Abstract
Background & Aims: Iron deficiency is often observed in obese individuals. The iron regulatory hormone hepcidin is regulated by iron and cytokines interleukin (IL) 6 and IL1β. We examine the relationship between obesity, circulating levels of hepcidin, and IL6 and IL1β, and other risk factors in patients with nonalcoholic fatty liver disease (NAFLD) with iron deficiency. Methods: We collected data on 675 adult subjects (>18 years old) enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network. Subjects with transferrin saturation <20% were categorized as iron deficient, whereas those with transferrin saturation ≥20% were classified as iron normal. We assessed clinical, demographic, anthropometric, laboratory, dietary, and histologic data from patients, and serum levels of hepcidin and cytokines IL6 and IL1β. Univariate and multivariate analysis were used to identify risk factors for iron deficiency. Results: One-third of patients (231 of 675; 34%) were iron deficient. Obesity, diabetes, and metabolic syndrome were more common in subjects with iron deficiency (P < .01), compared with those that were iron normal. Serum levels of hepcidin were significantly lower in subjects with iron deficiency (61 ± 45 vs 81 ± 51 ng/mL; P < .0001). Iron deficiency was significantly associated with female gender, obesity, increased body mass index and waist circumference, presence of diabetes, lower alcohol consumption, black or American Indian/Alaska Native race (P ≤ .018), and increased levels of IL6 and IL1β (6.6 vs 4.8 for iron normal, P ≤ .0001; and 0.45 vs 0.32 for iron normal, P ≤ .005). Conclusions: Iron deficiency is prevalent in patients with NAFLD and associated with female gender, increased body mass index, and nonwhite race. Serum levels of hepcidin were lower in iron-deficient subjects, reflecting an appropriate physiologic response to decreased circulating levels of iron, rather than a primary cause of iron deficiency in the setting of obesity and NAFLD.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1170-1178 |
| Number of pages | 9 |
| Journal | Clinical Gastroenterology and Hepatology |
| Volume | 12 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 2014 |
Keywords
- BMI
- Ferroportin
- Inflammation
- NAFLD
- NASH CRN
- Nutrition
ASJC Scopus subject areas
- Hepatology
- Gastroenterology
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Iron deficiency in patients with nonalcoholic fatty liver disease is associated with obesity, female gender, and low serum hepcidin. / Siddique, Asma; Nelson, James E.; Aouizerat, Bradley; Yeh, Matthew M.; Kowdley, Kris V.; Abrams, Stephanie H.; Himes, Ryan; Krisnamurthy, Rajesh; Maldonado, Leanel; Morris, Beverly; Brandt, Patricia; Dasarathy, Srinivasan; Dasarathy, Jaividhya; Hawkins, Carol; McCullough, Arthur J.; Pagadala, Mangesh; Pai, Rish; Sargent, Ruth; Shah, Shetal; Zein, Claudia; Bernstein, Kimberlee; Cecil, Kim; DeVore, Stephanie; Kohli, Rohit; Lake, Kathleen; Podberesky, Daniel; Slaughter, Crystal; Xanthakos, Stavra; Behr, Gerald; Lavine, Joel E.; Mencin, Ali; Ovchinsky, Nadia; Reynoso, Elena; Abdelmalek, Manal F.; Bashir, Mustafa; Buie, Stephanie; Diehl, Anna Mae; Guy, Cynthia; Kigongo, Christopher; Pan, Yi Ping; Piercy, Dawn; Wagner, Melissa; Alazraki, Adina; Cleeton, Rebecca; Karpen, Saul; Raviele, Nicholas; Vos, Miriam; Byam, Elizabeth; Chalasani, Naga; Cummings, Oscar W.; Fleming, Cynthia; Ghabril, Marwan; Klipsch, Ann; Marri, Smitha; Molleston, Jean