Association between familial hypobetalipoproteinemia and the risk of diabetes. Is this the other side of the cholesterol–diabetes connection? A systematic review of literature

go back to reference UK Prospective Diabetes Study (UKPDS) Group (1998) Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 352(9131):837–853CrossRef UK Prospective Diabetes Study (UKPDS) Group (1998) Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 352(9131):837–853CrossRef

go back to reference Cholesterol Treatment Trialists’ (CTT) Collaborators, Kearney PM, Blackwell L, Collins R, Keech A, Simes J, Peto R, Armitage J, Baigent C (2008) Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet 371(9607):117–125CrossRef Cholesterol Treatment Trialists’ (CTT) Collaborators, Kearney PM, Blackwell L, Collins R, Keech A, Simes J, Peto R, Armitage J, Baigent C (2008) Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet 371(9607):117–125CrossRef

go back to reference Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJ, Seshasai SR, McMurray JJ, Freeman DJ, Jukema JW, Macfarlane PW, Packard CJ, Stott DJ, Westendorp RG, Shepherd J, Davis BR, Pressel SL, Marchioli R, Marfisi RM, Maggioni AP, Tavazzi L, Tognoni G, Kjekshus J, Pedersen TR, Cook TJ, Gotto AM, Clearfield MB, Downs JR, Nakamura H, Ohashi Y, Mizuno K, Ray KK, Ford I (2010) Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet 375(9716):735–742. doi:10.1016/S0140-6736(09)61965-6 CrossRefPubMed Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJ, Seshasai SR, McMurray JJ, Freeman DJ, Jukema JW, Macfarlane PW, Packard CJ, Stott DJ, Westendorp RG, Shepherd J, Davis BR, Pressel SL, Marchioli R, Marfisi RM, Maggioni AP, Tavazzi L, Tognoni G, Kjekshus J, Pedersen TR, Cook TJ, Gotto AM, Clearfield MB, Downs JR, Nakamura H, Ohashi Y, Mizuno K, Ray KK, Ford I (2010) Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet 375(9716):735–742. doi:10.​1016/​S0140-6736(09)61965-6 CrossRefPubMed

go back to reference Swerdlow DI, Preiss D, Kuchenbaecker KB, Holmes MV, Engmann JE, Shah T, Sofat R, Stender S, Johnson PC, Scott RA, Leusink M, Verweij N, Sharp SJ, Guo Y, Giambartolomei C, Chung C, Peasey A, Amuzu A, Li K, Palmen J, Howard P, Cooper JA, Drenos F, Li YR, Lowe G, Gallacher J, Stewart MC, Tzoulaki I, Buxbaum SG, van der A DL, Forouhi NG, Onland-Moret NC, van der Schouw YT, Schnabel RB, Hubacek JA, Kubinova R, Baceviciene M, Tamosiunas A, Pajak A, Topor-Madry R, Stepaniak U, Malyutina S, Baldassarre D, Sennblad B, Tremoli E, de Faire U, Veglia F, Ford I, Jukema JW, Westendorp RG, de Borst GJ, de Jong PA, Algra A, Spiering W, Maitland-van der Zee AH, Klungel OH, de Boer A, Doevendans PA, Eaton CB, Robinson JG, Duggan D; DIAGRAM Consortium; MAGIC Consortium; InterAct Consortium, Kjekshus J, Downs JR, Gotto AM, Keech AC, Marchioli R, Tognoni G, Sever PS, Poulter NR, Waters DD, Pedersen TR, Amarenco P, Nakamura H, McMurray JJ, Lewsey JD, Chasman DI, Ridker PM, Maggioni AP, Tavazzi L, Ray KK, Seshasai SR, Manson JE, Price JF, Whincup PH, Morris RW, Lawlor DA, Smith GD, Ben-Shlomo Y, Schreiner PJ, Fornage M, Siscovick DS, Cushman M, Kumari M, Wareham NJ, Verschuren WM, Redline S, Patel SR, Whittaker JC, Hamsten A, Delaney JA, Dale C, Gaunt TR, Wong A, Kuh D, Hardy R, Kathiresan S, Castillo BA, van der Harst P, Brunner EJ, Tybjaerg-Hansen A, Marmot MG, Krauss RM, Tsai M, Coresh J, Hoogeveen RC, Psaty BM, Lange LA, Hakonarson H, Dudbridge F, Humphries SE, Talmud PJ, Kivimäki M, Timpson NJ, Langenberg C, Asselbergs FW, Voevoda M, Bobak M, Pikhart H, Wilson JG, Reiner AP, Keating BJ, Hingorani AD, Sattar N (2015). HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials. Lancet 385(9965):351–361. doi:10.1016/S0140-6736(14)61183-1 Swerdlow DI, Preiss D, Kuchenbaecker KB, Holmes MV, Engmann JE, Shah T, Sofat R, Stender S, Johnson PC, Scott RA, Leusink M, Verweij N, Sharp SJ, Guo Y, Giambartolomei C, Chung C, Peasey A, Amuzu A, Li K, Palmen J, Howard P, Cooper JA, Drenos F, Li YR, Lowe G, Gallacher J, Stewart MC, Tzoulaki I, Buxbaum SG, van der A DL, Forouhi NG, Onland-Moret NC, van der Schouw YT, Schnabel RB, Hubacek JA, Kubinova R, Baceviciene M, Tamosiunas A, Pajak A, Topor-Madry R, Stepaniak U, Malyutina S, Baldassarre D, Sennblad B, Tremoli E, de Faire U, Veglia F, Ford I, Jukema JW, Westendorp RG, de Borst GJ, de Jong PA, Algra A, Spiering W, Maitland-van der Zee AH, Klungel OH, de Boer A, Doevendans PA, Eaton CB, Robinson JG, Duggan D; DIAGRAM Consortium; MAGIC Consortium; InterAct Consortium, Kjekshus J, Downs JR, Gotto AM, Keech AC, Marchioli R, Tognoni G, Sever PS, Poulter NR, Waters DD, Pedersen TR, Amarenco P, Nakamura H, McMurray JJ, Lewsey JD, Chasman DI, Ridker PM, Maggioni AP, Tavazzi L, Ray KK, Seshasai SR, Manson JE, Price JF, Whincup PH, Morris RW, Lawlor DA, Smith GD, Ben-Shlomo Y, Schreiner PJ, Fornage M, Siscovick DS, Cushman M, Kumari M, Wareham NJ, Verschuren WM, Redline S, Patel SR, Whittaker JC, Hamsten A, Delaney JA, Dale C, Gaunt TR, Wong A, Kuh D, Hardy R, Kathiresan S, Castillo BA, van der Harst P, Brunner EJ, Tybjaerg-Hansen A, Marmot MG, Krauss RM, Tsai M, Coresh J, Hoogeveen RC, Psaty BM, Lange LA, Hakonarson H, Dudbridge F, Humphries SE, Talmud PJ, Kivimäki M, Timpson NJ, Langenberg C, Asselbergs FW, Voevoda M, Bobak M, Pikhart H, Wilson JG, Reiner AP, Keating BJ, Hingorani AD, Sattar N (2015). HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials. Lancet 385(9965):351–361. doi:10.​1016/​S0140-6736(14)61183-1

