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Background: Statins are the cornerstone treatment for patients with heterozygous familial hypercholesterolaemia but research suggests it could increase the risk of type 2 diabetes in the general population. A low prevalence of type 2 diabetes was reported in some familial hypercholesterolaemia cohorts, raising the question of whether these patients are protected against type 2 diabetes. Obesity is a well known risk factor for the development of type 2 diabetes. We aimed to investigate the associations of known key determinants of type 2 diabetes with its prevalence in people with heterozygous familial hypercholesterolaemia. Methods: This worldwide cross-sectional study used individual-level data from the EAS FHSC registry and included adults older than 18 years with a clinical or genetic diagnosis of heterozygous familial hypercholesterolaemia who had data available on age, BMI, and diabetes status. Those with known or suspected homozygous familial hypercholesterolaemia and type 1 diabetes were excluded. The main outcome was prevalence of type 2 diabetes overall and by WHO region, and in relation to obesity (BMI ≥30·0 kg/m2) and lipid-lowering medication as predictors. The study population was divided into 12 risk categories based on age (tertiles), obesity, and receiving statins, and the risk of type 2 diabetes was investigated using logistic regression. Findings: Among 46 683 adults with individual-level data in the FHSC registry, 24 784 with heterozygous familial hypercholesterolaemia were included in the analysis from 44 countries. 19 818 (80%) had a genetically confirmed diagnosis of heterozygous familial hypercholesterolaemia. Type 2 diabetes prevalence in the total population was 5·7% (1415 of 24 784), with 4·1% (817 of 19 818) in the genetically diagnosed cohort. Higher prevalence of type 2 diabetes was observed in the Eastern Mediterranean (58 [29·9%] of 194), South-East Asia and Western Pacific (214 [12·0%] of 1785), and the Americas (166 [8·5%] of 1955) than in Europe (excluding the Netherlands; 527 [8·0%] of 6579). Advancing age, a higher BMI category (obesity and overweight), and use of lipid-lowering medication were associated with a higher risk of type 2 diabetes, independent of sex and LDL cholesterol. Among the 12 risk categories, the probability of developing type 2 diabetes was higher in people in the highest risk category (aged 55–98 years, with obesity, and receiving statins; OR 74·42 [95% CI 47·04–117·73]) than in those in the lowest risk category (aged 18–38 years, without obesity, and not receiving statins). Those who did not have obesity, even if they were in the upper age tertile and receiving statins, had lower risk of type 2 diabetes (OR 24·42 [15·57–38·31]). The corresponding results in the genetically diagnosed cohort were OR 65·04 (40·67–104·02) for those with obesity in the highest risk category and OR 20·07 (12·73–31·65) for those without obesity. Interpretation: Adults with heterozygous familial hypercholesterolaemia in most WHO regions have a higher type 2 diabetes prevalence than in Europe. Obesity markedly increases the risk of diabetes associated with age and use of statins in these patients. Our results suggest that heterozygous familial hypercholesterolaemia does not protect against type 2 diabetes, hence managing obesity is essential to reduce type 2 diabetes in this patient population. Funding: Pfizer, Amgen, MSD, Sanofi-Aventis, Daiichi-Sankyo, and Regeneron.

