Heat and Exercise in Aging as Therapy (HEAT)

The main goal of this two-phase clinical trial is to learn whether local heat therapy, using heat pads applied to the legs, can enhance skeletal muscle health, physical function, and blood sugar control in a manner comparable to exercise, specifically High-Intensity Interval Training (HIIT), in older individuals with prediabetes. The study aims to answer the following questions:

1. Does local heat therapy improve muscle architecture (e.g., muscle cross-sectional area, capillary density, mitochondrial content), glucose tolerance, and frailty indicators similarly to HIIT in older individuals with prediabetes?
2. Does local heat therapy as a pre-conditioning method enhance the skeletal muscle response to HIIT in older individuals with prediabetes?

To achieve the study objectives, researchers will first compare the outcomes of local heat therapy to: 1) HIIT and 2) heat pads set to maintain normal skeletal muscle temperature (control group). Then, researchers will compare the outcomes of the local heat therapy and control groups after a subsequent HIIT intervention. This will enable the researchers to assess the effectiveness of local heat therapy (compared to HIIT and preceding HIIT) to improve skeletal muscle health, physical function, blood sugar control.

Study Procedures:

All participants will visit the laboratory over three days at the start of the study for baseline assessments and sample collection.

Participants in the Control (CON) and Local Heat Therapy (LHT) groups will:

Phase 1:

* Use heat pads on both thighs at a pre-determined temperature for 90 minutes daily, 7 days a week (6 days at home and 1 day in the laboratory; 12 laboratory visits) for the first 12 weeks.
* Maintain a log of each heat pad session.
* Visit the laboratory over three days at the end of Phase 1 for follow-up assessments and sample collection.

Phase 2:

* Visit the laboratory three days per week for 12 weeks (a total of 36 visits) for exercise training.
* Visit the laboratory over three days at the end of Phase 2 for final assessments and sample collection.

Participants in the HIIT Group will:

Phase 1:

* Visit the laboratory three days per week for 12 weeks (a total of 36 visits) for exercise training.
* Visit the laboratory over three days at the end of Phase 1 for final assessments and sample collection.

Eligibility Criteria:
Inclusion Criteria:

* Sedentary (structured exercise \<30 minutes, 3x/week)
* Meet criteria for prediabetes (fasting blood glucose 100-125 mg/dl and/or hemoglobin A1c 5.7-6.4%)
* Age ≥ 60 years
* Body weight ≥ 110 pounds
* Consume \<8 (women) or \<15 (men) alcohol-containing beverages per week
* Do not use nicotine or cannabis
* Not taking any medications that could interfere with responses to the interventions (e.g., corticosteroids, opiates, benzodiazepines, tricyclic antidepressants, beta blockers, sulfonylureas, insulin, metformin, anticoagulants, barbiturates, insulin sensitizers, fibrates \[PPAR gamma agonist\])

Exclusion Criteria:

* History of peripheral neuropathies
* Currently taking prescription blood thinners
* Medical complications that could would contraindicate participation in the high intensity interval training (HIIT) intervention including: orthopedic complications that would limit the ability of the participant to perform cycling exercise, significant cardiovascular impairments (e.g., history of arrhythmias, severe uncontrolled hypertension, etc.), diagnosed metabolic disease (e.g., diabetes), renal disease, and cancer in remission for \<6 months.
* Excessive subcutaneous fat over the muscle (greater than 1.5")
* Currently pregnant