Insulin ResistanceNCT02757560
Dietary Lipid Induced Insulin Resistance
A study testing SFA diet, MUFA diet and CARB diet in people with Insulin Resistance, run by Phoenix VA Health Care System at 1 site in United States.
Trial summary
The overall goal of the proposal is to use a saturated fatty acid (SFA)- enriched, high fat diet to rapidly induce insulin resistance (IR) to provide insight into underlying proximal mechanisms of reduced insulin signaling. Read more about this study
- Who is it for?
- Ages 40 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Insulin Resistance
- What is being tested?
- SFA diet, MUFA diet and CARB diet
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2012to Dec 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Body mass index (BMI) from 25-35 kg/m2
- normal glucose tolerance (NGT) diagnosis based on fasting glucose value 100mg/dl and 2 hr glucose <140 mg/dl after a standard 75 gm glucose load; impaired fasting glucose (IFG) on fasting glucose value ≥100 and <126 mg/dl and 2 hr glucose <140 mg/dl; impaired glucose tolerance (IGT) based on 2 hr glucose ≥140 and <200 mg/dl and a fasting glucose <126 mg/dl
- Fasting triglyceride levels <500 mg/dl
Who cannot join
- Type 1 or 2 diabetes mellitus or a hemoglobin A1c value ≥ 6.5 mg/dl
- Any diabetes medications in the past month, thiazolidinedione medications in the prior 3 months or prior regular use of insulin
- Use of diets, medications (e.g., steroids, weight loss medications ) or current or planned behavior changes (e.g. acute weight loss, exercise training) that will influence changes in IR
- Creatinine >2.0 mg/dl or other laboratory evidence of significant active disease, including hepatic enzyme elevation >2x normal and anemia, known "Nonalcoholic Fatty Liver Disease", bleeding risk
- Malabsorption of fat or other nutrients, severe lactose intolerance or other significant gastrointestinal or pancreatic problems, or recent history of nausea or vomiting
- Acute bacterial or viral illness or evidence of other active infection in the past 4 weeks
Show all 12Show fewer
- Cardiovascular event, stable or unstable angina or other major illness in the past 6 months
- Current regular use of anti-inflammatory medications (e.g. salicylates > 1 gm/ day) or antioxidants in excess of a daily multi-vitamin, including supplements (e.g. fish oils)
- Lipid lowering medications must be at a stable dose for at least 2 months prior to participation
- Ethanol consumption more than 4 oz day; more than occasional smoker
- Reproductively active women not on contraceptives
- Known allergies, prior reactions or contraindications to proposed clinical agents (e.g Octreotide)
Trial locations and contacts
1 site in 1 country.
United States1 site
Carl T. Hayden VA Medical Center
Phoenix, Arizona, 85012
About this study
Official title: Mechanisms of Dietary Lipid Induced Insulin Resistance
The overall goal of the proposal is to use a saturated fatty acid (SFA)- enriched, high fat diet to rapidly induce insulin resistance (IR) to provide insight into underlying proximal mechanisms of reduced insulin signaling. Specifically, investigators will identify the initial changes in metabolite concentrations/or pathway signaling ("pathways" will be used to broadly refer to these mechanism specific measures) and therefore the mechanisms most likely responsible for the development of IR during this high fat nutritional challenge. Investigators have assembled a multidisciplinary team that is versed with dietary studies, fatty acid metabolism, measurement of IR and potential mechanisms and mediators of IR, and has experience working with monocytes and the two tissues, muscle and adipose tissue, that are particularly relevant for understanding the effects of high fat diets on IR.
Read the detailed description
In the first aim, investigators will test whether a short-term high SFA-diet induces and increases insulin resistance in participants with normal and abnormal glucose tolerance, respectively, and determine the associated changes in muscle, adipose tissue and inflammatory cell composition, pathway activation and insulin signaling. Investigators will identify changes in specific signal pathways within these tissues and cells that are hypothesized to mediate or modulate insulin action. Primary mechanisms and pathways examined will include local tissue and systemic inflammation, formation of bioactive lipid intermediates, generation of endoplasmic reticulum (ER) stress, and mitochondrial dysfunction/reactive oxygen formation. By performing studies in participants with normal glucose tolerance and in those with abnormal glucose tolerance investigators will also determine whether the extent and mechanisms of insulin resistance vary with initial degrees of glucose intolerance.
