Monounsaturated Fatty Acid Supplementation for Overweight and Obese Individuals With Prediabetes

Specific aims of the study are as follows: 1) To test whether supplementation of POA, as compared to placebo, improves insulin sensitivity. 2) To test whether supplementation of POA, as compared to placebo, ameliorates hepatosteatosis and decreases whole-body fat mass, serum triglyceride, and LDL cholesterol. 3)To determine whether supplementation of POA, as compared to placebo, decreases plasma levels of fasting glucose, insulin, FABP4, glucagon, inflammatory cytokines, and hsCRP.

The investigators will recruit overweight and obese individuals (BMI 25-40) with mild insulin resistance, prediabetes and/or impaired glucose tolerance. The study is powered only for the primary endpoint, insulin sensitivity. After the screening visit confirms the eligibility for the study; the investigators will perform an oral glucose tolerance test (OGTT) for stratified randomization for better homogeneity between POA and placebo groups. The investigators aim to have 40 participants complete the study which will consist of 2 main overnight visits consisting of an insulin clamp procedure and a mixed meal tolerance test the night prior. Participants will also have a liver MRI and DEXA scan at these two visits. Participants will be asked to consume a palmitoleic acid minimized diet for 10 weeks which will start two weeks before the first overnight visit. This research study will compare insulin sensitivity before and 8 weeks after taking POA vs placebo in the same individuals. After the first overnight visit participants will be given either POA or placebo capsules to take daily for 8 weeks until the second overnight visit. There will also be a short blood draw visit 4 weeks after the first overnight visit.

Inclusion criteria

• Overweight and obese individuals with prediabetes and/or impaired glucose tolerance
• Age 18 to 70 years
• BMI 25-40 kg/m2
• HbA1c between 5.6 - 6.5, Impaired fasting plasma glucose levels (>99, ≤126 mg/dL) or OGTT blood glucose at 2 hours between 140-200 mg/dL or HOMA-IR >2.5
• BP <150/90 with or without medication
• GFR>60
• ALT, AST <300
• Normal thyroid function is defined as screening TSH within normal ranges, with or without medication

Exclusion criteria

• Use of any medications (except thyroid hormone with normal TSH, anti-hypertensives with blood pressure <150/90 and non-steroidal rescue inhalers for asthma)
• Pregnancy or breastfeeding
• Use of over-the-counter (OTC) supplements (except vitamin D). The investigators will ensure that study participants are not using supplements containing fish oil or other lipid supplements (e.g., macadamia oil, krill oil, flaxseed, primrose oil, sea buckthorn oil) within 3 months of study participation
• Greater than 3 servings/day combined of cheese, whole-fat milk, kefir, or whole-fat yogurt for the last 3 months before the study.
• Diagnosed with any type of diabetes mellitus and/or taking glucose-lowering medications
• Recent weight loss (more than 7% of total body weight loss in last 3 months)
• Established major chronic diseases such as major cardiovascular disease (history of myocardial infarction, stroke, symptomatic heart failure, coronary artery bypass graft, Atrial fibrillation, symptomatic peripheral arterial disease), bleeding disorder or anticoagulation use, active cancer, end-stage renal disease, proteinuria (>3g/day), dementia, severe chronic obstructive pulmonary disease (needs systemic steroid therapy), significant liver disease (ALT or AST>300)
• History of ongoing smoking cigarettes >1 pack/day, alcohol abuse, or illicit drug abuse
• Treatment with any investigational drug in the one month preceding the study