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

• Published in: LANCET DIABETES & ENDOCRINOLOGY
• Main Authors: 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; Alnouri, Fahad; 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; Marz, Winfried; Mirrakhimov, Erkin; Miserez, Andre R.; Mitchenko, Olena; Nawawi, Hapizah; Nordestgaard, Borge G.; Panayiotou, Andrie G.; Paragh, Gyorgy; Petrulioniene, Zaneta; Pojskic, Belma; Postadzhiyan, Arman; Reda, Ashraf; Reiner, Zeljko; 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; Thanh-Huong Truong; Tselepis, Alexandros D.; Tybjaerg-Hansen, Anne; Vazquez, Alejandra C.; Viigimaa, Margus; Vohnout, Branislav; Wang, Luya; Yamashita, Shizuya; Arca, Marcello; Averna, Maurizio; Ray, Kausik K.
• Format: Article
• Language: English
• Published: ELSEVIER SCIENCE INC 2024
• Subjects: Endocrinology & Metabolism
• Online Access: https://www-webofscience-com.uitm.idm.oclc.org/wos/woscc/full-record/WOS:001381420900001
• ISSN: 2213-8587; 2213-8595
• DOI: 10.1016/S2213-8587(24)00221-3

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 center dot 0 kg/m(2)) 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 center dot 7% (1415 of 24 784), with 4 center dot 1% (817 of 19 818) in the genetically diagnosed cohort. Higher prevalence of type 2 diabetes was observed in the Eastern Mediterranean (58 [29 center dot 9%] of 194), South-East Asia and Western Pacific (214 [12 center dot 0%] of 1785), and the Americas (166 [8 center dot 5%] of 1955) than in Europe (excluding the Netherlands; 527 [8 center dot 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 center dot 42 [95% CI 47 center dot 04-117 center dot 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 center dot 42 [15 center dot 57-38 center dot 31]). The corresponding results in the genetically diagnosed cohort were OR 65 center dot 04 (40 center dot 67-104 center dot 02) for those with obesity in the highest risk category and OR 20 center dot 07 (12 center dot 73-31 center dot 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. Copyright (c) 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.