Trial Outcomes & Findings for How Does Dietary Carbohydrate Influence the Formation of an Atherogenic Lipoprotein Phenotype (ALP)? (NCT NCT01790984)
NCT ID: NCT01790984
Last Updated: 2021-05-27
Results Overview
The in vivo production rate of VLDL-1 TAG, trace-labelled with \[1,1,2,3,3-H5\] glycerol, measured in units of grams/day.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
27 participants
Primary outcome timeframe
After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)
Results posted on
2021-05-27
Participant Flow
Participants were recruited over a period of 24 months (2009-2011) at the 'CEDAR' Centre for Endocrinology and Diabetes Research, Royal Surrey County Hospital, Guildford, Surrey, United Kingdom.
Men were selected on the basis of expressing increased cardio-metabolic risk and APOE E3E3 genotype. The men were screened for intracellular hepatic fat by magnetic resonance spectroscopy (MRS) and divided into two groups: low liver fat Controls (\<5% liver fat) and non-alcoholic fatty liver disease (NAFLD) with percentage liver fat \>5%.
Participant milestones
| Measure |
High Sugar / NAFLD
Men with NAFLD (\>5% liver fat) on a high sugar diet (25% total energy)
Please note: This was a randomised cross-over study. The men with NAFLD and Controls were randomised to either diet in the 'First Dietary Intervention (12 weeks)' period, and after the 'Wash-out (4 weeks)' period, crossed-over to the alternate diet in the 'Second Dietary Intervention (12 weeks)' period. This is why the number completing the First Intervention is not the same as the number starting the Second Dietary Intervention.
|
High Sugar / Controls
Controls (\<5% liver fat) on a high sugar (HS) diet.
Please note: This was a randomised cross-over study. The men with NAFLD and Controls were randomised to either diet in the 'First Dietary Intervention (12 weeks)' period, and after the 'Wash-out (4 weeks)' period, crossed-over to the alternate diet in the 'Second Dietary Intervention (12 weeks)' period. This is why the number completing the First Intervention is not the same as the number starting the Second Dietary Intervention.
|
Low Sugar / NAFLD
Men with NAFLD (\>5% liver fat) on a low sugar diet.
Please note: This was a randomised cross-over study. The men with NAFLD and Controls were randomised to either diet in the 'First Dietary Intervention (12 weeks)' period, and after the 'Wash-out (4 weeks)' period, crossed-over to the alternate diet in the 'Second Dietary Intervention (12 weeks)' period. This is why the number completing the First Intervention is not the same as the number starting the Second Dietary Intervention.
|
Low Sugar / Controls
Controls with low liver fat (\<5%) on a low sugar diet (5% total energy)
Please note: This was a randomised cross-over study. The men with NAFLD and Controls were randomised to either diet in the 'First Dietary Intervention (12 weeks)' period, and after the 'Wash-out (4 weeks)' period, crossed-over to the alternate diet in the 'Second Dietary Intervention (12 weeks)' period. This is why the number completing the First Intervention is not the same as the number starting the Second Dietary Intervention.
|
|---|---|---|---|---|
|
First Dietary Intervention (12 Weeks)
STARTED
|
6
|
8
|
6
|
7
|
|
First Dietary Intervention (12 Weeks)
COMPLETED
|
5
|
7
|
6
|
7
|
|
First Dietary Intervention (12 Weeks)
NOT COMPLETED
|
1
|
1
|
0
|
0
|
|
Wash-out (4 Weeks)
STARTED
|
5
|
7
|
6
|
7
|
|
Wash-out (4 Weeks)
COMPLETED
|
5
|
7
|
6
|
7
|
|
Wash-out (4 Weeks)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Second Dietary Intervention (12 Weeks)
STARTED
|
5
|
7
|
6
|
7
|
|
Second Dietary Intervention (12 Weeks)
COMPLETED
|
5
|
7
|
6
|
7
|
|
Second Dietary Intervention (12 Weeks)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
High Sugar / NAFLD
Men with NAFLD (\>5% liver fat) on a high sugar diet (25% total energy)
Please note: This was a randomised cross-over study. The men with NAFLD and Controls were randomised to either diet in the 'First Dietary Intervention (12 weeks)' period, and after the 'Wash-out (4 weeks)' period, crossed-over to the alternate diet in the 'Second Dietary Intervention (12 weeks)' period. This is why the number completing the First Intervention is not the same as the number starting the Second Dietary Intervention.
|
High Sugar / Controls
Controls (\<5% liver fat) on a high sugar (HS) diet.
