Insulin Sensitivity/Resistance, Lifestyle-related Condition, Type 2 Diabetes
Conditions
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.
Interventions
OTHERExperimental group: Exercise training
HIIT program, 3 times per week for 12 weeks
Sponsors
Finis Terrae University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
45 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insulin-stimulated non-oxidative plasma glucose disposal (NOGD) | 12 weeks | Insulin-stimulated NOGD will be measured upon hyperinsulinemic-euglycemic clamp test |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Chile
Contacts
CONTACTRodrigo Mancilla, PhD
PRINCIPAL_INVESTIGATORRodrigo Mancilla, PhD
Finis Terrae University
Outcome results
None listed