In the second aim, to determine if the extent and mechanisms of insulin resistance vary with dietary composition, investigators will determine whether diets of similar caloric content as the SFA-diet, but enriched in monounsaturated fatty acids or carbohydrates, also induce insulin resistance and whether similar or different mechanistic pathways are responsible. Identifying similarities and differences between diets in inflammatory cell and tissue changes and comparing their relationships with peripheral and tissue insulin action will further clarify which cell and tissue events are most closely linked to development of insulin resistance.
In the final aim, to identify the temporal sequence of mechanistic pathways for insulin resistance and the role of cell and tissue cross-talk in these events, investigators will evaluate inflammatory cell, skeletal muscle and adipose tissue composition and pathway changes after acute, subacute, and more chronic dietary challenges in the same individuals. This will also permit assessment of whether repeated dietary challenges create changes in tissues that resemble those found in more chronic and advanced states of insulin resistance.
- Conditions
- Insulin Resistance
- Being tested
- SFA diet, MUFA diet, CARB diet
- Keywords
- saturated fat, acute insulin resistance, insulin suppression test, dietary fatty acids
- Medical subject headings
- Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SFA dietOther
SFA versus control diet
MUFA dietOther
MUFA versus control diet
CARB dietOther
CARB versus control diet
| Study group | Role | What they receive |
|---|---|---|
| SFA versus control diet | Experimental | Participants will be randomized in a cross-over design to either a weight-maintaining, nutritionally-balanced American Heart Association based eucaloric control diet or a high calorie 24-hour saturated fatty acids enriched diet. For the control diet participants will follow a dietary plan for 72 hours prior to testing. For the SFA diet, participants will be provided with high caloric liquid shakes for breakfast, lunch, dinner and a bedtime snack. On the morning of each test day, participants will be admitted in the fasting state and will provided with a breakfast meal corresponding to the assigned diet (SFA or control). Three hours after completion of the meal, insulin sensitivity will be measured by insulin-suppression test (IST). Receives: Other: SFA diet |
| MUFA versus control diet | Experimental | Participants will be randomized in a cross-over design to either a weight-maintaining, nutritionally-balanced American Heart Association based eucaloric control diet or a high calorie 24-hour monounsaturated fatty acids (MUFA) enriched diet. For the control diet participants will follow a dietary plan for 72 hours prior to testing. For the MUFA diet, participants will be provided with high caloric liquid shakes for breakfast, lunch, dinner and a bedtime snack. On the morning of each test day, participants will be admitted in the fasting state and will provided with a breakfast meal corresponding to the assigned diet (MUFA or control). Three hours after completion of the meal, insulin sensitivity will be measured by insulin-suppression test (IST). Receives: Other: MUFA diet |
| CARB versus control diet | Experimental | Participants will be randomized in a cross-over design to either a weight-maintaining, nutritionally-balanced American Heart Association based eucaloric control diet or a high calorie 24-hour carbohydrate (CARB) enriched diet. For the control diet participants will follow a dietary plan for 72 hours prior to testing. For the CARB diet, participants will be provided with high caloric liquid shakes for breakfast, lunch, dinner and a bedtime snack. On the morning of each test day, participants will be admitted in the fasting state and will provided with a breakfast meal corresponding to the assigned diet (CARB or control). Three hours after completion of the meal, insulin sensitivity will be measured by insulin-suppression test (IST). Receives: Other: CARB diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Steady-state plasma glucose (SSPG)
Average plasma glucose concentrations during min 150-180 of the insulin suppression test (IST)
Measured: 150-180 min
Secondary outcomes (5)
Acylcarnitine species
Measured by chromatography electrospray ionization mass spectrometry on plasma and skeletal muscle samples.
Measured: Overnight fast, 3-hour post breakfast
Diacylglycerol species
Measured on plasma, skeletal muscle and subcutaneous adipose tissue samples.
Measured: Overnight fast, 3-hour post breakfast
Ceramides species
Measured on plasma, skeletal muscle and subcutaneous adipose tissue samples.
Measured: Overnight fast, 3-hour post breakfast
Insulin signaling proteins
Measured on skeletal muscle and subcutaneous adipose tissue samples.
