Type 2 Diabetes Mellitus
Conditions
Keywords
apolipoprotein, CVD, chylomicrons, evolocumab, kinetics
Brief summary
Postprandial lipemia is highly prevalent in type 2 diabetes subjects even with normal fasting triglyceride values. Humans are mostly in a postprandial rather than in a fasting state and therefore non-fasting triglyceride values reflect more accurately the continuous exposure of arterial wall to the substantial cholesterol load from remnant particles. Evolocumab lowers blood LDL-cholesterol. This study evaluates the effect of evolocumab on postprandial lipid metabolism in type 2 diabetes. All participants in this study receive evolocumab treatment.
Interventions
DRUGEvolocumab
Sponsors
Göteborg University
Marja-Riitta Taskinen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 77 Years
Healthy volunteers
No
Inclusion criteria
* Male or female (non-fertile or using a medically approved birth control method) overweight/obese subjects with Type 2 Diabetes Mellitus treated with lifestyle counselling and a stable metformin dose for at least three months * age 18-77 yrs. * body mass index 25-40 kg/m2 * triglycerides between 1.5-4.5 mmol/L and low-density-lipoprotein cholesterol \>1.8 but ≤4.0 mmol/L (on Atorvastatin 20 mg/day) * glycohemoglobin: ≤9%. * Each patient will attend a pre-screening visit (at week -5) where eligibility criteria will be evaluated. If the patient uses another statin than atorvastatin (20 mg) at screening visit the used statin is stopped and atorvastatin 20 mg will be initiated. If the patient is not using any statin, atorvastatin 20 mg will be initiated and the lipid values will be checked after 4 weeks when all inclusion/
Exclusion criteria
will be assessed.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean ApoB Concentration Before and After Evolocumab | Baseline and after 12 weeks | Change in apolipoprotein B concentration in total plasma measured by using turbidimetric immunoassay. |
| Mean TRL-C Concentration Before and After Evolocumab | Baseline and after 12 weeks | Change in TRL-cholesterol concentration in plasma samples measured by using automated direct assay (Denka Seiken, Tokyo, Japan) |
| Mean Total Production of ApoB48 Before and After Evolocumab | Baseline and after 12 weeks | Change in ApoB48 total production in plasma measured by using multicompartmental modeling. The power of mathematical modelling to describe the metabolic pathways of lipid and lipoprotein metabolism was demonstrated by Zech L et al (J Clin Invest 1979;63:1262-1273) and have been widely used over 30yrs. So far few studies have focused on the modelling of apo B48 and apo B100 after a meal that is more physiological than the fasting state (Björnson E et al. JIM 2019;285:562-577). Production rates for apo B48, apo B100 and triglycerides in chylomicrons, VLDL1 and VLDL2 were derived from samples taken before and after the tracer injection and after the meal at 0, 30, 45, 60, 75, 90, 120, 150 min and at 3, 4, 5, 6, 8, 10, 24 hrs and averages for 24 hrs. Analysis of tracer/ tracee curves of stable isotopes was used to derived the estimates of kinetic parameters using a new mathematical modeling per day. These figures per day are used to report the data from this study. |
| Mean LDL FCR of ApoB100 Before and After Evolocumab | Baseline and after 12 weeks | Change in low-density lipoprotein fractional catabolic rate of ApoB100 in LDL from plasma samples measured by multicompartmental modeling. Production rates were derived from samples taken before and after the tracer injection and after the meal at 0, 30, 45, 60, 75, 90, 120, 150 min and at 3, 4, 5, 6, 8, 10, 24 hrs and averages for 24 hrs. More detailed description see Outcome measure 3. |
| LDL Pool Size of ApoB100 Before and After Evolocumab | Baseline and after 12 weeks | Change in low-density lipoprotein pool size of ApoB100 in LDL fraction prepared from plasma samples using density ultracentrifugation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean VLDL2 ApoB100 Production Before and After Evolocumab | Baseline and after 12 weeks | Change in VLDL2 apoB100 production rates measured from isolated VLDL2 from plasma samples by using density ultracentrifugation and the enrichment of tracer was measured in isolated fractions following using mathematical modeling. Production rates were derived from samples taken before and after the tracer injection and after the meal at 0, 30, 45, 60, 75, 90, 120, 150 min and at 3, 4, 5, 6, 8, 10, 24 hrs and averages for 24 hrs. More detailed description see Outcome measure 3. |
