Clinical trial NCT05165706: Longitudinal Multi-Omic Profiles to Reveal Mechanisms of Obesity-Mediated Insulin Resistance
Official title: Longitudinal Multi-Omic Profiles to Reveal Mechanisms of Obesity-Mediated Insulin Resistance
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Diabetes Mellitus, Type 2
PreDiabetes
Insulin Resistance
Obesity
Nonalcoholic Steatohepatitis
Nonalcoholic Fatty Liver
Diet Modification
Keywords: Metabolomics
Low Fat Diet
Low Carbohydrate Diet
Microbiome
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2021-12-21
Enrollment: 110
Sex: ALL
Minimum age (years): 35
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This 12-week controlled diet and weight intervention study seeks to define the molecular pathways that link excess body weight to the development of insulin resistance (IR). Blood, adipose and stool are sampled at three timepoints; baseline, peak weight (4 weeks) and post weight loss to monitor changes in cellular processes. Additionally, direct insulin sensitivity testing, and radiological measurement of visceral fat and intrahepatic fat content is measured at three timepoints to correlate clinical indices with cellular changes.

Detailed description: Obesity has become an epidemic worldwide. Metabolic/cardiovascular complications of obesity are likely related to the fact that obese individuals tend to be insulin resistant (IR). While insulin- mediated glucose uptake (IMGU) correlates with adipose tissue mass, not all obese individuals are IR, and metabolic and cardiovascular profiles of those who are IR vs insulin sensitive (IS) differ significantly. Why one individual who reaches a BMI of 30 kg/m2 will develop IR and another with similar BMI and activity level remains IS is unclear. Furthermore, while insulin sensitivity improves with weight loss, this response varies as well. Given that fat mass per se does not fully explain the obesity contribution to IMGU, itis likely that differential adipocyte function plays a role. With this study, our purpose is to employ an integrated omics strategy to identify analyte/pathway signatures in blood and adipose tissue that characterize IR versus IS states and expand our biological knowledge of the mechanisms underlying IR.

Eligibility criteria: Inclusion Criteria:

* Age 35-65
* BMI 25-35 kg/m2
* Stable body weight
* Nondiabetic

Exclusion Criteria:

Patients with;

* diabetes
* major organ disease
* history of liposuction or bariatric surgery
* active eating or psychiatric disorder
* pregnancy or lactation, heavy alcohol use
* recent change in weight (over the past 12 weeks)
* use of weight loss medication, statins, or oral steroids

Clinical screening exclusions;

* hematocrit \< 33%
* fasting glucose \>/= 126 mg/dL
* blood pressure \>160/100 mmHg

Primary outcomes:
measure: Change from baseline on the 2-stage Steady State Plasma Glucose test
timeFrame: Peak weight (4 weeks)
measure: Change from baseline on the radiographic measurement of visceral to subcutaneous (V:S) fat ratio
timeFrame: Peak weight (4 weeks)
measure: Change from baseline on the magnetic-resonance based measurement of intrahepatic lipid deposition
timeFrame: Peak weight (4 weeks)
measure: Change from peak weight on the 2-stage Steady State Plasma Glucose test
timeFrame: Post-weight loss (8 weeks)
measure: Change from baseline on the radiographic measurement of visceral to subcutaneous (V:S) fat ratio
timeFrame: Post-weight loss (8 weeks)
measure: Change from baseline on the magnetic-resonance based measurement of intrahepatic lipid deposition
timeFrame: Post-weight loss (8 weeks)
measure: Measurement of markers of lipid and carbohydrate metabolism and inflammation from adipose mRNA
timeFrame: Baseline
measure: Quantification of plasma inflammatory cytokine levels in serum samples by Luminex immunoassay
timeFrame: Baseline
measure: Change from baseline in plasma inflammatory cytokine levels in serum samples as measured by Luminex immunoassay
timeFrame: Peak Weight (4 weeks)
Secondary outcomes:
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
Study officials:
affiliation: Stanford University, Department of Medicine, Division of Endocrinology
name: Tracey McLaughlin, MD
role: PRINCIPAL_INVESTIGATOR
References: