Objective People who have type 2 diabetes possess reduced cardiorespiratory fitness and metabolic impairments that are associated with weight problems and frequently occur before the advancement of type 2 diabetes. the amount of glucose intolerance independent of body and age composition. Keywords: type 2 diabetes, fat burning capacity, workout physiology, substrate oxidation Launch Over 26% of old Americans have got diagnosed or undiagnosed impaired blood sugar tolerance (IGT) (1), putting them at risky for advancement of type 2 diabetes. Weight problems is normally a significant risk aspect for type and IGT 2 diabetes, and is frequently followed by metabolic dysfunction such as for example abnormal unwanted fat and carbohydrate oxidation (2). These impairments might donate to metabolic inflexibility, previously thought as AMG-458 the incapability to change from unwanted fat to carbohydrate oxidation in response to meals or insulin administration (2). Obese, insulin resistant people and the ones with IGT are inflexible in response to insulin infusion metabolically, while lean, insulin delicate topics are metabolically versatile (2, 3). The concept of metabolic inflexibility also may extend to metabolism during aerobic exercise, wherein the normal response in the fasted state is to shift from utilizing excess fat to carbohydrate during the transition AMG-458 from rest to exercise of increasing intensity. Because fat cannot be oxidized at high enough rates to supply all of the energy for moderate to vigorous exercise, this shift from excess fat to carbohydrate oxidation supplies the necessary energy as exercise intensity increases (4). Previous studies show lower cardiorespiratory fitness levels in type 2 diabetes (5), and this may extend to obese, older adults with metabolic inflexibility and IGT. Middle-aged and older, overweight-obese subjects with IGT often have metabolic abnormalities such as impaired glucose uptake in response to insulin, and also have lower glycogen content in skeletal muscle and higher AMG-458 intramyocellular lipid levels in the postabsorptive state. These metabolic abnormalities may affect the ability to switch from excess fat to carbohydrate oxidation when going from rest to exercise of increasing intensity. The results of studies examining substrate oxidation during exercise in obese young and middle-aged subjects vary (6C9), but two studies in insulin resistant subjects report lower carbohydrate oxidation during exercise in young insulin-resistant women (10) and middle-aged subjects with Rabbit polyclonal to ACVRL1. type 2 diabetes (6). While these studies indicate that abnormalities in excess fat and carbohydrate oxidation during exercise are related to obesity and/or insulin resistance, the metabolic response to exercise of increasing intensity has not been established in obese, older subjects with a clinically-relevant designation of IGT or normal glucose tolerance (NGT) to our knowledge. Therefore, this study was designed to test the hypothesis that the ability to shift from excess fat to carbohydrate oxidation during submaximal exercise (metabolic flexibility during exercise) is lower in overweight-obese older subjects with IGT compared with NGT controls. To accomplish this, we AMG-458 assessed metabolic flexibility during aerobic exercise at 50% and 60% of maximal cardiorespiratory fitness (VO2max) levels and used a hyperinsulinemic-euglycemic clamp to confirm metabolic inflexibility during insulin infusion in obese, older adults with IGT compared with NGT controls. Research Design and Methods Subjects Twenty-three sedentary (self-reported moderate-intensity activity less than 20 minutes on 2 or fewer days per week), overweight-obese (BMI 25C38 kg/m2) men and women between the ages of 45 and 80 years aged were recruited from the Baltimore metropolitan area. All subjects were nonsmokers and had no previous diagnosis of diabetes or cardiovascular disease. Additional exclusion criteria included 1) cancer, thyroid, renal, hematological, or pulmonary diseases; 2) taking medications such as beta-blockers, steroids, or medications normally prescribed for diabetes; and 3) poorly controlled hypertension or dyslipidemia, anemia, or recent weight change of more than 2kg. Prior to participation, all subjects had an asymptomatic screening treadmill exercise test. All subjects provided written informed consent. All study procedures were approved by AMG-458 the Institutional Review Board at the University of Maryland School of Medicine. Study Protocol Prior to research testing, all subjects received training on maintaining a weight-stable, Therapeutic Lifestyle Changes (TLC) diet (11), by a Registered Dietitian one day per week for 6C8 weeks. All subjects were weight-stable (2%) for at least two weeks prior to research testing and were provided an isocaloric diet for two days before.