| IDL Pool Size of ApoB100 Before and After Evolocumab | Baseline and after 12 weeks | Change in intermediate-density lipoprotein pool size of ApoB100 in IDL fraction prepared from plasma samples using density ultracentrifugation. |
| Mean IDL to LDL Transfer of ApoB100 Before and After Evolocumab | Baseline and after 12 weeks | Change in ApoB100 intermediate-density lipoprotein to low-density lipoprotein transfer in isolated samples from plasma by ultracentrifugation and measured using multicompartmental modeling. Production rates were derived from samples taken before and after the tracer injection and after the meal at 0, 30, 45, 60, 75, 90, 120, 150 min and at 3, 4, 5, 6, 8, 10, 24 hrs and averages for 24 hrs. More detailed description see Outcome measure 3. |
| Mean VAT Before and After Evolocumab | Baseline and after 12 weeks | Change in visceral fat volume measured by magnetic resonance imaging |
| Mean Liver Fat Before and After Evolocumab | Baseline and after 12 weeks | Change in liver fat content measured by magnetic resonance imaging. |
| Mean SAT Before and After Evolocumab | Baseline and after 12 weeks | Change in subcutaneous fat volume measured by magnetic resonance imaging |
| Mean VLDL1 Triglyceride Production Before and After Evolocumab | Baseline and after 12 weeks | Change in VLDL1 triglyceride production measured from isolated VLDL1 from plasma samples by using density gradient ultracentrifugation. Production rates were derived from samples taken before and after the tracer injection and after the meal at 0, 30, 45, 60, 75, 90, 120, 150 min and at 3, 4, 5, 6, 8, 10, 24 hrs and averages for 24 hrs. More detailed description see Outcome measure 3. |
| Mean LDL-C Concentration Before and After Evolocumab | Baseline and after 12 weeks | Change in LDL-cholesterol concentration in plasma LDL fraction isolated by ultracentrifugation. |
| Mean VLDL2 Triglyceride Total Production Before and After Evolocumab | Baseline and after 12 weeks | Change in VLDL2 triglyceride total production measured in isolated VLDL2 from plasma samples by using density ultracentrifugation and measured by multicompartmental modeling. Production rates were derived from samples taken before and after the tracer injection and after the meal at 0, 30, 45, 60, 75, 90, 120, 150 min and at 3, 4, 5, 6, 8, 10, 24 hrs and averages for 24 hrs. More detailed description see Outcome measure 3. |
| Mean VLDL2 FCR of Triglyceride Before and After Evolocumab | Baseline and after 12 weeks | Change in VLDL2 fractional catabolic rate of triglyceride measured in isolated VLDL2 from plasma samples by using density ultracentrifugation and measured by multicompartmental modeling. Production rates were derived from samples taken before and after the tracer injection and after the meal at 0, 30, 45, 60, 75, 90, 120, 150 min and at 3, 4, 5, 6, 8, 10, 24 hrs and averages for 24 hrs. More detailed description see Outcome measure 3. |
| Mean Postprandial CM of ApoB48 Before and After Evolocumab | Baseline and after 12 weeks | Change in Postprandial chylomicron of ApoB48 measured from plasma samples by liquid chromatography-mass spectrometry with multicompartmental modeling assay. Production rates were derived from samples taken before and after the tracer injection and after the meal at 0, 30, 45, 60, 75, 90, 120, 150 min and at 3, 4, 5, 6, 8, 10, 24 hrs and averages for 24 hrs. More detailed description see Outcome measure 3. |
| Mean CM-apoB48 FCR of ApoB48 Metabolism Before and After Evolocumab | Baseline and after 12 weeks | Change in chylomicron-apoB48 fractional catabolic rate of ApoB48 in isolated chylomicrons from plasma samples measured by multicompartmental modeling assay. Production rates were derived from samples taken before and after the tracer injection and after the meal at 0, 30, 45, 60, 75, 90, 120, 150 min and at 3, 4, 5, 6, 8, 10, 24 hrs and averages for 24 hrs. More detailed description see Outcome measure 3. |