Association of BMI, lipid-lowering medication, and age with prevalence of type 2 diabetes in adults with heterozygous familial hypercholesterolaemia: a worldwide cross-sectional study / Elshorbagy, Amany; Lyons, Alexander R. M.; Vallejo-Vaz, Antonio J.; Stevens, Christophe A. T.; Dharmayat, Kanika I.; Brandts, Julia; Catapano, Alberico L.; Freiberger, Tomas; Hovingh, G. Kees; Mata, Pedro; Raal, Frederick J.; Santos, Raul D.; Soran, Handrean; Watts, Gerald F.; Abifadel, Marianne; Aguilar-Salinas, Carlos A.; Alhabib, Khalid F.; Alkhnifsawi, Mutaz; Almahmeed, Wael; Alonso, Rodrigo; Al-Rasadi, Khalid; Al-Sarraf, Ahmad; Ashavaid, Tester F.; Banach, Maciej; Binder, Christoph J.; Bourbon, Mafalda; Brunham, Liam R.; Chlebus, Krzysztof; Corral, Pablo; Cruz, Diogo; Davletov, Kairat; Descamps, Olivier S.; Ezhov, Marat; Gaita, Dan; Groselj, Urh; Harada-Shiba, Mariko; Holven, Kirsten B.; Kayikcioglu, Meral; Khovidhunkit, Weerapan; Lalic, Katarina; Latkovskis, Gustavs; Laufs, Ulrich; Liberopoulos, Evangelos; Lima-Martinez, Marcos M.; Lin, Jie; Maher, Vincent; Marais, A. David; März, Winfried; Mirrakhimov, Erkin; Miserez, André R.; Mitchenko, Olena; Nawawi, Hapizah; Nordestgaard, Børge G.; Panayiotou, Andrie G.; Paragh, György; Petrulioniene, Zaneta; Pojskic, Belma; Postadzhiyan, Arman; Reda, Ashraf; Reiner, Željko; Reyes, Ximena; Sadiq, Fouzia; Sadoh, Wilson E.; Schunkert, Heribert; Shek, Aleksandr B.; Stroes, Erik; Su, Ta-Chen; Subramaniam, Tavintharan; Susekov, Andrey V.; Tilney, Myra; Tomlinson, Brian; Truong, Thanh-Huong; Tselepis, Alexandros D.; Tybjærg-Hansen, Anne; Vázquez, Alejandra C.; Viigimaa, Margus; Vohnout, Branislav; Wang, Luya; Yamashita, Shizuya; Arca, Marcello; Averna, Maurizio; Schreier, Laura; Pang, Jing; Ebenbichler, Christoph; Dieplinger, Hans; Innerhofer, Reinhold; Winhofer-Stöckl, Yvonne; Greber-Platzer, Susanne; Krychtiuk, Konstantin; Speidl, Walter; Toplak, Hermann; Widhalm, Kurt; Stulnig, Thomas; Huber, Kurt; Höllerl, Florian; Rega-Kaun, Gersina; Kleemann, Lucas; Mäser, Martin; Scholl-Bürgi, Sabine; Säly, Christoph; Mayer, Florian J.; Sperone, Alexandra; Tanghe, Chloé; Gérard, Anne-Catherine; Pojskic, Lamija; Sisic, Ibrahim; Durak Nalbantic, Azra; Ejubovic, Malik; Jannes, Cinthia E.; Pereira, Alexandre C.; Krieger, Jose E.; Petrov, Ivo; Goudev, Assen; Nikolov, Fedya; Tisheva, Snejana; Yotov, Yoto; Tzvetkov, Ivajlo; Baass, Alexis; Bergeron, Jean; Bernard, Sophie; Brisson, Diane; Brunham, Liam R.; Cermakova, Lubomira; Couture, Patrick; Francis, Gordon A.; Gaudet, Daniel; Hegele, Robert A.; Khoury, Etienne; Mancini, G. B. John; Mccrindle, Brian