The evaluation of intracellular energy metabolism in prediabetic patients and patients newly diagnosed with type 2 diabetes mellitus

The evaluation of intracellular energy metabolism in prediabetic patients and patients newly diagnosed with type 2 diabetes mellitus

Background/aim: Increased susceptibility to infections is a serious problem in diabetics. Impairment in the energy metabolism of the immune system is the main source of the problem. Early diagnosis of the impairment in energy metabolism is crucial. Our study aimed to investigate the energy metabolism in leukocytes in patient groups such as prediabetics and patients newly diagnosed with type 2 diabetes mellitus. Materials and methods: Our study included 21 newly diagnosed type 2 diabetic patients (NDDP), 30 prediabetic patients, and 22 adult volunteers. 75 g oral glucose tolerance test (OGTT) was applied to all patients included in the study. Blood samples were taken after 9-16 h of fasting and fasting blood glucose (FBG), postprandial blood glucose (PBG) levels, total cholesterol (TC), triglyceride (TG), highdensity lipoprotein (HDL), fasting serum insulin, and hemoglobin A1c (HbA1c) levels were evaluated. After the cells were completely lysed, citrate levels from the released mononuclear leukocyte cells (MNC) content were manually studied, and lactate levels were applied to the autoanalyzer with the lactate kit. Lactate and citrate results were calculated as µg/mL. Statistical comparisons were done using Chi-square test, Mann-Whitney U test and student’s t test, and P < 0.05 values were accepted as significant. Results: A significant difference was found between the controls and the other groups (newly diagnosed diabetic patients (NDDP), impaired fasting glucose (IFG), and impaired glucose tolerance (IGT)) in terms of FBG levels (P < 0.001, P < 0.001 and P < 0.001, respectively). IFG and IGT patients had significantly higher PBG levels compared to the control group (P = 0.009 and P < 0.001, respectively). There was a significant difference between the IFG and IGT patients in terms of insulin levels (P = 0.019). There was a significant relationship between FBG levels and lactate production only in the NDDP group (r = 0.610, P = 0.003) Conclusion: The metabolic effects of hyperglycemia on leukocytes is in direction of anaerobic glycolysis. The increased anaerobic pathway is closely related to blood glucose levels and insulin resistance.Key words: Prediabetes, type 2 diabetes mellitus, intracellular energy, leukocyte