| Mean CM-TG Production of ApoB48 Before and After Evolocumab | Baseline and after 12 weeks | Change in chylomicron-triglycerides production of ApoB48 in isolated chylomicrons from plasma samples measured by multicompartmental modeling assay. Production rates were derived from samples taken before and after the tracer injection and after the meal at 0, 30, 45, 60, 75, 90, 120, 150 min and at 3, 4, 5, 6, 8, 10, 24 hrs and averages for 24 hrs. More detailed description see Outcome measure 3. |
| Mean CM TG-AUC Before and After Evolocumab | 0, 2, 4, 6, 8 hours after the meal at baseline and after 12 weeks | Change in chylomicron triglyceride area under curve in plasma at a particular time points after the meal. Area under the curve (AUC) was normalized so that 100% corresponds to the AUC before treatment; subsequently the percentage after treatment is in reference to this value. AUC values were calculated using the trapezoidal rule. |
| Mean ApoB48 iAUC Before and After Evolocumab | 0, 2, 4, 6, 8 hours after the meal at baseline and after 12 weeks | Change in apolipoprotein B48 incremental area under curve in plasma at a particular time points after the meal. Area under the curve (AUC) was normalized so that 100% corresponds to the AUC before treatment; subsequently the percentage after treatment is in reference to this value. AUC values were calculated using the trapezoidal rule. |
| Mean VLDL1 FCR of triglycerideBefore and After Evolocumab | Baseline and after 12 weeks | Change in VLDL1 fractional catabolic rate of triglyceride measured in isolated VLDL1 from plasma samples by using density ultracentrifugation and measured by multicompartmental modeling. Production rates were derived from samples taken before and after the tracer injection and after the meal at 0, 30, 45, 60, 75, 90, 120, 150 min and at 3, 4, 5, 6, 8, 10, 24 hrs and averages for 24 hrs. More detailed description see Outcome measure 3. |
| Mean ApoB48 Concentration Before and After Evolocumab | Baseline and after 12 weeks | Change in apolipoprotein B48 levels in total plasma measured by enzyme-linked immunosorbent assay. |
| Mean CM TG-iAUC Before and After Evolocumab | 0, 2, 4, 6, 8 hours after the meal at baseline and after 12 weeks | Change in chylomicron triglyceride incremental area under curve in plasma samples taken at particular time points after the meal. Area under the curve (AUC) was normalized so that 100% corresponds to the AUC before treatment; subsequently the percentage after treatment is in reference to this value. AUC values were calculated using the trapezoidal rule. |
| Mean ApoB48 AUC Before and After Evolocumab | 0, 2, 4, 6, 8 hours after the meal at baseline and after 12 weeks | Change in apolipoprotein B48 area under curve in plasma samples taken at particular time points after the meal. Area under the curve (AUC) was normalized so that 100% corresponds to the AUC before treatment; subsequently the percentage after treatment is in reference to this value. AUC values were calculated using the trapezoidal rule. |
| Mean VLDL1 ApoB100 Production Before and After Evolocumab | Baseline and after 12 weeks | Change in VLDL1 ApoB100 production rates measured from isolated VLDL from plasma samples using density ultracentrifugation and the enrichment of tracer was measured in isolated fractions following using mathematical modeling. Production rates were derived from samples taken before and after the tracer injection and after the meal at 0, 30, 45, 60, 75, 90, 120, 150 min and at 3, 4, 5, 6, 8, 10, 24 hrs and averages for 24 hrs. More detailed description see Outcome measure 3. |
Countries
Finland
Participant flow
Recruitment details
After an initial telephone interview of 195 subjects, 77 were invited for a screening visit. Of these, 63 subjects were excluded because of failure to meet inclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Evolocumab Evolocumab 140 mg subcutaneous injection once every 2 weeks for 12 weeks | 14 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | worsening of asthma symptoms resulting in oral prednisolone use. | 1 |
Baseline characteristics
| Characteristic | Evolocumab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 13 |
| other Total, other adverse events | 13 / 13 |
| serious Total, serious adverse events | 3 / 13 |
Outcome results
Primary
LDL Pool Size of ApoB100 Before and After Evolocumab
Change in low-density lipoprotein pool size of ApoB100 in LDL fraction prepared from plasma samples using density ultracentrifugation.
