pitavastatin and Diabetes-Mellitus

Statin treatment increases the risk of new-onset diabetes mellitus (NODM); however, data directly comparing the risk of NODM among individual statins is limited. We compared the risk of NODM between patients using pitavastatin and atorvastatin or rosuvastatin using reliable, large-scale data.. Data of electronic health records from ten hospitals converted to the Observational Medical Outcomes Partnership Common Data Model (n = 14,605,368 patients) were used to identify new users of pitavastatin, atorvastatin, or rosuvastatin (atorvastatin + rosuvastatin) for ≥ 180 days without a previous history of diabetes or HbA1c level ≥ 5.7%. We conducted a cohort study using Cox regression analysis to examine the hazard ratio (HR) of NODM after propensity score matching (PSM) and then performed an aggregate meta-analysis of the HR.. After 1:2 PSM, 10,238 new pitavastatin users (15,998 person-years of follow-up) and 18,605 atorvastatin + rosuvastatin users (33,477 person-years of follow-up) were pooled from 10 databases. The meta-analysis of the HRs demonstrated that pitavastatin resulted in a significantly reduced risk of NODM than atorvastatin + rosuvastatin (HR 0.72; 95% CI 0.59-0.87). In sub-analysis, pitavastatin was associated with a lower risk of NODM than atorvastatin or rosuvastatin after 1:1 PSM (HR 0.69; CI 0.54-0.88 and HR 0.74; CI 0.55-0.99, respectively). A consistently low risk of NODM in pitavastatin users was observed when compared with low-to-moderate-intensity atorvastatin + rosuvastatin users (HR 0.78; CI 0.62-0.98).. In this retrospective, multicenter active-comparator, new-user, cohort study, pitavastatin reduced the risk of NODM compared with atorvastatin or rosuvastatin.

Topics: Atorvastatin; Cohort Studies; Diabetes Mellitus; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Multicenter Studies as Topic; Quinolines; Retrospective Studies; Rosuvastatin Calcium

Despite attaining LDL-cholesterol targets, many patients with diabetes remain at risk of developing cardiovascular events. In addition, treatment with statins has been associated with a slight but significant increased risk of development of diabetes, particularly with high-intensity statins. Pitavastatin is a moderate- to high-intensity statin that effectively reduces LDL-cholesterol levels. Pitavastatin provides a sustained increase of HDL-cholesterol levels that may exhibit a neutral or positive effect on glucose metabolism, may not increase the risk of new-onset diabetes, may exhibit positive effects on renal function and urinary albumin excretion and the risk of drug-drug interactions is low. Therefore, it seems that pitavastatin should preferentially be considered in the treatment of dyslipidemia in diabetic patients or at risk of developing diabetes.

Topics: Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Quinolines

Whether adverse effect of statins on glycaemic indices is common to all statins remains controversial and as yet data for pitavastatin are limited. We sought to assess the effects of pitavastatin on glycaemia and new-onset diabetes (NOD) in non-diabetic individuals using data from RCT pooled together by means of a meta-analysis.. We searched Medline, Cochrane, Embase and clinical trials registries websites until November-2014 for ≥12-week follow-up placebo or statin-controlled RCT of pitavastatin that included participants without diabetes and reported on fasting blood glucose (FBG), HbA1c or NOD. We additionally sought studies by consulting with Kowa Ph. Ltd. The association of pitavastatin with the outcomes were estimated by random-effects meta-analyses. Heterogeneity was assessed by the I(2) statistic and sensitivity and subgroup analyses, and publication bias with funnel plots and Egger and Harbord Tests.. 15 studies (approx. 1600 person-years) were included. No significant differences associated with pitavastatin (vs. control) were observed for FBG (MD -0.01 mg/dL [95%CI -0.77, 0.74], I(2) = 0%), HbA1c (MD -0.03% [95%CI -0.11, 0.05], I(2) = 43%) or NOD (RR 0.70 [95%CI 0.30, 1.61]; RD 0.0 [95%CI -0.004, 0.003]; I(2) = 0%). Sensitivity and subgroup analyses (including type of control [placebo or other statin], pitavastatin dose or follow-up] did not yield significant results. Potential publication bias may occur for NOD.. In the present meta-analysis pitavastatin did not adversely affect glucose metabolism or diabetes development compared with placebo or other statins.

