Exercise for Insulin Resistance in Type 2 Diabetes
(EXPET Trial)
Recruiting in Palo Alto (17 mi)
Overseen byBret Goodpaster, PhD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Translational Research Institute for Metabolism and Diabetes, Florida
Must not be taking: Insulin, Incretin mimetics, Thiazolidinediones, others
Disqualifiers: Renal, Cardiac, Liver, Lung, others
No Placebo Group
Trial Summary
What is the purpose of this trial?The overall aim of this pilot study is to investigate the effects of exercise training on skeletal muscle and adipose tissue insulin resistance in subjects with Type 2 Diabetes (T2D).
Will I have to stop taking my current medications?
The trial requires that you are not currently taking insulin, injectable incretin mimetics, thiazolidinediones, or more than two glucose-lowering medications. You also cannot be on certain medications like blood thinners, anti-inflammatory drugs, or beta-blockers. If you are on these medications, you may need to stop them to participate.
What data supports the effectiveness of the treatment Exercise for Insulin Resistance in Type 2 Diabetes?
Research shows that insulin resistance is linked to the amount of fat stored in muscles and around the abdomen. Improving muscle function and reducing fat content through exercise can enhance insulin sensitivity, which is how well the body responds to insulin.
12345Is the exercise treatment for insulin resistance in type 2 diabetes safe?
The procedures involved in the study, such as adipose tissue biopsy and muscle biopsy, are generally safe. Adipose tissue biopsy using a mini-liposuction technique is safe with minimal restrictions on activities post-procedure. Muscle biopsy has a low incidence of minor side effects like pain and bruising, with no significant difference in safety between healthy and chronically ill individuals.
56789How does the treatment of adipose and muscle biopsy differ from other treatments for insulin resistance in type 2 diabetes?
Adipose and muscle biopsies are unique because they are not treatments themselves but diagnostic procedures that help researchers understand how exercise affects insulin resistance in type 2 diabetes. Unlike medications or lifestyle changes, these biopsies provide direct insights into the cellular and metabolic changes in muscle and fat tissue, which can guide more personalized treatment strategies.
1011121314Eligibility Criteria
This trial is for adults aged 30-65 with Type 2 Diabetes who are sedentary, have a BMI of 25-45 kg/m2, and haven't had significant weight changes recently. They must not be on more than two glucose-lowering medications or insulin and should be free from major diseases or conditions that could interfere with the study.Inclusion Criteria
I am between 30 and 65 years old.
Sedentary (1 day or less per week of structured exercise)
I have type 2 diabetes.
+4 more
Exclusion Criteria
Resting blood pressure ≥ 160/100 mm Hg
Triglycerides ≥ 500 mg/dL
Pregnancy during the previous 6 months, lactating, or planned pregnancy in the next year
+25 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Exercise Intervention
Participants undergo exercise training to assess effects on skeletal muscle and adipose tissue insulin resistance
Duration not specified
Assessment
Muscle glucose uptake is assessed pre and post exercise intervention using PET imaging and hyperinsulinemic euglycemic clamp
24 hours
Follow-up
Participants are monitored for safety and effectiveness after the exercise intervention
4 weeks
Participant Groups
The study tests how exercise affects insulin resistance in people with Type 2 Diabetes by using PET imaging, muscle and fat biopsies, and measuring maximum ATP production. Participants will undergo an exercise regimen to see if it improves their condition.
1Treatment groups
Experimental Treatment
Group I: All ParticipantsExperimental Treatment6 Interventions
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
AdventHealth Translational Research InstituteOrlando, FL
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Who Is Running the Clinical Trial?
Translational Research Institute for Metabolism and Diabetes, FloridaLead Sponsor
AdventHealth Translational Research InstituteLead Sponsor
References
Intermuscular Adipose Tissue Content and Intramyocellular Lipid Fatty Acid Saturation Are Associated with Glucose Homeostasis in Middle-Aged and Older Adults. [2022]Insulin resistance is associated with the higher content of intermuscular adipose tissue (IMAT) and the saturation of intramyocellular lipid (IMCL), but a paucity of data exist in humans. This study examined associations among IMAT content, IMCL saturation, and fasting glucose concentration in middle-aged and older adults with overweight or obesity.
Role of repeat skeletal muscle biopsy: how useful is it? [2018]The role of skeletal muscle biopsy is established; however, to our knowledge, no study has systematically evaluated the utility of a repeat biopsy.
Associations of serum adiponectin with skeletal muscle morphology and insulin sensitivity. [2012]Skeletal muscle morphology and function are strongly associated with insulin sensitivity.
