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      Effect of statins on fasting glucose in non-diabetic individuals: nationwide population-based health examination in Korea

      1 , 2 , , 3

      Cardiovascular Diabetology

      BioMed Central

      Statin, Glucose, Diabetes mellitus, Health examination

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          Abstract

          Background

          Increasing evidence suggest that statin therapy has a diabetogenic effect. Individual types of statin may have a different effect on glucose metabolism. Using the repeated nationwide population-based health screening data in Korea, we investigated the longitudinal changes in fasting glucose level of non-diabetic individuals by use of statins.

          Methods

          From the National Health Screening Cohort, we included 379,865 non-diabetic individuals who had ≥ 2 health screening examinations with fasting blood glucose level measured in 2002–2013. Using the prescription records of statins in the database, we calculated the proportion of days covered (PDC) and average number of defined daily doses per day (anDDD) by statins. We constructed multivariate linear mixed models to evaluate the effects of statins on the changes in fasting glucose (Δglu).

          Results

          High PDC by statins had a significant positive effect on Δglu (coefficient for PDC 0.093 mmol/L, standard error 0.007, p < 0.001). anDDD by statins was also positively associated with Δglu (coefficient for anDDD 0.119 mmol/L, standard error 0.009, p < 0.001). Unlike statins, the PDC by fibrate and ezetimibe were not significantly associated with Δglu. There was no significant interaction effect on Δglu between time interval and statin. Considering individual types of statins, use of atorvastatin, rosuvastatin, pitavastatin, and simvastatin were significantly associated with increase of Δglu. Pravastatin, lovastatin, and fluvastatin were also positively associated with Δglu, but were not statistically significant.

          Conclusions

          More adherent and intensive use of statins was significantly associated with an increase in fasting glucose of non-diabetic individuals. In subgroup analysis of individual statins, use of atorvastatin, rosuvastatin, pitavastatin and simvastatin had significant association with increase in fasting glucose. Pravastatin, lovastatin, and fluvastatin had non-significant trend toward an increased fasting glucose. Our findings suggest the medication class effect of statins inducing hyperglycemia.

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          Most cited references 51

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          Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial.

          Although statins reduce coronary and cerebrovascular morbidity and mortality in middle-aged individuals, their efficacy and safety in elderly people is not fully established. Our aim was to test the benefits of pravastatin treatment in an elderly cohort of men and women with, or at high risk of developing, cardiovascular disease and stroke. We did a randomised controlled trial in which we assigned 5804 men (n=2804) and women (n=3000) aged 70-82 years with a history of, or risk factors for, vascular disease to pravastatin (40 mg per day; n=2891) or placebo (n=2913). Baseline cholesterol concentrations ranged from 4.0 mmol/L to 9.0 mmol/L. Follow-up was 3.2 years on average and our primary endpoint was a composite of coronary death, non-fatal myocardial infarction, and fatal or non-fatal stroke. Analysis was by intention-to-treat. Pravastatin lowered LDL cholesterol concentrations by 34% and reduced the incidence of the primary endpoint to 408 events compared with 473 on placebo (hazard ratio 0.85, 95% CI 0.74-0.97, p=0.014). Coronary heart disease death and non-fatal myocardial infarction risk was also reduced (0.81, 0.69-0.94, p=0.006). Stroke risk was unaffected (1.03, 0.81-1.31, p=0.8), but the hazard ratio for transient ischaemic attack was 0.75 (0.55-1.00, p=0.051). New cancer diagnoses were more frequent on pravastatin than on placebo (1.25, 1.04-1.51, p=0.020). However, incorporation of this finding in a meta-analysis of all pravastatin and all statin trials showed no overall increase in risk. Mortality from coronary disease fell by 24% (p=0.043) in the pravastatin group. Pravastatin had no significant effect on cognitive function or disability. Pravastatin given for 3 years reduced the risk of coronary disease in elderly individuals. PROSPER therefore extends to elderly individuals the treatment strategy currently used in middle aged people.
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            Cohort profile: the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) in Korea

