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Current molecular aspects in the development and treatment of diabetes

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Abstract

Diabetes mellitus (DM) leads to microvascular, macrovascular, and neurological complications. Less is understood about the mechanisms of this disease that give rise to weak bones. The many molecular mechanisms proposed to explain the damage caused by chronic hyperglycemia are organ and tissue dependent. Since all the different treatments for DM involve therapeutic activity combined with side effects and each patient represents a unique condition, there is no generalized therapy. The alterations stemming from hyperglycemia affect metabolism, osmotic pressure, oxidative stress, and inflammation. In part, hemodynamic modifications are linked to the osmotic potential of the excess of carbohydrates implicated in the disease. The change in osmotic balance increases as the disease progresses because hyperglycemia becomes chronic. The aim of the current contribution is to provide an updated overview of the molecular mechanisms that participate in the development and treatment of diabetes.

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References

  1. 1.

    AboElAsrar MA, Elbarbary NS, Elshennawy DE et al (2012) Insulin-like growth factor-1 cytokines cross-talk in type 1, diabetes mellitus: relation-ship to microvascular complications and bone mineral density. Cytokine 59(1):86–93. https://doi.org/10.1016/j.cyto.2012.03.019

  2. 2.

    Adams GG, Meal A, Morgan PS et al (2018) Characterisation of insulin analogues therapeutically available to patients. PLoS One 13(3):e0195010. https://doi.org/10.1371/journal.pone.0195010

  3. 3.

    Alemán-González-Duhart D, Tamay-Cach F, Álvarez-Almazán S et al (2016) Current advances in the biochemical and physiological aspects of the treatment of type 2 diabetes mellitus with thiazolidinediones. PPAR Res 2016:7614270. https://doi.org/10.1155/2016/7614270

  4. 4.

    Álvarez-Almazán S, Bello M, Tamay-Cach F et al (2017) Study of new interactions of glitazone’s stereoisomers and the endogenous ligand 15d-PGJ2 on six different PPAR gamma proteins. Biochem Pharmacol 142:168–193. https://doi.org/10.1016/j.bcp.2017.07.012

  5. 5.

    American Diabetes Association (2017) 2. Classification and diagnosis of diabetes. Diabetes Care 38:S62–S69. https://doi.org/10.2337/dc17-S005

  6. 6.

    American Diabetes Association (2018) 8 pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2018. Diabetes Care 41(1):S73–S85. https://doi.org/10.2337/dc18-S008

  7. 7.

    American Diabetes Association (2017) Standards of medical care in diabetes-2017: summary of revisions. Diabetes Care 40(1):S4–S5. https://doi.org/10.2337/dc17-S003

  8. 8.

    Bilezikian JP, Watts NB, Usiskin K et al (2016) Evaluation of bone mineral density and bone biomarkers in patients with type 2 diabetes treated with canagliflozin. J Clin Endocrinol Metab 101(1):44–51. https://doi.org/10.1210/jc.2015-1860

  9. 9.

    Biondi-Zoccai GG, Abbate A, Liuzzo G et al (2003) Atherothrombosis, inflammation, and diabetes. J Am Coll Cardiol 41(7):1071–1077. https://doi.org/10.1016/S0735-1097(03)00088-3

  10. 10.

    Bollag RJ, Zhong Q, Phillips P et al (2000) Osteoblast-derived cells express functional glucose-dependent insulinotropic peptide receptors. Endocrinology 141(3):1228–1235. https://doi.org/10.1210/endo.141.3.7366

  11. 11.

    Chia CW, Egan JM (2008) Incretin-based therapies in type 2 diabetes mellitus. J Clin Endocrinol Metab 93(10):3703–3716. https://doi.org/10.1210/jc.2007-2109

  12. 12.

    Chilelli NC, Burlina S, Lapolla A (2013) AGEs, rather than hyperglycemia, are responsible for microvascular complications in diabetes: a “glycoxidation-centric” point of view. Nutr Metab Cardiovasc Dis 23:913–919. https://doi.org/10.1016/j.numecd.2013.04.004

  13. 13.

    Chung SS, Ho EC, Lam KS et al (2003) Contribution of polyol pathway to diabetes-induced oxidative stress. J Am Soc Nephrol 14(3):S233–S236. https://doi.org/10.1097/01.ASN.0000077408.15865.06

  14. 14.

    Cosentino F, Assenza GE (2004) Diabetes and inflammation. Herz 29:749–759. https://doi.org/10.1007/s00059-004-2635-8

  15. 15.

    Czemplik M, Kulma A, Fu Wang Y et al (2017) Therapeutic strategies of plant-derived compounds for diabetes via regulation of monocyte chemoattractant protein-1. Curr Med Chem 24(14):1453–1468. https://doi.org/10.2174/0929867324666170303162935

  16. 16.

    da Silva DC, Fontes GN, Erthal LC et al (2016) Amyloidogenesis of the amylin analogue pramlintide. Biophys Chem 219:1–8. https://doi.org/10.1016/j.bpc.2016.09.007

  17. 17.

    de Matos AM, de Macedo MP, Rauter AP (2018) Bridging type 2 diabetes and Alzheimer’s disease: assembling the puzzle pieces in the quest for the molecules with therapeutic and preventive potential. Med Res Rev 38(1):261–324. https://doi.org/10.1002/med.21440

  18. 18.

    Dede AD, Tournis S, Dontas I et al (2014) Type 2 diabetes mellitus and fracture risk. Metabolism 63(12):1480–1490. https://doi.org/10.1016/j.metabol.2014.09.002

  19. 19.