W.; Paquette, Martine; Ruel, Isabelle; Iatan, Iulia; Cuevas, Ada; Wang, Xumin; Meng, Kang; Song, Xiantao; Yong, Qiang; Jiang, Tao; Liu, Ziyou; Duan, Yanyu; Hong, Jing; Ye, Pucong; Chen, Yan; Qi, Jianguang; Liu, Zesen; Li, Yuntao; Zhang, Chaoyi; Peng, Jie; Yang, Ya; Yu, Wei; Wang, Qian; Yuan, Hui; Cheng, Shitong; Jiang, Long; Chong, Mei; Jiao, Jian; Wu, Yue; Wen, Wenhui; Xu, Liyuan; Zhang, Ruiying; Qu, Yichen; He, Jianxun; Fan, Xuesong; Wang, Zhenjia; Chow, Elaine; Pećin, Ivan; Perica, Dražen; Symeonides, Phivos; Vrablik, Michal; Ceska, Richard; Soska, Vladimir; Tichy, Lukas; Adamkova, Vera; Franekova, Jana; Cifkova, Renata; Kraml, Pavel; Vonaskova, Katerina; Cepova, Jana; Dusejovska, Magdalena; Pavlickova, Lenka; Blaha, Vladimir; Rosolova, Hana; Nussbaumerova, Barbora; Cibulka, Roman; Vaverkova, Helena; Cibickova, Lubica; Krejsova, Zdenka; Rehouskova, Katerina; Malina, Pavel; Budikova, Milena; Palanova, Vaclava; Solcova, Lucie; Lubasova, Alena; Podzimkova, Helena; Bujdak, Juraj; Vesely, Jiri; Jordanova, Marta; Salek, Tomas; Urbanek, Robin; Zemek, Stanislav; Lacko, Jan; Halamkova, Hana; Machacova, Sona; Mala, Sarka; Cubova, Eva; Valoskova, Katerina; Burda, Lukas; Benn, Marianne; Bendary, Ahmed; Daoud, Ihab; Emil, Sameh; Elbahry, Atef; Rafla, Samir; Sanad, Osama; Kazamel, Ghada; Ashraf, Dr Mohamed; Sobhy, Mohamed; El-Hadidy, Amro; Shafy, Mohamed Abdoul; Kamal, Saif; Bendary, Mohamed; Talviste, Grete; Christmann, Jutta; Dressel, Alexander; Fath, Felix; Ferraro, Chiara; Frenzke, Lydia; Gopon, Alica; Klein, Isabel; Pienkowska, Dominika; Sietmann, Tobias; Sonntag, Antonia; Adjan, Omar; Bahrmann, Philipp; Baessler, Andrea; Barkowski, Rasmus; Beckerdjian, Raffi; Berr, Christina; Birkenfeld, Andreas; Böll, Gereon; Carstensen, Avisha; Demuth, Ilya; Finkernagel, Holger; Gouni-Berthold, Ioanna; Hahmann, Harry; Hamerle, Michael; Halder, Julian; Heide, Maria; Julius, Ulrich; Kassner, Ursula; Katzmann, Julius L; Kirschbaum, Anja; Klose, Gerald; Könemann, Stephanie; König, Christel; König, Wolfgang; Krämer, Bernhard; Kuprat, Gerrit; Koschker, Ann-Cathrin; Krämer, Bernhard; Kilic, Özlem; Laufs, Ulrich; Lindenmeier, Gerd; Van de Loo, Iris; Lorenz, Babette; Lorenz, Elke; Löhr, Birgit; Mcchord, Johanna; Maslarska, Mariya; Methe, Heiko; Merkel, Martin; Moussaoui, Zineb; Müller-Kozarez, Irina; Olivier, Christoph B; Ong, Peter; Otte, Britta; Parhofer, Klaus; Partsch, Carl-Joachim; Paulus, Michael; Pehlivanli, Sinan; Pflederer, Tobias; Pusl, Thomas; Richter, Veronika; Rosner, Stefanie; Sanin, Veronika; Schäfer, Sebastian; Schäfer, Christoph; Schatz, Ulrike; Schirmer, Stephan; Schmidt, Christine; Seeger, Wolfgang; Sisovic, Snezna; Spens, Antje; Jablonski, Ksenija Stach; Stadelmann, Alexander; Steinhagen-Thiessen, Elisabeth; Stürzebecher, Paulina; Tafelmeier, Maria; Tillack, Dörthe; Tselmin, Sergey; Tünnemann-Tarr, Adrienn; Vogt, Anja; Beckerath, Jens von; Wilke, Andreas; Wolf, Ulrich; Zemmrich, Claudia; Rizos, Christos