go back to reference Beckett RD, Schepers SM, Gordon SK (2015) Risk of new-onset diabetes associated with statin use. SAGE Open Med. doi:10.1177/2050312115605518 PubMedPubMedCentral Beckett RD, Schepers SM, Gordon SK (2015) Risk of new-onset diabetes associated with statin use. SAGE Open Med. doi:10.​1177/​2050312115605518​ PubMedPubMedCentral

go back to reference Besseling J, Kastelein JJ, Defesche JC, Hutten BA, Hovingh GK (2015) Association between familial hypercholesterolemia and prevalence of type 2 diabetes mellitus. JAMA 313(10):1029–1036CrossRefPubMed Besseling J, Kastelein JJ, Defesche JC, Hutten BA, Hovingh GK (2015) Association between familial hypercholesterolemia and prevalence of type 2 diabetes mellitus. JAMA 313(10):1029–1036CrossRefPubMed

go back to reference Abifadel M, Varret M, Rabès JP, Allard D, Ouguerram K, Devillers M, Cruaud C, Benjannet S, Wickham L, Erlich D, Derré A, Villéger L, Farnier M, Beucler I, Bruckert E, Chambaz J, Chanu B, Lecerf JM, Luc G, Moulin P, Weissenbach J, Prat A, Krempf M, Junien C, Seidah NG, Boileau C (2003) Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet 34(2):154–156CrossRefPubMed Abifadel M, Varret M, Rabès JP, Allard D, Ouguerram K, Devillers M, Cruaud C, Benjannet S, Wickham L, Erlich D, Derré A, Villéger L, Farnier M, Beucler I, Bruckert E, Chambaz J, Chanu B, Lecerf JM, Luc G, Moulin P, Weissenbach J, Prat A, Krempf M, Junien C, Seidah NG, Boileau C (2003) Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet 34(2):154–156CrossRefPubMed

go back to reference Minicocci I, Santini S, Cantisani V, Stitziel N, Kathiresan S, Arroyo JA, Martí G, Pisciotta L, Noto D, Cefalù AB, Maranghi M, Labbadia G, Pigna G, Pannozzo F, Ceci F, Ciociola E, Bertolini S, Calandra S, Tarugi P, Averna M, Arca M (2013) Clinical characteristics and plasma lipids in subjects with familial combined hypolipidemia: a pooled analysis. J Lipid Res 54(12):3481–3490CrossRefPubMedPubMedCentral Minicocci I, Santini S, Cantisani V, Stitziel N, Kathiresan S, Arroyo JA, Martí G, Pisciotta L, Noto D, Cefalù AB, Maranghi M, Labbadia G, Pigna G, Pannozzo F, Ceci F, Ciociola E, Bertolini S, Calandra S, Tarugi P, Averna M, Arca M (2013) Clinical characteristics and plasma lipids in subjects with familial combined hypolipidemia: a pooled analysis. J Lipid Res 54(12):3481–3490CrossRefPubMedPubMedCentral

go back to reference Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, Shekelle P, Stewart LA, PRISMA-P Group (2015) Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ 349:g7647CrossRefPubMed Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, Shekelle P, Stewart LA, PRISMA-P Group (2015) Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ 349:g7647CrossRefPubMed

go back to reference Noto D, Barbagallo CM, Cefalù AB, Falletta A, Sapienza M, Cavera G, Amato S, Pagano M, Maggiore M, Carroccio A, Notarbartolo A, Averna MR (2008) The metabolic syndrome predicts cardiovascular events in subjects with normal fasting glucose: results of a 15 years follow-up in a Mediterranean population. Atherosclerosis 197(1):147–153CrossRefPubMed Noto D, Barbagallo CM, Cefalù AB, Falletta A, Sapienza M, Cavera G, Amato S, Pagano M, Maggiore M, Carroccio A, Notarbartolo A, Averna MR (2008) The metabolic syndrome predicts cardiovascular events in subjects with normal fasting glucose: results of a 15 years follow-up in a Mediterranean population. Atherosclerosis 197(1):147–153CrossRefPubMed

go back to reference Noto D, Cefalù AB, Barbagallo CM, Falletta A, Ganci A, Sapienza M, Cavera G, Nardi I, Pagano M, Notarbartolo A, Averna MR (2012) Prediction of incident type 2 diabetes mellitus based on a twenty-year follow-up of the Ventimiglia heart study. Acta Diabetol 49(2):145–151CrossRefPubMed Noto D, Cefalù AB, Barbagallo CM, Falletta A, Ganci A, Sapienza M, Cavera G, Nardi I, Pagano M, Notarbartolo A, Averna MR (2012) Prediction of incident type 2 diabetes mellitus based on a twenty-year follow-up of the Ventimiglia heart study. Acta Diabetol 49(2):145–151CrossRefPubMed