Topics: Biomarkers; Blood Glucose; Chi-Square Distribution; Diabetes Mellitus; Dyslipidemias; Glycated Hemoglobin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence; Odds Ratio; Quinolines; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Treatment Outcome

Pitavastatin is the last marketed statin. Different studies have shown that pitavastatin is more potent than pravastatin and simvastatin in reducing LDL-cholesterol levels, and equivalent to atorvastatin and rosuvastatin. Moreover, pitavastatin provides a significant and sustained increase of HDL-cholesterol levels. Remarkably, as pitavastatin is minimally metabolized by CYP, the risk of interactions with other drugs is low. Additionally, pitavastatin does not interfere with glucose metabolism in diabetics and non-diabetics, and exerts a beneficial effect in patients with renal dysfunction. However, although available information may suggest that pitavastatin can improve cardiovascular prognosis, data coming from specifically designed clinical trials are still warranted. The aim of this review was to update the available evidence about efficacy and safety of pitavastatin, and to analyze the place of pitavastatin in the current armamentarium for the treatment of patients with hypercholesterolemia.

Topics: Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus; Drug Interactions; Dyslipidemias; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Quinolines

Topics: Cardiovascular Diseases; Diabetes Mellitus; Dose-Response Relationship, Drug; Drug Interactions; Dyslipidemias; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Musculoskeletal Pain; Quinolines

Statins have proven beneficial for reducing both primary and secondary events in patients with coronary heart disease. Tight control of serum lipid parameters in these patients is recommended by the most recent clinical guidelines. Although numerous lipid-lowering treatments are available, only a small percentage of eligible patients receive therapy and fewer achieve their lipid-lowering goals. Thus it is clear that new treatment strategies to manage patients with lipid abnormalities are warranted. Pitavastatin (Lival; Kowa Pharmaceuticals America, Montgomery, AL, USA) has been recently approved for the treatment of hypercholesterolemia and combined dyslipidemia. Pitavastatin 1-4 mg/day has shown similar low-density lipoprotein-reducing activity to other commercially available statins, including simvastatin and atorvastatin. Adverse events occurred at similar rates to other statins in clinical trials with favorable effects seen in patients with dyslipidemia and metabolic syndrome. Pharmacokinetic drug-drug interactions are minimized due to the lack of significant metabolism of pitavastatin by the cytochrome P450 enzyme system, although some drugs affect its uptake into hepatocytes and should be avoided. In addition to its higher acquisition cost, pitavastatin has not been shown to improve clinical outcomes in high-risk patient populations and thus may not be the agent of choice in many patients at this time in lieu of cheaper, clinically proven alternatives.

Topics: Acute Coronary Syndrome; Comorbidity; Diabetes Mellitus; Drug Interactions; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Quinolines; Renal Insufficiency, Chronic

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, known as statins, have revolutionized the treatment of hypercholesterolemia and coronary artery disease prevention. However, there are considerable issues regarding statin safety and further development of residual risk control, particularly for diabetic and metabolic syndrome patients. Pitavastatin is a potent statin with low-density lipoprotein (LDL) cholesterol-lowering effects comparable to those of atorvastatin or rosuvastatin. Pitavastatin has a high-density lipoprotein (HDL) cholesterol raising effect, may improve insulin resistance, and has little influence on glucose metabolism. Considering these factors along with its unique pharmacokinetic properties, which suggest minimal drug-drug interaction, pitavastatin could provide an alternative treatment choice, especially in patients with glucose intolerance or diabetes mellitus. Many clinical trials are now underway to test the clinical efficacy of pitavastatin in various settings and are expected to provide further information.