Measured: Overnight fast, 3-hour post breakfast
Inflammation markers
Cytokines and adipokines will be measured in plasma after the diet treatments by ELISA techniques. Mononuclear cells inflammatory gene expression will be measured by real time polymerase chain reaction (RT-PCR). Inflammation will be measured in muscle and adipose tissue by RT-PCR and Western blood analysis.
Measured: Overnight fast, 3-hour post breakfast
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2016 (estimated)
- Study startFeb 2012
- Primary completionJul 2020 (estimated)
- Study completionDec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Insulin ResistanceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Phoenix VA Health Care System
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Peter D Reaven, MD, Principal investigator, Phoenix Veterans Affairs Health Care System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02757560
- Sponsor's protocol ID
- 029
- Status last verified
- Jul 2019
- First submitted
- 4 Aug 2015
- Last updated
- 1 Aug 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No: Subject to VA regulation.
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms of Dietary Lipid Induced Insulin Resistance
- ClinicalTrials.gov ID
- NCT02757560
- Acronym / sponsor ID
- 029
- Conditions
- Insulin Resistance
- Keywords
- saturated fat, acute insulin resistance, insulin suppression test, dietary fatty acids
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Phoenix VA Health Care SystemUS federal agency
- Study start
- Feb 2012
- Primary completion
- Jul 2020 (estimated)
- Study completion
- Dec 2020 (estimated)
- First posted
- 2 May 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The overall goal of the proposal is to use a saturated fatty acid (SFA)- enriched, high fat diet to rapidly induce insulin resistance (IR) to provide insight into underlying proximal mechanisms of reduced insulin signaling. Specifically, investigators will identify the initial changes in metabolite concentrations/or pathway signaling ("pathways" will be used to broadly refer to these mechanism specific measures) and therefore the mechanisms most likely responsible for the development of IR during this high fat nutritional challenge. Investigators have assembled a multidisciplinary team that is versed with dietary studies, fatty acid metabolism, measurement of IR and potential mechanisms and mediators of IR, and has experience working with monocytes and the two tissues, muscle and adipose tissue, that are particularly relevant for understanding the effects of high fat diets on IR.
Detailed description
In the first aim, investigators will test whether a short-term high SFA-diet induces and increases insulin resistance in participants with normal and abnormal glucose tolerance, respectively, and determine the associated changes in muscle, adipose tissue and inflammatory cell composition, pathway activation and insulin signaling. Investigators will identify changes in specific signal pathways within these tissues and cells that are hypothesized to mediate or modulate insulin action. Primary mechanisms and pathways examined will include local tissue and systemic inflammation, formation of bioactive lipid intermediates, generation of endoplasmic reticulum (ER) stress, and mitochondrial dysfunction/reactive oxygen formation. By performing studies in participants with normal glucose tolerance and in those with abnormal glucose tolerance investigators will also determine whether the extent and mechanisms of insulin resistance vary with initial degrees of glucose intolerance.
In the second aim, to determine if the extent and mechanisms of insulin resistance vary with dietary composition, investigators will determine whether diets of similar caloric content as the SFA-diet, but enriched in monounsaturated fatty acids or carbohydrates, also induce insulin resistance and whether similar or different mechanistic pathways are responsible. Identifying similarities and differences between diets in inflammatory cell and tissue changes and comparing their relationships with peripheral and tissue insulin action will further clarify which cell and tissue events are most closely linked to development of insulin resistance.
