运动联合二甲双胍对2型糖尿病乳酸代谢的影响:叠加还是拮抗作用

doi:10.15942/j.jcsu.2024.05.011

Abstract

Abstract: Type 2 diabetes patients are often accompanied by abnormal lactate metabolism. Exercise and metformin are the first-line treatment for type 2 diabetes and are recommended to be used in combination, according to the Chinese Guidelines for Type 2 Diabetes. When exercise and metformin are used separately, it has been shown to affect lactate metabolism, while the combined effects have not been clearly defined. Therefore, the current study summarized the relationships among lactate metabolism, exercise, and metformin, as well as their related mechanisms in type 2 diabetes. Particularly, the study discussed the issues related to the factors i.e., exercise type, metformin dose, and timing of metformin taking and exercise, when using combination treatments of exercise and metformin to maximize the benefit and eliminate the side effect for type 2 diabetes patients.

Key words: metformin, lactate, type 2 diabetes, exercise intervention, integration of sports and medicine

CLC Number:

G804.5

YAO Wu, ZHAO Tong, ZHANG Yuan, ZHAO Jiexiu, CHENG Shulin. Combined Effects of Exercise and Metformin on Lactate Metabolism in Type 2 Diabetes Patients: Additive or Antagonistic?[J]. Journal of Chengdu Sport University, 2024, 50(5): 92-100.