Please note: This was a randomised cross-over study. The men with NAFLD and Controls were randomised to either diet in the 'First Dietary Intervention (12 weeks)' period, and after the 'Wash-out (4 weeks)' period, crossed-over to the alternate diet in the 'Second Dietary Intervention (12 weeks)' period. This is why the number completing the First Intervention is not the same as the number starting the Second Dietary Intervention.
|
Low Sugar / NAFLD
Men with NAFLD (\>5% liver fat) on a low sugar diet.
Please note: This was a randomised cross-over study. The men with NAFLD and Controls were randomised to either diet in the 'First Dietary Intervention (12 weeks)' period, and after the 'Wash-out (4 weeks)' period, crossed-over to the alternate diet in the 'Second Dietary Intervention (12 weeks)' period. This is why the number completing the First Intervention is not the same as the number starting the Second Dietary Intervention.
|
Low Sugar / Controls
Controls with low liver fat (\<5%) on a low sugar diet (5% total energy)
Please note: This was a randomised cross-over study. The men with NAFLD and Controls were randomised to either diet in the 'First Dietary Intervention (12 weeks)' period, and after the 'Wash-out (4 weeks)' period, crossed-over to the alternate diet in the 'Second Dietary Intervention (12 weeks)' period. This is why the number completing the First Intervention is not the same as the number starting the Second Dietary Intervention.
|
|---|---|---|---|---|
|
First Dietary Intervention (12 Weeks)
Withdrawal by Subject
|
1
|
1
|
0
|
0
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
NAFLD (>5% Liver Fat)
n=12 Participants
Men with non-alcoholic fatty liver disease (NAFLD) n=12
|
Controls (<5% Liver Fat)
n=15 Participants
Controls (men without NAFLD \<5% liver fat) n=15
|
Total
n=27 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
59 years
STANDARD_DEVIATION 4.7 • n=12 Participants
|
54 years
STANDARD_DEVIATION 7.3 • n=15 Participants
|
57 years
STANDARD_DEVIATION 6.7 • n=27 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=12 Participants
|
0 Participants
n=15 Participants
|
0 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=12 Participants
|
15 Participants
n=15 Participants
|
27 Participants
n=27 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Body weight
|
89.7 kilograms
STANDARD_DEVIATION 7.8 • n=12 Participants
|
89.6 kilograms
STANDARD_DEVIATION 9.1 • n=15 Participants
|
89.7 kilograms
STANDARD_DEVIATION 8.4 • n=27 Participants
|
|
Body mass index
|
28.8 kg/m2
STANDARD_DEVIATION 1.4 • n=12 Participants
|
28.5 kg/m2
STANDARD_DEVIATION 1.5 • n=15 Participants
|
28.6 kg/m2
STANDARD_DEVIATION 1.4 • n=27 Participants
|
|
Serum cholesterol
|
5.90 mmol/L
STANDARD_DEVIATION 0.83 • n=12 Participants
|
5.51 mmol/L
STANDARD_DEVIATION 1.00 • n=15 Participants
|
5.70 mmol/L
STANDARD_DEVIATION 1.00 • n=27 Participants
|
|
Serum triacylglycerol
|
2.05 mmol/L
STANDARD_DEVIATION 0.88 • n=12 Participants
|
1.51 mmol/L
STANDARD_DEVIATION 0.87 • n=15 Participants
|
1.70 mmol/L
STANDARD_DEVIATION 0.90 • n=27 Participants
|
|
Serum glucose
|
5.73 mmol/L
STANDARD_DEVIATION 0.45 • n=12 Participants
|
5.46 mmol/L
STANDARD_DEVIATION 0.45 • n=15 Participants
|
5.58 mmol/L
STANDARD_DEVIATION 0.43 • n=27 Participants
|
|
Serum HDL cholesterol
|
1.35 mmol/L
STANDARD_DEVIATION 0.28 • n=12 Participants
|
1.34 mmol/L
STANDARD_DEVIATION 0.30 • n=15 Participants
|
1.34 mmol/L
STANDARD_DEVIATION 0.29 • n=27 Participants
|
|
Systolic blood pressure
|
134 mmHg
STANDARD_DEVIATION 19 • n=12 Participants
|
132 mmHg
STANDARD_DEVIATION 13 • n=15 Participants
|
133 mmHg
STANDARD_DEVIATION 16 • n=27 Participants
|
|
Diastolic blood pressure
|
85 mmHg
STANDARD_DEVIATION 13 • n=12 Participants
|
83 mmHg
STANDARD_DEVIATION 9 • n=15 Participants
|
85 mmHg
STANDARD_DEVIATION 11 • n=27 Participants
|
PRIMARY outcome
Timeframe: After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)Population: Population consisted of two groups: Group 1: men with non-alcoholic fatty liver disease (NAFLD) raised liver fat (\>5%) n=11. Group 2: Controls; men with low liver fat (\<5%) n=14.