Independent influences of central fat and skeletal muscle lipids on insulin sensitivity. [2011]Insulin resistance is closely associated with two disparate aspects of lipid storage: the intracellular lipid content of skeletal muscle and the magnitude of central adipose beds. Our aim was to determine their relative contribution to impaired insulin action.
Adipose tissue content, muscle performance and physical function in obese adults with type 2 diabetes mellitus and peripheral neuropathy. [2022]To determine leg intermuscular (IMAT) and subcutaneous (SQAT) adipose tissue and their relationships with muscle performance and function in obese adults with and without type 2 diabetes and peripheral neuropathy (T2DMPN).
Human Subcutaneous Adipose Tissue Sampling using a Mini-liposuction Technique. [2021]Studies on adipose tissue are useful in understanding metabolic and other conditions. Human subcutaneous adipose tissue is accessible. With appropriate training and strict adherence to aseptic technique, subcutaneous adipose samples can be safely and efficiently obtained in a non-clinical setting by researchers. Following the administration of local anesthetic lateral to the umbilicus, a 14 G needle attached to a 5 or 10 mL syringe is inserted through the skin into the subcutaneous tissue. Under suction, the syringe is moved in a reciprocating, slicing motion to isolate fragments of adipose tissue. Withdrawing the plunger is enough to ensure that adipose tissue fragments are aspirated through the needle into the syringe. A single biopsy can collect about 200 mg of tissue. This biopsy technique is very safe for both participants and research staff. Following the biopsy, participants can resume most everyday activities, although they should avoid swimming and overly strenuous activities for 48 h to avoid excessive bleeding. Participants can safely undergo 2 biopsies within a single day, meaning that the technique can be applied in before-after acute intervention studies.
Percutaneous adipose tissue biopsy by mini-liposuction for metabolic studies. [2017]Large fat-biopsy samples are necessary for extensive simultaneous assays. Subcutaneous adipose tissue is generally obtained either by needle-biopsy aspiration (approximately 1 g) or by open surgical biopsy for larger samples. We propose a reliable technique that permits the removal of large adipose tissue samples percutaneously.
Incidence of adverse events associated with percutaneous muscular biopsy among healthy and diseased subjects. [2012]The development of the percutaneous muscle biopsy technique is recognized as one of the most important scientific contributions in advancing our understanding of skeletal muscle physiology. However, a concern that this procedure may be associated with adverse events still exists. We reported the incidence of adverse outcomes associated with percutaneous muscle biopsy in healthy and diseased subjects. Medical records of 274 volunteers (496 muscle biopsies) were reviewed. This included 168 healthy subjects (330 muscle biopsies) as well as 106 chronically ill patients (166 muscle biopsies). This latter group encompassed patients with type II diabetes (n=28), osteoarthritis (n=39), inclusion body myositis (n=4), polymyositis (n=4), and chronic heart failure (n=31). The most common occurrences were pain (1.27%), erythema (1.27%), and ecchymosis (1.27%). Panic episode, bleeding, and edema were also reported (0.21%, 0.42%, and 0.84%, respectively), while infection, hematoma, inflammation, denervation, numbness, atrophy, and abnormal scarring were not verified. The percent of incidents did not differ between healthy and ill individuals. In conclusion, the incidence of complications associated with percutaneous muscle biopsy is scarce and of minor clinical relevance. Additionally, the rate of adverse events is comparable between healthy and chronically ill subjects.
How to Measure Adipose Tissue Insulin Sensitivity. [2022]Adipose tissue insulin resistance may cause hepatic and skeletal muscle insulin resistance by releasing excess free fatty acids (FFAs). Because no consensus exists on how to quantify adipose tissue insulin sensitivity we compared three methods for measuring adipose tissue insulin sensitivity: the single step insulin clamp, the multistep pancreatic clamp, and the adipose tissue insulin resistance index (Adipo-IR).
Exercise and insulin resistance in type 2 diabetes mellitus: A systematic review and meta-analysis. [2019]Insulin resistance is a determining factor in the pathophysiology of type 2 diabetes mellitus (T2DM). Exercise is known to improve insulin resistance, but a systematic review of the literature is lacking.