Topics: Animals; Coronary Artery Disease; Diabetes Mellitus; Drug Interactions; Glucose; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Insulin Resistance; Quinolines

The diabetogenic action of statins remains a concern, particularly in patients at high risk for diabetes receiving intensive statin therapy. Despite the risk of diabetes with statin use being considered a potential class effect, recent studies have suggested that pitavastatin exerts neutral or favorable effects on diabetogenicity. However, no randomized trial has compared the long-term effects of pitavastatin with those of other statins on glycemic control in populations at high risk for diabetes. Hence, we aim to assess the long-term effects of pitavastatin in comparison with atorvastatin on glucose metabolism in patients with metabolic syndrome (MetS).. The Long-term Effects of high-doSe pitavaStatin on Diabetogenicity in comparison with atorvastatin in patients with Metabolic syndrome (LESS-DM) trial is a prospective, randomized, open-label, active control clinical trial of patients with MetS. We plan to randomize 500 patients with MetS (1:1) to receive high-dose pitavastatin (4 mg) or atorvastatin (20 mg) daily for 24 months. The primary endpoint will be the change in hemoglobin A1c after statin treatment. Secondary endpoints will include the following: (1) changes in biochemical markers, including insulin, C-peptide, homeostasis model assessment of insulin resistance and insulin secretion, and adiponectin; (2) changes in imaging parameters, including carotid elasticity metrics and indices of cardiac function; and (3) the incidence of clinical events, including new-onset diabetes and cardiovascular disease.. In this trial, we will explore whether pitavastatin 4 mg does not disturb glucose metabolism in patients with MetS. It will also provide mechanistic information on statin type-dependent diabetogenic effects and surrogate data regarding vascular and cardiac changes achieved by intensive statin therapy.. ClinicalTrials.gov, NCT02940366 . Registered on 19 October 2016.

Topics: Atorvastatin; Biomarkers; Blood Glucose; C-Peptide; Cardiovascular Diseases; Clinical Protocols; Diabetes Mellitus; Glycated Hemoglobin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Insulin; Metabolic Syndrome; Prospective Studies; Quinolines; Republic of Korea; Research Design; Risk Factors; Time Factors; Treatment Outcome

Statin treatment may impair glucose homeostasis and increase the risk of new-onset diabetes mellitus, although this may depend on the statin, dose and patient population. We evaluated the effects of pitavastatin 4 mg/day on glucose homeostasis in patients with metabolic syndrome in the CAPITAIN trial. Findings were validated in a subset of patients enrolled in PREVAIL-US.. Participants with a well defined metabolic syndrome phenotype were recruited to CAPITAIN to reduce the influence of confounding factors. Validation and comparison datasets were selected comprising phenotypically similar subsets of individuals enrolled in PREVAIL-US and treated with pitavastatin or pravastatin, respectively. Mean change from baseline in parameters of glucose homeostasis (fasting plasma glucose [FPG], glycated hemoglobin [HbA1c], insulin, quantitative insulin-sensitivity check index [QUICKI] and homeostasis model of assessment-insulin resistance [HOMA-IR]) and plasma lipid profile were assessed at 6 months (CAPITAIN) and 3 months (PREVAIL-US) after initiating treatment.. In CAPITAIN (n = 12), no significant differences from baseline in HbA1c, insulin, HOMA-IR and QUICKI were observed at day 180 in patients treated with pitavastatin. A small (4%) increase in FPG from baseline to day 180 (P < 0.05), was observed. In the validation dataset (n = 9), no significant differences from baseline in glycemic parameters were observed at day 84 (all comparisons P > 0.05). Similar results were observed for pravastatin in the comparison dataset (n = 14).. Other than a small change in FPG in the CAPITAIN study, neutral effects of pitavastatin on glucose homeostasis were observed in two cohorts of patients with metabolic syndrome, independent of its efficacy in reducing levels of atherogenic lipoproteins. The small number of patients and relatively short follow-up period represent limitations of the study. Nevertheless, these data suggest that statin-induced diabetogenesis may not represent a class effect.

