Metabolic Syndrome
Conditions
Keywords
metabolic syndrome, Volunteers recruited from the community
Brief summary
To characterize features of metabolic syndrome in volunteers. To undertake a randomised trial to determine whether treatment with a statin improves muscle microvascular blood flow.
Detailed description
To characterise features of the metabolic syndrome, including body fat, insulin sensitivity, and liver fat together with muscle micorvascular blood flow. To undertake a randomised controlled trial of atorvastatin 40 mg. o.d for 6 months to determine whether any of the above measures change with treatment.
Interventions
DRUGatorvastatin
40 m.g. o.d. tablets for 6 months
DRUGplacebo
Placebo
Sponsors
University Hospital Southampton NHS Foundation Trust
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
Body mass index (BMI) 20-35 kg/m\^2 and \> 3 criteria for the metabolic syndrome (NCEP III ATP criteria - see below) , one of which will be hypertriglyceridaemia, i.e. fasting plasma triglycerides \>2.0 mmol/L - a cardinal lipid abnormality of the syndrome NCEP III ATP metabolic syndrome criteria are: Waist greater than or equal to 102 cm BP greater than 130 / 85 mmHg TG greater than or equal to 1.7mmol/l Glucose greater than or equal to 6.1 mmol/l HDL less than 1.0 mmol/l
Exclusion criteria
Aged \<18 years Aged \>75 years Known diabetes; renal, liver, or uncontrolled thyroid disease; uncontrolled hypertension; treatment with lipid-modifying drugs; antihypertensive medication; corticosteroid therapy; or hormone replacement therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Muscle Microvascular Function | 6 months | Skeletal muscle microvascular function assessed (Filtrass plethysmographic system) using a passive inductive transducer (Compumedics.dwl, Singen, Germany) and a small pressure step venous congestion protocol. Fluid filtration rate (Jv mL min-1 100 mL-1), measured from the slope of limb volume change in response to each pressure step (10 mmHg steps to 60 mmHg around the thigh) over the last 2 minutes of its application, to allow for completion of vascular filling, and plotted against cuff pressure (Pcuff). The slope of this relationship, at pressures above those giving rise to net filtration, is a measure of Kf, microvascular filtration capacity, a function of exchange surface area and permeability. The CV for Kf measurement was 14.5%. |
| Insulin Sensitivity Index | 6 months | Insulin sensitivity index was assessed during the final steady state 30 minutes of a high dose hyperinsulinaemic euglycaemic clamp (insulin infusion rate 1.5 mIU/kg/min). During this part of the clamp, insulin was infused at 1.5mIU/kg/min and the glucose concentration was maintained at 5 mmol/L using a dextrose infusion. The whole body insulin mediated glucose disposal rate (M value - mg/kg/min) was estimated from the total amount of glucose infused during the last 30 minutes of the clamp. The mean of four serum insulin concentrations was taken during this 30 minutes to determine the steady state insulin concentration (I value - milliunits/litre). M value/I value defined the insulin sensitivity index. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Atorvastatin Active arm atorvastatin 40 mg. o.d.
atorvastatin: 40 m.g. o.d. tablets for 6 months Age 18-75 years, body mass index (BMI) 20-35 kg/m2, with \> 3 criteria for the metabolic syndrome , one of which will be hypertriglyceridaemia, i.e. fasting plasma triglycerides \>2.0 mmol/L - a cardinal lipid abnormality of the syndrome. | 20 |
| Placebo Placebo arm dummy pill
placebo: Placebo Age 18-75 years, body mass index (BMI) 20-35 kg/m2, with \> 3 criteria for the metabolic syndrome , one of which will be hypertriglyceridaemia, i.e. fasting plasma triglycerides \>2.0 mmol/L - a cardinal lipid abnormality of the syndrome. | 19 |
| Total | 39 |
Baseline characteristics
| Characteristic | Total | Atorvastatin | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 39 Participants | 20 Participants | 19 Participants |
| Age, Continuous | 51.4 years STANDARD_DEVIATION 9 | 51.4 years STANDARD_DEVIATION 9 | 51.4 years STANDARD_DEVIATION 9 |
| Region of Enrollment United Kingdom | 39 participants | 20 participants | 19 participants |
| Sex: Female, Male Female | 22 Participants | 12 Participants | 10 Participants |
| Sex: Female, Male Male | 17 Participants | 8 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 20 | 0 / 20 |
| serious Total, serious adverse events | 1 / 20 | 0 / 20 |
Outcome results
Primary
Insulin Sensitivity Index
Insulin sensitivity index was assessed during the final steady state 30 minutes of a high dose hyperinsulinaemic euglycaemic clamp (insulin infusion rate 1.5 mIU/kg/min). During this part of the clamp, insulin was infused at 1.5mIU/kg/min and the glucose concentration was maintained at 5 mmol/L using a dextrose infusion. The whole body insulin mediated glucose disposal rate (M value - mg/kg/min) was estimated from the total amount of glucose infused during the last 30 minutes of the clamp. The mean of four serum insulin concentrations was taken during this 30 minutes to determine the steady state insulin concentration (I value - milliunits/litre). M value/I value defined the insulin sensitivity index.
Time frame: 6 months
Population: There was missing data in four people in the atorvastatin arm and two people in the placebo arm
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin | Insulin Sensitivity Index | 0.56 mg*kg^-1*min^-1*mIU^-1*L^-1 | Standard Deviation 0.21 |
| Placebo | Insulin Sensitivity Index | 0.41 mg*kg^-1*min^-1*mIU^-1*L^-1 | Standard Deviation 0.14 |
Primary
Muscle Microvascular Function
Skeletal muscle microvascular function assessed (Filtrass plethysmographic system) using a passive inductive transducer (Compumedics.dwl, Singen, Germany) and a small pressure step venous congestion protocol. Fluid filtration rate (Jv mL min-1 100 mL-1), measured from the slope of limb volume change in response to each pressure step (10 mmHg steps to 60 mmHg around the thigh) over the last 2 minutes of its application, to allow for completion of vascular filling, and plotted against cuff pressure (Pcuff). The slope of this relationship, at pressures above those giving rise to net filtration, is a measure of Kf, microvascular filtration capacity, a function of exchange surface area and permeability. The CV for Kf measurement was 14.5%.
Time frame: 6 months
Population: There was missing data on two participants in the atorvastatin arm and two participants in the placebo arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin | Muscle Microvascular Function | 3.7 10^3 mL*min^-1*100ml^-1*mmHg^-1 | Standard Deviation 1.4 |
| Placebo | Muscle Microvascular Function | 4.0 10^3 mL*min^-1*100ml^-1*mmHg^-1 | Standard Deviation 1.1 |