr. 2004, 80: 1689S-1696S.PubMed
28.
go back to reference Lips P: Vitamin D status and nutrition in Europe and Asia. J Steroid Biochem Mol Biol. 2007, 103: 620-625. 10.1016/j.jsbmb.2006.12.076.CrossRefPubMed Lips P: Vitamin D status and nutrition in Europe and Asia. J Steroid Biochem Mol Biol. 2007, 103: 620-625. 10.1016/j.jsbmb.2006.12.076.CrossRefPubMed
29.
go back to reference Targher G, Bertolini L, Scala L, Cigolini M, Zenari L, Falezza G, et al: Associations between serum 25-hydroxyvitamin D3 concentrations and liver histology in patients with non-alcoholic fatty liver disease. Nutr Metab Cardiovasc Dis. 2007, 17: 517-524. 10.1016/j.numecd.2006.04.002.CrossRefPubMed Targher G, Bertolini L, Scala L, Cigolini M, Zenari L, Falezza G, et al: Associations between serum 25-hydroxyvitamin D3 concentrations and liver histology in patients with non-alcoholic fatty liver disease. Nutr Metab Cardiovasc Dis. 2007, 17: 517-524. 10.1016/j.numecd.2006.04.002.CrossRefPubMed
30.
go back to reference Flegal KM, Shepherd JA, Looker AC, Graubard BI, Borrud LG, Ogden CL, et al: Comparisons of percentage body fat, body mass index, waist circumference, and waist-stature ratio in adults. Am J Clin Nutr. 2009, 89: 500-508. 10.3945/ajcn.2008.26847.CrossRefPubMed Flegal KM, Shepherd JA, Looker AC, Graubard BI, Borrud LG, Ogden CL, et al: Comparisons of percentage body fat, body mass index, waist circumference, and waist-stature ratio in adults. Am J Clin Nutr. 2009, 89: 500-508. 10.3945/ajcn.2008.26847.CrossRefPubMed
31.
go back to reference Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF: Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr. 2000, 72: 690-693.PubMed Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF: Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr. 2000, 72: 690-693.PubMed
32.
go back to reference Artaza JN, Norris KC: Vitamin D reduces the expression of collagen and key profibrotic factors by inducing an antifibrotic phenotype in mesenchymal multipotent cells. J Endocrinol. 2009, 200: 207-221.CrossRefPubMed Artaza JN, Norris KC: Vitamin D reduces the expression of collagen and key profibrotic factors by inducing an antifibrotic phenotype in mesenchymal multipotent cells. J Endocrinol. 2009, 200: 207-221.CrossRefPubMed
33.
go back to reference Garc ıade Leo, Model C, Montfort I, Tello Montes E, et al: Hepatocyte production of modulators of extracellular liver matrix in normal and cirrhotic rat liver. Exp Mol Pathol. 2006, 80 (1): 97-108.CrossRef Garc ıade Leo, Model C, Montfort I, Tello Montes E, et al: Hepatocyte production of modulators of extracellular liver matrix in normal and cirrhotic rat liver. Exp Mol Pathol. 2006, 80 (1): 97-108.CrossRef
34.
go back to reference Lange CM, Bojunga J, Ramos-Lopez E, von Wagner M, Hassler A, Vermehren J, et al: Vitamin D deficiency and a CYP27B1-1260 promoter polymorphism are associated with chronic hepatitis C and poor response to interferon-alfa based therapy. J Hepatol. 2011 Lange CM, Bojunga J, Ramos-Lopez E, von Wagner M, Hassler A, Vermehren J, et al: Vitamin D deficiency and a CYP27B1-1260 promoter polymorphism are associated with chronic hepatitis C and poor response to interferon-alfa based therapy. J Hepatol. 2011
35.
go back to reference Petta S, Cammà C, Scazzone C, Tripodo C, Di Marco V, Bono A, Cabibi D, et al: Low vitamin D serum level is related to severe fibrosis and low responsiveness to interferon-based therapy in genotype 1 chronic hepatitis C. Hepatology. 2010, 51 (4): 1158-1167. 10.1002/hep.23489.CrossRefPubMed Petta S, Cammà C, Scazzone C, Tripodo C, Di Marco V, Bono A, Cabibi D, et al: Low vitamin D serum level is related to severe fibrosis and low responsiveness to interferon-based therapy in genotype 1 chronic hepatitis C. Hepatology. 2010, 51 (4): 1158-1167. 10.1002/hep.23489.CrossRefPubMed
36.
go back to reference Bitetto D, Fabris C, Fornasiere E, Pipan C, Fumolo E, Cussigh A, et al: Vitamin D supplementation improves response to antiviral treatment for recurrent hepatitis C. Transpl Int. 2011, 24 (1): 43-50. 10.1111/j.1432-2277.2010.01141.x.CrossRefPubMed Bitetto D, Fabris C, Fornasiere E, Pipan C, Fumolo E, Cussigh A, et al: Vitamin D supplementation improves response to antiviral treatment for recurrent hepatitis C. Transpl Int. 2011, 24 (1): 43-50. 10.1111/j.1432-2277.2010.01141.x.CrossRefPubMed
37.
go back to reference Petta S, Camma C, Di Marco V, Alessi N, Cabibi D, Caldarella R, et al: Insulin resistance and diabetes increase fibrosis in the liver of patients with genotype 1 HCV infection. Am J Gastroenterol. 2008, 103: 1136-44. 10.1111/j.1572-0241.2008.01813.x.CrossRefPubMed Petta S, Camma C, Di Marco V, Alessi N, Cabibi D, Caldarella R, et al: Insulin resistance and diabetes increase fibrosis in the liver of patients with genotype 1 HCV infection. Am J Gastroenterol. 2008, 103: 1136-44. 10.1111/j.1572-0241.2008.01813.x.CrossRefPubMed
38.
go back to reference Moucari R, Asselah T, Cazals-Hatem D, Voitot H, Boyer N, Ripault MP, et al: Insulin resistance in chronic hepatitis C: association with genotypes 1 and 4, serum HCV RNA level, and liver fibrosis. Gastroenterology. 2008, 134: 416-423. 10.1053/j.gastro.2007.11.010.CrossRefPubMed Moucari R, Asselah T, Cazals-Hatem D, Voitot H, Boyer N, Ripault MP, et al: Insulin resistance in chronic hepatitis C: association with genotypes 1 and 4, serum HCV RNA level, and liver fibrosis. Gastroenterology. 2008, 134: 416-423. 10.1053/j.gastro.2007.11.010.CrossRefPubMed
Metadata
Title
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
Authors
Ilaria Barchetta
Francesco Angelico
Maria Del Ben
Marco Giorgio Baroni
Paolo Pozzilli
Sergio Morini
Maria Gisella Cavallo
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2011
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/1741-7015-9-85

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