Topics: Blood Glucose; Cholesterol, LDL; Cohort Studies; Diabetes Mellitus; Dose-Response Relationship, Drug; Homeostasis; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipid Metabolism; Male; Metabolic Syndrome; Middle Aged; Pravastatin; Quinolines; Triglycerides

To evaluate the effect of pitavastatin on blood glucose in patients with hypercholesterolemia, and to investigate the efficacy of pitavastatin in diabetic patients combined with hypercholesterolemia.. This study was a 12-week, multi-center, open-label, without parallel-group comparison, phase IV clinical trail.. Contrasting to baseline, the prevalences at week 4 and 12 post-treatment of abnormal fasting plasma glucose (FPG) and glycosylated hemoglobin A1c (HbA1c) (FPG: 14.2%vs 14.1% and 11.0%; HbA1c: 14.3% vs 15.1% and 16.1%) in the safety set subjects without diabetes mellitus (DM), as well as in those with DM but not taking glucose-lowering drugs (FPG: 7/7 vs 4/7 and 5/7; HbA1c: 5/5 vs 4/4 and 5/5) had no significant changes (all P values > 0.05). Contrasting to baseline, the levels of TC [(6.51 ± 0.94) mmol/L vs (5.12 ± 0.93) mmol/L and (4.54 ± 1.00) mmol/L], LDL-C [(4.11 ± 0.79) mmol/L vs (3.02 ± 0.81) mmol/L and (2.51 ± 0.70) mmol/L] and TG [2.10 (1.53, 2.54) mmol/L vs 1.62 (1.26, 2.00) mmol/L and 1.35 (1.10, 1.86) mmol/L]at week 4 and 12 post-treatment in the per protocol set 55 subjects with DM were significantly reduced (all P values < 0.05); 33.3% of subjects at high risk and 10.0% of subjects at very high risk had achieved a TC target value; 55.6% of subjects at high risk and 40.0% of subjects at very high risk had achieved a LDL-C target value.. Pitavastatin has a safe effect on blood glucose and it could be used to treat diabetic patients combined with hypercholesterolemia in China.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Quinolines

The Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome (JAPAN-ACS) trial has found that early aggressive statin therapy in patients with acute coronary syndrome (ACS) significantly reduces the plaque volume (PV) of non-culprit coronary lesions. The purpose of the present study was to evaluate clinical factors that have an impact on plaque regression using statin therapy.. Serial intravascular ultrasound observations over 8-12 months were performed in 252 ACS patients receiving pitavastatin or atorvastatin. Linear regression analysis identified the presence of diabetes mellitus (DM) and PV at baseline as inhibiting factors, and serum remnant-like particle-cholesterol level at baseline as a significant factor significantly affecting the degree of plaque regression. Significant correlation between % change of PV and low-density lipoprotein cholesterol (LDL-C) level was found in patients with DM (n=73, P<0.05, r=0.4), whereas there was no significant correlation between the 2 parameters in patients without DM (n=178).. The regression of coronary plaque induced by statin therapy after ACS was weaker in diabetic patients than their counterparts. Moreover, vigorous reduction of the LDL-C levels might induce a greater degree of plaque regression in ACS patients with DM.

Topics: Acute Coronary Syndrome; Aged; Atorvastatin; Coronary Artery Disease; Diabetes Mellitus; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Pyrroles; Quinolines; Treatment Outcome; Ultrasonography, Interventional

We have shown that aggressive lipid lowering by pitavastatin and atorvastatin results in marked regression of atherosclerotic coronary lesions after acute coronary syndrome (ACS). The purpose of this study was to address the association of lipid levels after statin therapy with regression of atherosclerotic coronary lesions and major cardiovascular events in patients after ACS.. JAPAN-ACS is a prospective, randomized open-label study performed at 33 centers in Japan. Patients with ACS undergoing intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) were randomly assigned to receive either 4 mg/day pitavastatin or 20 mg/day atorvastatin within 72 hours after PCI. IVUS image was obtained in 251 patients, including 73 diabetic patients. Lipid profiles at the end of the study were divided into quartiles and the association with the percent change in non-culprit coronary plaque volume (PV) was assessed in total and diabetic patients. We also studied whether baseline and follow-up levels of HDL-cholesterol are associated with restenosis after PCI.. Decreasing LDL-cholesterol, non-HDL-cholesterol, LDL-C/HDL-C ratio, apolipoprotein B quartiles were associated with a progressively smaller plaque burden in total and diabetic patients. In diabetic patients, further reduction of these parameters was associated with a significantly greater reduction in PV. We also found that patients with lower HDL-cholesterol had a significantly higher incidence of target lesion revascularization.. Early intensive statin therapy in patients after ACS results in remarkable regression of coronary PV. Diabetic patients can have a benefit with more intensive therapy to achieve a lower target level in Japanese.