V.; Skoumas, Ioannis; Tziomalos, Konstantinos; Rallidis, Loukianos; Kotsis, Vasileios; Doumas, Michalis; Athyros, Vasileios; Skalidis, Emmanouil; Kolovou, Genovefa; Kolovou, Vana; Garoufi, Anastasia; Bilianou, Eleni; Koutagiar, Iosif; Kiouri, Estela; Antza, Christina; Zacharis, Evangelos; Attilakos, Achilleas; Sfikas, George; Koumaras, Charalambos; Anagnostis, Panagiotis; Anastasiou, Georgia; Liamis, George; Koutsogianni, Amalia-Despoina; Petkou, Ermioni; Milionis, Haralambos; Koulouri, Anastasia; Prodromiadou, Elisavet; Karányi, Zsolt; Harangi, Mariann; Bajnok, László; Audikovszky, Mária; Márk, László; Benczúr, Béla; Reiber, István; Nagy, Gergely; Nagy, András; Reddy, Lakshmi Lavanya; Shah, Swarup A. V; Ponde, Chandrashekhar K.; Dalal, Jamshed J.; Sawhney, Jitendra P. S.; Verma, Ishwar C.; Altaey, Mays; Al-Jumaily, Khalid; Rasul, Dilshad; Abdalsahib, Ali Fawzi; Jabbar, Amer Abdl; Al-ageedi, Mohanad; Abdalsahib, Ali Fawzi; Al-ageedi, Mohanad; Dhamin, Mohammed; Alfil, Sarmad; Khadhim, Foad; Miahy, Sabah; Agar, Ruth; Catapano, Alberico Luigi; Arca, Marcello; Averna, Maurizio; Calandra, Sebastiano; Tarugi, Patrizia; Casula, Manuela; Galimberti, Federica; Olmastroni, Elena; Sarzani, Riccardo; Ferri, Claudio; Repetti, Elena; Piro, Salvatore; Suppressa, Patrizia; Meregalli, Giancarla; Borghi, Claudio; Muntoni, Sandro; Calabrò, Paolo; Cipollone, Francesco; Purrello, Francesco; Pujia, Arturo; Passaro, Angelina; Marcucci, Rossella; Pecchioli, Valerio; Pisciotta, Livia; Mandraffino, Giuseppe; Pellegatta, Fabio; Mombelli, Giuliana; Branchi, Adriana; Fiorenza, Anna Maria; Pederiva, Cristina; Werba, Josè Pablo; Parati, Gianfranco; Carubbi, Francesca; Iughetti, Lorenzo; Fortunato, Giuliana; Iannuzzi, Arcangelo; Iannuzzo, Gabriella; Cefalù, Angelo Baldassare; Biasucci, Giacomo; Zambon, Sabina; Pirro, Matteo; Sbrana, Francesco; Trenti, Chiara; D'Erasmo, Laura; Federici, Massimo; Ben, Maria Del; Bartuli, Andrea; Giaccari, Andrea; Pipolo, Antonio; Citroni, Nadia; Guardamagna, Ornella; Lia, Salvatore; Benso, Andrea; Biolo, Gianni; Maroni, Lorenzo; Lupi, Alessandro; Bonanni, Luca; Rinaldi, Elisabetta; Zenti, Maria Grazia; Matsuki, Kota; Hori, Mika; Ogura, Masatsune; Masuda, Daisaku; Kobayashi, Takuya; Nagahama, Kumiko; Al-Jarallah, Mohammed; Radovic, Mirjana; Lunegova, Olga; Bektasheva, Erkayim; Abilova, Saamay; Erglis, Andrejs; Gilis, Dainus; Nesterovics, Georgijs; Saripo, Vita; Meiere, Ruta; Skudrina, Gunda; Terauda, Elizabete; Jambart, Selim; Ayoub, Carine; Ghaleb, Youmna; Aliosaitiene, Urte; Kutkiene, Sandra; Abdul Kadir, Siti Hamimah Sheikh; Kasim, Noor Alicezah Mohd; Nor, Noor Shafina Mohd; Abdul Hamid, Hasidah; Abdul Razak, Suraya; Al-Khateeb, Alyaa; Abd Muid, Suhaila; Abdul Rahman, Thuhairah; Kasim, Sazzli Shahlan; Radzi, Ahmad Bakhtiar Md; Ibrahim, Khairul