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  • 1. The Society of Endocrinology and Metabolism of Turkey. Clinical Practice Guideline for Diagnosis, Treatment and Follow-up of Diabetes Mellitus and Its Complications. English Version of the 12th Edition Istanbul, Turkey: Bayt; 2019. pp. 15
  • 2. Martin SP, Chaudhuri S, Green R, McKinney GR. The effect of adrenal steroids on aerobic lactic acid formation in human leukocytes. The Journal of Clinical Investigation 1954; 33 (3): 358-360. doi: 10.1172/JCI102907
  • 3. Alba-Loureiro T, Hirabara S, Mendonca J, Curi R, Pithon-Curi T. Diabetes causes marked changes in function and metabolism of rat neutrophils. Journal of Endocrinology 2006; 188 (2): 295-303. doi: 10.1677/joe.1.064381677/joe.1.06438
  • 4. Baczynski R, Massry SG, Kohan R, Magott M, Saglikes Y et al. Effect of parathyroid hormone on myocardial energy metabolism in the rat. Kidney International 1985; 27 (5): 718- 725. doi: 10.1038/ki.1985.71
  • 5. Trump BF, Berezesky IK, Smith MW, Phelps PC, Elliget KA. The relationship between cellular ion deregulation and acute and chronic toxicity. Toxicology and Applied Pharmacology 1989; 97 (1): 6-22. doi: 10.1016/0041-008x(89)90051-3
  • 6. Ozsari L, Karadurmus N, Sahin M, Uckaya G, Ural AU et al. Comparison of lymphomononuclear cell energy metabolism between healthy, impaired glucose intolerance and type 2 diabetes mellitus patients. Endocrine 2010; 37 (1): 135-139. doi: 10.1007/s12020-009-9281-0
  • 7. Rodwell VW, Weil PA, Bender DA, Botham KM, Kennelly PJ. Harper’s Illustrated Biochemistry. 30th ed. United States: Mc Graw-Hill Education; 2015. pp. 161-175.
  • 8. Champe PC, Harvey RA. Lippincott’s Illustrated Reviews. 2nd edition. USA: J.B. Lippincott Company; 1994.
  • 9. Kraut, Jeffrey A, Madias, Nicolaos E. Lactic acidosis. The New England Journal of Medicine 2014; 371 (24): 2309-2319. doi: 10.1056/nejmra1309483
  • 10. Curto M, Piccinini M, Rabbone I, Mioletti S, Mostert M et al. G proteins and regulation of pyruvate dehydrogenase activity by insulin in human circulating lymphocytes. The International Journal of Biochemistry & Cell Biology 1997; 29 (10): 1207- 1217. doi: 10.1016/S1357-2725(97)00049-6
  • 11. Mostert M, Rabbone I, Piccinini M, Curto M, Vai S et al. Derangements of pyruvate dehydrogenase in circulating lymphocytes of NIDDM patients and their healthy offspring. Journal of Endocrinological Investigation 1999; 22 (7): 519- 526. doi: 10.1007/BF03343603
  • 12. Fox CJ, Hammerman PS, Thompson CB. Fuel feeds function: energy metabolism and the T-cell response. Nature Reviews Immunology 2005; 5 (11): 844-852. doi: 10.1038/nri1710
  • 13. Mowat AG, Baum J. Chemotaxis of polymorphonuclear leukocytes from patients with diabetes mellitus. New England Journal of Medicine 1971; 284 (12): 621-627. doi: 10.1056/ NEJM197103252841201
  • 14. Molenaar D, Palumbo P, Wilson W, Ritts Jr R. Leukocyte chemotaxis in diabetic patients and their nondiabetic firstdegree relatives. Diabetes. 1976; 25 (2 SUPPL): 880-883. PMID: 971792
  • 15. Alexiewicz JM, Kumar D, Smogorzewski M, Klin M, Massry SG. Polymorphonuclear leukocytes in non-insulin-dependent diabetes mellitus: abnormalities in metabolism and function. Annals of Internal Medicine 1995; 123 (12): 919-924. doi: 10.7326/0003-4819-123-12-199512150-00004
  • 16. Edmonds M, Foster A. The use of antibiotics in the diabetic foot. The American Journal of Surgery 2004; 187 (5): 25-28. doi: 10.1016/S0002-9610(03)00300-3
  • 17. Alba-Loureiro T, Munhoz C, Martins J, Cerchiaro G, Scavone C et al. Neutrophil function and metabolism in individuals with diabetes mellitus. Brazilian Journal of Medical and Biological Research 2007; 40 (8): 1037-1044. doi: 10.1590/ s0100-879x2006005000143
  • 18. Esmann V. The polymorphonuclear leukocyte in diabetes mellitus. Journal of Clinical Chemistry and Clinical Biochemistry Zeitschrift fur Klinische Chemie und Klinische Biochemie 1983; 21 (9): 561-567. PMID: 6226761
  • 19. Bensadoun A, Weinstein D. Assay of proteins in the presence of interfering materials. Analytical Biochemistry. 1976;70 (1):241-50. doi: 10.1016/s0003-2697(76)80064-4
  • 20. Delamaire M, Maugendre D, Moreno M, Le Goff MC, Allannic H et al. Impaired leucocyte functions in diabetic patients. Diabetic Medicine 1997; 14 (1): 29-34. doi: 10.1002/ (SICI)1096-9136(199701)14:1<29::AID-DIA300>3.0.CO;2-V
  • 21. Geerlings SE, Brouwer EC, Van Kessel KC, Gaastra W, Stolk RP et al. Cytokine secretion is impaired in women with diabetes mellitus. European Journal of Clinical Investigation 2000; 30 (11): 995-1001. doi: 10.1046/j.1365-2362.2000.00745.x
  • 22. Reinhold D, Ansorge S. Elevated glucose levels stimulate transforming growth factor-β1 (TGF-β1), suppress interleukin IL-2, IL-6 and IL-10 production and DNA synthesis in peripheral blood mononuclear cells. Hormone and Metabolic Research 1996; 28 (06): 267-270. doi: 10.1055/s-2007-979789
  • 23. Otton R, Mendonca J, Curi R. Diabetes causes marked changes in lymphocyte metabolism. Journal of Endocrinology 2002; 174 (1): 55-62. doi: 10.1677/joe.0.1740055
  • 24. Moreno-Aurioles VR, Montaño R, Conde M, Sobrino F. Streptozotocin-induced diabetes increases fructose 2, 6-biphosfhate levels and glucose metabolism in thymus lymphocytes. Life Sciences 1996; 58 (6): 477-484. doi: 10.1016/0024-3205(95)02312-7
  • 25. Walrand S, Guillet C, Boirie Y, Vasson M-P. Insulin differentially regulates monocyte and polymorphonuclear neutrophil functions in healthy young and elderly humans. The Journal of Clinical Endocrinology & Metabolism 2006; 91 (7): 2738-2748. doi: 10.1210/jc.2005-1619
  • 26. MacIver NJ, Jacobs SR, Wieman HL, Wofford JA, Coloff JL et al. Glucose metabolism in lymphocytes is a regulated process with significant effects on immune cell function and survival. Journal of Leukocyte Biology 2008; 84 (4): 949-957. doi: 10.1189/jlb.0108024
  • 27. Diabetes Control and Complications Trial Research Group, Nathan D, Genuth S, Lachin J, Cleary P et al. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The New England Journal Medicine 1993; 329 (14): 977-986. doi: 10.1056/NEJM199309303291401
  • 28. United Kingdom Prospective Diabetes Study Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). The Lancet 1998; 352 (9131): 854-865. 10.1016/ S0140-6736(98)07037-8
  • 29. United Kingdom Prospective Diabetes Study Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). The Lancet 1998; 352 (9131): 837-853. doi: 10.1016/S0140-6736(98)07019-6
Turkish Journal of Medical Sciences-Cover
  • ISSN: 1300-0144
  • Yayın Aralığı: Yılda 6 Sayı
  • Yayıncı: TÜBİTAK
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