High Intensity Interval Training and Insulin Sensitivity in Type 2 Diabetes
- Conditions
- Type 2 DiabetesLifestyle-related ConditionInsulin Sensitivity/Resistance
- Registration Number
- NCT06688461
- Lead Sponsor
- Finis Terrae University
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 15
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Primary Outcome Measures
Name Time Method Insulin-stimulated non-oxidative plasma glucose disposal (NOGD) 12 weeks Insulin-stimulated NOGD will be measured upon hyperinsulinemic-euglycemic clamp test
- Secondary Outcome Measures
Name Time Method Metabolic flexibility 12 weeks Metabolic flexibility will be measured via indirect calorimetry during the clamp test
Total fat mass 12 weeks Total fat mass will be measured in kilograms and/or percentage
Fat-free mass 12 weeks Fat-free mass will be measured in kilograms and/or percentage
Skeletal muscle insulin sensitivity 12 weeks Skeletal muscle insulin sensitivity will be measured as the rate of insulin-stimulated plasma glucose disposal (Rd) measured upon hyperinsulinemic-euglycemic clamp test
Insulin-stimulated glucose oxidation 12 weeks Insulin-stimulated glucose oxidation will be measured via indirect calorimetry during clamp test
Liver insulin sensitivity 12 weeks Liver insulin sensitivity will be measured as the rate of insulin-mediated suppression of endogenous glucose production (EGP) upon hyperinsulinemic-euglycemic clamp test
Intrahepatic lipid content and composition 12 weeks Intrahepatic lipid content and composition will be measured by magnetic resonance spectroscopy of protons (1H-MRS)
De novo lipogenesis (DNL) 12 weeks DNL will be measured by the use of deuterated water (D2O)
24 hours glycemic profile 12 weeks 24 hours glycemic profile will be measured by the use of continuous glucose monitoring device
Skeletal muscle glycogen content 12 weeks Muscle glycogen content will be quantified in muscle biopsies
Proteins that regulate oxidative metabolism 12 weeks Content of proteins that regulate oxidative phosphorylation system (OXPHOS) will be quantified in muscle biopsies
Maximal aerobic capacity 12 weeks Maximal aerobic capacity will be measure upon a progressive cycling test
Body weight 12 weeks Body weight will be measured in kilograms
Total muscle mass 12 weeks total muscle mass will be measured in kilograms and/or percentage
Trial Locations
- Locations (1)
Finis Terrae University
🇨🇱Santiago, Chile