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| ID | Type | Description | Link |
|---|---|---|---|
| BB/G009899/1 | Other Grant/Funding Number | BBSRC |
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| Name | Class |
|---|---|
| Imperial College London | OTHER |
| University of Cambridge | OTHER |
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The hypothesis of this study is that a diet high in sugars will increase abnormalities in blood lipids which are associated with increased cardiovascular disease risk, relative to a diet which is low in sugar. We predict that this potentially adverse effect of dietary sugars on blood lipids will be more pronounced in people with a raised level of stored fat inside their liver, as compared to people with a low level of stored fat.
This study aims to determine the metabolic mechanism(s) by which dietary extrinsic sugars (sucrose and fructose), promote the formation of a high risk dyslipidaemia, known as an atherogenic lipoprotein phenotype (raised plasma triglyceride, low HDL and predominance of small, dense LDL), in men with raised cardio-metabolic risk and percentage of liver fat, as determined by magnetic resonance spectroscopy (MRS). The study examined the impact of diets high and low in extrinsic sugars, on the metabolism of lipids and lipoproteins in vivo, of two groups of men with a high (>10%)and low (<2%)percentage of liver fat, by the trace-labelling of these lipid moieties with stable isotopes, and detection by gas chromatography mass spectrometry. The study had a two-way cross-over design, with two, 12 week dietary interventions separated by a six week wash-out period. The dietary intervention with high and low sugars was achieved by a dietary exchange with supermarket foods, which were consumed within the homes of the participants.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| High sugar low starch diet | Experimental | A high sugar, low starch diet was provided by the exchange of two thirds of the participants daily intake of carbohydrate. This was achieved by exchanging foods with low sugar to starch content, with foods containing a high sugar to starch content to reach a target ratio of starch to sugar of 1:1.2 |
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| Low sugar high starch diet | Experimental | A high sugar, low starch diet was provided by the exchange of two thirds of the participants daily intake of carbohydrate. This was achieved by exchanging 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 |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| High sugar low starch diet | Other |
| ||
| Low sugar high starch diet |
| Measure | Description | Time Frame |
|---|---|---|
| Production Rate of VLDL-1 Triacylglycerol (TAG) | 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. | After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14) |
| Production Rate VLDL-1 Apoprotein B | 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. | After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14) |
| Measure | Description | Time Frame |
|---|---|---|
| Kinetics of Systemic Non-esterified Fatty Acids by [C-13]-Trace-labelled Palmitate | 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). | After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bruce A Griffin, PhD | University of Surrey | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Surrey | Guildford | Surrey | GU2 7XH | 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%.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| FG002 | 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. |
| FG003 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Dietary Intervention (12 Weeks) |
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| Wash-out (4 Weeks) |
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| Second Dietary Intervention (12 Weeks) |
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Entry criteria for the two study groups of men included an APO e3/e3 genotype, and either a high percentage of liver fat of greater than 5% (by volume) = NAFLD (if excess alcohol intake excluded) or low percentage of liver fat of less than 5% ('Control' status) at baseline, before being randomised to the two dietary treatments in a two-way cross-over design.
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| ID | Title | Description |
|---|---|---|
| BG000 | NAFLD (>5% Liver Fat) | Men with non-alcoholic fatty liver disease (NAFLD) n=12 |
| BG001 | Controls (<5% Liver Fat) | Controls (men without NAFLD <5% liver fat) n=15 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Production Rate of VLDL-1 Triacylglycerol (TAG) | 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. | 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. | Posted | Mean | Standard Error | grams/day | After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14) |
|
24 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | High Sugar Diet in NAFLD Men (n=11) | 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. |
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A limitation of metabolic studies is their small sample size, which is a consequence of the invasive nature, extent, labour intensity, and high cost ($850,000) of the metabolic investigations e.g. infusion/ingestion of 4 stable isotope tracers.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Professor Bruce A.Griffin | University of Surrey | +44 0483 689724 | b.griffin@surrey.ac.uk |
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| ID | Term |
|---|---|
| D065626 | Non-alcoholic Fatty Liver Disease |
| D005234 | Fatty Liver |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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| Other |
|
| De Novo Lipogenesis (Rate of Triacylglycerol (TAG) Synthesis in the Liver) as Measured by Contribution to VLDL-1 TAG Production Rate | 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. | After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14) |
| Intra-hepatocellular Lipid (IHCL) or % Liver Fat | Percentage of intra-hepatocellular lipid (IHCL or % liver fat) was measured by magnetic resonance spectroscopy (MRS). | After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14) |
| Plasma Concentration of Triacylglycerol | 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) | After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14) |
| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
|
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Body weight | Mean | Standard Deviation | kilograms |
|
| Body mass index | Mean | Standard Deviation | kg/m2 |
|
| Serum cholesterol | Mean | Standard Deviation | mmol/L |
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| Serum triacylglycerol | Mean | Standard Deviation | mmol/L |
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| Serum glucose | Mean | Standard Deviation | mmol/L |
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| Serum HDL cholesterol | Mean | Standard Deviation | mmol/L |
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| Systolic blood pressure | Mean | Standard Deviation | mmHg |
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| Diastolic blood pressure | Mean | Standard Deviation | mmHg |
|
| OG001 | Low Sugar Diet (12 Weeks) in Men With NAFLD | 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 |
| OG002 | High Sugar Diet (12 Weeks) in Controls | 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. |