Time frame: Baseline and after 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evolocumab | LDL Pool Size of ApoB100 Before and After Evolocumab | Baseline | 1500 mg | Standard Deviation 470 |
| Evolocumab | LDL Pool Size of ApoB100 Before and After Evolocumab | Week 12 | 460 mg | Standard Deviation 270 |
p-value: <0.001Wilcoxon (Mann-Whitney)
Primary
Mean ApoB Concentration Before and After Evolocumab
Change in apolipoprotein B concentration in total plasma measured by using turbidimetric immunoassay.
Time frame: Baseline and after 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evolocumab | Mean ApoB Concentration Before and After Evolocumab | Baseline | 75.9 mg/dL | Standard Deviation 14.5 |
| Evolocumab | Mean ApoB Concentration Before and After Evolocumab | Week 12 | 35.3 mg/dL | Standard Deviation 10.9 |
p-value: <0.001Wilcoxon (Mann-Whitney)
Primary
Mean LDL FCR of ApoB100 Before and After Evolocumab
Change in low-density lipoprotein fractional catabolic rate of ApoB100 in LDL from plasma samples measured by multicompartmental modeling. Production rates were derived from samples taken before and after the tracer injection and after the meal at 0, 30, 45, 60, 75, 90, 120, 150 min and at 3, 4, 5, 6, 8, 10, 24 hrs and averages for 24 hrs. More detailed description see Outcome measure 3.
Time frame: Baseline and after 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evolocumab | Mean LDL FCR of ApoB100 Before and After Evolocumab | Baseline | 0.32 pools/d | Standard Deviation 0.15 |
| Evolocumab | Mean LDL FCR of ApoB100 Before and After Evolocumab | Week 12 | 0.78 pools/d | Standard Deviation 0.34 |
p-value: <0.001Wilcoxon (Mann-Whitney)
Primary
Mean Total Production of ApoB48 Before and After Evolocumab
Change in ApoB48 total production in plasma measured by using multicompartmental modeling. The power of mathematical modelling to describe the metabolic pathways of lipid and lipoprotein metabolism was demonstrated by Zech L et al (J Clin Invest 1979;63:1262-1273) and have been widely used over 30yrs. So far few studies have focused on the modelling of apo B48 and apo B100 after a meal that is more physiological than the fasting state (Björnson E et al. JIM 2019;285:562-577). Production rates for apo B48, apo B100 and triglycerides in chylomicrons, VLDL1 and VLDL2 were derived from samples taken before and after the tracer injection and after the meal at 0, 30, 45, 60, 75, 90, 120, 150 min and at 3, 4, 5, 6, 8, 10, 24 hrs and averages for 24 hrs. Analysis of tracer/ tracee curves of stable isotopes was used to derived the estimates of kinetic parameters using a new mathematical modeling per day. These figures per day are used to report the data from this study.