go back to reference Tarugi P, Averna M, Di Leo E, Cefalù AB, Noto D, Magnolo L, Cattin L, Bertolini S, Calandra S (2007) Molecular diagnosis of hypobetalipoproteinemia: an ENID review. Atherosclerosis 195(2):19–27CrossRef Tarugi P, Averna M, Di Leo E, Cefalù AB, Noto D, Magnolo L, Cattin L, Bertolini S, Calandra S (2007) Molecular diagnosis of hypobetalipoproteinemia: an ENID review. Atherosclerosis 195(2):19–27CrossRef

go back to reference Burnett JR, Zhong S, Jiang ZG, Hooper AJ, Fisher EA, McLeod RS, Zhao Y, Barrett PH, Hegele RA, van Bockxmeer FM, Zhang H, Vance DE, McKnight CJ, Yao Z (2007) Missense mutations in APOB within the betaalpha1 domain of human APOB-100 result in impaired secretion of ApoB and ApoB-containing lipoproteins in familial hypobetalipoproteinemia. J Biol Chem 282(33):24270–24283CrossRefPubMed Burnett JR, Zhong S, Jiang ZG, Hooper AJ, Fisher EA, McLeod RS, Zhao Y, Barrett PH, Hegele RA, van Bockxmeer FM, Zhang H, Vance DE, McKnight CJ, Yao Z (2007) Missense mutations in APOB within the betaalpha1 domain of human APOB-100 result in impaired secretion of ApoB and ApoB-containing lipoproteins in familial hypobetalipoproteinemia. J Biol Chem 282(33):24270–24283CrossRefPubMed

go back to reference Noto D, Cefalù AB, Cannizzaro A, Minà M, Fayer F, Valenti V, Barbagallo CM, Tuttolomondo A, Pinto A, Sciumè C, Licata G, Averna M (2009) Familial hypobetalipoproteinemia due to apolipoprotein B R463 W mutation causes intestinal fat accumulation and low postprandial lipemia. Atherosclerosis 206(1):193–198CrossRefPubMed Noto D, Cefalù AB, Cannizzaro A, Minà M, Fayer F, Valenti V, Barbagallo CM, Tuttolomondo A, Pinto A, Sciumè C, Licata G, Averna M (2009) Familial hypobetalipoproteinemia due to apolipoprotein B R463 W mutation causes intestinal fat accumulation and low postprandial lipemia. Atherosclerosis 206(1):193–198CrossRefPubMed

go back to reference Zhao Z, Tuakli-Wosornu Y, Lagace TA, Kinch L, Grishin NV, Horton JD, Cohen JC, Hobbs HH (2006) Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote. Am J Hum Genet 79(3):514–523CrossRefPubMedPubMedCentral Zhao Z, Tuakli-Wosornu Y, Lagace TA, Kinch L, Grishin NV, Horton JD, Cohen JC, Hobbs HH (2006) Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote. Am J Hum Genet 79(3):514–523CrossRefPubMedPubMedCentral

go back to reference Fasano T, Cefalù AB, Di Leo E, Noto D, Pollaccia D, Bocchi L, Valenti V, Bonardi R, Guardamagna O, Averna M, Tarugi P (2007) A novel loss of function mutation of PCSK9 gene in white subjects with low-plasma low-density lipoprotein cholesterol. Arterioscler Thromb Vasc Biol 27(3):677–681CrossRefPubMed Fasano T, Cefalù AB, Di Leo E, Noto D, Pollaccia D, Bocchi L, Valenti V, Bonardi R, Guardamagna O, Averna M, Tarugi P (2007) A novel loss of function mutation of PCSK9 gene in white subjects with low-plasma low-density lipoprotein cholesterol. Arterioscler Thromb Vasc Biol 27(3):677–681CrossRefPubMed

go back to reference Di Filippo M, Moulin P, Roy P, Samson-Bouma ME, Collardeau-Frachon S, Chebel-Dumont S, Peretti N, Dumortier J, Zoulim F, Fontanges T, Parini R, Rigoldi M, Furlan F, Mancini G, Bonnefont-Rousselot D, Bruckert E, Schmitz J, Scoazec JY, Charrière S, Villar-Fimbel S, Gottrand F, Dubern B, Doummar D, Joly F, Liard-Meillon ME, Lachaux A, Sassolas A (2014) Homozygous MTTP and APOB mutations may lead to hepatic steatosis and fibrosis despite metabolic differences in congenital hypocholesterolemia. J Hepatol 61(4):891–902CrossRefPubMed Di Filippo M, Moulin P, Roy P, Samson-Bouma ME, Collardeau-Frachon S, Chebel-Dumont S, Peretti N, Dumortier J, Zoulim F, Fontanges T, Parini R, Rigoldi M, Furlan F, Mancini G, Bonnefont-Rousselot D, Bruckert E, Schmitz J, Scoazec JY, Charrière S, Villar-Fimbel S, Gottrand F, Dubern B, Doummar D, Joly F, Liard-Meillon ME, Lachaux A, Sassolas A (2014) Homozygous MTTP and APOB mutations may lead to hepatic steatosis and fibrosis despite metabolic differences in congenital hypocholesterolemia. J Hepatol 61(4):891–902CrossRefPubMed

