The overall purpose of the study is to test the effect exercise time of day in adults with type 2 diabetes or prediabetes. The overarching hypothesis is that afternoon exercise in the afternoon may promote better changes in metabolic and vascular insulin sensitivity. We anticipate that these changes will correlate with glycemic control and blood pressure changes.

Type 2 diabetes (T2D) is associated with a 3-fold cardiovascular disease (CVD) mortality risk compared with healthy controls, and it is estimated that 30 million adults in the United States have the disease. In recent years the American Diabetes Association (ADA) and American College of Sports Medicine (ACSM) recommend moderate intensity (40-60% heart rate max, HRmax) aerobic exercise 3-5d/wk for the management of T2D. The statement also recognized that higher exercise intensity (>60% HRmax) predicts better blood glucose control than exercise volume. Cardiovascular health (e.g. fitness, blood pressure, etc.) also appears to respond in an exercise dose dependent manner. Despite these suggestions, many people exercising compensate by eating calories back from exercise, thereby negating weight loss. Moreover, compliance and adherence to exercise and diet medical counsel is disappointingly low.

Recent work has begun to target the best time of day to exercise in effort to improve weight loss and related health. This has evolved in part since circadian biology reveals people tend to become glucose intolerant, and develop insulin resistance and endothelial dysfunction in the evening compared with morning. As a result, it would be reasonable to hypothesize that exercise in the afternoon may be best at combating natural declines in health as well as optimizing training adaptations. However, not all studies agree that afternoon is the best time to exercise. In fact, some have demonstrated that 12 wks of aerobic plus resistance exercise improved glycemic control whether performed in the morning or afternoon in adults with T2D. Moreover, consistent morning exercise has been suggested to improve exercise adherence through possible enjoyment as well as lead to greater weight loss. Taken together, additional work is warranted to understand time of day in which exercise is performed given circadian influence may contribute to variations in favorable metabolic as well as vascular adaptation for CVD prevention/treatment. Excitingly, we have preliminary data showing that afternoon exercise induces greater weight loss, reductions in food intake as well as perceptions of appetite and increased insulin sensitivity when compared to morning exercisers. Thus, the overall purpose of this proposal is to determine whether exercise time of day differentially enhances likelihood of weight loss via appetite regulation as well as glycemic control. Our overarching hypothesis is that afternoon exercise will enhance the effectiveness of exercise to induce weight loss, improve appetite and improve glycemic regulation compared to exercise in the morning. Taken together, findings from this study will inform public health recommendations to contemporary behavioral strategies to treat T2D. The study will also provide much needed experimental evidence to time of day in which exercise is performed influences public health risk.

Inclusion Criteria:

• Male or female >30 and <80 years old.
• Has a body mass index >25 and <45 kg/m2.
• Previously diagnosed with prediabetes and/or T2D.
• If not previously diagnosed, has a fasting blood glucose ≥ 100 mg/dL and/or HbA1c ≥ 5.7%

Exclusion Criteria:

• Morbidly obese patients (BMI >45 kg/m2) and lean patients (BMI <25 kg/m2)
• Evidence of type 1 diabetes and diabetics requiring insulin therapy.
• Subjects who have not been weight stable (>2 kg weight change in past 3 months)
• Subjects who have been recently active (>30 min of moderate/high intensity exercise, 3 times/week).
• Subjects who are smokers or who have quit smoking <1 years ago
• Subjects with abnormal estimated glomerular filtration rate (eGFR).
• Hypertriglyceridemic (>400 mg/dl) and hypercholesterolemic (>260 mg/dl) subjects
• Hypertensive (>160/100 mmHg)
• Subjects with a history of significant metabolic, cardiac, congestive heart failure, cerebrovascular, hematological, pulmonary, gastrointestinal, liver, renal, or endocrine disease or cancer that in the investigator's opinion would interfere with, alter the outcome measures, or impact subject safety.
• Pregnant (as evidenced by positive urine pregnancy test) or nursing women.
• Subjects with contraindications to participation in an exercise training program
• Currently taking active weight suppression medication (e.g. phentermine,orlistat, lorcaserin, naltrexone-bupropion in combination, liraglutide, benzphetamine, diethylpropion, phendimetrazine)
• Known hypersensitivity to perflutren (contained in Definity)