Time frame: Baseline and after 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evolocumab | Mean Total Production of ApoB48 Before and After Evolocumab | Baseline | 570 mg/d | Standard Deviation 60 |
| Evolocumab | Mean Total Production of ApoB48 Before and After Evolocumab | Week 12 | 580 mg/d | Standard Deviation 75 |
p-value: 0.31Wilcoxon (Mann-Whitney)
Primary
Mean TRL-C Concentration Before and After Evolocumab
Change in TRL-cholesterol concentration in plasma samples measured by using automated direct assay (Denka Seiken, Tokyo, Japan)
Time frame: Baseline and after 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evolocumab | Mean TRL-C Concentration Before and After Evolocumab | Baseline | 33.4 mg/dL | Standard Deviation 10.9 |
| Evolocumab | Mean TRL-C Concentration Before and After Evolocumab | Week 12 | 17.8 mg/dL | Standard Deviation 6.5 |
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
IDL Pool Size of ApoB100 Before and After Evolocumab
Change in intermediate-density lipoprotein pool size of ApoB100 in IDL fraction prepared from plasma samples using density ultracentrifugation.
Time frame: Baseline and after 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evolocumab | IDL Pool Size of ApoB100 Before and After Evolocumab | Baseline | 190 mg | Standard Deviation 50 |
| Evolocumab | IDL Pool Size of ApoB100 Before and After Evolocumab | Week 12 | 130 mg | Standard Deviation 49 |
p-value: 0.003Wilcoxon (Mann-Whitney)
Secondary
Mean ApoB48 AUC Before and After Evolocumab
Change in apolipoprotein B48 area under curve in plasma samples taken at particular time points after the meal. Area under the curve (AUC) was normalized so that 100% corresponds to the AUC before treatment; subsequently the percentage after treatment is in reference to this value. AUC values were calculated using the trapezoidal rule.
Time frame: 0, 2, 4, 6, 8 hours after the meal at baseline and after 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evolocumab | Mean ApoB48 AUC Before and After Evolocumab | Baseline | 66.8 (mg/l)*h | Standard Deviation 31.2 |
| Evolocumab | Mean ApoB48 AUC Before and After Evolocumab | Week 12 | 57.4 (mg/l)*h | Standard Deviation 26.5 |
p-value: 0.31Kruskal-Wallis
Secondary
Mean ApoB48 Concentration Before and After Evolocumab
Change in apolipoprotein B48 levels in total plasma measured by enzyme-linked immunosorbent assay.
Time frame: Baseline and after 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evolocumab | Mean ApoB48 Concentration Before and After Evolocumab | Baseline | 6.1 mg/L | Standard Deviation 3.8 |
| Evolocumab | Mean ApoB48 Concentration Before and After Evolocumab | Week 12 | 5.3 mg/L | Standard Deviation 3.3 |
p-value: 0.27Wilcoxon (Mann-Whitney)
Secondary
Mean ApoB48 iAUC Before and After Evolocumab
Change in apolipoprotein B48 incremental area under curve in plasma at a particular time points after the meal. Area under the curve (AUC) was normalized so that 100% corresponds to the AUC before treatment; subsequently the percentage after treatment is in reference to this value. AUC values were calculated using the trapezoidal rule.
Time frame: 0, 2, 4, 6, 8 hours after the meal at baseline and after 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evolocumab | Mean ApoB48 iAUC Before and After Evolocumab | Baseline | 18.4 (mg/l)*h | Standard Deviation 25.5 |
| Evolocumab | Mean ApoB48 iAUC Before and After Evolocumab | Week 12 | 13.9 (mg/l)*h | Standard Deviation 17.5 |
p-value: 0.89Wilcoxon (Mann-Whitney)
Secondary
Mean CM-apoB48 FCR of ApoB48 Metabolism Before and After Evolocumab
Change in chylomicron-apoB48 fractional catabolic rate of ApoB48 in isolated chylomicrons from plasma samples measured by multicompartmental modeling assay. Production rates were derived from samples taken before and after the tracer injection and after the meal at 0, 30, 45, 60, 75, 90, 120, 150 min and at 3, 4, 5, 6, 8, 10, 24 hrs and averages for 24 hrs. More detailed description see Outcome measure 3.
