Dietary Lipid Induced Insulin Resistance

NCT02757560 | Unknown

• 1 other identifier: 029
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Insulin Resistance

Keywords

saturated fat; acute insulin resistance; insulin suppression test; dietary fatty acids

Outcome Measures

Primary Outcomes (1)

• Steady-state plasma glucose (SSPG)

  Average plasma glucose concentrations during min 150-180 of the insulin suppression test (IST)

  150-180 min

Secondary Outcomes (5)

• Acylcarnitine species

  Overnight fast, 3-hour post breakfast

• Diacylglycerol species

  Overnight fast, 3-hour post breakfast

• Ceramides species

  Overnight fast, 3-hour post breakfast

• Insulin signaling proteins

  Overnight fast, 3-hour post breakfast

• Inflammation markers

  Overnight fast, 3-hour post breakfast

Study Arms (3)

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).

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).

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).

Other: CARB diet

Interventions

SFA diet OTHER

SFA versus control diet

SFA versus control diet

MUFA diet OTHER

MUFA versus control diet

MUFA versus control diet

CARB diet OTHER

CARB versus control diet

CARB versus control diet

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• Phoenix VA Health Care System: lead

Study Sites (1)

Carl T. Hayden VA Medical Center

Phoenix, Arizona, 85012, United States

Location

MeSH Terms

Conditions

Insulin Resistance

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Peter D Reaven, MD

  Phoenix Veterans Affairs Health Care System

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2015
• First Posted: May 2, 2016
• Study Start: February 1, 2012
• Primary Completion: July 1, 2020
• Study Completion: December 1, 2020
• Last Updated: August 1, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)