- Email: [email protected]
Diabetes, statins and FH
Diabetes, statins and FH F. Fuentes, J.F. Alcal´a-D´ıaz, G.F. Watts, P. Mata PII: DOI: Reference:
S0167-5273(15)30803-2 doi: 10.1016/j.ijcard.2015.10.235 IJCA 21526
To appear in:
International Journal of Cardiology
Received date: Accepted date:
29 October 2015 30 October 2015
Please cite this article as: Fuentes F, Alcal´a-D´ıaz JF, Watts GF, Mata P, Diabetes, statins and FH, International Journal of Cardiology (2015), doi: 10.1016/j.ijcard.2015.10.235
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Letter to the editor Title: Diabetes, statins and FH Authors: Fuentes F1*, Alcalá-Díaz JF1, Watts GF2, Mata P3. 1
PT
IMIBIC/HospitalUniversitarioReinaSofía/UniversidaddeCórdoba,Córdoba,Spain
CIBER
SC RI
Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Córdoba, Spain
2 Lipid Disorders Clinic, Department of Cardiology, Royal Perth Hospital, School of
NU
Medicine and Pharmacology, University of Western Australia 3 Fundación Hipercolesterolemia Familiar, Madrid, Spain
MA
* Corresponding author: [email protected] . Phone number: +34957012902,
ED
Fax number: +34957204763
We thank Qi Yu et al, for their constructive comments and interest in our work. We
PT
excluded patients with homozygous FH from the analysis because, as explained in the
CE
methodology section of the article, they were very rare in the SAFEHEART cohort and would not be representative of the larger cohort of heterozygotes who would have
AC
received a statin later in life. The lower mean plasma levels of LDL-cholesterol that the authors point out was related to a large proportion of the patients in the cohort receiving treatment with high-intensity statins for several years. We excluded patients who were already diabetic at the entry into the cohort to avoid confounding of our analyses. In relation to the reported by Besseling et al (1), we also showed in our cohort that people with FH have less prevalent type 2 diabetes, which may be plausibly related to the lower uptake of cholesterol by pancreatic β cells (1). Another factor that may contribute to this lower prevalence of diabetes in both studies is the average age of affected individuals. In the Dutch study, the average age of patients was even younger than our cohort. We have shown that age is a major driver of the onset of diabetes in FH, as seen in the general population.
ACCEPTED MANUSCRIPT That statins increase the risk of developing diabetes is clearly demonstrated in populations of patients with high cardiovascular risk (2,3), although the risk is very modest and is outweighed markedly by the reduction in cardiovascular events from taking a statin. Our
PT
data have important implications for clinical practice, for FH patients are commonly
SC RI
prescribed high-potency statins from an early age, but this does not apparently increase their risk of developing diabetes.
The mechanistic issue concerning whether the lack of LDL receptor activity in pancreatic
NU
β cells offsets the diabetogenic effects of statins in FH is still unclear. Finally, we recommend larg, longitudinal registry studies to delineate the long-term, non-
MA
cardiovascular sequelae of statins in younger patients with FH.
ED
References
1. Besseling J, Kastelein JJ, Defesche JC, Hutten BA, Hovingh GK. Association between
PT
familial hypercholesterolemia and prevalence of type 2 diabetes mellitus. JAMA 2015; 313:
CE
1029-36.
2. N. Sattar, D. Preiss, H.M. Murray, et al., Statins and risk of incident diabetes: a
AC
collaborative meta-analysis of randomised statin trials. Lancet 2010; 375: 735–742. 3. D.Preiss, S.R.Seshasai, P.Welsh, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA 2011; 305: 2556– 2564.
S0167-5273(15)30803-2 doi: 10.1016/j.ijcard.2015.10.235 IJCA 21526
To appear in:
International Journal of Cardiology
Received date: Accepted date:
29 October 2015 30 October 2015
Please cite this article as: Fuentes F, Alcal´a-D´ıaz JF, Watts GF, Mata P, Diabetes, statins and FH, International Journal of Cardiology (2015), doi: 10.1016/j.ijcard.2015.10.235
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Letter to the editor Title: Diabetes, statins and FH Authors: Fuentes F1*, Alcalá-Díaz JF1, Watts GF2, Mata P3. 1
PT
IMIBIC/HospitalUniversitarioReinaSofía/UniversidaddeCórdoba,Córdoba,Spain
CIBER
SC RI
Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Córdoba, Spain
2 Lipid Disorders Clinic, Department of Cardiology, Royal Perth Hospital, School of
NU
Medicine and Pharmacology, University of Western Australia 3 Fundación Hipercolesterolemia Familiar, Madrid, Spain
MA
* Corresponding author: [email protected] . Phone number: +34957012902,
ED
Fax number: +34957204763
We thank Qi Yu et al, for their constructive comments and interest in our work. We
PT
excluded patients with homozygous FH from the analysis because, as explained in the
CE
methodology section of the article, they were very rare in the SAFEHEART cohort and would not be representative of the larger cohort of heterozygotes who would have
AC
received a statin later in life. The lower mean plasma levels of LDL-cholesterol that the authors point out was related to a large proportion of the patients in the cohort receiving treatment with high-intensity statins for several years. We excluded patients who were already diabetic at the entry into the cohort to avoid confounding of our analyses. In relation to the reported by Besseling et al (1), we also showed in our cohort that people with FH have less prevalent type 2 diabetes, which may be plausibly related to the lower uptake of cholesterol by pancreatic β cells (1). Another factor that may contribute to this lower prevalence of diabetes in both studies is the average age of affected individuals. In the Dutch study, the average age of patients was even younger than our cohort. We have shown that age is a major driver of the onset of diabetes in FH, as seen in the general population.
ACCEPTED MANUSCRIPT That statins increase the risk of developing diabetes is clearly demonstrated in populations of patients with high cardiovascular risk (2,3), although the risk is very modest and is outweighed markedly by the reduction in cardiovascular events from taking a statin. Our
PT
data have important implications for clinical practice, for FH patients are commonly
SC RI
prescribed high-potency statins from an early age, but this does not apparently increase their risk of developing diabetes.
The mechanistic issue concerning whether the lack of LDL receptor activity in pancreatic
NU
β cells offsets the diabetogenic effects of statins in FH is still unclear. Finally, we recommend larg, longitudinal registry studies to delineate the long-term, non-
MA
cardiovascular sequelae of statins in younger patients with FH.
ED
References
1. Besseling J, Kastelein JJ, Defesche JC, Hutten BA, Hovingh GK. Association between
PT
familial hypercholesterolemia and prevalence of type 2 diabetes mellitus. JAMA 2015; 313:
CE
1029-36.
2. N. Sattar, D. Preiss, H.M. Murray, et al., Statins and risk of incident diabetes: a
AC
collaborative meta-analysis of randomised statin trials. Lancet 2010; 375: 735–742. 3. D.Preiss, S.R.Seshasai, P.Welsh, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA 2011; 305: 2556– 2564.