References

[1] DAVIES M J, ARODA V R, COLLINS B S, et al. Management of hyperglycemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)[J]. Diabetes Care, 2022, 45(11): 2753-2786.
[2] 中华医学会糖尿病学分会.中国2型糖尿病防治指南(2020年版)[J]. 中华糖尿病杂志, 2021, 13 (4): 315-409.
[3] CRAWFORD S O, HOOGEVEEN R C, BRANCATI F L, et al. Association of blood lactate with type 2 diabetes: the atherosclerosis risk in communities carotid mri study[J]. Int J Epidemiol, 2010, 39(6): 1647-1655.
[4] RISHU A H, KHAN R, AL-DORZI H M, et al. Even mild hyperlactatemia is associated with increased mortality in critically ill patients[J]. Crit Care, 2013, 17(5): R197.
[5] WU Y, DONG Y, ATEFI M, et al. Lactate, a neglected factor for diabetes and cancer interaction[J]. Mediators Inflamm, 2016, 2016: 6456018.
[6] BRINKMANN C, BRIXIUS K. Hyperlactatemia in type 2 diabetes: can physical training help[J]. J Diabetes Complications, 2015, 29(7): 965-969.
[7] ZHAO T, LE S, FREITAG N, et al. Effect of chronic exercise training on blood lactate metabolism among patients with type 2 diabetes mellitus: a systematic review and meta-analysis[J]. Front Physiol, 2021, 12: 652023.
[8] LIRA V A, BENTON C R, YAN Z, et al. PGC-1α regulation by exercise training and its influences on muscle function and insulin sensitivity[J]. Am J Physiol Endocrinol Metab, 2010, 299(2): E145-E161.
[9] ALLENBERG K, JOHANSEN K, SALTIN B. Skeletal muscle adaptations to physical training in type II (non-insulin-dependent) diabetes mellitus[J]. Acta Med Scand, 1988, 223(4): 365-373.
[10] WILSON J M, LOENNEKE J P, JO E, et al. The effects of endurance, strength, and power training on muscle fiber type shifting[J]. J Strength Cond Res, 2012, 26(6): 1724-1729.
[11] VAN TIENEN F, PRAET S F, DE FEYTER H, et al. Physical activity is the key determinant of skeletal muscle mitochondrial function in type 2 diabetes[J]. J Clin Endocrinol Metab, 2012, 97(9): 3261-3269.
[12] BERHANE F, FITE A, DABOUL N, et al. Plasma lactate levels increase during hyperinsulinemic euglycemic clamp and oral glucose tolerance test[J]. J Diabetes Res, 2015, 2015: 102054.
[13] HAWLEY J A, LESSARD S J. Exercise training-induced improvements in insulin action[J]. Acta Physiol (Oxf), 2008, 192(1): 127-135.
[14] JANSSON P, LARSSON A, SMITH U, et al. Lactate release from the subcutaneous tissue in lean and obese men[J]. J Clin Invest, 1994, 93(1): 240-246.
[15] ABE T, SONG J S, BELL Z W, et al. Comparisons of calorie restriction and structured exercise on reductions in visceral and abdominal subcutaneous adipose tissue: a systematic review[J]. Eur J Clin Nutr, 2022, 76(2): 184-195.
[16] CORVERA S, GEALEKMAN O. Adipose tissue angiogenesis: impact on obesity and type-2 diabetes[J]. Biochim Biophys Acta, 2014, 1842(3): 463-472.
[17] STANFORD K I, MIDDELBEEK R J W, TOWNSEND K L, et al. A novel role for subcutaneous adipose tissue in exercise-induced improvements in glucose homeostasis[J]. Diabetes, 2015, 64(6): 2002-2014.
[18] PY G, LAMBERT K, PEREZ-MARTIN A, et al. Impaired sarcolemmal vesicle lactate uptake and skeletal muscle MCT1 and MCT4 expression in obese Zucker rats[J]. Am J Physiol Endocrinol Metab, 2001, 281(6): E1308-E1315.
[19] JUEL C, HOLTEN M K, DELA F. Effects of strength training on muscle lactate release and MCT1 and MCT4 content in healthy and type 2 diabetic humans[J]. J Physiol, 2004, 556(1): 297-304.
[20] OPITZ D, LENZEN E, SCHIFFER T, et al. Endurance training alters skeletal muscle MCT contents in T2DM men[J]. Int J Sports Med, 2014, 35(13): 1065-1071.
[21] MONDON C E, JONES I R, AZHAR S, et al. Lactate production and pyruvate dehydrogenase activity in fat and skeletal muscle from diabetic rats[J]. Diabetes, 1992, 41(12): 1547-1554.
[22] WU P, INSKEEP K, BOWKER-KINLEY M M, et al. Mechanism responsible for inactivation of skeletal muscle pyruvate dehydrogenase complex in starvation and diabetes[J]. Diabetes, 1999, 48(8): 1593-1599.
[23] CONSITT L A, SAXENA G, SANEDA A, et al. Age-related impairments in skeletal muscle PDH phosphorylation and plasma lactate are indicative of metabolic inflexibility and the effects of exercise training[J]. Am J Physiol Endocrinol Metab, 2016, 311(1): E145-E156.
[24] BIENSØ R S, OLESEN J, GLIEMANN L, et al. Effects of exercise training on regulation of skeletal muscle glucose metabolism in elderly men[J]. J Gerontol A Biol Sci Med Sci, 2015, 70(7): 866-872.
[25] DE SOUSA M V, FUKUI R, DAGOGO-JACK S, et al. Biomarkers of insulin action during single soccer sessions before and after a 12-week training period in type 2 diabetes patients on a caloric-restricted diet[J]. Physiol Behav, 2019, 209: 112618.