The in vivo production rate of VLDL-1 TAG, trace-labelled with \[1,1,2,3,3-H5\] glycerol, measured in units of grams/day.
Outcome measures
| Measure |
High Sugar Diet (12 Weeks) in Men With NAFLD
n=11 Participants
A high sugar (27% total energy), low starch diet was provided by the exchange of 66% of the participants daily intake of carbohydrate. This was achieved by exchanging foods with a low sugar to starch content, with foods containing a high sugar to starch content to reach a target ratio of starch to sugar 1: 1.2.
|
Low Sugar Diet (12 Weeks) in Men With NAFLD
n=11 Participants
A low sugar (9% total energy), high starch diet was provided by the exchange of 66% of the participants daily intake of carbohydrate. This was achieved by replacing foods with a high sugar to starch content, with foods containing a low sugar to starch content to reach a target ratio of starch to sugar of 5:1
|
High Sugar Diet (12 Weeks) in Controls
n=14 Participants
A high sugar (28% total energy), low starch diet was provided by the exchange of 66% of the participants daily intake of carbohydrate. This was achieved by exchanging foods with a low sugar to starch content, with foods containing a high sugar to starch content to reach a target ratio of starch to sugar 1: 1.2.
|
Low Sugar Diet (12 Weeks) in Controls
n=14 Participants
A low sugar (10% total energy), high starch diet was provided by the exchange of 66% of the participants daily intake of carbohydrate. This was achieved by replacing foods with a high sugar to starch content, with foods containing a low sugar to starch content to reach a target ratio of starch to sugar of 5:1.
|
|---|---|---|---|---|
|
Production Rate of VLDL-1 Triacylglycerol (TAG)
|
20.9 grams/day
Standard Error 2.1
|
18.9 grams/day
Standard Error 2.1
|
16.6 grams/day
Standard Error 1.4
|
12.4 grams/day
Standard Error 1.2
|
PRIMARY outcome
Timeframe: After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)Population: Population consisted of two groups: Group 1: NAFLD; men with raised liver fat ( \>5%), n=11. Group 2: Controls; men with low liver fat (\<5%) n=14.
The in vivo production rate of VLDL-1 apoprotein B, trace-labelled with \[I-13C\] leucine (leucine with carbon-13), measured in units of milligrams/day.
Outcome measures
| Measure |
High Sugar Diet (12 Weeks) in Men With NAFLD
n=11 Participants
A high sugar (27% total energy), low starch diet was provided by the exchange of 66% of the participants daily intake of carbohydrate. This was achieved by exchanging foods with a low sugar to starch content, with foods containing a high sugar to starch content to reach a target ratio of starch to sugar 1: 1.2.
|
Low Sugar Diet (12 Weeks) in Men With NAFLD
n=11 Participants
A low sugar (9% total energy), high starch diet was provided by the exchange of 66% of the participants daily intake of carbohydrate. This was achieved by replacing foods with a high sugar to starch content, with foods containing a low sugar to starch content to reach a target ratio of starch to sugar of 5:1
|
High Sugar Diet (12 Weeks) in Controls
n=14 Participants
A high sugar (28% total energy), low starch diet was provided by the exchange of 66% of the participants daily intake of carbohydrate. This was achieved by exchanging foods with a low sugar to starch content, with foods containing a high sugar to starch content to reach a target ratio of starch to sugar 1: 1.2.
|
Low Sugar Diet (12 Weeks) in Controls
n=14 Participants
A low sugar (10% total energy), high starch diet was provided by the exchange of 66% of the participants daily intake of carbohydrate. This was achieved by replacing foods with a high sugar to starch content, with foods containing a low sugar to starch content to reach a target ratio of starch to sugar of 5:1.
|
|---|---|---|---|---|
|
Production Rate VLDL-1 Apoprotein B
|
481 mg/day
Standard Error 76
|
492 mg/day
Standard Error 58
|
546 mg/day
Standard Error 56
|
414 mg/day
Standard Error 54
|
SECONDARY outcome
Timeframe: After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)Population: Population consisted of two groups: Group 1: NAFLD; men with raised liver fat ( \>5%), n=11. Group 2: Controls; men with low liver fat (\<5%) n=14.
