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

Prior treatment

• 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.

Other illness

• Diagnosis of congenital adrenal hyperplasia, or Cushing syndrome o These conditions are associated with significantly high androgens in need of medical treatment.

Other

• Pregnant or trying to become pregnant
• Postmenopausal as testosterone naturally increases with menopause
• BMI of \<25.0 or \>50.0 kg/m2
• 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).

• 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)