High Intensity Interval Training and Insulin Sensitivity in Type 2 Diabetes

NCT06688461 | Recruiting DMC

• 1 other identifier: 24-001
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

A recognized driver for cardiovascular complications of type 2 diabetes mellitus (T2DM) is impaired plasma glucose homeostasis as consequence of skeletal muscle insulin resistance. Insulin-mediated plasma glucose disposal in skeletal muscle comprises oxidative glucose disposal (cellular glucose uptake for oxidation) and non-oxidative glucose disposal (NOGD; cellular glucose uptake for storage as glycogen), both processes being impaired in T2DM patients. Excessive intrahepatic fat accumulation (particularly monounsaturated (MUFA) and saturated (SFA)) is commonly observed in T2DM patients and tightly associates with plasma glucose dysregulation. It has been hypothesized that skeletal muscle insulin resistance redistributes circulating glucose away from muscle which together with hyperinsulinemia promotes intrahepatic lipid accretion via de novo lipogenesis (DNL). As saturated lipids is the final product of DNL, improving skeletal muscle insulin sensitivity, next to enhance plasma glucose homeostasis, might lower intrahepatic lipid content particularly intrahepatic saturated lipids. Regular exercise is a cornerstone in the treatment of T2DM and to improve skeletal muscle insulin sensitivity. Interestingly, a conventional exercise program (aerobic-type combined with strength-type exercise) restores insulin-stimulated oxidative glucose disposal in T2DM patients to levels observed in age-matched normoglycemic subjects. Non-oxidative glucose disposal (NOGD), however, does not improve upon such conventional exercise programs. In this regard, for full restoration of compromised glucose disposal, it is pivotal to come up with effective training methods to target NOGD. High intensity interval training (HIIT) has the potential to expands the glycogen synthesis capacity in athletes by repetitive cycles of glycogen depletion/repletion, hence holds promise to improve NOGD in T2DM patients. Of note, HIIT also lowers the intrahepatic fat content in pre-diabetes individuals. Nevertheless, whether HIIT reduces the intrahepatic fat content and modifies its composition in T2DM patients is unknown. In this regard, it is hypothesized that HIIT expands the NOGD capacity in skeletal muscle of overweight/obese type 2 diabetes patients. By doing so, it is postulated that HIIT improves skeletal muscle insulin sensitivity and therefore benefits the 24 hours glycaemic profile in T2DM patients. In line, it is hypothesized that the HIIT-mediated improvements on NOGD and skeletal muscle insulin sensitivity coexist with the reduction of intrahepatic lipid content -particularly reduced saturated lipids- via lowering DNL.

Conditions

Type 2 Diabetes; Lifestyle-related Condition; Insulin Sensitivity/Resistance

Outcome Measures

Primary Outcomes (1)

• Insulin-stimulated non-oxidative plasma glucose disposal (NOGD)

  Insulin-stimulated NOGD will be measured upon hyperinsulinemic-euglycemic clamp test

  12 weeks

Secondary Outcomes (1)

• Skeletal muscle insulin sensitivity

  12 weeks

Other Outcomes (14)

• Insulin-stimulated glucose oxidation

  12 weeks

• Metabolic flexibility

  12 weeks

• Liver insulin sensitivity

  12 weeks

Study Arms (3)

T2D-HIIT

EXPERIMENTAL

This arm will perform HIIT under supervision. The post training condition of this arm will be compared to an age and BMI matched, normoglycemic non-intervention group.

Other: Experimental group: Exercise training

T2D-CON

NO INTERVENTION

This corresponds to a non-training, control group, of age-, BMI matched, type 2 diabetes individuals.

NORM

NO INTERVENTION

A group of normoglycemic individuals will the reference comparison for the T2D-HIIT arm post-intervention

Interventions

Experimental group: Exercise training OTHER

HIIT program, 3 times per week for 12 weeks

T2D-HIIT

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants are able to provide signed and dated written informed consent prior to any study specific procedures
• Aged ≥ 45 and ≤ 75 years
• BMI: 25-35 kg/m2
• Diagnosed as T2DM patients for at least 1 year and not longer than 5 years
• HbA1c ≥ 6.5% and ≤ 8.5%
• Fasting blood glucose \<130 mg/dL
• Women are post-menopausal (\>1 year cessation of menses),
• Being stable on medication use of metformin and/or sulfonylurea derivatives for the previous 3 months or more and other medication naïve.

You may not qualify if:

• Type 1 diabetes
• Patients with congestive heart failure and and/or severe renal and or liver insufficiency
• Contraindications for MRI/MRS examination
• Active diabetic foot
• Polyneuropathy or retinopathy
• Signs of active liver or kidney dysfunction
• BMI \>35 kg/m2
• Exogeneous insulin therapy
• Use of antidiabetic medication other than metformin or sulfonylurea derivatives treatment within 3 months before screening
• Use of SGLT2 inhibitors
• Unstable body weight (variations \>5kg in the last 3 months)
• Ongoing weight loss diet or use of weight loss agents
• Uncontrolled hypertension
• Engagement in regular exercise program or any other medical condition that will impede the safe performance of the experiments

Sponsors & Collaborators

• Finis Terrae University: lead

Study Sites (1)

Finis Terrae University

Santiago, Chile

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Mental Disorders; Insulin Resistance

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Study Officials

• Rodrigo Mancilla, PhD

  Finis Terrae University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rodrigo Mancilla, PhD

CONTACT

+56953676588; rmancilla@uft.cl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor, PhD

Model Details: 1 interventional group of type 2 diabetes participants will undergo the 12-weeks of the HIIT program. 1 non-intervention control group of, age- and BMI matched type 2 diabetes participants. 1 non-interventional group of, age- and BMI matched, normoglycemic individuals will be the reference comparison for the post-training condition.

Study Record Dates

• First Submitted: November 11, 2024
• First Posted: November 14, 2024
• Study Start: October 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CL (1)