Adaptations to exercise training within skeletal muscle in adults with type 2 diabetes or impaired glucose tolerance: a systematic review. [2018]The aim of this investigation was to review morphological and metabolic adaptations within skeletal muscle to exercise training in adults with type 2 diabetes mellitus (T2DM) or impaired glucose tolerance (IGT). A comprehensive, systematic database search for manuscripts was performed from 1966 to March 2008 using computerized databases, including Medline, Premedline, CINAHL, AMED, EMBASE and SportDiscus. Three reviewers independently assessed studies for potential inclusion (exposure to exercise training, T2DM or IGT, muscle biopsy performed). A total of 18 exercise training studies were reviewed. All morphological and metabolic outcomes from muscle biopsies were collected. The metabolic outcomes were divided into six domains: glycogen, glucose facilitated transporter 4 (GLUT4) and insulin signalling, enzymes, markers of inflammation, lipids metabolism and so on. Beneficial adaptations to exercise were seen primarily in muscle fiber area and capillary density, glycogen, glycogen synthase and GLUT4 protein expressions. Few randomized controlled trials including muscle biopsy data existed, with a small number of subjects involved. More trials, especially robustly designed exercise training studies, are needed in this field. Future research should focus on the insulin signalling pathway to better understand the mechanism of the improvements in insulin sensitivity and glucose homeostasis in response to various modalities and doses of exercise in this cohort.
Insulin resistance and associated metabolic abnormalities in muscle: effects of exercise. [2019]Skeletal muscle is a major site of insulin resistance. In addition to glucose transport, oxidative disposal and storage defects, insulin resistant muscle exhibit many other metabolic abnormalities. After a brief review of insulin resistance determinants, we will focus on muscular abnormalities in obesity and type 2 diabetes. Glucose and lipid metabolism defects will be analysed and their interactions discussed. Exercise can improve many of these muscular abnormalities and the mechanisms underlying exercise-induced benefits have been clarified during the past decades. Therefore, exercise training has proved to be useful in the management of insulin resistant states, i.e. mainly obesity, especially in its truncal distribution, and type 2 diabetes. However, exercise prescription remains poorly codified, and results on glycaemic control are sometimes conflicting. In the last part of this review, we will emphasize the pathophysiological basis for an individualized exercise prescription in insulin resistant subjects.
Resistance exercise did not alter intramuscular adipose tissue but reduced retinol-binding protein-4 concentration in individuals with type 2 diabetes mellitus. [2022]Lipid accumulation in muscle is associated with diminished insulin sensitivity. It was hypothesized that resistance exercise decreases muscular adipose tissue and reduces the level of retinol-binding protein-4 (RBP4), which is linked to adipose tissue and insulin sensitivity in diabetics. Forty-four women with type 2 diabetes were randomly assigned to three groups for a period of 12 weeks: control (asked to maintain a sedentary lifestyle); resistance exercise (elastic band exercise at moderate intensity five times per week); and aerobic exercise (walking for 60 min at moderate intensity five times per week). Subcutaneous (SCAT), subfascial (SFAT) and intramuscular (IMAT) adipose tissues at mid-thigh level were assessed using computed tomography, and RBP4 level and insulin sensitivity (fractional disappearance rate of insulin, k(ITT)) were assessed before and after intervention. Changes in SCAT, SFAT, IMAT, RBP4 and k(ITT) were similar among the three groups. Within-group analysis revealed that body mass index and waist circumference decreased significantly in both exercise groups, but RBP4 decreased significantly only with resistance exercise. Resistance exercise did not alter muscular adipose tissue or improve insulin sensitivity.
Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans: a 1H-13C nuclear magnetic resonance spectroscopy assessment in offspring of type 2 diabetic parents. [2022]Insulin resistance is the best prediction factor for the clinical onset of type 2 diabetes. It was suggested that intramuscular triglyceride store may be a primary pathogenic factor for its development. To test this hypothesis, 14 young lean offspring of type 2 diabetic parents, a model of in vivo insulin resistance with increased risk to develop diabetes, and 14 healthy subjects matched for anthropomorphic parameters and life habits were studied with 1) euglycemic-hyperinsulinemic clamp to assess whole body insulin sensitivity, 2) localized 1H nuclear magnetic resonance (NMR) spectroscopy of the soleus (higher content of fiber type I, insulin sensitive) and tibialis anterior (higher content of fiber type IIb, less insulin sensitive) muscles to assess intramyocellular triglyceride content, 3) 13C NMR of the calf subcutaneous adipose tissue to assess composition in saturated/unsaturated carbons of triglyceride fatty acid chains, and 4) dual X-ray energy absorption to assess body composition. Offspring of diabetic parents, notwithstanding normal fat content and distribution, were characterized by insulin resistance and increased intramyocellular triglyceride content in the soleus (P