Time frame: Baseline and after 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evolocumab | Mean CM-apoB48 FCR of ApoB48 Metabolism Before and After Evolocumab | Baseline | 37 pools/d | Standard Deviation 24 |
| Evolocumab | Mean CM-apoB48 FCR of ApoB48 Metabolism Before and After Evolocumab | Week 12 | 46 pools/d | Standard Deviation 32 |
p-value: 0.27Wilcoxon (Mann-Whitney)
Secondary
Mean CM TG-AUC Before and After Evolocumab
Change in chylomicron triglyceride area under curve in plasma at a particular time points after the meal. Area under the curve (AUC) was normalized so that 100% corresponds to the AUC before treatment; subsequently the percentage after treatment is in reference to this value. AUC values were calculated using the trapezoidal rule.
Time frame: 0, 2, 4, 6, 8 hours after the meal at baseline and after 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evolocumab | Mean CM TG-AUC Before and After Evolocumab | Baseline | 9.5 (mmol/l)*h | Standard Deviation 4.9 |
| Evolocumab | Mean CM TG-AUC Before and After Evolocumab | Week 12 | 8.9 (mmol/l)*h | Standard Deviation 5.9 |
p-value: 0.84Wilcoxon (Mann-Whitney)
Secondary
Mean CM TG-iAUC Before and After Evolocumab
Change in chylomicron triglyceride incremental area under curve in plasma samples taken at particular time points after the meal. Area under the curve (AUC) was normalized so that 100% corresponds to the AUC before treatment; subsequently the percentage after treatment is in reference to this value. AUC values were calculated using the trapezoidal rule.
Time frame: 0, 2, 4, 6, 8 hours after the meal at baseline and after 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evolocumab | Mean CM TG-iAUC Before and After Evolocumab | Baseline | 6.8 (mmol/l)*h | Standard Deviation 3.6 |
| Evolocumab | Mean CM TG-iAUC Before and After Evolocumab | Week 12 | 5.8 (mmol/l)*h | Standard Deviation 4.4 |
p-value: 0.22Wilcoxon (Mann-Whitney)
Secondary
Mean CM-TG Production of ApoB48 Before and After Evolocumab
Change in chylomicron-triglycerides production of ApoB48 in isolated chylomicrons from plasma samples measured by multicompartmental modeling assay. Production rates were derived from samples taken before and after the tracer injection and after the meal at 0, 30, 45, 60, 75, 90, 120, 150 min and at 3, 4, 5, 6, 8, 10, 24 hrs and averages for 24 hrs. More detailed description see Outcome measure 3.
Time frame: Baseline and after 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evolocumab | Mean CM-TG Production of ApoB48 Before and After Evolocumab | Baseline | 66.5 g/d | Standard Deviation 0 |
| Evolocumab | Mean CM-TG Production of ApoB48 Before and After Evolocumab | Week 12 | 66.5 g/d | Standard Deviation 0 |
Secondary
Mean IDL to LDL Transfer of ApoB100 Before and After Evolocumab
Change in ApoB100 intermediate-density lipoprotein to low-density lipoprotein transfer in isolated samples from plasma by ultracentrifugation and measured using multicompartmental modeling. Production rates were derived from samples taken before and after the tracer injection and after the meal at 0, 30, 45, 60, 75, 90, 120, 150 min and at 3, 4, 5, 6, 8, 10, 24 hrs and averages for 24 hrs. More detailed description see Outcome measure 3.
Time frame: Baseline and after 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evolocumab | Mean IDL to LDL Transfer of ApoB100 Before and After Evolocumab | Baseline | 450 mg/d | Standard Deviation 190 |
| Evolocumab | Mean IDL to LDL Transfer of ApoB100 Before and After Evolocumab | Week 12 | 310 mg/d | Standard Deviation 140 |
p-value: 0.027Wilcoxon (Mann-Whitney)
Secondary
Mean LDL-C Concentration Before and After Evolocumab
Change in LDL-cholesterol concentration in plasma LDL fraction isolated by ultracentrifugation.