Palmitate was labelled in vivo by the infusion of \[U-13 carbon\]. This provides a measure of the rate of intra-cellular lipolysis and contribution of systemic palmitate to the synthesis of triacylglycerol in the liver in units of micro mols/L (umol/L).
Outcome measures
| Measure |
High Sugar Diet (12 Weeks) in Men With NAFLD
n=11 Participants
A high sugar (27% total energy), low starch diet was provided by the exchange of 66% of the participants daily intake of carbohydrate. This was achieved by exchanging foods with a low sugar to starch content, with foods containing a high sugar to starch content to reach a target ratio of starch to sugar 1: 1.2.
|
Low Sugar Diet (12 Weeks) in Men With NAFLD
n=11 Participants
A low sugar (9% total energy), high starch diet was provided by the exchange of 66% of the participants daily intake of carbohydrate. This was achieved by replacing foods with a high sugar to starch content, with foods containing a low sugar to starch content to reach a target ratio of starch to sugar of 5:1
|
High Sugar Diet (12 Weeks) in Controls
n=14 Participants
A high sugar (28% total energy), low starch diet was provided by the exchange of 66% of the participants daily intake of carbohydrate. This was achieved by exchanging foods with a low sugar to starch content, with foods containing a high sugar to starch content to reach a target ratio of starch to sugar 1: 1.2.
|
Low Sugar Diet (12 Weeks) in Controls
n=14 Participants
A low sugar (10% total energy), high starch diet was provided by the exchange of 66% of the participants daily intake of carbohydrate. This was achieved by replacing foods with a high sugar to starch content, with foods containing a low sugar to starch content to reach a target ratio of starch to sugar of 5:1.
|
|---|---|---|---|---|
|
Kinetics of Systemic Non-esterified Fatty Acids by [C-13]-Trace-labelled Palmitate
|
169 umol/L
Standard Error 11
|
147 umol/L
Standard Error 12
|
168 umol/L
Standard Error 15
|
168 umol/L
Standard Error 17
|
SECONDARY outcome
Timeframe: After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)Population: Population consisted of two groups: Group 1: NAFLD; men with raised liver fat ( \>5%), n=11. Group 2: Controls; men with low liver fat (\<5%) n=14.
Acetyl CoA (Co-enzyme-A) is labelled in vivo by the consumption of \[2H20\] (2H20=deuterated 'heavy'-labelled water). Recovery and detection of this label in VLDL-1 by GC-MS (Gas Chromatography-Mass Spectrometry), provides a measure of fatty acid and TAG synthesis in the liver in terms of its contribution to the production rate of VLDL-1 TAG in units of grams/day.
Outcome measures
| Measure |
High Sugar Diet (12 Weeks) in Men With NAFLD
n=11 Participants
A high sugar (27% total energy), low starch diet was provided by the exchange of 66% of the participants daily intake of carbohydrate. This was achieved by exchanging foods with a low sugar to starch content, with foods containing a high sugar to starch content to reach a target ratio of starch to sugar 1: 1.2.
|
Low Sugar Diet (12 Weeks) in Men With NAFLD
n=11 Participants
A low sugar (9% total energy), high starch diet was provided by the exchange of 66% of the participants daily intake of carbohydrate. This was achieved by replacing foods with a high sugar to starch content, with foods containing a low sugar to starch content to reach a target ratio of starch to sugar of 5:1
|
High Sugar Diet (12 Weeks) in Controls
n=14 Participants
A high sugar (28% total energy), low starch diet was provided by the exchange of 66% of the participants daily intake of carbohydrate. This was achieved by exchanging foods with a low sugar to starch content, with foods containing a high sugar to starch content to reach a target ratio of starch to sugar 1: 1.2.
|
Low Sugar Diet (12 Weeks) in Controls
n=14 Participants
A low sugar (10% total energy), high starch diet was provided by the exchange of 66% of the participants daily intake of carbohydrate. This was achieved by replacing foods with a high sugar to starch content, with foods containing a low sugar to starch content to reach a target ratio of starch to sugar of 5:1.
|
|---|---|---|---|---|
|
De Novo Lipogenesis (Rate of Triacylglycerol (TAG) Synthesis in the Liver) as Measured by Contribution to VLDL-1 TAG Production Rate
|
1.66 grams/day
Standard Error 0.39
|
1.59 grams/day
Standard Error 0.34
|
1.32 grams/day
Standard Error 0.43
|
0.56 grams/day
Standard Error 0.14
|
SECONDARY outcome
Timeframe: After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)Population: Population consisted of two groups: Group 1: NAFLD; men with raised liver fat ( \>5%), n=11. Group 2: Controls; men with low liver fat (\<5%) n=14.