Shafiq; Rosli, Marshima Mohd; Razali, Rafezah; Chua, Yung An; Razman, Aimi Zafira; Nazli, Sukma Azureen; Aziz, Nazirul; Rosman, Azhari; Abdul Murad, Norazian; Jalaludin, Mohd Amin; Abdul Latif, Ahmad Zubaidi; Azzopardi, C.; Mehta, Roopa; Martagon, Alexandro J.; Ramirez, Gabriela A. Galan; Villa, Neftali E Antonio; Vazquez, Arsenio Vargas; Elias-Lopez, Daniel; Retana, Gustavo Gonzalez; Rodriguez, Betsabel; Macías, Jose J. Ceballos; Zazueta, Alejandro Romero; Alvarado, Rocio Martinez; Portano, Julieta D. Morales; Lopez, Humberto Alvares; Sauque-Reyna, Leobardo; Herrera, Laura G. Gomez; Mendia, Luis E. Simental; Aguilar, Humberto Garcia; Cooremans, Elizabeth Ramirez; Aparicio, Berenice Peña; Zubieta, Victoria Mendoza; Gonzalez, Perla A. Carrillo; Ferreira-Hermosillo, Aldo; Portilla, Nacu Caracas; Dominguez, Guadalupe Jimenez; Garcia, Alinna Y. Ruiz; Cazares, Hector E. Arriaga; Gonzalez, Jesus R.; Valencia, Carla V. Mendez; Padilla, Francisco G.; Prado, Ramon Madriz; Ibarra, Manuel O. De los Rios; Villicaña, Ruy D. Arjona; Rivera, Karina J. Acevedo; Carrera, Ricardo Allende; Alvarez, Jose A.; Martinez, Jose C. Amezcua; Bustillo, Manuel de los Reyes Barrera; Vargas, Gonzalo Carazo; Chacon, Roberto Contreras; Andrade, Mario H. Figueroa; Ortega, Ashanty Flores; Alcala, Hector Garcia; de Leon, Laura E. Garcia; Guzman, Berenice Garcia; Garcia, Jose J. Garduño; Cuellar, Juan C. Garnica; Cruz, Jose R. Gomez; Garcia, Anell Hernandez; Almada, Jesus R. Holguin; Herrera, Ursulo Juarez; Sobrevilla, Fabiola Lugo; Rodriguez, Eduardo Marquez; Sibaja, Cristina Martinez; Rodriguez, Alma B. Medrano; Oyervides, Jose C. Morales; Vazquez, Daniel I. Perez; Rodriguez, Eduardo A. Reyes; Osorio, Ma. Ludivina Robles; Saucedo, Juan Rosas; Tamayo, Margarita Torres; Talavera, Luis A. Valdez; Arroyo, Luis E. Vera; Carrillo, Eloy A. Zepeda; Stroes, Erik S; Defesche, J; Zuurbier, L; Reeskamp, L; Ibrahim, S; Roeters van Lennep, Jeanine; Wiegman, Albert; Isara, Alphonsus; Obaseki, Darlington E.; Al-Waili, Khalid; Al-Zadjali, Fahad; Al-Zakwani, Ibrahim; Al-Kindi, Mohammed; Al-Mukhaini, Suad; Al-Barwani, Hamida; Rana, Asim; Shah, Lahore Saeed Ullah; Al-Nouri, Fahad; Starostecka, Ewa; Konopka, Agnieszka; Bielecka-Dabrowa, Agata; Lewek, Joanna; Sosnowska, Bozena; Gąsior, Mariusz; Dyrbuś, Krzysztof; Jóźwiak, Jacek; Pajkowski, Marcin; Romanowska-Kocejko, Marzena; Żarczyńska-Buchowiecka, Marta; Chmara, Magdalena; Wasąg, Bartosz; Stróżyk, Aneta; Michalska-Grzonkowska, Aleksandra; Medeiros, Ana Margarida; Alves, Ana Catarina; Silva, Francisco; Lobarinhas, Goreti; Palma, Isabel; de Moura, Jose Pereira; Rico, Miguel Toscano; Rato, Quitéria; Pais, Patrícia; Correia, Susana; Moldovan, Oana; Virtuoso, Maria João; Araujo, Francisco; Salgado, Jose