Time frame: Baseline and after 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evolocumab | Mean LDL-C Concentration Before and After Evolocumab | Baseline | 1500 mg | Standard Deviation 470 |
| Evolocumab | Mean LDL-C Concentration Before and After Evolocumab | Week 12 | 460 mg | Standard Deviation 270 |
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Mean Liver Fat Before and After Evolocumab
Change in liver fat content measured by magnetic resonance imaging.
Time frame: Baseline and after 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evolocumab | Mean Liver Fat Before and After Evolocumab | Baseline | 6.6 fat % | Standard Deviation 6.6 |
| Evolocumab | Mean Liver Fat Before and After Evolocumab | Week 12 | 6.3 fat % | Standard Deviation 7.2 |
p-value: 0.59Wilcoxon (Mann-Whitney)
Secondary
Mean Postprandial CM of ApoB48 Before and After Evolocumab
Change in Postprandial chylomicron of ApoB48 measured from plasma samples by liquid chromatography-mass spectrometry with multicompartmental modeling assay. Production rates were derived from samples taken before and after the tracer injection and after the meal at 0, 30, 45, 60, 75, 90, 120, 150 min and at 3, 4, 5, 6, 8, 10, 24 hrs and averages for 24 hrs. More detailed description see Outcome measure 3.
Time frame: Baseline and after 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evolocumab | Mean Postprandial CM of ApoB48 Before and After Evolocumab | Baseline | 240 mg/d | Standard Deviation 50 |
| Evolocumab | Mean Postprandial CM of ApoB48 Before and After Evolocumab | Week 12 | 230 mg/d | Standard Deviation 43 |
p-value: 0.91Wilcoxon (Mann-Whitney)
Secondary
Mean SAT Before and After Evolocumab
Change in subcutaneous fat volume measured by magnetic resonance imaging
Time frame: Baseline and after 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evolocumab | Mean SAT Before and After Evolocumab | Baseline | 3900 cm3 | Standard Deviation 1700 |
| Evolocumab | Mean SAT Before and After Evolocumab | Week 12 | 4110 cm3 | Standard Deviation 1600 |
p-value: 0.81Wilcoxon (Mann-Whitney)
Secondary
Mean VAT Before and After Evolocumab
Change in visceral fat volume measured by magnetic resonance imaging
Time frame: Baseline and after 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evolocumab | Mean VAT Before and After Evolocumab | Baseline | 2420 cm3 | Standard Deviation 960 |
| Evolocumab | Mean VAT Before and After Evolocumab | Week 12 | 2450 cm3 | Standard Deviation 1100 |
p-value: 0.84Wilcoxon (Mann-Whitney)
Secondary
Mean VLDL1 ApoB100 Production Before and After Evolocumab
Change in VLDL1 ApoB100 production rates measured from isolated VLDL from plasma samples using density ultracentrifugation and the enrichment of tracer was measured in isolated fractions following using mathematical modeling. Production rates were derived from samples taken before and after the tracer injection and after the meal at 0, 30, 45, 60, 75, 90, 120, 150 min and at 3, 4, 5, 6, 8, 10, 24 hrs and averages for 24 hrs. More detailed description see Outcome measure 3.
Time frame: Baseline and after 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evolocumab | Mean VLDL1 ApoB100 Production Before and After Evolocumab | Week 12 | 750 mg/d | Standard Deviation 230 |
| Evolocumab | Mean VLDL1 ApoB100 Production Before and After Evolocumab | Baseline | 790 mg/d | Standard Deviation 230 |
p-value: 0.61Wilcoxon (Mann-Whitney)
Secondary
Mean VLDL1 FCR of triglycerideBefore and After Evolocumab
Change in VLDL1 fractional catabolic rate of triglyceride measured in isolated VLDL1 from plasma samples by using density ultracentrifugation and measured by multicompartmental modeling. Production rates were derived from samples taken before and after the tracer injection and after the meal at 0, 30, 45, 60, 75, 90, 120, 150 min and at 3, 4, 5, 6, 8, 10, 24 hrs and averages for 24 hrs. More detailed description see Outcome measure 3.