P.; Ragozzino, Linda; Sandrasegaran, Kumar; Subbarao, Girish; Vuppalanchi, Raj; Pfeifer, Kimberly; Scheimann, Ann; Torbenson, Michael; Arnon, Ronen; Boyd, Mariel; Amsden, Katie; Fishbein, Mark H.; Kirwan, Elizabeth; Mohammad, Saeed; Quinn, Ann; Rigsby, Cynthia; Whitington, Peter F.; Barlow, Sarah; Derdoy, Jose; Jain, Ajay; King, Debra; Osmack, Pat; Siegner, Joan; Stewart, Susan; Neuschwander-Tetri, Brent A.; Romo, Dana; Ang, Brandon; Arroyo, Sandra; Behling, Cynthia; Bhatt, Archana; Collins, Jennifer; Doycheva, Iliana; Durelle, Janis; Hassanein, Tarek; Loomba, Rohit; Middleton, Michael; Newton, Kimberly; Nguyen, Phirum; Noureddin, Mazen; Paiz, Melissa; Patton, Heather; Schwimmer, Jeffrey B.; Sirlin, Claude; Ugalde-Nicalo, Patricia; Bass, Nathan M.; Brandman, Danielle; Ferrell, Linda D.; Fleck, Shannon; Gill, Ryan; Hameed, Bilal; Ko, Alexander; Langlois, Camille; Perito, Emily Rothbaum; Qayyum, Aliya; Rosenthal, Philip; Terrault, Norah; Tsai, Patrika; Atla, Pradeep; Hurtado, Cathy; Garcia, Rebekah; Garcia, Sonia; Sheikh, Muhammad; Singh, Mandeep; Cooper, Kara; Horslen, Simon; Hsu, Evelyn; Murray, Karen; Otto, Randolph; Rich, Deana; Yeh, Matthew; Young, Melissa; Boyett, Sherry; Carucci, Laura; Contos, Melissa J.; Fuchs, Michael; Jones, Amy; Kraft, Kenneth; Luketic, Velimir A.C.; Noble, Kimberly; Puri, Puneet; Sandhu, Bimalijit; Sanyal, Arun J.; Sargeant, Carol; Schlosser, Jolene; Siddiqui, Mohhamad S.; Wolford, Ben; White, Melanie; Ackermann, Sarah; Cooney, Shannon; Coy, David; Gelinas, Katie; Lee, Maximillian; Pierce, Tracey; Mooney, Jody; Siekas, Lacey; Shaw, Cheryl; Wang, Chia; Brunt, Elizabeth M.; Fowler, Kathryn; Kleiner, David E.; Grave, Gilman D.; Doo, Edward C.; Hoofnagle, Jay H.; Robuck, Patricia R.; Sherker, Averell; Belt, Patricia; Clark, Jeanne M.; Corless, Erin; Donithan, Michele; Isaacson, Milana; May, Kevin P.; Miriel, Laura; Sternberg, Alice; Tonascia, James; Aynur ünalp-Arida, ünalp-Arida; Natta, Mark Van; Vaughn, Ivana; Wilson, Laura; Yates, Katherine.
In: Clinical Gastroenterology and Hepatology, Vol. 12, No. 7, 07.2014, p. 1170-1178.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Iron deficiency in patients with nonalcoholic fatty liver disease is associated with obesity, female gender, and low serum hepcidin
AU - Siddique, Asma
AU - Nelson, James E.
AU - Aouizerat, Bradley
AU - Yeh, Matthew M.
AU - Kowdley, Kris V.
AU - Abrams, Stephanie H.
AU - Himes, Ryan
AU - Krisnamurthy, Rajesh
AU - Maldonado, Leanel
AU - Morris, Beverly
AU - Brandt, Patricia
AU - Dasarathy, Srinivasan
AU - Dasarathy, Jaividhya
AU - Hawkins, Carol
AU - McCullough, Arthur J.
AU - Pagadala, Mangesh
AU - Pai, Rish
AU - Sargent, Ruth
AU - Shah, Shetal
AU - Zein, Claudia
AU - Bernstein, Kimberlee
AU - Cecil, Kim
AU - DeVore, Stephanie
AU - Kohli, Rohit
AU - Lake, Kathleen
AU - Podberesky, Daniel
AU - Slaughter, Crystal
AU - Xanthakos, Stavra
AU - Behr, Gerald
AU - Lavine, Joel E.
AU - Mencin, Ali
AU - Ovchinsky, Nadia
AU - Reynoso, Elena
AU - Abdelmalek, Manal F.
AU - Bashir, Mustafa
AU - Buie, Stephanie
AU - Diehl, Anna Mae
AU - Guy, Cynthia
AU - Kigongo, Christopher
AU - Pan, Yi Ping
AU - Piercy, Dawn
AU - Wagner, Melissa
AU - Alazraki, Adina
AU - Cleeton, Rebecca
AU - Karpen, Saul
AU - Raviele, Nicholas
AU - Vos, Miriam
AU - Byam, Elizabeth
AU - Chalasani, Naga
AU - Cummings, Oscar W.
AU - Fleming, Cynthia
AU - Ghabril, Marwan
AU - Klipsch, Ann
AU - Marri, Smitha
AU - Molleston, Jean P.