| OG003 | Low Sugar Diet (12 Weeks) in Controls | 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. |
|
|
|
| Primary | Production Rate VLDL-1 Apoprotein B | 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. | 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. | Posted | Mean | Standard Error | mg/day | After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14) |
|
|
|
|
| Secondary | Kinetics of Systemic Non-esterified Fatty Acids by [C-13]-Trace-labelled Palmitate | 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). | 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. | Posted | Mean | Standard Error | umol/L | After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14) |
|
|
|
|
| Secondary | De Novo Lipogenesis (Rate of Triacylglycerol (TAG) Synthesis in the Liver) as Measured by Contribution to VLDL-1 TAG Production Rate | 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. | 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. | Posted | Mean | Standard Error | grams/day | After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14) |
|
|
|
|
| Secondary | Intra-hepatocellular Lipid (IHCL) or % Liver Fat | Percentage of intra-hepatocellular lipid (IHCL or % liver fat) was measured by magnetic resonance spectroscopy (MRS). | 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. | Posted | Mean | Standard Error | Percentage of liver fat | After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14) |
|
|
|
|
| Secondary | Plasma Concentration of Triacylglycerol | 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) | 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. | Posted | Geometric Mean | Standard Error | mmol/L | After (post-diet) two 12 week diets (high sugar versus low sugar) in men with NAFLD (n=11) versus Controls (n=14) |
|
|
|
|
| 0 |
| 11 |
| 0 |
| 11 |
| EG001 | Low Sugar Diet in NAFLD Men (n=11) | 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. | 0 | 11 | 0 | 11 |
| EG002 | High Sugar Diet in Controls (n=14) | 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. | 0 | 14 | 0 | 14 |
| EG003 | Low Sugar Diet in Controls (n=14) | 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. | 0 | 14 | 0 | 14 |
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Details of our statistical analyses are given below. |
| Other |
For outcome measures for which there were four samples from each participant (pre- and post-diets, for each period), the post-diet measurements were analysed as dependent variables in a general linear mixed model, with the following fixed categorical, non-random, explanatory effects: period, treatment (low and high sugar diet), period by treatment interaction (to detect carry-over effects), liver fat level (NAFLD and Control) and treatment by liver fat level interaction. The pre-diet measurements for each period, and bodyweights (pre- and post-diets) were included as covariates in the model, with participant as a model random effect. For outcome measures for which there were two samples for each participant (post-diets; end of each dietary intervention period only), each measurement for the combined groups (NAFLD and controls), for the 2-period cross-over, were analysed in a general linear mixed model with the same fixed categorical effects and bodyweights as covariates. |
Details of our statistical analyses are given below. |
| Other |
For outcome measures for which there were four samples from each participant (pre- and post-diets, for each period), the post-diet measurements were analysed as dependent variables in a general linear mixed model, with the following fixed categorical, non-random, explanatory effects: period, treatment (low and high sugar diet), period by treatment interaction (to detect carry-over effects), liver fat level (NAFLD and Control) and treatment by liver fat level interaction. The pre-diet measurements for each period, and bodyweights (pre- and post-diets) were included as covariates in the model, with participant as a model random effect. For outcome measures for which there were two samples for each participant (post-diets; end of each dietary intervention period only), each measurement for the combined groups (NAFLD and controls), for the 2-period cross-over, were analysed in a general linear mixed model with the same fixed categorical effects and bodyweights as covariates. |
Details of our statistical approach are given below. |
| Other |
For outcome measures for which there were four samples from each participant (pre- and post-diets, for each period), the post-diet measurements were analysed as dependent variables in a general linear mixed model, with the following fixed categorical, non-random, explanatory effects: period, treatment (low and high sugar diet), period by treatment interaction (to detect carry-over effects), liver fat level (NAFLD and Control) and treatment by liver fat level interaction. The pre-diet measurements for each period, and bodyweights (pre- and post-diets) were included as covariates in the model, with participant as a model random effect. For outcome measures for which there were two samples for each participant (post-diets; end of each dietary intervention period only), each measurement for the combined groups (NAFLD and controls), for the 2-period cross-over, were analysed in a general linear mixed model with the same fixed categorical effects and bodyweights as covariates. |
Details of our statistical analyses are described below. |
| Other |
For outcome measures for which there were four samples from each participant (pre- and post-diets, for each period), the post-diet measurements were analysed as dependent variables in a general linear mixed model, with the following fixed categorical, non-random, explanatory effects: period, treatment (low and high sugar diet), period by treatment interaction (to detect carry-over effects), liver fat level (NAFLD and Control) and treatment by liver fat level interaction. The pre-diet measurements for each period, and bodyweights (pre- and post-diets) were included as covariates in the model, with participant as a model random effect. For outcome measures for which there were two samples for each participant (post-diets; end of each dietary intervention period only), each measurement for the combined groups (NAFLD and controls), for the 2-period cross-over, were analysed in a general linear mixed model with the same fixed categorical effects and bodyweights as covariates. |
Details of our statistical analyses are given below. |
| Other |
For outcome measures for which there were four samples from each participant (pre- and post-diets, for each period), the post-diet measurements were analysed as dependent variables in a general linear mixed model, with the following fixed categorical, non-random, explanatory effects: period, treatment (low and high sugar diet), period by treatment interaction (to detect carry-over effects), liver fat level (NAFLD and Control) and treatment by liver fat level interaction. The pre-diet measurements for each period, and bodyweights (pre- and post-diets) were included as covariates in the model, with participant as a model random effect. For outcome measures for which there were two samples for each participant (post-diets; end of each dietary intervention period only), each measurement for the combined groups (NAFLD and controls), for the 2-period cross-over, were analysed in a general linear mixed model with the same fixed categorical effects and bodyweights as covariates. |