Miguel; Colaço, Ines; Dumitrescu, Andreea; Lengher, Calin; Mosteoru, Svetlana; Meshkov, Alexey; Ershova, Alexandra; Rozhkova, Tatiana; Korneva, Victoria; Yu, Kuznetsova T.; Zafiraki, Vitaliy; Voevoda, Mikhail; Gurevich, Victor; Duplyakov, Dmitry; Ragino, Yulia; Chubykina, Uliana; Shaposhnik, Igor; Alkaf, Fahmi; Khudari, Alia; Rwaili, Nawal; Al-Allaf, Faisal; Alghamdi, Mohammad; Batais, Mohammed A; Almigbal, Turky H; Kinsara, Abdulhalim; Alqudaimi, Ashraf Hammouda Ahmed; Awan, Zuhier; Elamin, Omer A; Altaradi, Hani; Popovic, Ljiljana; Singh, Sandra; Rasulic, Iva; Petakov, Ana; Lalic, Nebojsa M.; Lam, Carolyn; Le, Tan Ju; Siang, Eric Lim Tien; Dissanayake, Sanjaya; I-Shing, Justin Tang; Shyong, Tai E; Jin, Terrance Chua Siang; Ting, Sharon Pek Li; Ming, Jeremy Hoe Kian; Drum, Chester Lee; Nastar, Fathima Ashna; Jia, Loh Wann; Ya, Natalie Koh Si; Jie, Marvin Chua Wei; Dalan, Rinkoo; Wei, Yong Quek; Sian, Tiong Yee; Keong, Yeo Khung; Rong, Siau Kai; Jin, Darren Seah Ee; Ming, Ian Koh Jan; Chang, Tan Hong; Peng, Fabian Yap Kok; Vasanwala, Rashida Farhad; Raslova, Katarina; Balinth, Karin; Buganova, Ingrid; Fabryova, Lubomira; Kadurova, Michaela; Klabnik, Alexander; Kozárová, Miriam; Sirotiakova, Jana; Battelino, Tadej; Cevc, Matija; Debeljak, Marusa; Torkar, Ana Drole; Fras, Zlatko; Jug, Borut; Cugalj, Barbara Kern; Kovac, Jernej; Mlinaric, Matej; Sikonja, Jaka; Pilcher, Gillian Joan; Blom, D J; Wolmarans, K H; Brice, B C; Muñiz-Grijalvo, Ovidio; Díaz-Díaz, Jose Luis; de Isla, Leopoldo Pérez; Fuentes, Francisco; Badimon, Lina; Martin, François; Miserez, Eleonore B.; Shipton, Janine L.; Ganokroj, Poranee; Chattranukulchai, Pairoj; Jiamjarasrungsi, Wiroj; Thongtang, Nuntakorn; Krittayaphong, Rungroj; Vathesatogkit, Prin; Sriphrapradang, Chutintorn; Phimphilai, Mattabhorn; Leelawattana, Rattana; Anthanont, Pimjai; Suraamornkul, Swangjit; Deerochanawong, Chaicharn; Senthong, Vichai; Torpongpun, Artit; Suteerayongprasert, Panuwat; Pengpong, Nawarat; Sathavarodom, Nattapol; Sunanta, Usanee; Porntharukchareon, Thachanun; Kiatpanabhikul, Phatharaporn; Kaewkrasaesin, Chatchon; Kongkit, Jaruwan; Umphonsathien, Mongkontida; Akbulut, Mehmet; Alici, Gökhan; Bayram, Fahri; Can, Levent Hürkan; Celik, Ahmet; Ceyhan, Ceyhun; Coskun, Fatma Yilmaz; Demir, Mesut; Demircan, Sabri; Dogan, Volkan; Durakoglugil, Emre; Dural, İbrahim Etem; Gedikli, Omer; Hacioglu, Aysa; Ildizli, Muge; Kilic, Salih; Kirilmaz, Bahadir; Kutlu, Merih; Oguz, Aytekin; Ozdogan, Oner; Onrat, Ersel; Ozer, Savas; Sabuncu, Tevfik; Sahin, Tayfun; Sivri, Fatih; Sonmez, Alper; Temizhan, Ahmet; Topcu, Selim; Tokgozoglu, Lale; Tuncez, Abdullah; Vural, Mirac; Yenercag, Mustafa; Yesilbursa, Dilek; Yigit, Zerrin; Yildirim, Aytul Belgi; Yildirir, Aylin; Yilmaz, Mehmet Birhan; Atallah, Bassam; Traina, Mahmoud; Sabbour, Hani; Abdul