The good and bad effects of statins on insulin sensitivity and secretion

Muscogiuri, Giovanna; Sarno, Gerardo; Gastaldelli, Amalia; Savastano, Silvia; Arillo, Antonio; Colao, Annamaria; Orio, Francesco

doi:10.3109/07435800.2014.952018

Cited by 29 publications

(22 citation statements)

References 54 publications

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“…Statins also have pleiotropic effects such as improving endothelial function, stabilizing atherosclerotic plaques and reducing oxidative stress and inflammation (Zhou and Liao, 2010). On the other hand, some association between statin use and diabetes onset has previously been shown in patients with cardiovascular disease (Shah and Goldfine, 2012), and possibly worsening insulin resistance, secretion and metabolic control (Muscogiuri et al, 2014). However, the general consensus is that the positive effects of statins on LDL outweighs the negative effects on metabolic control (Rocco, 2012, Shah and Goldfine, 2012).…”

Section: Discussionmentioning

confidence: 99%

Risk of mortality and recurrent cardiovascular events in patients with acute coronary syndromes on high intensity statin treatment

Rockberg¹,

Jørgensen²,

Taylor

et al. 2017

Preventive Medicine Reports

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Several randomized controlled trials have shown a benefit of high-dose intensive statin treatment in reducing risk of death and second cardiovascular disease (CVD) events in patients previously diagnosed with an acute coronary syndrome (ACS). Non-randomized studies in clinical settings support these findings, but large, long-term, observational studies addressing CVD and non-CVD endpoints are lacking. In this retrospective longitudinal study, we followed ACS patients in Sweden during 2001–2012 using national health registry and medical record data. A total of 49,857 patients were identified, of whom 10,092 (20.2%) received high dose statins and 21,174 (42.7%) received no statins. Royston-Parmar parametric time-to-event models were implemented to model hazard for second CVD events and death, stratified by gender and diabetes diagnosis. We found that risk of a second CVD event developed similarly in both treatment groups, but was much higher in the no statin group. Risk of CVD-related death remained relatively constant for the high-statin group, while it increased over time for the no-statin group. Interestingly, males had higher mortality rates in the no-statin group, but not in the high-statin group. All-cause mortality and non-CVD-related death followed similar trends to those observed for CVD-related death. This work provides additional real-world evidence for effect of statins in CVD-related mortality. The hazard functions presented here can provide a basis for future survival modeling and health economic evaluation.

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Section: Discussionmentioning

confidence: 99%

Risk of mortality and recurrent cardiovascular events in patients with acute coronary syndromes on high intensity statin treatment

Rockberg¹,

Jørgensen²,

Taylor

et al. 2017

Preventive Medicine Reports

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“…Although statins are well recognised to confer cardio-protective benefits [ 1 – 3 ], there is increasing evidence of a link between statin use and new-onset diabetes [ 6 – 8 ]. The cardiovascular benefits usually outweigh the risk of developing insulin resistance [ 22 ]. More recently, systematic reviews of randomised trials and observational studies have shown a modest adverse effect of statin therapy on glycaemic control (specifically HbA1c) [ 10 – 14 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of background statin therapy on glycemic response and cardiovascular events following initiation of insulin therapy in type 2 diabetes: a large UK cohort study