Topics: Acute Coronary Syndrome; Aged; Atorvastatin; Cholesterol, HDL; Cholesterol, LDL; Coronary Artery Disease; Diabetes Complications; Diabetes Mellitus; Female; Follow-Up Studies; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Japan; Male; Middle Aged; Prospective Studies; Pyrroles; Quinolines; Treatment Outcome; Ultrasonography, Interventional

Most statins increase the risk of new-onset diabetes. Unlike other statins, pitavastatin is reported to exert neutral effects on serum glucose level, but the precise mechanism is unknown.. Eight-week-old male C57BL/6J mice (n=26) were fed high-fat diet (HFD, 45% fat) with 0.01% placebo, rosuvastatin, or pitavastatin for 12 weeks. Cultured HepG2, C2C12, and 3T3-L1 cells and visceral adipocytes from HFD-fed mice were treated with vehicle or 10 µM statins for 24 h. The effects of pitavastatin and rosuvastatin on intracellular insulin signaling and glucose transporter 4 (GLUT4) translocation were evaluated.. After 12 weeks, the fasting blood glucose level was significantly lower in pitavastatin-treated group than in rosuvastatin-treated group (115.2±7.0 versus 137.4±22.3 mg/dL, p=0.024). Insulin tolerance significantly improved in pitavastatin-treated group as compared with rosuvastatin-treated group, and no significant difference was observed in glucose tolerance. Although plasma adiponectin and insulin levels were not different between the two statin treatment groups, the insulin-induced protein kinase B phosphorylation was weakly attenuated in pitavastatin-treated adipocytes than in rosuvastatin-treated adipocytes. Furthermore, minor attenuation in insulin-induced GLUT4 translocation to the plasma membrane of adipocytes was observed in pitavastatin-treated group.. Pitavastatin showed lower diabetogenic effects than rosuvastatin in mice that may be mediated by minor attenuations in insulin signaling in adipocytes.

Topics: Adipocytes; Adiponectin; Animals; Anticholesteremic Agents; Blood Glucose; Cells, Cultured; Correlation of Data; Diabetes Mellitus; Glucose Transporter Type 4; Humans; Insulin; Intra-Abdominal Fat; Mice; Mice, Inbred C57BL; Quinolines; Rosuvastatin Calcium; Signal Transduction

Although statin use in patients with acute myocardial infarction (AMI) is mandatory, it has been suggested to be associated with new-onset diabetes mellitus (NODM). In real world practice, moderate-intensity statin therapy is more commonly used than high-intensity statin therapy. In this study, we investigated the impact of moderate-intensity pitavastatin (2 to 4 mg) compared with moderate-intensity atorvastatin (10 to 20 mg) and rosuvastatin (5 to 10 mg) on the development of NODM during a follow-up period of up to 3years. Between November 2011 and May 2015, 2001 patients with AMI who did not have diabetes mellitus were investigated. The cumulative incidence of NODM was evaluated in all groups. To adjust for potential confounders, multinomial propensity scores were used. Cox proportional hazard models were used to assess the hazard ratio of NODM in the atorvastatin and rosuvastatin groups compared with pitavastatin group. The cumulative incidence of NODM was significantly lower in pitavastatin group compared with the atorvastatin and rosuvastatin groups (3.0% vs 8.4% vs 10.4%, respectively; Log-rank p value = 0.001). After weighting the baseline characteristics of the 3 statin groups by multinomial propensity scores, atorvastatin (hazard ratio: 2.615, 95% confidence interval: 1.163 to 5.879) and rosuvastatin (hazard ratio: 3.906, 95% confidence interval: 1.756 to 8.688) were found to be associated with a higher incidence of NODM compared with pitavastatin therapy on multivariable analysis. Moderate-intensity pitavastatin therapy is associated with a lower incidence of NODM in patients with AMI andhas similar clinical outcomes to moderate-intensity atorvastatin and rosuvastatin therapy.