Hay, Dana; Luqman, Neama; Elfatih, Abubaker; Abdulrasheed, Arshad; Manla, Yosef; Kwok, See; Delloca, Nicolas; Alieva, Rano B.; Fozilov, Khurshid G.; Hoshimov, Shavkat U.; Nizamov, Ulugbek I.; Kan, Liliya E.; Kim, Andrey R.; Abdullaeva, Guzal J.; Abdullaev, Alisher A.; Do, Doan Loi; Nguyen, Mai Ngoc Thi; Kim, Ngoc Thanh; Le, Thanh Tung; Le, Hong An; Ray, Kausik K.. - In: THE LANCET DIABETES & ENDOCRINOLOGY. - ISSN 2213-8587. - 12:11(2024), pp. 811-823. [10.1016/s2213-8587(24)00221-3]

Association of BMI, lipid-lowering medication, and age with prevalence of type 2 diabetes in adults with heterozygous familial hypercholesterolaemia: a worldwide cross-sectional study

Arca, Marcello;D'Erasmo, Laura;
2024

Abstract

Background: Statins are the cornerstone treatment for patients with heterozygous familial hypercholesterolaemia but research suggests it could increase the risk of type 2 diabetes in the general population. A low prevalence of type 2 diabetes was reported in some familial hypercholesterolaemia cohorts, raising the question of whether these patients are protected against type 2 diabetes. Obesity is a well known risk factor for the development of type 2 diabetes. We aimed to investigate the associations of known key determinants of type 2 diabetes with its prevalence in people with heterozygous familial hypercholesterolaemia. Methods: This worldwide cross-sectional study used individual-level data from the EAS FHSC registry and included adults older than 18 years with a clinical or genetic diagnosis of heterozygous familial hypercholesterolaemia who had data available on age, BMI, and diabetes status. Those with known or suspected homozygous familial hypercholesterolaemia and type 1 diabetes were excluded. The main outcome was prevalence of type 2 diabetes overall and by WHO region, and in relation to obesity (BMI ≥30·0 kg/m2) and lipid-lowering medication as predictors. The study population was divided into 12 risk categories based on age (tertiles), obesity, and receiving statins, and the risk of type 2 diabetes was investigated using logistic regression. Findings: Among 46 683 adults with individual-level data in the FHSC registry, 24 784 with heterozygous familial hypercholesterolaemia were included in the analysis from 44 countries. 19 818 (80%) had a genetically confirmed diagnosis of heterozygous familial hypercholesterolaemia. Type 2 diabetes prevalence in the total population was 5·7% (1415 of 24 784), with 4·1% (817 of 19 818) in the genetically diagnosed cohort. Higher prevalence of type 2 diabetes was observed in the Eastern Mediterranean (58 [29·9%] of 194), South-East Asia and Western Pacific (214 [12·0%] of 1785), and the Americas (166 [8·5%] of 1955) than in Europe (excluding the Netherlands; 527 [8·0%] of 