Time frame: Baseline and after 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evolocumab | Mean VLDL1 FCR of triglycerideBefore and After Evolocumab | Baseline | 38 pools/d | Standard Deviation 27 |
| Evolocumab | Mean VLDL1 FCR of triglycerideBefore and After Evolocumab | Week 12 | 37 pools/d | Standard Deviation 23 |
p-value: 1Wilcoxon (Mann-Whitney)
Secondary
Mean VLDL1 Triglyceride Production Before and After Evolocumab
Change in VLDL1 triglyceride production measured from isolated VLDL1 from plasma samples by using density gradient ultracentrifugation. Production rates were derived from samples taken before and after the tracer injection and after the meal at 0, 30, 45, 60, 75, 90, 120, 150 min and at 3, 4, 5, 6, 8, 10, 24 hrs and averages for 24 hrs. More detailed description see Outcome measure 3.
Time frame: Baseline and after 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evolocumab | Mean VLDL1 Triglyceride Production Before and After Evolocumab | Baseline | 34 g/d | Standard Deviation 18 |
| Evolocumab | Mean VLDL1 Triglyceride Production Before and After Evolocumab | Week 12 | 33 g/d | Standard Deviation 13 |
p-value: 0.91Wilcoxon (Mann-Whitney)
Secondary
Mean VLDL2 ApoB100 Production Before and After Evolocumab
Change in VLDL2 apoB100 production rates measured from isolated VLDL2 from plasma samples by using density ultracentrifugation and the enrichment of tracer was measured in isolated fractions following using mathematical modeling. Production rates were derived from samples taken before and after the tracer injection and after the meal at 0, 30, 45, 60, 75, 90, 120, 150 min and at 3, 4, 5, 6, 8, 10, 24 hrs and averages for 24 hrs. More detailed description see Outcome measure 3.
Time frame: Baseline and after 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evolocumab | Mean VLDL2 ApoB100 Production Before and After Evolocumab | Baseline | 270 mg/d | Standard Deviation 91 |
| Evolocumab | Mean VLDL2 ApoB100 Production Before and After Evolocumab | Week 12 | 230 mg/d | Standard Deviation 96 |
p-value: 0.11Wilcoxon (Mann-Whitney)
Secondary
Mean VLDL2 FCR of Triglyceride Before and After Evolocumab
Change in VLDL2 fractional catabolic rate of triglyceride measured in isolated VLDL2 from plasma samples by using density ultracentrifugation and measured by multicompartmental modeling. Production rates were derived from samples taken before and after the tracer injection and after the meal at 0, 30, 45, 60, 75, 90, 120, 150 min and at 3, 4, 5, 6, 8, 10, 24 hrs and averages for 24 hrs. More detailed description see Outcome measure 3.
Time frame: Baseline and after 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evolocumab | Mean VLDL2 FCR of Triglyceride Before and After Evolocumab | Baseline | 10 pools/d | Standard Deviation 6.3 |
| Evolocumab | Mean VLDL2 FCR of Triglyceride Before and After Evolocumab | Week 12 | 15 pools/d | Standard Deviation 8.7 |
p-value: 0.013Wilcoxon (Mann-Whitney)
Secondary
Mean VLDL2 Triglyceride Total Production Before and After Evolocumab
Change in VLDL2 triglyceride total production measured in isolated VLDL2 from plasma samples by using density ultracentrifugation and measured by multicompartmental modeling. Production rates were derived from samples taken before and after the tracer injection and after the meal at 0, 30, 45, 60, 75, 90, 120, 150 min and at 3, 4, 5, 6, 8, 10, 24 hrs and averages for 24 hrs. More detailed description see Outcome measure 3.
Time frame: Baseline and after 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evolocumab | Mean VLDL2 Triglyceride Total Production Before and After Evolocumab | Baseline | 8.8 g/d | Standard Deviation 3.8 |
| Evolocumab | Mean VLDL2 Triglyceride Total Production Before and After Evolocumab | Week 12 | 8.5 g/d | Standard Deviation 2.7 |
p-value: 0.68Wilcoxon (Mann-Whitney)