go back to reference Tanoli T, Yue P, Yablonskiy D, Schonfeld G (2004) Fatty liver in familial hypobetalipoproteinemia: roles of the APOB defects, intra-abdominal adipose tissue, and insulin sensitivity. J Lipid Res 45(5):941–947CrossRefPubMed Tanoli T, Yue P, Yablonskiy D, Schonfeld G (2004) Fatty liver in familial hypobetalipoproteinemia: roles of the APOB defects, intra-abdominal adipose tissue, and insulin sensitivity. J Lipid Res 45(5):941–947CrossRefPubMed

go back to reference Tarugi P, Lonardo A, Ballarini G, Grisendi A, Pulvirenti M, Bagni A, Calandra S (1996) Fatty liver in heterozygous hypobetalipoproteinemia caused by a novel truncated form of apolipoprotein B. Gastroenterology 111(4):1125–1133CrossRefPubMed Tarugi P, Lonardo A, Ballarini G, Grisendi A, Pulvirenti M, Bagni A, Calandra S (1996) Fatty liver in heterozygous hypobetalipoproteinemia caused by a novel truncated form of apolipoprotein B. Gastroenterology 111(4):1125–1133CrossRefPubMed

go back to reference Sankatsing RR, Fouchier SW, de Haan S, Hutten BA, de Groot E, Kastelein JJ, Stroes ES (2005) Hepatic and cardiovascular consequences of familial hypobetalipoproteinemia. Arterioscler Thromb Vasc Biol 25(9):1979–1984CrossRefPubMed Sankatsing RR, Fouchier SW, de Haan S, Hutten BA, de Groot E, Kastelein JJ, Stroes ES (2005) Hepatic and cardiovascular consequences of familial hypobetalipoproteinemia. Arterioscler Thromb Vasc Biol 25(9):1979–1984CrossRefPubMed

go back to reference Tarugi P, Lonardo A, Ballarini G, Erspamer L, Tondelli E, Bertolini S, Calandra S (2000) A study of fatty liver disease and plasma lipoproteins in a kindred with familial hypobetalipoproteinemia due to a novel truncated form of apolipoprotein B (APO B-54.5). J Hepatol 33(3):361–370CrossRefPubMed Tarugi P, Lonardo A, Ballarini G, Erspamer L, Tondelli E, Bertolini S, Calandra S (2000) A study of fatty liver disease and plasma lipoproteins in a kindred with familial hypobetalipoproteinemia due to a novel truncated form of apolipoprotein B (APO B-54.5). J Hepatol 33(3):361–370CrossRefPubMed

go back to reference Katsuda S, Kawashiri MA, Inazu A, Tada H, Tsuchida M, Kaneko Y, Nozue T, Nohara A, Okada T, Kobayashi J, Michishita I, Mabuchi H, Yamagishi M (2009) Apolipoprotein B gene mutations and fatty liver in Japanese hypobetalipoproteinemia. Clin Chim Acta 399(1–2):64–68CrossRefPubMed Katsuda S, Kawashiri MA, Inazu A, Tada H, Tsuchida M, Kaneko Y, Nozue T, Nohara A, Okada T, Kobayashi J, Michishita I, Mabuchi H, Yamagishi M (2009) Apolipoprotein B gene mutations and fatty liver in Japanese hypobetalipoproteinemia. Clin Chim Acta 399(1–2):64–68CrossRefPubMed

go back to reference Welty FK (2014) Hypobetalipoproteinemia and abetalipoproteinemia. Curr Opin Lipidol 25(3):161–168CrossRefPubMedPubMedCentral Welty FK (2014) Hypobetalipoproteinemia and abetalipoproteinemia. Curr Opin Lipidol 25(3):161–168CrossRefPubMedPubMedCentral

go back to reference Lam MC, Singham J, Hegele RA, Riazy M, Hiob MA, Francis G, Steinbrecher UP (2012) Familial hypobetalipoproteinemia-induced nonalcoholic steatohepatitis. Case Rep Gastroenterol 6(2):429–437CrossRefPubMedPubMedCentral Lam MC, Singham J, Hegele RA, Riazy M, Hiob MA, Francis G, Steinbrecher UP (2012) Familial hypobetalipoproteinemia-induced nonalcoholic steatohepatitis. Case Rep Gastroenterol 6(2):429–437CrossRefPubMedPubMedCentral

go back to reference Whitfield AJ, Barrett PH, Robertson K, Havlat MF, van Bockxmeer FM, Burnett JR (2005) Liver dysfunction and steatosis in familial hypobetalipoproteinemia. Clin Chem 51(1):266–269CrossRefPubMed Whitfield AJ, Barrett PH, Robertson K, Havlat MF, van Bockxmeer FM, Burnett JR (2005) Liver dysfunction and steatosis in familial hypobetalipoproteinemia. Clin Chem 51(1):266–269CrossRefPubMed

go back to reference Heeks LV, Hooper AJ, Adams LA, Robbins P, Barrett PH, van Bockxmeer FM, Burnett JR (2013) Non-alcoholic steatohepatitis-related cirrhosis in a patient with APOB L343 V familial hypobetalipoproteinaemia. Clin Chim Acta 421:121–125CrossRefPubMed Heeks LV, Hooper AJ, Adams LA, Robbins P, Barrett PH, van Bockxmeer FM, Burnett JR (2013) Non-alcoholic steatohepatitis-related cirrhosis in a patient with APOB L343 V familial hypobetalipoproteinaemia. Clin Chim Acta 421:121–125CrossRefPubMed

go back to reference Cefalù AB, Pirruccello JP, Noto D, Gabriel S, Valenti V, Gupta N, Spina R, Tarugi P, Kathiresan S, Averna MR (2013) A novel APOB mutation identified by exome sequencing cosegregates with steatosis, liver cancer, and hypocholesterolemia. Arterioscler Thromb Vasc Biol 33(8):2021–2025CrossRefPubMed Cefalù AB, Pirruccello JP, Noto D, Gabriel S, Valenti V, Gupta N, Spina R, Tarugi P, Kathiresan S, Averna MR (2013) A novel APOB mutation identified by exome sequencing cosegregates with steatosis, liver cancer, and hypocholesterolemia. Arterioscler Thromb Vasc Biol 33(8):2021–2025CrossRefPubMed