[26] WIDJAJA A, MORRIS R J, LEVY J C, et al. Within-and between-subject variation in commonly measured anthropometric and biochemical variables[J]. Clin Chem, 1999, 45(4): 561-566.
[27] FORETZ M, GUIGAS B, VIOLLET B. Understanding the glucoregulatory mechanisms of metformin in type 2 diabetes mellitus[J]. Nat Rev Endocrinol, 2019, 15(10): 569-589.
[28] MADIRAJU A K, ERION D M, RAHIMI Y, et al. Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase[J]. Nature, 2014, 510(7506): 542-546.
[29] KIM Y D, PARK K-G, LEE Y-S, et al. Metformin inhibits hepatic gluconeogenesis through AMP-activated protein kinase-dependent regulation of the orphan nuclear receptor SHP[J]. Diabetes, 2008, 57(2): 306-314.
[30] ZHOU T, XU X, DU M, et al. A preclinical overview of metformin for the treatment of type 2 diabetes[J]. Biomed Pharmacother, 2018, 106: 1227-1235.
[31] STEPHENNE X, FORETZ M, TALEUX N, et al. Metformin activates AMP-activated protein kinase in primary human hepatocytes by decreasing cellular energy status[J]. Diabetologia, 2011,54(12): 3101-3110.
[32] WANG Y, AN H, LIU T, et al. Metformin improves mitochondrial respiratory activity through activation of AMPK[J]. Cell Rep, 2019, 29(6): 1511-1523.e1515.
[33] ANDRZEJEWSKI S, GRAVEL S P, POLLAK M, et al. Metformin directly acts on mitochondria to alter cellular bioenergetics[J]. Cancer Metab, 2014, 2(1): 1-14.
[34] SALPETER S, GREYBER E, PASTERNAK G, et al. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus[J]. Cochrane Database Syst Rev, 2010, 4: CD002967.
[35] DAVIS T M, JACKSON D, DAVIS W A, et al. The relationship between metformin therapy and the fasting plasma lactate in type 2 diabetes: The Fremantle Diabetes Study[J]. Br J Clin Pharmacol, 2001, 52(2): 137-144.
[36] LOVE-OSBORNE K, SHEEDER J, ZEITLER P. Addition of metformin to a lifestyle modification program in adolescents with insulin resistance[J]. J Pediatr, 2008, 152(6): 817-822.
[37] RAMACHANDRAN A, SNEHALATHA C, MARY S, et al. The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1)[J]. Diabetologia, 2006, 49(2): 289-297.
[38] BOULÉ N G, KENNY G P, LAROSE J, et al. Does metformin modify the effect on glycaemic control of aerobic exercise, resistance exercise or both[J]. Diabetologia, 2013, 56(11): 2378-2382.
[39] KONOPKA A R, LAURIN J L, SCHOENBERG H M, et al. Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults[J]. Aging Cell, 2019, 18(1): e12880.
[40] TERADA T, BOULÉ N G. Does metformin therapy influence the effects of intensive lifestyle intervention? Exploring the interaction between first line therapies in the Look AHEAD trial[J]. Metabolism, 2019, 94: 39-46.
[41] KANALEY J A, COLBERG S R, CORCORAN M H, et al. Exercise/physical activity in individuals with type 2 diabetes: a consensus statement from the American College of Sports Medicine[J]. Med Sci Sports Exerc, 2022, 54(2): 353-368.
[42] CZYYK A, LAO B, BARTOSIEWICZ W, et al. The effect of short-term administration of antidiabetic biguanide derivatives on the blood lactate levels in healthy subjects[J]. Diabetologia, 1978, 14(2): 89-94.
[43] MALIN S K, STEPHENS B R, SHAROFF C G, et al. Metformin’s effect on exercise and postexercise substrate oxidation[J]. Int J Sport Nutr Exerc Metab, 2010, 20(1): 63-71.
[44] MORENO-CABAAS A, MORALES-PALOMO F, ÁLVAREZ-JIMENEZ L, et al. Metformin and exercise effects on postprandial insulin sensitivity and glucose kinetics in pre-and-diabetic adults[J]. Am J Physiol Endocrinol Metab, 2023, 325(4): E310-E324.
[45] GUDAT U, CONVENT G, HEINEMANN L. Metformin and exercise: no additive effect on blood lactate levels in health volunteers[J]. Diabet Med, 1997, 14(2): 138-142.
[46] CUNHA M R, DA SILVA M E, MACHADO H A, et al. The effects of metformin and glibenclamide on glucose metabolism, counter-regulatory hormones and cardiovascular responses in women with type 2 diabetes during exercise of moderate intensity[J]. Diabet Med, 2007, 24(6): 592-599.
[47] MALIN S K, GERBER R, CHIPKIN S R, et al. Independent and combined effects of exercise training and metformin on insulin sensitivity in individuals with prediabetes[J]. Diabetes Care, 2011, 35(1): 131-136.
[48] DUNN C J, PETERS D H. Metformin[J]. Drugs, 1995, 49: 721-749.
[49] HUANG T, LU C, SCHUMANN M, et al. Timing of exercise affects glycemic control in type 2 diabetes patients treated with metformin[J]. J Diabetes Res, 2018, 2018: 2483273.
[50] MOHOLDT T, PARR E B, DEVLIN B L, et al. The effect of morning vs evening exercise training on glycaemic control and serum metabolites in overweight/obese men: a randomised trial[J]. Diabetologia, 2021, 64(9): 2061-2076.

Combined Effects of Exercise and Metformin on Lactate Metabolism in Type 2 Diabetes Patients: Additive or Antagonistic?

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