6579). Advancing age, a higher BMI category (obesity and overweight), and use of lipid-lowering medication were associated with a higher risk of type 2 diabetes, independent of sex and LDL cholesterol. Among the 12 risk categories, the probability of developing type 2 diabetes was higher in people in the highest risk category (aged 55–98 years, with obesity, and receiving statins; OR 74·42 [95% CI 47·04–117·73]) than in those in the lowest risk category (aged 18–38 years, without obesity, and not receiving statins). Those who did not have obesity, even if they were in the upper age tertile and receiving statins, had lower risk of type 2 diabetes (OR 24·42 [15·57–38·31]). The corresponding results in the genetically diagnosed cohort were OR 65·04 (40·67–104·02) for those with obesity in the highest risk category and OR 20·07 (12·73–31·65) for those without obesity. Interpretation: Adults with heterozygous familial hypercholesterolaemia in most WHO regions have a higher type 2 diabetes prevalence than in Europe. Obesity markedly increases the risk of diabetes associated with age and use of statins in these patients. Our results suggest that heterozygous familial hypercholesterolaemia does not protect against type 2 diabetes, hence managing obesity is essential to reduce type 2 diabetes in this patient population. Funding: Pfizer, Amgen, MSD, Sanofi-Aventis, Daiichi-Sankyo, and Regeneron.
2024
BMI; lipid-lowering medication; age; type 2 diabetes; heterozygous familial hypercholesterolaemia
01 Pubblicazione su rivista::01a Articolo in rivista
Association of BMI, lipid-lowering medication, and age with prevalence of type 2 diabetes in adults with heterozygous familial hypercholesterolaemia: a worldwide cross-sectional study / Elshorbagy, Amany; Lyons, Alexander R. M.; Vallejo-Vaz, Antonio J.; Stevens, Christophe A. T.; Dharmayat, Kanika I.; Brandts, Julia; Catapano, Alberico L.; Freiberger, Tomas; Hovingh, G. Kees; Mata, Pedro; Raal, Frederick J.; Santos, Raul D.; Soran, Handrean; Watts, Gerald F.; Abifadel, Marianne; Aguilar-Salinas, Carlos A.; Alhabib, Khalid F.; Alkhnifsawi, Mutaz; Almahmeed, Wael; Alonso, Rodrigo; Al-Rasadi, Khalid; Al-Sarraf, Ahmad; Ashavaid, Tester F.; Banach, Maciej; Binder, Christoph J.; Bourbon, Mafalda; Brunham, Liam R.; Chlebus, Krzysztof; Corral, Pablo; Cruz, Diogo; Davletov, Kairat; Descamps, Olivier S.; Ezhov, Marat; Gaita, Dan; Groselj, Urh; Harada-Shiba, Mariko; Holven, Kirsten B.; Kayikcioglu, Meral; Khovidhunkit, Weerapan; Lalic, Katarina; Latkovskis, Gustavs; Laufs, Ulrich; Liberopoulos, Evangelos; Lima-Martinez, Marcos M.; Lin, Jie; Maher, Vincent; Marais, A. 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[10.1016/s2213-8587(24)00221-3]
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