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Cardiovascular and Metabolic Risk
Incidence of type 2 diabetes in familial combined hyperlipidemia
  1. Martijn C G J Brouwers1,
  2. Jacqueline de Graaf2,
  3. Nynke Simons1,3,
  4. Steven Meex4,
  5. Sophie ten Doeschate1,
  6. Shadana van Heertum1,
  7. Britt Heidemann1,
  8. Jim Luijten1,
  9. Douwe de Boer4,
  10. Nicolaas Schaper1,
  11. Coen D A Stehouwer5,
  12. Marleen M J van Greevenbroek3
  1. 1Department of Internal Medicine, Division of Endocrinology and Metabolic Disease, CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, The Netherlands
  2. 2Department of Internal Medicine, Radboud Institute for Health Sciences, Radboudumc, Nijmegen, The Netherlands
  3. 3Department of Internal Medicine, Division of General Internal Medicine, Laboratory for Metabolism and Vascular Medicine, CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands
  4. 4Central Diagnostic Laboratory, Maastricht University Medical Centre, Maastricht, The Netherlands
  5. 5Department of Internal Medicine, CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, The Netherlands
  1. Correspondence to Professor Martijn C G J Brouwers; mcgj.brouwers{at}mumc.nl

Abstract

Objective Familial combined hyperlipidemia (FCHL) is common among survivors of a premature myocardial infarction. FCHL patients are characterized by visceral obesity, fatty liver, and insulin resistance. The aim of the present study was to determine the incidence and determinants of type 2 diabetes (T2D) in a longitudinal cohort of FCHL pedigrees.

Research design and methods FCHL patients, their unaffected relatives and spouses included in our baseline cohort in 1998–2005 (n=596) were re-invited to determine the incidence of self-reported T2D (that was confirmed by medical records), used as the primary outcome measure. The Fatty Liver Index (FLI) and Homeostasis Model Assessment Insulin Resistance (HOMA2-IR) were used as markers of fatty liver and insulin resistance, respectively. A subset of the original cohort underwent ultrasound of the liver, and subcutaneous and visceral fat in 2002–2005 (n=275; ‘ultrasound subcohort’).

Results Follow-up data (median: 15 years) was acquired for 76%. The incidence rate of T2D was significantly higher in FCHL patients compared with spouses (19.2 per 1000 person-years vs 2.8 per 1000 person-years; HR : 6.3, 95% CI: 2.4 to 16.8), whereas no differences were observed between unaffected relatives and spouses (HR: 0.9, 95% CI: 0.3 to 2.6). Cox’s proportional hazard regression analyses showed that baseline HOMA2-IR and FLI≥60, but not waist circumference, BMI, or the FCHL affected state, were independently associated with incident T2D. Similar results were obtained in the ultrasound subcohort (median follow-up: 11 years), in which baseline HOMA2-IR and fatty liver (assessed by ultrasound) were independently associated with incident T2D.

Conclusion This study further corroborates the suggestion that the liver plays a central role in the pathogenesis of cardiometabolic complications in FCHL. It supports periodical screening for T2D in this high-risk population.

  • insulin resistance
  • liver fat
  • hyperlipidemia
  • epidemiology
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjdrc-2019-001107

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    Footnotes

    • Contributors MCGJB and MMJvG were responsible for the study concept and design and participated in the interpretation of the data. NS, StD, SvH, BH, and JL were involved in recruitment of participants and clinical measurements. SM and DdB were reponsible for the laboratory measurements at the Central Diagnostic Laboratory. All authors critically revised the manuscript and approved the final version to be published.

    • Funding This work was supported by the Biobanking and Biomolecular Research Infrastructure the Netherlands (BBMRI-NL CP2013- 80).

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Ethics approval The study protocol was approved by the Medical Ethics Committee from Maastricht University. All individuals gave written informed consent.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement Data are available upon reasonable request.