Exercise Resistance in Type 2 Diabetes

Type 2 Diabetes Inclusion Criteria (Group 1)

• Age 30 to 65 years.
• Male and Female
• Type 2 diabetes determined by self-report or by a fasting glucose > 126mg/dl
• POCT HbA1c result is 5.7-8.8% or for those on anti-diabetic medications, POCT HbA1c < 8.9% (no lower limit defined to account for those who illustrate tight glycemic control due to anti-diabetic medications).
• HbA1c between 6.0% and 8.5% or for those on anti-diabetic medications, HbA1c ≤ 8.5% (no lower limit defined to account for those who illustrate tight glycemic control due to anti-diabetic medications). If a participant misses the screening HbA1c by a small margin (HbA1c ± 0.1%), the HbA1c can be repeated once.
• Not involved in regular exercise program
• Willing to exercise every day for the study period
• If applicable, those currently taking anti-diabetic medication are taking metformin, a sulfonylurea, DPP IV inhibitor, alpha-glucosidase inhibitor, a meglitinide, colesevelam, cycloset or a SGLT2 inhibitor. Those taking 2 of these medications may proceed.
• If applicable, willing to cease anti-diabetic medication use for the duration of the intervention.
• BMI ≥ 22 kg/m2

Young Athletes Inclusion Criteria (Group 2)

• Age 18 to 50 years
• Male and Female
• Engaged in a minimum of 4 cumulative hours of moderate to vigorous intensity aerobic exercise, over a minimum of 3 days per week.
• BMI between 18 and 29.9 kg/m2
• VO2max > 45 ml/min/kg BW

Non-diabetes Inclusion Criteria (Group 3)

• Age 30 to 65 years
• Male and Female
• Not involved in a regular exercise program
• Willing to exercise every day for the study period
• BMI ≥ 22 kg/m2

General Exclusion Criteria A=all groups, Ex=exercise group only, ND=Non-diabetes group only

• Resting blood pressure ≥ 160/100 mm Hg (A)
• Triglycerides > 500 mg/dL (A)
• HbA1c ≥ 6.5% (ND)
• Previous or current use of an insulin pump or multiple insulin injections per day or any diabetes medications that the participant cannot refrain from for the duration of the study. (A)
• Treatment with thiazolidinediones (TZDs) or GLP-1 agonists within the last 3 months. (A)
• Unable or unwilling to communicate with staff or to provide written informed consent. (A)
• Failure to complete baseline testing. (A)
• Not physically capable of performing the exercise required of the study protocols. (Ex)
• Consuming >14 alcoholic beverages per week. (A)
• Plans to be away >2 weeks in the next 3 months. (A)
• Lack of support from primary health care provider and/or family members.(Ex)
• Significant weight loss in the past year (>20 lbs) or current use of weight loss medications. (A)
• Bariatric surgery or planning bariatric surgery in the next 6 months.(Ex)
• Presence of clinically significant abnormalities on ECG (A)
• Any renal, cardiac, liver, lung, or neurological disease that in the opinion of the Investigator would compromise participant safety (A)
• Use of drugs known to affect energy metabolism or body weight: including, but not limited to: orlistat, sibutramine, ephedrine, phenylpropanolamine, corticosterone, etc (A)
• Current treatment with blood thinners or anti-platelet medications that cannot be safely stopped for testing procedures. (A)
• New onset (<3 months on a stable regime) hormone replacement therapy. (A)
• Current use of beta-adrenergic blocking agents (A)
• Alcohol or other drug abuse (A)
• Current smokers (smoking within the past 3 months) (A)
• Gait problems (Ex)
• Unwilling or unable to abstain from caffeine, alcohol or strenuous exercise (48h) prior to metabolic rate measurements (A)
• Increased liver function tests (AST/ALT/GGT/or alkaline phosphatase greater than 2.5 times the upper limit of normal) (A)
• Metal objects that would interfere with the measurement of body composition /MRS such as implanted rods, surgical clips, etc (A)
• Any NYHA class of CHF (A)
• Abnormal blood count/Anemia, blood transfusion or blood donation within the last 2 months. (A)
• Major surgery on the abdomen, pelvis, or lower extremities within previous 3 months (A)
• Bariatric surgery or liposuction within the previous 3 years (Ex)
• Cancer (active malignancy with or without concurrent chemotherapy) (A)
• Rheumatoid disease (A)
• Bypass graft in limb (A)
• Known genetic factor (Factor V Leiden, etc) or hypercoagulable state (A)
• Peripheral neuropathy, involving more than the toes (A)
• Claustrophobia (A)
• Major Depression (Ex)
• Presence of an eating disorder or eating attitudes/behaviors that could interfere with the study completion (Ex)
• Females that are currently or have been pregnant or are currently or have nursed a child within the last 12 months (A)
• Presence of any condition that, in the opinion of the investigator, compromises participant safety or data integrity or the participants' ability to complete the training protocol (Ex).