Evaluating the Influence of Diet-induced Weight Loss on Fat (Adipose) Tissue's Insulin Sensitivity and Testosterone Synthesis in Women With Overweight or Obesity, Insulin Resistance, and Hyperandrogenemia

NCT06998238 | Active Not Recruiting

• 1 other identifier: 2095704
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators will measure plasma concentrations of the hormones insulin and testosterone as well as measures of insulin sensitivity in women with overweight or obesity who have insulin resistance (IR). Women who meet these criteria that also have elevated total or free testosterone will be eligible to participate in the diet intervention. The dietary intervention is designed to produce a 5% reduction in starting body weight to test whether weight loss will acutely lower fasting insulin and testosterone concentrations.

Conditions

Hyperandrogenemia; Insulin Resistance; Overweight and Obesity

Keywords

Insulin resistance; Hyperandrogenemia; Weight loss; Mediterranean Diet; Women; Overweight or Obesity

Outcome Measures

Primary Outcomes (4)

• Change in fasting hormone concentrations.

  Fasting insulin (µU/mL) will be measured and compared to baseline values. Samples are sent to an external CLIA-compliant lab (Quest Diagnostics) for analysis.

  Day 0, day 7, day 14, day 28, day 42, and day 56 for the intervention group and day 0 and day 56 for the control group.

• Change in fasting hormone concentrations.

  Fasting testosterone (ng/dL) will be measured and compared to baseline values. Samples are sent to an external CLIA-compliant lab (Quest Diagnostics) for analysis.

  Day 0, day 7, day 14, day 28, day 42, and day 56 for the intervention group and day 0 and day 56 for the control group.

• Change in body weight (kg).

  Change from baseline values will be measured using a calibrated, standard, clinical scale.

  Day 0, day 7, day 14, day 28, day 42, and day 56 for the intervention group and day 0 and day 56 for the control group.

• Change in fasting blood biochemistries.

  Fasting SHBG (nmol/L) will be measured and compared to baseline values. Samples are sent to an external CLIA-compliant lab (Quest Diagnostics) for analysis.

  Day 0, day 7, day 14, day 28, day 42, and day 56 for the intervention group and day 0 and day 56 for the control group.

Secondary Outcomes (6)

• Change in whole body insulin sensitivity.

  Day 0, day 14, day 28, day 56 for the intervention group and day 0 and day 56 for the control group.

• Indirect measure of change in adipose insulin sensitivity.

  Day 0, day 14, day 28, day 56 for the intervention group and day 0 and day 56 for the control group.

• Direct measure of change in adipose insulin sensitivity.

  Day 0, day 14, day 28, day 56 for the intervention group and day 0 and day 56 for the control group.

• Change in measures of biochemical hyperandrogenemia.

  Day 0, day 7, day 14, day 28, day 42, and day 56 for the intervention group and day 0 and day 56 for the control group.

• Change in body composition.

  Day 0, day 7, day 14, day 28, day 42, and day 56 for the intervention group and day 0 and day 56 for the control group.

Study Arms (2)

Dietary intervention

EXPERIMENTAL

Group receiving the study diet and nutrition counseling.

Behavioral: Mediterranean-based, carbohydrate restricted, calorie reduced diet

Control

NO INTERVENTION

Group that performs repeat measures over the span of 8 weeks without any intervention or influence from study team in the interim.

Interventions

Mediterranean-based, carbohydrate restricted, calorie reduced diet BEHAVIORAL

Dietary intervention - calorie reduced (300-500 kcal/day below estimated energy needs), carbohydrate restricted (\<100 grams of available carbohydrates per day), Mediterranean-based (high fat diet with an emphasis on the addition of healthy fats - nuts, avocados, olive oil, increasing whole grains, increasing fruit and vegetables, replacing red meats with fish and poultry, reducing dairy, and reducing added sugars) diet.

Dietary intervention

Eligibility Criteria

• Age: 21 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Women (female sex, premenopausal)
• Age 21-45y
• Overweight/obesity with BMI ≥25.0 or ≤50.0 kg/m2
• Prediabetic (fasting glucose between 100-125 mg/dL,HbA1c between 5.7-6.4%, blood glucose ≥ 140 mg/dL, but ≤ 200 mg/dL at 2 hours into OGTT) or diabetic with a fasting glucose \<200 mg/dL, stably treated with metformin for 2 months or longer
• Alternatively: if not prediabetic as evidenced by abnormal fasting blood glucose or glucose tolerance, evidence of insulin resistance such as fasting insulin value ≥ 10 µU/mL, elevated HOMA-IR or elevated QUICKI may be substituted
• o Prediabetes and diabetes are associated with insulin resistance and excess body weight. Our study seeks to improve impaired insulin signaling through weight loss from dietary restriction. Therefore, insulin resistance in the presence of normal glucose tolerance may still be improved through this intervention.
• Plasma testosterone concentration \<200 ng/dL, as measured at screening visit

You may not qualify if:

• Presence of central (android) obesity as defined by WHR \> 0.8 or waist circumference \> 80 cm
• No use or active use of hormonal contraceptives (IUD, oral contraceptive pill, Nexplanon)
• o Hormonal contraceptives are not expected to alter the outcomes of this study; therefore, their use is not prohibited. However, it is not a requirement that women use hormonal contraception to be part of this study.
• Willingness to consume a defined diet (Intervention arm - Weight loss)
• Pregnant or trying to become pregnant
• Postmenopausal as testosterone naturally increases with menopause
• BMI of \<25.0 or \>50.0 kg/m2
• Use of tobacco, cannabis, or other recreational drug products.
• o Tobacco and other recreational drugs products are excluded as they known to increase adipose lipolysis. Cannabis products are excluded as they are fat soluble compounds and could alter the adipose gene and protein expression.
• Taking medications known to affect adipose tissue metabolism (steroids, niacin)
• Use of antiandrogen medications (spironolactone, flutamide, finasteride) within the last 3 months o These medications are designed to lower testosterone concentrations.
• Already undergoing weight loss. o As this study is investigating the impact of weight loss, the goal is to obtain samples before and after weight loss (intervention arm) or during weight stability (control arm).
• Diagnosis of congenital adrenal hyperplasia, or Cushing syndrome o These conditions are associated with significantly high androgens in need of medical treatment.

Sponsors & Collaborators

• University of Missouri-Columbia: lead

Study Sites (1)

University of Missouri

Columbia, Missouri, 65211, United States

Location

MeSH Terms

Conditions

Overweight; Obesity; Insulin Resistance; Weight Loss

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Body Weight Changes

Study Officials

• Elizabeth J Parks, PhD

  University of Missouri-Columbia

  PRINCIPAL INVESTIGATOR

• Jean Ricci Goodman, MD

  University of Missouri-Columbia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 24, 2025
• First Posted: May 31, 2025
• Study Start: January 7, 2024
• Primary Completion: October 5, 2024
• Study Completion: April 1, 2026
• Last Updated: March 17, 2026

Record last verified: 2026-03

Locations

US (1)