Recruiting

Observational Study

Sponsor:

Bettina Mittendorfer

Code:

NCT06335771

Conditions

Obesity

Nonalcoholic Fatty Liver

Diabetes Type 2

Healthy

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Accepted

Interventions

Dietary consultation weight loss intervention

Study Details

Brief summary:

The goal of this study is to evaluate the role of transcription factor EB (TFEB) in adipose (fat) tissue macrophages (ATM) in regulating adipose tissue and systemic metabolic function in obesity. The investigators will assess the differences in ATM lipid metabolism in people with metabolically abnormal obesity and lean individuals.

Both groups will have:

  • screening visit
  • imaging (body composition testing - dual-energy x-ray absorptiometry (DEXA) scans, magnetic resonance imaging \[MRI\] and magnetic resonance spectroscopy \[MRS\] scans)
  • Overnight visit with intravenous infusion (IV), muscle, and fat tissue biopsies Participants with obesity will complete meetings with study team members for a weight loss intervention to achieve a 10% body weight loss.

Conditions

Obesity

Nonalcoholic Fatty Liver

Diabetes Type 2

Healthy

Study ID

NCT06335771

Start date

Aug 1, 2024

Status verified date

Aug, 2026

Completion date

Mar, 2028

Anticipated

Primary completion date

Mar, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Accepted

Inclusion Criteria :

  • age: ≥18 but ≤70 years
  • not pregnant or breastfeeding
  • weight stable and sedentary before enrollment
  • no use tobacco products, excessive amounts of alcohol, or dietary supplements, or medications known to or suspected to affect glucose and lipid metabolism (aside from certain medications used to treat diabetes in the metabolically abnormal obesity \[MAO\]-Type 2 Diabetes group)
  • no evidence of significant organ system dysfunction or disease (e.g. chronic severe kidney disease, cancer)
  • participants must fulfil all of the following group-specific inclusion criteria below:

Lean group:

  • Body mass index (BMI) ≥18.5 but <25.0 kg/m2
  • Intrahepatic triglyceride (IHTG) content <5%
  • fasting blood glucose concentration: <100 mg/dl
  • blood glucose concentration 2 h after a 75 g oral glucose challenge: <140 mg/dl
  • Hemoglobin A1C (HbA1c) <5.7 %

Metabolically normal obesity (MNO) group:

  • BMI ≥30.0 but <45.0 kg/m2
  • IHTG content <5%
  • fasting blood glucose concentration: <100 mg/dl
  • blood glucose concentration 2 h after a 75 g oral glucose challenge: <140 mg/dl
  • HbA1c <5.7 %

Metabolically abnormal obesity (MAO)-insulin resistance and non-alcoholic fatty liver disease (NAFLD) group:

  • BMI ≥30.0 but <45.0 kg/m2
  • IHTG content >7.5%
  • fasting blood glucose concentration: ≥100 but <126 mg/dl
  • blood glucose concentration 2 h after a 75 g oral glucose challenge: ≥140 but <200 mg/dl
  • HbA1c: ≥5.7 but <6.4 %

MAO-type 2 diabetes group:

  • BMI ≥30.0 but <45.0 kg/m2
  • clinical diagnosis of type 2 diabetes or fasting blood glucose concentration >126 mg/dl or blood glucose concentration 2 h after a 75 g oral glucose challenge>200 mg/dl or HbA1c >6.4 % without medication if not diagnosed and medically treated for diabetes

Exclusion Criteria:

\- Individuals that do not meet all inclusion Criterion

Study Design

Enrollment

60 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

no intervention: Lean Individuals

No intervention will be administered.

experimental: Metabolically abnormal obese Individuals (obesity with normoglycemia and abnormal liver fat content)

Participants will undergo a dietary weight loss intervention to achieve 10% weight loss over about 6 months.

experimental: Metabolically normal obese Individuals (obesity with normoglycemia and normal liver fat content)

Participants will undergo a dietary weight loss intervention to achieve 10% weight loss over about 6 months.

experimental: Individuals with Type 2 Diabetes Mellitus

Participants will undergo a dietary weight loss intervention to achieve 10% weight loss over about 6 months.

Interventions

Dietary consultation weight loss intervention

Participants will meet with a member of the study team biweekly for about 6 months.

Primary outcome measure

  • Insulin sensitivity assessed as insulin-mediated glucose disposal during a hyperinsulinemic-euglycemic clamp procedure. [ Time Frame: up to 6 months after the intervention ]
  • 24-hour plasma glucose concentration [ Time Frame: up to 6 months after the intervention ]
  • Macrophage isolation in adipose tissue biopsy [ Time Frame: up to 6 months after the intervention ]
  • Macrophage isolation in skeletal muscle tissue [ Time Frame: up to 6 months after the intervention ]

Central Contacts and Locations

Central contacts

Heather McHatton

(573) 882-7619heathermchatton@health.missouri.edu

Aman Pritish Aher

amanpritishaher@umsystem.edu

Locations

University of Missouri School of Medicine

Recruiting

Columbia, Missouri, United States, 65212

Contacts

Bettina Mittendorfer

573-882-9377b.mittendorfer@missouri.edu

More Information

Sponsor

Bettina Mittendorfer

Last update posted

Aug 6, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Bettina Mittendorfer on 2026-08-06.