go back to reference Bonnefont-Rousselot D, Condat B, Sassolas A, Chebel S, Bittar R, Federspiel MC, Cazals-Hatem D, Bruckert E (2009) Cryptogenic cirrhosis in a patient with familial hypocholesterolemia due to a new truncated form of apolipoprotein B. Eur J Gastroenterol Hepatol 21(1):104–108CrossRefPubMed Bonnefont-Rousselot D, Condat B, Sassolas A, Chebel S, Bittar R, Federspiel MC, Cazals-Hatem D, Bruckert E (2009) Cryptogenic cirrhosis in a patient with familial hypocholesterolemia due to a new truncated form of apolipoprotein B. Eur J Gastroenterol Hepatol 21(1):104–108CrossRefPubMed

go back to reference Della Corte C, Fintini D, Giordano U, Cappa M, Brufani C, Majo F, Mennini C, Nobili V (2013) Fatty liver and insulin resistance in children with hypobetalipoproteinemia: the importance of aetiology. Clin Endocrinol (Oxf) 79(1):49–54CrossRef Della Corte C, Fintini D, Giordano U, Cappa M, Brufani C, Majo F, Mennini C, Nobili V (2013) Fatty liver and insulin resistance in children with hypobetalipoproteinemia: the importance of aetiology. Clin Endocrinol (Oxf) 79(1):49–54CrossRef

go back to reference Amaro A, Fabbrini E, Kars M, Yue P, Schechtman K, Schonfeld G, Klein S (2010) Dissociation between intrahepatic triglyceride content and insulin resistance in familial hypobetalipoproteinemia. Gastroenterology 139(1):149–153CrossRefPubMedPubMedCentral Amaro A, Fabbrini E, Kars M, Yue P, Schechtman K, Schonfeld G, Klein S (2010) Dissociation between intrahepatic triglyceride content and insulin resistance in familial hypobetalipoproteinemia. Gastroenterology 139(1):149–153CrossRefPubMedPubMedCentral

go back to reference Visser ME, Lammers NM, Nederveen AJ, van der Graaf M, Heerschap A, Ackermans MT, Sauerwein HP, Stroes ES, Serlie MJ (2011) Hepatic steatosis does not cause insulin resistance in people with familial hypobetalipoproteinaemia. Diabetologia 54(8):2113–2121CrossRefPubMedPubMedCentral Visser ME, Lammers NM, Nederveen AJ, van der Graaf M, Heerschap A, Ackermans MT, Sauerwein HP, Stroes ES, Serlie MJ (2011) Hepatic steatosis does not cause insulin resistance in people with familial hypobetalipoproteinaemia. Diabetologia 54(8):2113–2121CrossRefPubMedPubMedCentral

go back to reference Musunuru K, Pirruccello JP, Do R, Peloso GM, Guiducci C, Sougnez C, Garimella KV, Fisher S, Abreu J, Barry AJ, Fennell T, Banks E, Ambrogio L, Cibulskis K, Kernytsky A, Gonzalez E, Rudzicz N, Engert JC, DePristo MA, Daly MJ, Cohen JC, Hobbs HH, Altshuler D, Schonfeld G, Gabriel SB, Yue P, Kathiresan S (2010) Exome sequencing, ANGPTL3 mutations, and familial combined hypolipidemia. N Engl J Med 363(23):2220–2227CrossRefPubMedPubMedCentral Musunuru K, Pirruccello JP, Do R, Peloso GM, Guiducci C, Sougnez C, Garimella KV, Fisher S, Abreu J, Barry AJ, Fennell T, Banks E, Ambrogio L, Cibulskis K, Kernytsky A, Gonzalez E, Rudzicz N, Engert JC, DePristo MA, Daly MJ, Cohen JC, Hobbs HH, Altshuler D, Schonfeld G, Gabriel SB, Yue P, Kathiresan S (2010) Exome sequencing, ANGPTL3 mutations, and familial combined hypolipidemia. N Engl J Med 363(23):2220–2227CrossRefPubMedPubMedCentral

go back to reference Noto D, Cefalù AB, Valenti V, Fayer F, Pinotti E, Ditta M, Spina R, Vigna G, Yue P, Kathiresan S, Tarugi P, Averna MR (2012) Prevalence of ANGPTL3 and APOB gene mutations in subjects with combined hypolipidemia. Arterioscler Thromb Vasc Biol 32(3):805–809CrossRefPubMed Noto D, Cefalù AB, Valenti V, Fayer F, Pinotti E, Ditta M, Spina R, Vigna G, Yue P, Kathiresan S, Tarugi P, Averna MR (2012) Prevalence of ANGPTL3 and APOB gene mutations in subjects with combined hypolipidemia. Arterioscler Thromb Vasc Biol 32(3):805–809CrossRefPubMed

go back to reference Mattijssen F, Kersten S (2012) Regulation of triglyceride metabolism by Angiopoietin-like proteins. Biochim Biophys Acta 1821(5):782–789CrossRefPubMed Mattijssen F, Kersten S (2012) Regulation of triglyceride metabolism by Angiopoietin-like proteins. Biochim Biophys Acta 1821(5):782–789CrossRefPubMed

go back to reference Inukai K, Nakashima Y, Watanabe M, Kurihara S, Awata T, Katagiri H, Oka Y, Katayama S (2004) ANGPTL3 is increased in both insulin-deficient and -resistant diabetic states. Biochem Biophys Res Commun 317(4):1075–1079CrossRefPubMed Inukai K, Nakashima Y, Watanabe M, Kurihara S, Awata T, Katagiri H, Oka Y, Katayama S (2004) ANGPTL3 is increased in both insulin-deficient and -resistant diabetic states. Biochem Biophys Res Commun 317(4):1075–1079CrossRefPubMed

go back to reference Quagliarini F, Wang Y, Kozlitina J, Grishin NV, Hyde R, Boerwinkle E, Valenzuela DM, Murphy AJ, Cohen JC, Hobbs HH (2012) Atypical angiopoietin-like protein that regulates ANGPTL3. Proc Natl Acad Sci USA 109(48):19751–19756CrossRefPubMedPubMedCentral Quagliarini F, Wang Y, Kozlitina J, Grishin NV, Hyde R, Boerwinkle E, Valenzuela DM, Murphy AJ, Cohen JC, Hobbs HH (2012) Atypical angiopoietin-like protein that regulates ANGPTL3. Proc Natl Acad Sci USA 109(48):19751–19756CrossRefPubMedPubMedCentral

go back to reference Köster A, Chao YB, Mosior M, Ford A, Gonzalez-DeWhitt PA, Hale JE, Li D, Qiu Y, Fraser CC, Yang DD, Heuer JG, Jaskunas SR, Eacho P (2005) Transgenic angiopoietin-like (angptl)4 overexpression and targeted disruption of angptl4 and angptl3: regulation of triglyceride metabolism. Endocrinology 146(11):4943–4950CrossRefPubMed Köster A, Chao YB, Mosior M, Ford A, Gonzalez-DeWhitt PA, Hale JE, Li D, Qiu Y, Fraser CC, Yang DD, Heuer JG, Jaskunas SR, Eacho P (2005) Transgenic angiopoietin-like (angptl)4 overexpression and targeted disruption of angptl4 and angptl3: regulation of triglyceride metabolism. Endocrinology 146(11):4943–4950CrossRefPubMed

go back to reference Koishi R, Ando Y, Ono M, Shimamura M, Yasumo H, Fujiwara T, Horikoshi H, Furukawa H (2002) Angptl3 regulates lipid metabolism in mice. Nat Genet 30(2):151–157CrossRefPubMed Koishi R, Ando Y, Ono M, Shimamura M, Yasumo H, Fujiwara T, Horikoshi H, Furukawa H (2002) Angptl3 regulates lipid metabolism in mice. Nat Genet 30(2):151–157CrossRefPubMed

go back to reference Mehta N, Qamar A, Qu L, Qasim AN, Mehta NN, Reilly MP, Rader DJ (2014) Differential association of plasma angiopoietin-like proteins 3 and 4 with lipid and metabolic traits. Arterioscler Thromb Vasc Biol 34(5):1057–1063CrossRefPubMedPubMedCentral Mehta N, Qamar A, Qu L, Qasim AN, Mehta NN, Reilly MP, Rader DJ (2014) Differential association of plasma angiopoietin-like proteins 3 and 4 with lipid and metabolic traits. Arterioscler Thromb Vasc Biol 34(5):1057–1063CrossRefPubMedPubMedCentral

go back to reference Wang Y, Gusarova V, Banfi S, Gromada J, Cohen JC, Hobbs HH (2015) Inactivation of ANGPTL3 reduces hepatic VLDL-triglyceride secretion. J Lipid Res 56(7):1296–1307CrossRefPubMedPubMedCentral Wang Y, Gusarova V, Banfi S, Gromada J, Cohen JC, Hobbs HH (2015) Inactivation of ANGPTL3 reduces hepatic VLDL-triglyceride secretion. J Lipid Res 56(7):1296–1307CrossRefPubMedPubMedCentral

go back to reference Robciuc MR, Maranghi M, Lahikainen A, Rader D, Bensadoun A, Öörni K, Metso J, Minicocci I, Ciociola E, Ceci F, Montali A, Arca M, Ehnholm C, Jauhiainen M (2013) Angptl3 deficiency is associated with increased insulin sensitivity, lipoprotein lipase activity, and decreased serum free fatty acids. Arterioscler Thromb Vasc Biol 33(7):1706–1713CrossRefPubMed Robciuc MR, Maranghi M, Lahikainen A, Rader D, Bensadoun A, Öörni K, Metso J, Minicocci I, Ciociola E, Ceci F, Montali A, Arca M, Ehnholm C, Jauhiainen M (2013) Angptl3 deficiency is associated with increased insulin sensitivity, lipoprotein lipase activity, and decreased serum free fatty acids. Arterioscler Thromb Vasc Biol 33(7):1706–1713CrossRefPubMed

go back to reference Wang X, Wang D, Shan Z (2015) Clinical and genetic analysis of a family diagnosed with familial hypobetalipoproteinemia in which the proband was diagnosed with diabetes mellitus. Atherosclerosis 239(2):552–556CrossRefPubMed Wang X, Wang D, Shan Z (2015) Clinical and genetic analysis of a family diagnosed with familial hypobetalipoproteinemia in which the proband was diagnosed with diabetes mellitus. Atherosclerosis 239(2):552–556CrossRefPubMed

go back to reference Horton JD, Goldstein JL, Brown MS (2002) SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Investig 109:1125–1131CrossRefPubMedPubMedCentral Horton JD, Goldstein JL, Brown MS (2002) SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Investig 109:1125–1131CrossRefPubMedPubMedCentral

go back to reference Shimano H (2001) Sterol regulatory element-binding proteins (SREBPs): transcriptional regulators of lipid synthetic genes. Prog Lipid Res 40(6):439–452CrossRefPubMed Shimano H (2001) Sterol regulatory element-binding proteins (SREBPs): transcriptional regulators of lipid synthetic genes. Prog Lipid Res 40(6):439–452CrossRefPubMed