Topics: Atorvastatin; Biomarkers; Diabetes Mellitus; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence; Male; Middle Aged; Myocardial Infarction; Quinolines; Registries; Republic of Korea; Risk Factors; Rosuvastatin Calcium

Very few studies conducted in Korea have investigated the relationship between statins and the incidence of diabetes. Therefore, we analyzed the progression from normal blood glucose to prediabetes and then to diabetes mellitus (DM) according to the type, intensity, and dose of statin prescribed.. Data of patients who were first prescribed statins between 2009 and 2011 were extracted from electronic medical records. Patients with normal blood glucose or prediabetes were observed for 4 years after initiation of statin therapy.. A total of 2890 patients were included in our study and analyzed on the basis of the first statin they were prescribed. The incidence rate of DM in patients with prediabetes was 1.72 times that of patients with normal glucose levels (odds ratio = 1.72, 95% confidence interval = 1.41-2.10, P < .001). Regarding progression from normal blood glucose to prediabetes, the incidence rate of prediabetes was significantly lower in patients prescribed pitavastatin (odds ratio = 0.62, 95% confidence interval = 0.40-0.96, P = .031) compared to that in patients prescribed atorvastatin. Regarding the progression from normal blood glucose or prediabetes to DM, there were no significant differences among all statins.. Lower DM incidence in patients prescribed pitavastatin appears to be primarily because of the lower rate of progression from normal blood glucose to prediabetes. These findings indicate that avoiding statins because of DM risk is unjustified and that clinicians should prescribe statins from the appropriate potency group.

Topics: Aged; Atorvastatin; Blood Glucose; Diabetes Mellitus; Disease Progression; Electronic Health Records; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Incidence; Male; Middle Aged; Prediabetic State; Quinolines; Republic of Korea; Retrospective Studies

3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) are used to control blood cholesterol levels and reduce cardiovascular disease. It has been repeatedly reported that statins may cause new-onset diabetes mellitus (DM). However, limited evidence exists from direct head to head comparisons of statins on whether the risk of DM differs among statins. We investigated the risk of development of new-onset diabetes in subjects treated with different statins.. We retrospectively enrolled consecutive 3680 patients without DM or impaired fasting glucose who started receiving statin treatment for cholesterol control. We evaluated the incidence of new-onset diabetes according to the type of statin.. The mean duration of follow-up was 62.6±15.3 months. The incidence of DM was significantly higher in the pitavastatin group (49 of 628; 7.8%) compared to that in the other statin groups [atorvastatin (68 of 1327; 5.1%), rosuvastatin (77 of 1191; 6.5%), simvastatin (11 of 326; 3.4%), and pravastatin (12 of 298; 5.8%); p=0.041]. The risk of diabetes was the highest in the pitavastatin group compared with that in the simvastatin group [hazard ratio (HR)=2.68, p=0.011]. Other statins showed no significant risk differences compared to that for simvastatin. Fasting blood glucose (FBG) level at baseline and body-mass index (BMI) were associated with the development of diabetes [FBG, HR=1.11, p<0.001; BMI, HR=1.02, p=0.005].. Among the five statins, pitavastatin showed the strongest effect on the development of new-onset diabetes.

Topics: Aged; Atorvastatin; Diabetes Mellitus; Female; Fluorobenzenes; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Middle Aged; Pravastatin; Pyrimidines; Pyrroles; Quinolines; Retrospective Studies; Risk Factors; Rosuvastatin Calcium; Simvastatin; Sulfonamides

