Diabetes Mellitus, Prediabetic State
Conditions
Keywords
Pravastatin, Insulin Resistance
Brief summary
An increased risk of incident diabetes with statin therapy have been reported in several studies. However, it is not recommended to limit the use of statin for this reason since the absolute risk increase was small, and the cardiovascular event rate reduction with statins overweighed the risk of new diabetes (Scatter N et al. Lancet, 2010). Moreover, each statin may have different effect on the development of incident diabetes. In the West of Scotland Coronary Prevention Study, pravastatin therapy reduced the hazard of becoming diabetic by 30%. Also, with pravastatin use, an increase in adiponectin level, which is related to the improvement in insulin sensitivity, has been reported. In this clinical trial, the investigators are aiming to evaluate the effect of pravastatin on insulin resistance, insulin secretion, glycemic control, and adiponectin level in participants with prediabetes or early diabetes by assigning them in a 24 weeks of pravastatin therapy group or in a placebo group.
Interventions
DRUGPravastatin
Pravastatin 40mg once daily for 24 weeks and nutritional education by a nutritionist
DRUGPlacebo (for Pravastatin)
Pill manufactured to mimic pravastatin 40mg tablet once daily for 24 weeks and nutritional education by a nutritionist
BEHAVIORALNutritional education only
Only nutritional education by a nutritionist
Sponsors
Daiichi Sankyo Korea Co., Ltd.
Samsung Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Masking description
This study was initially designed as a single center, double-blind, placebo-controlled, 2-group factorial randomized trial (placebo or pravastatin 40mg once daily for 24 weeks). Subjects were randomly assigned, in a 1:1 ratio, to receive pravastatin in a blinded fashion at a dose of 40 mg once daily or placebo. However, because of the problem of expiration date of the placebo drug, the study was converted to an open-label trial, and subjects without any medications were enrolled in an open-label control group in contrast to the pravastatin group. Therefore, the study cohort comprised the pravastatin group, placebo group, and the open-label control group. The placebo group and the open-label control group were classified as the control group.
Eligibility
Sex/Gender
ALL
Age
20 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* Subjects have early diabetes mellitus or prediabetes. Early diabetes mellitus or prediabetes are defined according to the following criteria; Subjects have two or more of the following three, or they have one of them at the initial test and the repeat test. 1. hemoglobin A1C 5.7-9.0% 2. fasting plasma glucose level 100mg/dL or more 3. plasma glucose level 140mg/dL or more at 2 hours after 75g oral glucose tolerance test * Subjects have one of the following three; 1. Low-density lipoprotein cholesterol (LDL-cholesterol) 130mg/dL or more, and body mass index (BMI) \> 23 kg/m2, 2. 10 year atherosclerotic cardiovascular disease (ASCVD) risk of 7.5% or more, which is assessed by the ASCVD-Risk-Estimator (Circulation.2014;129:S1-S45) 3. In diabetic patients, LDL-cholesterol 100mg/dL or more
Exclusion criteria
* Hemoglobin A1C \> 9.0% * History of statin use in three months * Use of oral antidiabetic drugs except for metformin in three months * History of malignant diseases (cancers) * History of coronary artery diseases, heart failure, arrhythmia, valvular heart diseases, or cerebrovascular diseases * Pregnant * serum creatinine level \> 1.5 mg/dL * aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels higher than 80 U/l * Taking weight loss medications, corticosteroids, Angiotensin converting enzyme (ACE) inhibitors, or estrogen replacement therapy * Chronic hepatitis B or chronic hepatitis C
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insulin resistance assessed by HOMA-IR (homeostatic model assessment index for insulin resistance) | at the end of the 24 weeks of medication period | compared to the HOMA-IR level calculated at the initial visit (at the beginning of the 24 weeks of medication period) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Insulin secretion capacity assessed by insulinogenic index (INS index) during 75g oral glucose tolerance test | at the end of the 24 weeks of medication period | the ratio relating enhancement of circulating insulin in 30min \[in pmol/L\] to magnitude of corresponding glycemic stimulus in 30min \[in mmol/L\] during the oral glucose tolerance test (H.S. Seltze et al. J. Clin. Investig., 1967), compared to the results at the initial visit (at the beginning of the 24 weeks of medication period) |
| Insulin resistance assessed by the quantitative insulin sensitivity check index (QUICKI) | at the end of the 24 weeks of medication period | calculated using fasting insulin in uIU/mL and fasting plasma glucose in mg/dL according to the method described in a previous study (A. Katz et al. J. Clin. Endocrinol. Metab., 2000), compared to the results at the initial visit (at the beginning of the 24 weeks of medication period) |
| Insulin secretory capacity relative to insulin resistance assessed by the oral disposition index | at the end of the 24 weeks of medication period | calculated according to a method described in a previous study (K.M. Utzschneider et al.Diabetes Care, 2008), compared to the results at the initial visit (at the beginning of the 24 weeks of medication period) |
| Glycemic control evaluated by fasting glucose level (mg/dL) | at the end of the 24 weeks of medication period | compared to the values at the initial visit |
| Insulin resistance assessed by Matsuda index calculated through 75g oral glucose tolerance test | at the end of the 24 weeks of medication period | calculated according to a method described in a previous study (Matsuda M et al. Diabetes Care, 1999), compared to the results at the initial visit (at the beginning of the 24 weeks of medication period). It takes 120 minutes to perform 75g oral glucose tolerance test |
| Plasma adioponectin level (μg/ml), an adipocyte-derived insulin-sensitizing hormone level | at the end of the 24 weeks of medication period | compared to the values at the initial visit |
| Biomarkers predicting cardiovascular diseases, assessed by high sensitive C-reactive protein (hsCRP) (mg/dL) | at the end of the 24 weeks of medication period | compared to the values at the initial visit |
| Biomarkers predicting cardiovascular diseases, assessed by plasminogen activator inhibitor-1 (PAI-1) (ng/mL) | at the end of the 24 weeks of medication period | compared to the values at the initial visit |
| Glycemic control evaluated by hemoglobin A1C (%) | at the end of the 24 weeks of medication period | compared to the values at the initial visit |
Countries
South Korea
Outcome results
None listed