Percentage of intra-hepatocellular lipid (IHCL or % liver fat) was measured by magnetic resonance spectroscopy (MRS).
Outcome measures
| Measure |
High Sugar Diet (12 Weeks) in Men With NAFLD
n=11 Participants
A high sugar (27% total energy), low starch diet was provided by the exchange of 66% of the participants daily intake of carbohydrate. This was achieved by exchanging foods with a low sugar to starch content, with foods containing a high sugar to starch content to reach a target ratio of starch to sugar 1: 1.2.
|
Low Sugar Diet (12 Weeks) in Men With NAFLD
n=11 Participants
A low sugar (9% total energy), high starch diet was provided by the exchange of 66% of the participants daily intake of carbohydrate. This was achieved by replacing foods with a high sugar to starch content, with foods containing a low sugar to starch content to reach a target ratio of starch to sugar of 5:1
|
High Sugar Diet (12 Weeks) in Controls
n=14 Participants
A high sugar (28% total energy), low starch diet was provided by the exchange of 66% of the participants daily intake of carbohydrate. This was achieved by exchanging foods with a low sugar to starch content, with foods containing a high sugar to starch content to reach a target ratio of starch to sugar 1: 1.2.
|
Low Sugar Diet (12 Weeks) in Controls
n=14 Participants
A low sugar (10% total energy), high starch diet was provided by the exchange of 66% of the participants daily intake of carbohydrate. This was achieved by replacing foods with a high sugar to starch content, with foods containing a low sugar to starch content to reach a target ratio of starch to sugar of 5:1.
|
|---|---|---|---|---|
|
Intra-hepatocellular Lipid (IHCL) or % Liver Fat
|
24.2 Percentage of liver fat
Standard Error 6.8
|
14.2 Percentage of liver fat
Standard Error 3.2
|
3.6 Percentage of liver fat
Standard Error 1.3
|
1.5 Percentage of liver fat
Standard Error 0.3
|
SECONDARY outcome
Timeframe: After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14)Population: Population consisted of two groups: Group 1: NAFLD; men with raised liver fat ( \>5%), n=11. Group 2: Controls; men with low liver fat (\<5%) n=14.
Plasma concentration of triacylglycerol (TAG) was measured in the post-absorptive state (after 12h fast) and expressed in units of mmol/L (shown as log transformed geometric means)
Outcome measures
| Measure |
High Sugar Diet (12 Weeks) in Men With NAFLD
n=11 Participants
A high sugar (27% total energy), low starch diet was provided by the exchange of 66% of the participants daily intake of carbohydrate. This was achieved by exchanging foods with a low sugar to starch content, with foods containing a high sugar to starch content to reach a target ratio of starch to sugar 1: 1.2.
|
Low Sugar Diet (12 Weeks) in Men With NAFLD
n=11 Participants
A low sugar (9% total energy), high starch diet was provided by the exchange of 66% of the participants daily intake of carbohydrate. This was achieved by replacing foods with a high sugar to starch content, with foods containing a low sugar to starch content to reach a target ratio of starch to sugar of 5:1
|
High Sugar Diet (12 Weeks) in Controls
n=14 Participants
A high sugar (28% total energy), low starch diet was provided by the exchange of 66% of the participants daily intake of carbohydrate. This was achieved by exchanging foods with a low sugar to starch content, with foods containing a high sugar to starch content to reach a target ratio of starch to sugar 1: 1.2.
|
Low Sugar Diet (12 Weeks) in Controls
n=14 Participants
A low sugar (10% total energy), high starch diet was provided by the exchange of 66% of the participants daily intake of carbohydrate. This was achieved by replacing foods with a high sugar to starch content, with foods containing a low sugar to starch content to reach a target ratio of starch to sugar of 5:1.
|
|---|---|---|---|---|
|
Plasma Concentration of Triacylglycerol
|
2.05 mmol/L
Standard Error 0.24
|
1.77 mmol/L
Standard Error 0.22
|
1.33 mmol/L
Standard Error 0.15
|
1.13 mmol/L
Standard Error 0.08
|
Adverse Events
High Sugar Diet in NAFLD Men (n=11)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Low Sugar Diet in NAFLD Men (n=11)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
High Sugar Diet in Controls (n=14)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Low Sugar Diet in Controls (n=14)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place