Active, not recruitingNot applicableInterventional
What this study is about
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.
A promising-looking record is not the same as confirmed eligibility. The study team must review the full criteria and current recruitment status.
Basic eligibility
Age21 Years to 45 Years
SexFemale
Healthy volunteersNot accepted
ConditionOverweight and Obesity, Hyperandrogenemia, Insulin Resistance
Full registry criteria
Inclusion Criteria: * 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 * Weight stable: No fluctuations in body weight of greater than 4 kg in the last 2 months (see exclusion criteria for undergoing weight loss) * 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) Exclusion Criteria: * 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.
Treatments and study arms
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.
Primary outcomes
Change in fasting hormone concentrations.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.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.
Change in fasting hormone concentrations.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.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.
Change in body weight (kg).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 from baseline values will be measured using a calibrated, standard, clinical scale.
Change in fasting blood biochemistries.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.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.
