Astaxanthin is a natural compound, present in many foodstuffs and available as a nutritional supplement that has been shown to have beneficial effects on many of the features of insulin resistance/glucose intolerance, at least in animals. The goal of this project is to provide a validation of astaxanthin effects on metabolic regulation in humans and their mechanism(s) of action, to determine if astaxanthin could have any value as a "neutraceutical" to help improve regulation of glucose and fat metabolism in subjects with insulin resistance/ glucose intolerance.

Astaxanthin is a molecule of the carotenoid class that is abundant in marine animals and plants, with the algae Haematococcus pluvialis being a particularly rich source. Astaxanthin is a potent anti-oxidant with a unique property of being able to insert into membranes and lipid bilayers. Astaxanthin has also been shown to be a potent anti-inflammatory agent. As oxidative stress and inflammation are present in individuals with insulin resistance, astaxanthin offers promise as a potential therapeutic for this patient population.

There are a number of formulations of astaxanthin that are available for use in humans. With regard to controlled studies in humans, astaxanthin has been given at doses as high as 40 mg/day for periods from 2 to 12 weeks. Improvements in inflammation and oxidative stress were frequently observed. With regard to metabolic regulation, improvements have been seen in HDL and LDL levels, while others have found no changes. Glucose and insulin levels appear to be unaltered: This lack of effect may be due to only healthy, though in some cases overweight or obese, subjects being studied. In none of these studies, were any abnormal safety lab values or adverse events reported. One of the intents of the current project is to perform more detailed metabolic characterization of astaxanthin treatment effects in research participants with insulin resistance/glucose intolerance.

The hyperinsulinemic-euglycemic glucose clamp procedure (HEC) will be used to assess insulin sensitivity and responsiveness by measuring glucose disposal rate (GDR). Investigators will also perform Oral Glucose Tolerance Tests (OGTT), indirect calorimetry (IDC), and 24 hour measurement of ambulatory blood pressure (ABPM).

Inclusion Criteria:

• Age: 18-75 years (inclusive)
• Both males and females
• If female, must be post-menopausal or not capable of becoming pregnant
• Able to give informed consent to the procedures
• Dyslipidemia - [TG]>150, or [LDL]>100 or [HDL]<40 for males, <50 for females or taking a statin or fibrate
• BMI = 25-39
• Impaired fasting glucose 95>[FG]<125 and/or elevated HbA1c (5.7-6.4%)
• Concomitant medication use stable for 30 days prior to screening visit (Acceptable medications: anti-hypertensive if blood pressure criteria met statins or fibrates)

Exclusion Criteria:

• Type 2 diabetes
• Type 1 diabetes
• Pregnant
• Younger than 18 or older than 75 years of age.
• Clinically significant abnormalities in liver (> 3x ULN) or kidney function (eGFR < 30)
• Myocardial Infarction (MI) (within 6 months of screening)
• Stroke (within 6 months of screening)
• Blood pressure (BP) >160 mmHg Systolic and >100 mmHg Diastolic
• The following medications are exclusionary: thiazolidinediones, any steroids, anti-depressants, weight loss, and OTC antioxidants (if taking OTC antioxidant supplements, subjects must be willing to stop taking them immediately upon site verifying that the subject qualifies for enrollment and for the duration of the entire study. Some OTC antioxidants may be acceptable upon approval by the Principal Investigator.)
• Other disease, besides type 2 diabetes, influencing carbohydrate metabolism.