Role of Elevated Lactate Levels on Lipid and Carbohydrate Metabolism.

Обзор

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.

Подробное описание

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.

Вмешательства

• Другое hyperlactacidemia
  Raise blood lactate in metabolically healthy individuals to the levels of individuals with metabolic syndrome
• Другое Saline (0.9%, sterile, for infusion)
  Saline infusion as a control treatment

Первичные конечные точки

• Lipolysis rate at rest, exercise and OGTT when blood lactate is elevated in MH individuals [Срок оценки: through study completion, an average of 2 years]
• Effect of Na-Lactate on glucose tolerance to an oral load [Срок оценки: through study completion, an average of 2 years]

Вторичные конечные точки (11)

• Insulin sensitivity [Срок оценки: through study completion, an average of 2 years]
• Indirect calorimetry [Срок оценки: through study completion, an average of 2 years]
• Blood sample-insulin [Срок оценки: through study completion, an average of 2 years]
• Blood samples - glucose [Срок оценки: through study completion, an average of 2 years]
• Blood samples - Free fatty acids [Срок оценки: through study completion, an average of 2 years]
• Blood samples - Glycerol [Срок оценки: through study completion, an average of 2 years]
• Blood samples - Lactate [Срок оценки: through study completion, an average of 2 years]
• Blood tracer/tracee ratio of 13C/12C glucose [Срок оценки: through study completion, an average of 2 years]
• 13CO2 / 12CO2 in expired air [Срок оценки: through study completion, an average of 2 years]
• Blood tracer to tracee ratio of D2 glucose / unlabeled glucose [Срок оценки: through study completion, an average of 2 years]
• Blood tracer to tracee ratio of D5 glycerol / unlabeled glycerol [Срок оценки: through study completion, an average of 2 years]

Критерии участия

Критерии включения

• 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

Критерии исключения

• Chronic illness that prevents them from exercising
• Affected blood samples at screening, as assessed by the PI
• Assessed as unsuitable by PI

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Двойное слепое

Основная цель

Фундаментальное исследование

Центры проведения

Испания · 1 центр

• Facultad de Ciencias del Deporte — San Javier

Публикации

• Emhoff CA, Messonnier LA, Horning MA, Fattor JA, Carlson TJ, Brooks GA. Direct and indirect lactate oxidation in trained and untrained men. J Appl Physiol (1985). 2013 Sep;115(6):829-38. doi: 10.1152/japplphysiol.00538.2013. Epub 2013 Jun 20. PMID 23788576
• Ahmed K, Tunaru S, Tang C, Muller M, Gille A, Sassmann A, Hanson J, Offermanns S. An autocrine lactate loop mediates insulin-dependent inhibition of lipolysis through GPR81. Cell Metab. 2010 Apr 7;11(4):311-9. doi: 10.1016/j.cmet.2010.02.012. PMID 20374963
• Pedersen MGB, Rittig N, Bangshaab M, Berg-Hansen K, Gopalasingam N, Gormsen LC, Sondergaard E, Moller N. Effects of exogenous lactate on lipid, protein, and glucose metabolism-a randomized crossover trial in healthy males. Am J Physiol Endocrinol Metab. 2024 Apr 1;326(4):E443-E453. doi: 10.1152/ajpendo.00301.2023. Epub 2024 Feb 7. PMID 38324259
• Ferrannini E, Natali A, Brandi LS, Bonadonna R, De Kreutzemberg SV, DelPrato S, Santoro D. Metabolic and thermogenic effects of lactate infusion in humans. Am J Physiol. 1993 Sep;265(3 Pt 1):E504-12. doi: 10.1152/ajpendo.1993.265.3.E504. PMID 8214058
• Jones TE, Pories WJ, Houmard JA, Tanner CJ, Zheng D, Zou K, Coen PM, Goodpaster BH, Kraus WE, Dohm GL. Plasma lactate as a marker of metabolic health: Implications of elevated lactate for impairment of aerobic metabolism in the metabolic syndrome. Surgery. 2019 Nov;166(5):861-866. doi: 10.1016/j.surg.2019.04.017. Epub 2019 Jun 25. PMID 31253418

Идентификаторы

NCT: NCT07426172 · EPSP2025LACT

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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