go back to reference Pramfalk C, Jiang ZY, Cai Q, Hu H, Zhang SD, Han TQ, Eriksson M, Parini P (2010) HNF1alpha and SREBP2 are important regulators of NPC1L1 in human liver. J Lipid Res 51(6):1354–1362CrossRefPubMedPubMedCentral Pramfalk C, Jiang ZY, Cai Q, Hu H, Zhang SD, Han TQ, Eriksson M, Parini P (2010) HNF1alpha and SREBP2 are important regulators of NPC1L1 in human liver. J Lipid Res 51(6):1354–1362CrossRefPubMedPubMedCentral

go back to reference Zhao C, Dahlman-Wright K (2010) Liver X receptor in cholesterol metabolism. J Endocrinol 204(3):233–240CrossRefPubMed Zhao C, Dahlman-Wright K (2010) Liver X receptor in cholesterol metabolism. J Endocrinol 204(3):233–240CrossRefPubMed

go back to reference Zelcer N, Hong C, Boyadjian R, Tontonoz P (2009) LXR regulates cholesterol uptake through Idol-dependent ubiquitination of the LDL receptor. Science 325(5936):100–104CrossRefPubMedPubMedCentral Zelcer N, Hong C, Boyadjian R, Tontonoz P (2009) LXR regulates cholesterol uptake through Idol-dependent ubiquitination of the LDL receptor. Science 325(5936):100–104CrossRefPubMedPubMedCentral

go back to reference Goodwin B, Watson MA, Kim H, Miao J, Kemper JK, Kliewer SA (2003) Differential regulation of rat and human CYP7A1 by the nuclear oxysterol receptor liver X receptor-alpha. Mol Endocrinol 17(3):386–394CrossRefPubMed Goodwin B, Watson MA, Kim H, Miao J, Kemper JK, Kliewer SA (2003) Differential regulation of rat and human CYP7A1 by the nuclear oxysterol receptor liver X receptor-alpha. Mol Endocrinol 17(3):386–394CrossRefPubMed

go back to reference Calkin AC, Tontonoz P (2010) Liver x receptor signaling pathways and atherosclerosis. Arterioscler Thromb Vasc Biol 30(8):1513–1518CrossRefPubMed Calkin AC, Tontonoz P (2010) Liver x receptor signaling pathways and atherosclerosis. Arterioscler Thromb Vasc Biol 30(8):1513–1518CrossRefPubMed

go back to reference Parikh M, Patel K, Soni S, Gandhi T (2014) Liver X receptor: a cardinal target for atherosclerosis and beyond. J Atheroscler Thromb 21(6):519–531PubMed Parikh M, Patel K, Soni S, Gandhi T (2014) Liver X receptor: a cardinal target for atherosclerosis and beyond. J Atheroscler Thromb 21(6):519–531PubMed

go back to reference Hao M, Head WS, Gunawardana SC, Hasty AH, Piston DW (2007) Direct effect of cholesterol on insulin secretion: a novel mechanism for pancreatic beta-cell dysfunction. Diabetes 56(9):2328–2338CrossRefPubMed Hao M, Head WS, Gunawardana SC, Hasty AH, Piston DW (2007) Direct effect of cholesterol on insulin secretion: a novel mechanism for pancreatic beta-cell dysfunction. Diabetes 56(9):2328–2338CrossRefPubMed

go back to reference Hoeg JM, Edge SB, Demosky SJ Jr, Starzl TE, Triche T, Gregg RE, Brewer HB Jr (1986) Metabolism of low-density lipoproteins by cultured hepatocytes from normal and homozygous familial hypercholesterolemic subjects. Biochim Biophys Acta 876(3):646–657CrossRefPubMedPubMedCentral Hoeg JM, Edge SB, Demosky SJ Jr, Starzl TE, Triche T, Gregg RE, Brewer HB Jr (1986) Metabolism of low-density lipoproteins by cultured hepatocytes from normal and homozygous familial hypercholesterolemic subjects. Biochim Biophys Acta 876(3):646–657CrossRefPubMedPubMedCentral

go back to reference Telford DE, Sutherland BG, Edwards JY, Andrews JD, Barrett PH, Huff MW (2007) The molecular mechanisms underlying the reduction of LDL apoB-100 by ezetimibe plus simvastatin. J Lipid Res 48(3):699–708CrossRefPubMed Telford DE, Sutherland BG, Edwards JY, Andrews JD, Barrett PH, Huff MW (2007) The molecular mechanisms underlying the reduction of LDL apoB-100 by ezetimibe plus simvastatin. J Lipid Res 48(3):699–708CrossRefPubMed

go back to reference Maejima T, Sugano T, Yamazaki H, Yoshinaka Y, Doi T, Tanabe S, Nishimaki-Mogami T (2011) Pitavastatin increases ABCA expression by dual mechanisms: SREBP2-driven transcriptional activation and PPARα-dependent protein stabilization but without activating LXR in rat hepatoma McARH7777 cells. J Pharmacol Sci 116(1):107–115CrossRefPubMed Maejima T, Sugano T, Yamazaki H, Yoshinaka Y, Doi T, Tanabe S, Nishimaki-Mogami T (2011) Pitavastatin increases ABCA expression by dual mechanisms: SREBP2-driven transcriptional activation and PPARα-dependent protein stabilization but without activating LXR in rat hepatoma McARH7777 cells. J Pharmacol Sci 116(1):107–115CrossRefPubMed

go back to reference Soufi M, Ruppert V, Kurt B, Schaefer JR (2012) The impact of severe LDL receptor mutations on SREBP-pathway regulation in homozygous familial hypercholesterolemia (FH). Gene 499(1):218–222CrossRefPubMed Soufi M, Ruppert V, Kurt B, Schaefer JR (2012) The impact of severe LDL receptor mutations on SREBP-pathway regulation in homozygous familial hypercholesterolemia (FH). Gene 499(1):218–222CrossRefPubMed

