Egy hazai matematikai felmérés eredményei nemzetközi összehasonlításban

<p><b>Comparisons of the effect of different dipeptidyl peptidase-4 inhibitor treatment for 1 year on adjusted mean changes in fasting plasma glucose (FPG) (A) and glycated hemoglobin (HbA</b>_<b>1</b><b>c) (B) in the patients with a low and high hemoglobin glycation index (HGI).</b> Factors included in the analysis of variance statistical model were baseline oral anti-diabetes drugs, age, sex and renal function. VI = vildagliptin (n = 24 in the low HGI and n = 36 in the high HGI groups), LI = linagliptin (n = 33 in the low HGI and n = 31 in the high HGI groups), SA = saxagliptin (n = 45 in low HGI and n = 64 in the high HGI groups), SI = sitagliptin (n = 97 in the low HGI and n = 138 in the high HGI group). Error bars represent 95% confidence interval (CI). p-value for between-group difference. (To convert glucose to millimoles per liter, multiply by 0.0555)</p

Study Subjects Selection Flow Chart.

<p>Study Subjects Selection Flow Chart.</p

Demographics of study subjects according to their drug using status.

<p>a. Diagnosed type 2 diabetes mellitus (T2DM) patients who did not use statin before the end of follow up date.</p><p>b. The statin regular user is the patient who uses statin continuously at least over one year in the follow up time that nearby 2 statin prescriptions can't exceed 120 days.</p><p>This group of diagnosed T2DM patients is statin regular user group.</p><p>c. Wilcoxon rank sum test or Pearson's Chi-square test.</p><p>d. The case number is calculated before patient's index date.</p><p>The index date of patient who never uses statin before the end of follow up date is the T2DM diagnosed date.</p><p>The index date of patient who is statin regular user is the date of staring to take statin regularly.</p><p>e. The case number is the regular use of statin after patient's T2DM diagnosed date.</p><p>f. The case number is the regular use of the anti-diabetic drug before patient's index date.</p><p>g. Charlson comorbidity index (CCI): The diagnoses recorded in the National Health Insurance Research Database before the index date is used to calculate CCI score.</p><p>We exclude the diagnosis of diabetes mellitus and stroke from CCI score calculation, because these two disease entities are considered separately.</p

Effects of Statins on Incident Dementia in Patients with Type 2 DM: A Population-Based Retrospective Cohort Study in Taiwan

<div><p>Background</p><p>Patients with Type 2 diabetes (T2DM) are prone to develop dementia. Results from a recent study indicated that statin users had lower chance of developing incident dementia. However there is little information on the potential benefits of statin use on dementia in patients with T2DM cohort.</p><p>Method</p><p>A population-based retrospective study using a nationwide cohort of National Health Insurance Research Database in Taiwan was performed. T2DM cohort with regular use of statins was followed up to 8 years. Multivariate cox-proportional hazards regression model was used to estimate the association between statin use and incidence of dementia including Alzheimer's disease and non-Alzheimer dementia after adjusting for several potential confounders.</p><p>Results</p><p>Among 28,321 patients diagnosed with T2DM age above 50 and without history of dementia before 2000/1/1, 15,770 patients who had never used statin and 2,400 patients who regularly used statin drugs were enrolled. After adjusting for age group, gender, CCI (Charlson-Deyo comorbidity index) group, stroke types and anti-diabetic drugs, regular statin use was associated with a decreased risk of developing incident Alzheimer's disease dementia (adjusted HR: 0.48, 95% CI 0.30 – 0.76, p<0.001), but not in non-Alzheimer dementia (adjusted HR: 1.07, 95% CI 0.54–2.12 p = 0.844) in patients with T2DM. Further analysis showed significant protective effects of the use of atorvastatin and simvastatin.</p><p>Conclusion</p><p>Regular use of statins might decrease the risk of developing Alzheimer's disease in patients with T2DM while no benefit was observed in non-Alzheimer dementia. Among statins, both atorvastatin and simvastatin showed significant benefits.</p></div

Risk of Alzheimer's disease plus non-Alzheimer dementia, Alzheimer's disease and non-Alzheimer dementia among T2DM patients compared to diabetic subjects without statin.

<p>a. Mean daily dose (mg)  =  cumulative doses start from the regular taking drug date to the end of observation date/days between the start regular taking drug date and the end of observation date.</p><p>b. Adjust age group, gender, CCI group, stroke types and anti-diabetic drugs.</p

Survival Curves_ Alzheimer Disease and Non-Alzheimer Dementia.

<p>Survival Curves_ Alzheimer Disease and Non-Alzheimer Dementia.</p

<i>ABCA1</i> 3'-UTR activity and relative miR-33 expression after statin treatment in RAW264.7 macrophages and BMDMs.

<p>Reporter containing sequence complementary to miR-33a in 3'-UTR of <i>ABCA1</i> was constructed in downstream of the luciferase gene of the pGL3-<i>ABCA1</i> plasmid (A). Macrophages were transfected with the pGL3-<i>ABCA1</i> plasmid and/or statins for 24 h, and then assayed of luciferase activity. A pCMV-β-galactosidase vector encoding β-galactosidase was co-transfected as an internal control. Dose-dependent effects of atorvastatin and pitavastatin on the luciferase activity were analyzed in RAW264.7 macrophages (B). The luciferase activity was normalized to β-galactosidase activity. Data are expressed as ratios relative to the values obtained from the untreated pGL3-<i>ABCA1</i> control group defined as 1.0. The mRNA levels of <i>ABCA1</i> were determined by semi-quantitative RT-PCR (C) and quantitative real-time PCR (D) as described in the Materials and Methods. The histogram shows the relative fold of <i>ABCA1</i> mRNA levels compared with the control group (set as 1). Results are expressed as mean±SEM of at least three independent experiments. *<i>P</i> < 0.05, **<i>P</i> < 0.01, ***<i>P</i> < 0.001 versus control group.</p

Correlation between biochemical parameters and miRNA levels in all subjects.

<p>Correlation between biochemical parameters and miRNA levels in all subjects.</p

Statins stimulate miR-33 expression in RAW264.7 macrophages and BMDMs.

<p>The effect of atorvastatin or pivatostatin on relative miR-33 levels in the cell lysate and medium was investigated in Raw264.7 murine macrophages (A,B) and BMDMs (C,D) by quantitative miRNA real-time PCR as described in the Materials and Methods. The histogram shows the relative fold of miRNA level compared with the control group (set as 1). Results are expressed as mean±SEM of at least three independent experiments. *<i>P</i> < 0.05, **<i>P</i> < 0.01, ***<i>P</i> < 0.001 versus control group.</p

Glucose stimulates miR-33 expression in RAW264.7 macrophages and BMDMs.

<p>The effect of glucose on miR-33 levels in the cell lysate and medium was investigated in Raw264.7 murine macrophages (A) and BMDMs (B) by quantitative miRNA real-time PCR. Trizol reagent was used to extract total RNA in cellular lysates and medium from macrophages treated with glucose from 5 to 30 mM. Preparation of microRNA was isolated using the mirVANA microRNA isolation kit and microRNA assays were performed by real-time PCR. The relative miR-33 expression was calculated via the 2^−ΔΔCt method using cel-miR-39 as an endogenous control. The histogram shows the relative fold compared with the control group (set as 1). Results are expressed as mean±SEM of at least three independent experiments. *<i>P</i> < 0.05, **<i>P</i> < 0.01, ***<i>P</i> < 0.001 versus control group.</p