Hyperlactatemia, Metabolic Syndrome (MetS), Lipolysis, Exercise
Conditions
Keywords
blood lactate, lipolysis, oral glucose tolerance test, stable isotopes, indirect calorimetry, carbohydrate oxidation, fat oxidation, exercise, metabolic flexibility, metabolic syndrome
Brief summary
The purpose of this study is to investigate whether the elevated circulating lactate levels of individuals with metabolic syndrome are responsible for their reduced lipolysis and glucose tolerance. The investigators will conduct an intervention study in which blood lactate levels will be elevated via intravenous infusion of sodium lactate. State of the art metabolic assessment using stable isotopes and indirect calorimetry will be used to study alterations in fat and carbohydrate metabolism.
Detailed description
Individuals with metabolic syndrome and insulin resistance exhibit higher resting lactate concentrations than age-matched counterparts without metabolic disease. Recent studies suggest that lactate is not just a by-product of accelerated glycolysis but a signaling molecule that could even affect gene expression. However, the role of lactate in carbohydrate and fat metabolism at rest and during exercise remains incompletely described. In this study, the investigators will elevate blood lactate levels in metabolically healthy individuals to levels observed in individuals with metabolic syndrome while measuring fat and carbohydrate metabolism in a fasted state, during exercise, and in response to an oral glucose load (oral glucose tolerance test). 10 metabolically healthy (MH) and 10 metabolically impaired (MI) individuals matched for sex and physical activity will participate in the study. MH will undergo two trials: one with intravenous lactate infusion and the other with isovolumetric saline infusion. The MI group will undergo only the saline trial. Each trial consists of a 150 min basal period, an exercise period, followed by a 2-hour oral glucose tolerance test (OGTT). During the test, the investigators will: Measure insulin sensitivity during the OGTT (Matsuda Index). Measure fat and carbohydrate oxidation using indirect calorimetry. Use stable isotope infusion to measure glycerol and glucose turnover rates in plasma using \[1,1,2,3,3 2H\]-glycerol and \[6-6 2H\], \[U, 13C\] - glucose. Collect blood samples of relevant hormones, metabolites, and cytokines.
Interventions
OTHERhyperlactacidemia
Raise blood lactate in metabolically healthy individuals to the levels of individuals with metabolic syndrome
Saline infusion as a control treatment
Sponsors
Ricardo Mora
University of Castilla-La Mancha
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Men and women * \>18 years of age * Women non-pregnant or taking contraceptive medication * Physically active according to WHO's guidelines * Metabolic syndrome as IDF 2009 criteria (Alberti et al., Circulation) * Written and verbal consent to participation
Exclusion criteria
* Chronic illness that prevents them from exercising * Affected blood samples at screening, as assessed by the PI * Assessed as unsuitable by PI
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Lipolysis rate at rest, exercise and OGTT when blood lactate is elevated in MH individuals | through study completion, an average of 2 years | Change in plasma \[1,1,2,3,3 D\] glycerol turnover rates |
| Effect of Na-Lactate on glucose tolerance to an oral load | through study completion, an average of 2 years | Change in plasma \[6,6 D\]-glucose turnover rate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Insulin sensitivity | through study completion, an average of 2 years | The difference between groups and interventions in Matsuda ISI during the glucose tolerance test |
| Indirect calorimetry | through study completion, an average of 2 years | Changes in fat and carbohydrate oxidation during treatments in both groups. |
| Blood sample-insulin | through study completion, an average of 2 years | Insulin concentrations. Difference between interventions and groups |
| Blood samples - glucose | through study completion, an average of 2 years | Glucose concentrations. Difference between interventions and groups |
| Blood samples - Free fatty acids | through study completion, an average of 2 years | Free fatty acids concentration. Difference between interventions and groups |
| Blood samples - Glycerol | through study completion, an average of 2 years | Glycerol concentrations. Difference between interventions and groups |
| Blood samples - Lactate | through study completion, an average of 2 years | lactate concentrations. Difference between interventions and groups |
| Blood tracer/tracee ratio of 13C/12C glucose | through study completion, an average of 2 years | Tracer/tracee ratio measured by CGMS of 13C/12C glucose |
| 13CO2 / 12CO2 in expired air | through study completion, an average of 2 years | Analisys of 13CO2 / 12CO2 by IRMS |
| Blood tracer to tracee ratio of D2 glucose / unlabeled glucose | through study completion, an average of 2 years | Ratio of plasma D2 glucose / unlabeled glucose measured by GCMS |
| Blood tracer to tracee ratio of D5 glycerol / unlabeled glycerol | through study completion, an average of 2 years | Blood ratio of D5 glycerol / unlabeled glycerol measured with GCMS |
Countries
Spain
Contacts
CONTACTRicardo MORA RODRIGUEZ, PhD
CONTACTJesus Garcia-Pallares, PhD
PRINCIPAL_INVESTIGATORRicardo Mora Rodriguez, PhD
University of Castilla-La Mancha
PRINCIPAL_INVESTIGATORJesus Garcia-Pallares, PhD
Universidad de Murcia
Outcome results
None listed