go back to reference Chamberlain LH (2001) Inhibition of isoprenoid biosynthesis causes insulin resistance in 3 T3-L1 adipocytes. FEBS Lett 507(3):357–361CrossRefPubMed Chamberlain LH (2001) Inhibition of isoprenoid biosynthesis causes insulin resistance in 3 T3-L1 adipocytes. FEBS Lett 507(3):357–361CrossRefPubMed

go back to reference Ashcroft FM, Proks P, Smith PA et al (1994) Stimulus–secretion coupling in pancreatic β cells. J Cell Biochem 55(S1994A):54–65CrossRefPubMed Ashcroft FM, Proks P, Smith PA et al (1994) Stimulus–secretion coupling in pancreatic β cells. J Cell Biochem 55(S1994A):54–65CrossRefPubMed

go back to reference Brault M, Ray J, Gomez YH, Mantzoros CS, Daskalopoulou SS (2014) Statin treatment and new-onset diabetes: a review of proposed mechanisms. Metabolism 63(6):735–745CrossRefPubMed Brault M, Ray J, Gomez YH, Mantzoros CS, Daskalopoulou SS (2014) Statin treatment and new-onset diabetes: a review of proposed mechanisms. Metabolism 63(6):735–745CrossRefPubMed

go back to reference Vallejo-Vaz AJ, Kondapally Seshasai SR, Kurogi K, Michishita I, Nozue T, Sugiyama S, Tsimikas S, Yoshida H, Ray KK (2015) Effect of pitavastatin on glucose, HbA1c and incident diabetes: a meta-analysis of randomized controlled clinical trials in individuals without diabetes. Atherosclerosis 241(2):409–418CrossRefPubMed Vallejo-Vaz AJ, Kondapally Seshasai SR, Kurogi K, Michishita I, Nozue T, Sugiyama S, Tsimikas S, Yoshida H, Ray KK (2015) Effect of pitavastatin on glucose, HbA1c and incident diabetes: a meta-analysis of randomized controlled clinical trials in individuals without diabetes. Atherosclerosis 241(2):409–418CrossRefPubMed

go back to reference Arnaboldi L, Corsini A (2015) Could changes in adiponectin drive the effect of statins on the risk of new-onset diabetes? The case of pitavastatin. Atheroscler Suppl 16:1–27CrossRefPubMed Arnaboldi L, Corsini A (2015) Could changes in adiponectin drive the effect of statins on the risk of new-onset diabetes? The case of pitavastatin. Atheroscler Suppl 16:1–27CrossRefPubMed

go back to reference Barkas F, Elisaf M, Liberopoulos E, Klouras E, Liamis G, Rizos EC (2016) Statin therapy with or without ezetimibe and the progression to diabetes. J Clin Lipidol 10(2):306–313CrossRefPubMed Barkas F, Elisaf M, Liberopoulos E, Klouras E, Liamis G, Rizos EC (2016) Statin therapy with or without ezetimibe and the progression to diabetes. J Clin Lipidol 10(2):306–313CrossRefPubMed

go back to reference Lin X, Chen Z, Yue P, Averna MR, Ostlund RE Jr, Watson MA, Schonfeld G (2006) A targeted apoB38.9 mutation in mice is associated with reduced hepatic cholesterol synthesis and enhanced lipid peroxidation. Am J Physiol Gastrointest Liver Physiol 290(6):G1170–G1176CrossRefPubMed Lin X, Chen Z, Yue P, Averna MR, Ostlund RE Jr, Watson MA, Schonfeld G (2006) A targeted apoB38.9 mutation in mice is associated with reduced hepatic cholesterol synthesis and enhanced lipid peroxidation. Am J Physiol Gastrointest Liver Physiol 290(6):G1170–G1176CrossRefPubMed

go back to reference Miettinen TA, Tilvis RS, Kesäniemi YA (1990) Serum plant sterols and cholesterol precursors reflect cholesterol absorption and synthesis in volunteers of a randomly selected male population. Am J Epidemiol 131(1):20–31PubMed Miettinen TA, Tilvis RS, Kesäniemi YA (1990) Serum plant sterols and cholesterol precursors reflect cholesterol absorption and synthesis in volunteers of a randomly selected male population. Am J Epidemiol 131(1):20–31PubMed

go back to reference Miettinen TA, Gylling H, Nissinen MJ (2011) The role of serum non-cholesterol sterols as surrogate markers of absolute cholesterol synthesis and absorption. Nutr Metab Cardiovasc Dis 21(10):765–769CrossRefPubMed Miettinen TA, Gylling H, Nissinen MJ (2011) The role of serum non-cholesterol sterols as surrogate markers of absolute cholesterol synthesis and absorption. Nutr Metab Cardiovasc Dis 21(10):765–769CrossRefPubMed

go back to reference Björkhem I, Miettinen T, Reihnér E, Ewerth S, Angelin B, Einarsson K (1987) Correlation between serum levels of some cholesterol precursors and activity of HMG-CoA reductase in human liver. J Lipid Res 28(10):1137–1143PubMed Björkhem I, Miettinen T, Reihnér E, Ewerth S, Angelin B, Einarsson K (1987) Correlation between serum levels of some cholesterol precursors and activity of HMG-CoA reductase in human liver. J Lipid Res 28(10):1137–1143PubMed

go back to reference Noto D, Cefalù AB, Barraco G, Fayer F, Minà M, Yue P, Tarugi P, Schonfeld G, Averna MR (2011) Plasma non-cholesterol sterols in primary hypobetalipoproteinemia. Atherosclerosis 216(2):409–413CrossRefPubMed Noto D, Cefalù AB, Barraco G, Fayer F, Minà M, Yue P, Tarugi P, Schonfeld G, Averna MR (2011) Plasma non-cholesterol sterols in primary hypobetalipoproteinemia. Atherosclerosis 216(2):409–413CrossRefPubMed