In the final aim, to identify the temporal sequence of mechanistic pathways for insulin resistance and the role of cell and tissue cross-talk in these events, investigators will evaluate inflammatory cell, skeletal muscle and adipose tissue composition and pathway changes after acute, subacute, and more chronic dietary challenges in the same individuals. This will also permit assessment of whether repeated dietary challenges create changes in tissues that resemble those found in more chronic and advanced states of insulin resistance.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| SFA versus control diet | Experimental | Other: SFA dietParticipants will be randomized in a cross-over design to either a weight-maintaining, nutritionally-balanced American Heart Association based eucaloric control diet or a high calorie 24-hour saturated fatty acids enriched diet. For the control diet participants will follow a dietary plan for 72 hours prior to testing. For the SFA diet, participants will be provided with high caloric liquid shakes for breakfast, lunch, dinner and a bedtime snack. On the morning of each test day, participants will be admitted in the fasting state and will provided with a breakfast meal corresponding to the assigned diet (SFA or control). Three hours after completion of the meal, insulin sensitivity will be measured by insulin-suppression test (IST). |
| MUFA versus control diet | Experimental | Other: MUFA dietParticipants will be randomized in a cross-over design to either a weight-maintaining, nutritionally-balanced American Heart Association based eucaloric control diet or a high calorie 24-hour monounsaturated fatty acids (MUFA) enriched diet. For the control diet participants will follow a dietary plan for 72 hours prior to testing. For the MUFA diet, participants will be provided with high caloric liquid shakes for breakfast, lunch, dinner and a bedtime snack. On the morning of each test day, participants will be admitted in the fasting state and will provided with a breakfast meal corresponding to the assigned diet (MUFA or control). Three hours after completion of the meal, insulin sensitivity will be measured by insulin-suppression test (IST). |
| CARB versus control diet | Experimental | Other: CARB dietParticipants will be randomized in a cross-over design to either a weight-maintaining, nutritionally-balanced American Heart Association based eucaloric control diet or a high calorie 24-hour carbohydrate (CARB) enriched diet. For the control diet participants will follow a dietary plan for 72 hours prior to testing. For the CARB diet, participants will be provided with high caloric liquid shakes for breakfast, lunch, dinner and a bedtime snack. On the morning of each test day, participants will be admitted in the fasting state and will provided with a breakfast meal corresponding to the assigned diet (CARB or control). Three hours after completion of the meal, insulin sensitivity will be measured by insulin-suppression test (IST). |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Body mass index (BMI) from 25-35 kg/m2
- normal glucose tolerance (NGT) diagnosis based on fasting glucose value 100mg/dl and 2 hr glucose <140 mg/dl after a standard 75 gm glucose load; impaired fasting glucose (IFG) on fasting glucose value ≥100 and <126 mg/dl and 2 hr glucose <140 mg/dl; impaired glucose tolerance (IGT) based on 2 hr glucose ≥140 and <200 mg/dl and a fasting glucose <126 mg/dl
- Fasting triglyceride levels <500 mg/dl
Key exclusion criteria (12 listed)
- Type 1 or 2 diabetes mellitus or a hemoglobin A1c value ≥ 6.5 mg/dl
- Any diabetes medications in the past month, thiazolidinedione medications in the prior 3 months or prior regular use of insulin
- Use of diets, medications (e.g., steroids, weight loss medications ) or current or planned behavior changes (e.g. acute weight loss, exercise training) that will influence changes in IR
- Creatinine >2.0 mg/dl or other laboratory evidence of significant active disease, including hepatic enzyme elevation >2x normal and anemia, known "Nonalcoholic Fatty Liver Disease", bleeding risk
- Malabsorption of fat or other nutrients, severe lactose intolerance or other significant gastrointestinal or pancreatic problems, or recent history of nausea or vomiting
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SFA dietSFA versus control diet | Other | SFA versus control diet |
| MUFA dietMUFA versus control diet | Other | MUFA versus control diet |
| CARB dietCARB versus control diet | Other | CARB versus control diet |
Primary outcome
Steady-state plasma glucose (SSPG)
Time frame: 150-180 min
Average plasma glucose concentrations during min 150-180 of the insulin suppression test (IST)
5 secondary outcomes
Acylcarnitine species
Time frame: Overnight fast, 3-hour post breakfast
Diacylglycerol species
Time frame: Overnight fast, 3-hour post breakfast
Ceramides species
Time frame: Overnight fast, 3-hour post breakfast
Insulin signaling proteins
Time frame: Overnight fast, 3-hour post breakfast
Inflammation markers
Time frame: Overnight fast, 3-hour post breakfast
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2019.
- Individual participant dataSharing planned: No. Subject to VA regulation.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter D Reaven, MD principal investigator
Phoenix Veterans Affairs Health Care System
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing SFA diet, MUFA diet and CARB diet in people with Insulin Resistance, run by Phoenix VA Health Care System at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Steady-state plasma glucose (SSPG) (time frame: 150-180 min). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2019.