Statins do not increase the risk of developing type 2 diabetes in familial hypercholesterolemia: The SAFEHEART study

Fuentes, Francisco; Alcalá‐Díaz, Juan F.; Watts, Gerald F.; Alonso, Rodrigo; Muñiz, Ovidio; Díaz‐Díaz, José Luis; Mata, Nelva; Muñoz-Torrero, Juan Francisco Sánchez; Brea, Ángel; Galiana, Jesús; Figueras, R.; Aguado, Rocío; Piedecausa, Mar; Cepeda, José María; Vidal, J I; Rodríguez-Cantalejo, Fernando; Mata, Pedro

doi:10.1016/j.ijcard.2015.07.107

Cited by 33 publications

(16 citation statements)

References 32 publications

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“…They also concluded that long duration of high statin treatment did not seem to be associated with diabetic risk in FH patients. These results were confirmed by other studies ( Table 1 ) (Kusters et al, 2014; Fuentes et al, 2015). A recent cross-sectional study may provide some novel insights into the inverse association between FH and prevalence of DM ( Table 1 ) (Besseling et al, 2015).…”

Section: Inverse Association Of Fh and The Risk Of T2dmsupporting

confidence: 91%

Statins and New-Onset Diabetes Mellitus: LDL Receptor May Provide a Key Link

Chen

2017

Front. Pharmacol.

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Numerous studies have noted that populations treated with statins have increased risk for new-onset diabetes mellitus; however, the underlying molecular mechanisms are not fully understood. Interestingly, familial hypercholesterolemia (FH) patients with mutations in the low-density lipoprotein receptor (LDLR) gene are protected against diabetes mellitus (DM), despite these patients being subjected to long-term statin therapy. Since the common pathway between FH and statin therapy is LDLR-mediated cellular cholesterol uptake, the arising question is whether the LDLR plays an important role in the diabetogenic effect of statins. Indeed, given that statins can regulate the LDLR expression in liver and peripheral tissue, there is a possible mechanism that the increased LDLR causes cellular cholesterol accumulation and dysfunction in pancreatic islets, explaining why statins fail to increase the risk of DM in FH patients. In this paper, with regarded to recent literatures, we highlight the role of LDLR in the pathophysiology of cholesterol-induced pancreatic islets dysfunction, which may provide the key link between statins treatment and the increased risk of new-onset diabetes mellitus.

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Section: Inverse Association Of Fh and The Risk Of T2dmsupporting

confidence: 91%

Statins and New-Onset Diabetes Mellitus: LDL Receptor May Provide a Key Link

Chen

2017

Front. Pharmacol.

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“…Fouchier et al performed parametric linkage analysis combined with exome sequencing in a family with autosomal-dominant hypercholesterolemia and identified a variant in signal-transducing adaptor family member 1 (STAP1) associated with the disease 6) . Further Sanger sequencing of STAP1 in 400 additional unrelated autosomal-dominant hypercholesterolemia probands identified 3 additional missense vari-metabolic syndrome that predicted increased risk of new-onset of type 2 diabetes in FH 42) . Similar findings were reported by others 43) .…”

Section: Other Genetic Factors Contributing To the Phenotypes Of Famimentioning

confidence: 99%

“…Although recent studies have suggested that high doses of statins can increase the risk of developing type 2 diabetes 40,41) , the cardiovascular benefits of statin therapy clearly outweigh the risk of developing diabetes in this group of high-risk patients. Recent data from a large prospective cohort of FH patients treated with statins and their unaffected relatives showed that in patients with FH, long-term treatment with high doses of statins did not increase the risk of developing type 2 diabetes 42) . The best predictors for the development of type 2 diabetes in patients with FH were increasing age (range 50 -75 years) and the presence of metabolic syndrome at entry, with the plasma glucose levels being the only component of the have a higher plasma level of Lp(a) than the general population or patients with nonfamilial hypercholesterolemia.…”

Section: Ezetimibementioning

confidence: 99%

Management of Familial Hypercholesterolemia in Hong Kong

Hooper

Bockxmeer

et al. 2016

JAT

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“…19,20 Complicating the risk assessment in children is a recent study reporting a significantly lower prevalence of T2DMamong patients with heFH compared to their unaffected relatives, and a randomized controlled trial reporting no increased risk of T2DM in patients with heFH treated with statins. 21,22 Results from these studies raise the possibility that the gene mutation resulting in FH may also confer protection from T2DM.…”

Section: Introductionmentioning

confidence: 97%

Statin Use and the Risk of Type 2 Diabetes Mellitus in Children and Adolescents

Joyce

Zachariah

Eaton

et al. 2017

Academic Pediatrics

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Objective There is increasing evidence of an association between statin use and type 2 diabetes (T2DM) in adults, yet this relationship has never been studied in children or adolescents and may have important implications for assessing risks and benefits of treatment in this population.” We estimated the association between statin use and the risk of T2DMin children with and without a dyslipidemia diagnosis. Methods Propensity scores were used to match new users of statins with a minimum 50 percent of days covered (PDC) in the first year of use to up to 10 non-users. Analyses were stratified by a dyslipidemia diagnosis based on recent evidence suggesting a potentially protective effect of familial hypercholesterolemia on T2DM. In sensitivity analyses we varied this period of exclusion and PDC. Cox proportional hazard models compared the hazard of the outcome between the exposed and unexposed patients. Results A total of 21,243,305 patients met eligibility criteria, 2,085 (0.01%) of whom met the exposure definition of which 1,046 (50%) had a dyslipidemia diagnosis. Statin use was associated with an increased risk of type 2 diabetes in children without dyslipidemia (HR 1.96, 95% CI 1.20–3.22), but not in children with a dyslipidemia (HR 1.11, 95% CI 0.65–1.90). The results were consistent across variations in the exclusion period and PDC. Conclusions Statin use was associated with an increased likelihood of developing T2DM in children without dyslipidemia. Physicians and patients need to weigh the possible risk of T2DM against the long-term benefits of statin therapy at a young age.

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Statins do not increase the risk of developing type 2 diabetes in familial hypercholesterolemia: The SAFEHEART study

Cited by 33 publications

References 32 publications

Statins and New-Onset Diabetes Mellitus: LDL Receptor May Provide a Key Link

Statins and New-Onset Diabetes Mellitus: LDL Receptor May Provide a Key Link

Management of Familial Hypercholesterolemia in Hong Kong

Statin Use and the Risk of Type 2 Diabetes Mellitus in Children and Adolescents

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