To determine the effect of different statins on the induction of diabetes mellitus.. Four statins (atorvastatin, pravastatin, rosuvastatin, and pitavastatin) were used. Cytotoxicity, insulin secretion, glucose-stimulated insulin secretion, and G0/G1 phase cell cycle arrest were investigated in human pancreas islet β cells, and glucose uptake and signaling were studied in human skeletal muscle cells (HSkMCs).. Human pancreas islet β cells treated with 100 nM atorvastatin, pravastatin, rosuvastatin, and pitavastatin had reduced cell viability (32.12%, 41.09%, 33.96%, and 29.19%, respectively) compared to controls. Such cytotoxic effect was significantly attenuated by decreasing the dose to 10 and 1 nM, ranged from 1.46% to 17.28%. Cells treated with 100 nM atorvastatin, pravastatin, rosuvastatin, and pitavastatin had a reduction in the rate of insulin secretion rate by 34.07%, 30.06%, 26.78%, and 19.22%, respectively. The inhibitory effect was slightly attenuated by decreasing the dose to 10 and 1 nM, ranging from 10.84% to 29.60%. Insulin secretion stimulated by a high concentration of glucose (28 mmol/L) was significantly higher than a physiologic concentration of glucose (5.6 mmol/L) in all treatment groups. The glucose uptake rates at a concentration of 100 nM were as follows: atorvastatin (58.76%) < pravastatin (60.21%) < rosuvastatin (72.54%) < pitavastatin (89.96%). We also found that atorvastatin and pravastatin decreased glucose transporter (GLUT)-2 expression and induced p-p38 MAPK levels in human pancreas islet β cells. Atorvastatin, pravastatin, and rosuvastatin inhibited GLUT-4, p-AKT, p-GSK-3β, and p-p38 MAPK levels in HSkMCs.. Statins similar but different degree of effects on pancreas islet β cells damage and induce insulin resistance in HSkMC.

Topics: Atorvastatin; Cell Cycle; Cell Survival; Cells, Cultured; Diabetes Mellitus; Dose-Response Relationship, Drug; Glucose; Humans; Insulin; Insulin Resistance; Insulin-Secreting Cells; Muscle, Skeletal; Pravastatin; Quinolines; Rosuvastatin Calcium; Signal Transduction; Structure-Activity Relationship

Prevention of cardiovascular complications in obese patients frequently includes statin administration for coexisting dyslipidemia. Herein, we investigated the impacts of pitavastatin at clinically relevant doses on adipose dysfunction and insulin resistance.. We treated 3T3-L1 preadipocytes with 10-100 ng/ml pitavastatin from initiation of differentiation (Day 0) to Day 8 (differentiation/maturation phase) or from Day 8 to Day 16 (post-maturation phase). Subsequently, we administered pitavastatin (6.2mg/day/kg) to 7-week-old female KKAy mice for 6 weeks; untreated KKAy mice served as obese controls.. Pitavastatin impaired neither lipogenesis nor adiponectin expression during the differentiation/maturation phase. During the post-maturation phase, pitavastatin prevented excessive triglyceride accumulation, which was associated with attenuated glucose transporter-4 expression, and dose-dependently upregulated hormone-sensitive lipase expression. Decrements in the adiponectin/plasminogen activator-1 ratio were also dose-dependently inhibited. In KKAy mice, Coulter counter analyses revealed that pitavastatin treatment significantly decreased (by 16.8%) the frequency of hypertrophic adipocytes (>150 microm in diameter) in parametrial adipose pads, of which total weight remained unaltered. Correspondingly, plasma adiponectin was significantly higher in pitavastatin-treated KKAy mice than in the untreated KKAy mice (12.5+/-3.8 microg/ml vs. 8.3+/-1.5 microg/ml, p<0.05). Moreover, the area under the time-glucose curve after intraperitoneal insulin was decreased by 16% in pitavastatin-treated KKAy mice (p<0.05 vs. untreated controls).. Pitavastatin did not impair differentiation/maturation of preadipocytes and prevented their deterioration with hypertrophy after maturation at clinical concentrations in vitro. These effects likely contributed to improved insulin sensitivity, in an obese model, via prevention of adipocyte hypertrophy and adipocytokine dysregulation.

Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Adiponectin; Animals; Blood Glucose; Cell Size; Diabetes Mellitus; Disease Models, Animal; Dose-Response Relationship, Drug; Dyslipidemias; Female; Glucose Transporter Type 4; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertrophy; Insulin; Insulin Resistance; Lipogenesis; Lipoprotein Lipase; Mice; Obesity; Plasminogen Activator Inhibitor 1; Quinolines; Time Factors; Triglycerides