Anyanwagu

Mamza

Donnelly

et al. 2017

Cardiovasc Diabetol

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AimStatins may increase the risk of new-onset diabetes and adversely affect glycaemic control, but their effects on the glycemic response and mortality outcomes following commencement of insulin therapy in patients with Type 2 Diabetes (T2D) are unclear.MethodsA retrospective cohort study was conducted in 12,725 insulin initiators with T2D using The Health Improvement Network (THIN) UK database. Changes in HbA1c at 6, 12, 24 and 36 months, and the 5-year risk of mortality and (3-point) major adverse cardiovascular events (MACE), were compared between prior users (n = 10,682) and non-users (n = 2043) of statin therapy who were newly commenced on insulin treatment. Cox proportional hazard models were used to estimate the hazard ratios of the different outcomes.ResultsMean age of the cohort was 58.7 ± 14.0 years (51% male) and mean baseline HbA1c was 8.7 ± 1.8%. A greater initial reduction in HbA1c was observed following insulin initiation in the non-users of statins compared with the users, which was significant in the short term (−0.34% vs −0.26% at 6 months; mean diff = −0.09%, p = 0.004) but not in the long term: −0.31% versus −0.35% at 3 years (mean diff = 0.05%, p = 0.344). CV events (3-point MACE) were 878 versus 217 in statin users versus non-users (20.7 vs 30.9 per 1000 person-years; adjusted Hazard Ratio (aHR) 1.36 (95% CI 1.15–1.62; p < 0.0001). In a subgroup analysis of individual statins, HbA1c was higher throughout the study duration with all statins relative to non-users of statin therapy (p < 0.05). The aHRs for 3-point MACE for atorvastatin, simvastatin, rosuvastatin and pravastatin were 0.82 (95% CI 0.68–0.98), 0.67 (0.55–0.82), 0.56 (0.39–0.81) and 0.78 (0.60–1.01), respectively.ConclusionsFollowing initiation of insulin therapy in patients with T2D in routine care, concurrent use of a statin was associated with less good glycaemic control in the short-term but a much lower risk of major adverse CV events.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-017-0587-6) contains supplementary material, which is available to authorized users.

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“…On the other hand, we and others have hypothesized that insulin signaling in their target tissues (such as muscle) could also be impaired by chronic statin treatment. However, studies relating statins therapy and insulin sensitivity are controversial [206][207][208]. A meta-analysis by Baker and colleagues shows that while pravastatin improved insulin sensitivity, atorvastatin, simvastatin, and rosuvastatin worsened it [209].…”

Section: Statins and New Onset Of Diabetesmentioning

confidence: 99%

Mitochondrial Oxidative Stress and Calcium-Dependent Permeability Transition are Key Players in the Mechanisms of Statins-Associated Side Effects

Busanello¹,

Marques²,

Lorza‐Gil³

et al. 2018

Mitochondrial Diseases

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Statins are cholesterol-lowering medicines utilized worldwide and are associated with reduced risk of cardiovascular mortality and events. However, 0.5-10% of patients suffer from adverse effects especially on skeletal muscle. Recently, new onset of diabetes has been reported in subjects on statin therapy. Pro-and anti-oxidant effects of statins have been reported, thus fostering a debate. Previously reported data provide evidence that statins induce alterations in intracellular calcium homeostasis and mitochondrial dysfunctions that can be counteracted by antioxidants (e.g., CoQ10, creatine, and L-carnitine). Therefore, we have proposed that statin-induced inhibition of mitochondrial respiration leads to oxidative stress that opens a calcium-dependent permeability transition pore, an event that may lead to cell death. In addition, mitochondrial oxidative stress caused by statin treatment may be a signal for cellular antioxidant system responses such as catalase upregulation, possibly explaining the alleged statins' antioxidant properties. Muscle mitochondrial dysfunction induced by statin treatment may be associated with the peripheral insulin resistance and may explain statins-induced new onset of diabetes. Together, the data presented in this review suggest that the statins' detrimental effects can be prevented by co-administration of antioxidants.

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The good and bad effects of statins on insulin sensitivity and secretion

Cited by 29 publications

References 54 publications

Risk of mortality and recurrent cardiovascular events in patients with acute coronary syndromes on high intensity statin treatment

Risk of mortality and recurrent cardiovascular events in patients with acute coronary syndromes on high intensity statin treatment

Effects of background statin therapy on glycemic response and cardiovascular events following initiation of insulin therapy in type 2 diabetes: a large UK cohort study

Mitochondrial Oxidative Stress and Calcium-Dependent Permeability Transition are Key Players in the Mechanisms of Statins-Associated Side Effects

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