AU - Ragozzino, Linda
AU - Sandrasegaran, Kumar
AU - Subbarao, Girish
AU - Vuppalanchi, Raj
AU - Pfeifer, Kimberly
AU - Scheimann, Ann
AU - Torbenson, Michael
AU - Arnon, Ronen
AU - Boyd, Mariel
AU - Amsden, Katie
AU - Fishbein, Mark H.
AU - Kirwan, Elizabeth
AU - Mohammad, Saeed
AU - Quinn, Ann
AU - Rigsby, Cynthia
AU - Whitington, Peter F.
AU - Barlow, Sarah
AU - Derdoy, Jose
AU - Jain, Ajay
AU - King, Debra
AU - Osmack, Pat
AU - Siegner, Joan
AU - Stewart, Susan
AU - Neuschwander-Tetri, Brent A.
AU - Romo, Dana
AU - Ang, Brandon
AU - Arroyo, Sandra
AU - Behling, Cynthia
AU - Bhatt, Archana
AU - Collins, Jennifer
AU - Doycheva, Iliana
AU - Durelle, Janis
AU - Hassanein, Tarek
AU - Loomba, Rohit
AU - Middleton, Michael
AU - Newton, Kimberly
AU - Nguyen, Phirum
AU - Noureddin, Mazen
AU - Paiz, Melissa
AU - Patton, Heather
AU - Schwimmer, Jeffrey B.
AU - Sirlin, Claude
AU - Ugalde-Nicalo, Patricia
AU - Bass, Nathan M.
AU - Brandman, Danielle
AU - Ferrell, Linda D.
AU - Fleck, Shannon
AU - Gill, Ryan
AU - Hameed, Bilal
AU - Ko, Alexander
AU - Langlois, Camille
AU - Perito, Emily Rothbaum
AU - Qayyum, Aliya
AU - Rosenthal, Philip
AU - Terrault, Norah
AU - Tsai, Patrika
AU - Atla, Pradeep
AU - Hurtado, Cathy
AU - Garcia, Rebekah
AU - Garcia, Sonia
AU - Sheikh, Muhammad
AU - Singh, Mandeep
AU - Cooper, Kara
AU - Horslen, Simon
AU - Hsu, Evelyn
AU - Murray, Karen
AU - Otto, Randolph
AU - Rich, Deana
AU - Yeh, Matthew
AU - Young, Melissa
AU - Boyett, Sherry
AU - Carucci, Laura
AU - Contos, Melissa J.
AU - Fuchs, Michael
AU - Jones, Amy
AU - Kraft, Kenneth
AU - Luketic, Velimir A.C.
AU - Noble, Kimberly
AU - Puri, Puneet
AU - Sandhu, Bimalijit
AU - Sanyal, Arun J.
AU - Sargeant, Carol
AU - Schlosser, Jolene
AU - Siddiqui, Mohhamad S.
AU - Wolford, Ben
AU - White, Melanie
AU - Ackermann, Sarah
AU - Cooney, Shannon
AU - Coy, David
AU - Gelinas, Katie
AU - Lee, Maximillian
AU - Pierce, Tracey
AU - Mooney, Jody
AU - Siekas, Lacey
AU - Shaw, Cheryl
AU - Wang, Chia
AU - Brunt, Elizabeth M.
AU - Fowler, Kathryn
AU - Kleiner, David E.
AU - Grave, Gilman D.
AU - Doo, Edward C.
AU - Hoofnagle, Jay H.
AU - Robuck, Patricia R.
AU - Sherker, Averell
AU - Belt, Patricia
AU - Clark, Jeanne M.
AU - Corless, Erin
AU - Donithan, Michele
AU - Isaacson, Milana
AU - May, Kevin P.
AU - Miriel, Laura
AU - Sternberg, Alice
AU - Tonascia, James
AU - Aynur ünalp-Arida, ünalp-Arida
AU - Natta, Mark Van
AU - Vaughn, Ivana
AU - Wilson, Laura
AU - Yates, Katherine
N1 - Funding Information: Funding The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (grants U01DK061718 , U01DK061728 , U01DK061731 , U01DK061732 , U01DK061734 , U01DK061737 , U01DK061738 , U01DK061730 , and U01DK061713 ) and the National Institute of Child Health and Human Development . Several clinical centers use support from the National Center for Advancing Translational Sciences in conduct of NASH CRN Studies (grants UL1TR000439 , UL1TR000077 , UL1TR000436 , UL1TR000150 , UL1TR000424 , UL1TR000006 , UL1TR000448 , UL1TR000040 , UL1TR000100 , UL1TR000004 , UL1TR000423 , UL1TR000058 , UL1TR000067 , and UL1TR000454 ). This work was supported in part by the Intramural Research Program of the National Cancer Institute .