            Purpose The National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) is a cohort of participants who participated in health screening programmes provided by the NHIS in the Republic of Korea. The NHIS constructed the NHIS-HEALS cohort database in 2015. The purpose of this cohort is to offer relevant and useful data for health researchers, especially in the field of non-communicable diseases and health risk factors, and policy-maker. Participants To construct the NHIS-HEALS database, a sample cohort was first selected from the 2002 and 2003 health screening participants, who were aged between 40 and 79 in 2002 and followed up through 2013. This cohort included 514 866 health screening participants who comprised a random selection of 10% of all health screening participants in 2002 and 2003. Findings to date The age-standardised prevalence of anaemia, diabetes mellitus, hypertension, obesity, hypercholesterolaemia and abnormal urine protein were 9.8%, 8.2%, 35.6%, 2.7%, 14.2% and 2.0%, respectively. The age-standardised mortality rate for the first 2 years (through 2004) was 442.0 per 100 000 person-years, while the rate for 10 years (through 2012) was 865.9 per 100 000 person-years. The most common cause of death was malignant neoplasm in both sexes (364.1 per 100 000 person-years for men, 128.3 per 100 000 person-years for women). Future plans This database can be used to study the risk factors of non-communicable diseases and dental health problems, which are important health issues that have not yet been fully investigated. The cohort will be maintained and continuously updated by the NHIS.
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              Statin adverse effects : a review of the literature and evidence for a mitochondrial mechanism.

              HMG-CoA reductase inhibitors (statins) are a widely used class of drug, and like all medications, have potential for adverse effects (AEs). Here we review the statin AE literature, first focusing on muscle AEs as the most reported problem both in the literature and by patients. Evidence regarding the statin muscle AE mechanism, dose effect, drug interactions, and genetic predisposition is examined. We hypothesize, and provide evidence, that the demonstrated mitochondrial mechanisms for muscle AEs have implications to other nonmuscle AEs in patients treated with statins. In meta-analyses of randomized controlled trials (RCTs), muscle AEs are more frequent with statins than with placebo. A number of manifestations of muscle AEs have been reported, with rhabdomyolysis the most feared. AEs are dose dependent, and risk is amplified by drug interactions that functionally increase statin potency, often through inhibition of the cytochrome P450 3A4 system. An array of additional risk factors for statin AEs are those that amplify (or reflect) mitochondrial or metabolic vulnerability, such as metabolic syndrome factors, thyroid disease, and genetic mutations linked to mitochondrial dysfunction. Converging evidence supports a mitochondrial foundation for muscle AEs associated with statins, and both theoretical and empirical considerations suggest that mitochondrial dysfunction may also underlie many nonmuscle statin AEs. Evidence from RCTs and studies of other designs indicates existence of additional statin-associated AEs, such as cognitive loss, neuropathy, pancreatic and hepatic dysfunction, and sexual dysfunction. Physician awareness of statin AEs is reportedly low even for the AEs most widely reported by patients. Awareness and vigilance for AEs should be maintained to enable informed treatment decisions, treatment modification if appropriate, improved quality of patient care, and reduced patient morbidity.
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                Author and article information

                Contributors
                antithrombus@gmail.com
                hslee1@yuhs.ac
                +82-2-2019-3325 , kylee@yuhs.ac
                Journal
                Cardiovasc Diabetol
                Cardiovasc Diabetol
                Cardiovascular Diabetology
                BioMed Central (London )
                1475-2840
                5 December 2018
                5 December 2018
                2018
                : 17
                Affiliations
                [1 ]ISNI 0000 0004 0647 3511, GRID grid.410886.3, Department of Neurology, CHA Bundang Medical Center, , CHA University College of Medicine, ; Seongnam, Republic of Korea
                [2 ]ISNI 0000 0004 0470 5454, GRID grid.15444.30, Biostatistics Collaboration Unit, , Yonsei University College of Medicine, ; Seoul, Republic of Korea
                [3 ]ISNI 0000 0004 0470 5454, GRID grid.15444.30, Department of Neurology, , Gangnam Severance Hospital, Yonsei University College of Medicine, ; 211 Eonju-ro, Gangnam-gu, Seoul, 06273 Republic of Korea
                Article
                799
                10.1186/s12933-018-0799-4
                6280428
                30518364
                © The Author(s) 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                Funding
                Funded by: Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education
                Award ID: 2017R1D1A1B03033382
                Award Recipient :
                Categories
                Original Investigation
                Custom metadata
                © The Author(s) 2018

                Endocrinology & Diabetes

                statin, glucose, diabetes mellitus, health examination

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