PY - 2014/7
Y1 - 2014/7
N2 - Background & Aims: Iron deficiency is often observed in obese individuals. The iron regulatory hormone hepcidin is regulated by iron and cytokines interleukin (IL) 6 and IL1β. We examine the relationship between obesity, circulating levels of hepcidin, and IL6 and IL1β, and other risk factors in patients with nonalcoholic fatty liver disease (NAFLD) with iron deficiency. Methods: We collected data on 675 adult subjects (>18 years old) enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network. Subjects with transferrin saturation <20% were categorized as iron deficient, whereas those with transferrin saturation ≥20% were classified as iron normal. We assessed clinical, demographic, anthropometric, laboratory, dietary, and histologic data from patients, and serum levels of hepcidin and cytokines IL6 and IL1β. Univariate and multivariate analysis were used to identify risk factors for iron deficiency. Results: One-third of patients (231 of 675; 34%) were iron deficient. Obesity, diabetes, and metabolic syndrome were more common in subjects with iron deficiency (P < .01), compared with those that were iron normal. Serum levels of hepcidin were significantly lower in subjects with iron deficiency (61 ± 45 vs 81 ± 51 ng/mL; P < .0001). Iron deficiency was significantly associated with female gender, obesity, increased body mass index and waist circumference, presence of diabetes, lower alcohol consumption, black or American Indian/Alaska Native race (P ≤ .018), and increased levels of IL6 and IL1β (6.6 vs 4.8 for iron normal, P ≤ .0001; and 0.45 vs 0.32 for iron normal, P ≤ .005). Conclusions: Iron deficiency is prevalent in patients with NAFLD and associated with female gender, increased body mass index, and nonwhite race. Serum levels of hepcidin were lower in iron-deficient subjects, reflecting an appropriate physiologic response to decreased circulating levels of iron, rather than a primary cause of iron deficiency in the setting of obesity and NAFLD.
AB - Background & Aims: Iron deficiency is often observed in obese individuals. The iron regulatory hormone hepcidin is regulated by iron and cytokines interleukin (IL) 6 and IL1β. We examine the relationship between obesity, circulating levels of hepcidin, and IL6 and IL1β, and other risk factors in patients with nonalcoholic fatty liver disease (NAFLD) with iron deficiency. Methods: We collected data on 675 adult subjects (>18 years old) enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network. Subjects with transferrin saturation <20% were categorized as iron deficient, whereas those with transferrin saturation ≥20% were classified as iron normal. We assessed clinical, demographic, anthropometric, laboratory, dietary, and histologic data from patients, and serum levels of hepcidin and cytokines IL6 and IL1β. Univariate and multivariate analysis were used to identify risk factors for iron deficiency. Results: One-third of patients (231 of 675; 34%) were iron deficient. Obesity, diabetes, and metabolic syndrome were more common in subjects with iron deficiency (P < .01), compared with those that were iron normal. Serum levels of hepcidin were significantly lower in subjects with iron deficiency (61 ± 45 vs 81 ± 51 ng/mL; P < .0001). Iron deficiency was significantly associated with female gender, obesity, increased body mass index and waist circumference, presence of diabetes, lower alcohol consumption, black or American Indian/Alaska Native race (P ≤ .018), and increased levels of IL6 and IL1β (6.6 vs 4.8 for iron normal, P ≤ .0001; and 0.45 vs 0.32 for iron normal, P ≤ .005). Conclusions: Iron deficiency is prevalent in patients with NAFLD and associated with female gender, increased body mass index, and nonwhite race. Serum levels of hepcidin were lower in iron-deficient subjects, reflecting an appropriate physiologic response to decreased circulating levels of iron, rather than a primary cause of iron deficiency in the setting of obesity and NAFLD.
KW - BMI
KW - Ferroportin
KW - Inflammation
KW - NAFLD
KW - NASH CRN
KW - Nutrition
UR - http://www.scopus.com/inward/record.url?scp=84902533159&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84902533159&partnerID=8YFLogxK
U2 - 10.1016/j.cgh.2013.11.017
DO - 10.1016/j.cgh.2013.11.017
M3 - Article
C2 - 24269922
AN - SCOPUS:84902533159
VL - 12
SP - 1170
EP - 1178
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
SN - 1542-3565
IS - 7
ER -