    Driessen JH, Henry RM, van Onzenoort HA et al (2015) Bone fracture risk is not associated with the use of glucagon-like peptide-1 receptor agonists: a population-based cohort analysis. Calcif Tissue Int 97(2):104–112. https://doi.org/10.1007/s00223-015-9993-5

  20. 20.

    Dröge W (2002) Free radicals in the physiological control of cell function. Physiol Rev 83:47–95. https://doi.org/10.1152/physrev.00018.2001

  21. 21.

    Edelman S, Maier H, Wilhelm K (2008) Pramlintide in the treatment of diabetes mellitus. BioDrugs 22(6):375–386. https://doi.org/10.2165/0063030-200822060-00004

  22. 22.

    Ernster L, Dallner G (1995) Biochemical, physiological and medical aspects of ubiquinone function. Biochim Biophys Acta 1271:195–204. https://doi.org/10.1016/0925-4439(95)00028-3

  23. 23.

    Forbes JM, Cooper ME (2013) Mechanisms of diabetic complications. Physiol Rev 93:137–188. https://doi.org/10.1152/physrev.00045.2011

  24. 24.

    Fu J, Zhu J, Hao Y et al (2016) Dipeptidyl peptidase-4 inhibitors and fracture risk: an updated meta-analysis of randomized clinical trials. Sci Rep 6:29104. https://doi.org/10.1038/srep2910

  25. 25.

    Garbossa SG, Folli F (2017) Vitamin D, sub-inflammation and insulin resistance. A window on a potential role for the interaction between bone and glucose metabolism. Rev Endocr Metab Disord 18(2):243–258. https://doi.org/10.1007/s11154-017-9423-2

  26. 26.

    Garla V, Yanes-Cardozo L, Lien LF (2017) Current therapeutic approaches in the management of hyperglycemia in chronic renal disease. Rev Endocr Metab Disord 18(1):5–19. https://doi.org/10.1007/s11154-017-9416-1

  27. 27.

    Ghosal S, Sinha B (2018) Liraglutide and dulaglutide therapy in addition to SGLT-2 inhibitor and metformin treatment in Indian type 2 diabetics: a real world retrospective observational study. Clin Diabetes Endocrinol 4:11. https://doi.org/10.1186/s40842-018-0061-8

  28. 28.

    Gilbert MP, Marre M, Holst JJ et al (2016) Comparison of the long-term effects of liraglutide and glimepiride monotherapy on bone mineral density in patients with type 2 diabetes. Endocr Pract 22(4):406–411. https://doi.org/10.4158/EP15758.OR

  29. 29.

    Gilbert MP, Pratley RE (2015) The impact of diabetes and diabetes medications on bone health. Endocr Rev 36(2):194–213. https://doi.org/10.1210/er.2012-1042

  30. 30.

    Grammatiki M, Rapti E, Karras S et al (2017) Vitamin D and diabetes mellitus: causal or casual association? Rev Endocr Metab Disord 18(2):227–241. https://doi.org/10.1007/s11154-016-9403-y

  31. 31.

    Guthrie RA, Guthrie DW (2004) Pathophysiology of diabetes mellitus. Crit Care Nurs Q 27:113–125

  32. 32.

    Guyton AC, Hall JE (2006) Guyton and Hall textbook of medical physiology with student consult online access, 11th edn. Elsevier Saunders, Philadelphia

  33. 33.

    Higgins LS, Depaoli AM (2010) Selective peroxisome proliferator-activated receptor gamma (PPARgamma) modulation as a strategy for safer therapeutic PPARgamma activation. Am J Clin Nutr 91(1):267S–272S. https://doi.org/10.3945/ajcn.2009.28449E

  34. 34.

    Huang S, Kaw M, Harris MT et al (2010) Decreased osteoclastogenesis and high bone mass in mice with impaired insulin clearance due to liver-specific inactivation to CEACAM1. Bone 46(4):1138–1145. https://doi.org/10.1016/j.bone.2009.12.020

  35. 35.

    Hunter SJ, Garvey WT (1998) Insulin action and insulin resistance: diseases involving defects in insulin receptors, signal transduction, and the glucose transport effector system. Am J Med 105(4):331–345. https://doi.org/10.1016/S0002-9343(98)00300-3

  36. 36.

    Ilyas Z, Chaiban JT, Krikorian A (2017) Novel insights into the pathophysiology and clinical aspects of diabetic nephropathy. Rev Endocr Metab Disord 18(1):21–28. https://doi.org/10.1007/s11154-017-9422-3

  37. 37.

    Inzucchi SE, Bergenstal RM, Buse JB et al (2015) Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 38:140–149. https://doi.org/10.2337/dc14-2441

  38. 38.

    Jong CJ, Azuma J, Schaffer S (2012) Mechanism underlying the antioxidant activity of taurine: prevention of mitochondrial oxidant production. Amino Acids 42(6):2223–2232. https://doi.org/10.1007/s00726-011-0962-7

  39. 39.

    Kahn SE, Cooper ME, Del Prato S (2014) Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future. Lancet 383(9922):1068–1083. https://doi.org/10.1016/S0140-6736(13)62154-6

  40. 40.

    Kanazawa I, Tanaka KI, Notsu M et al (2017) Long-term efficacy and safety of vildagliptin add-on therapy in type 2 diabetes mellitus with insulin treatment. Diabetes Res Clin Pract 123:9–17. https://doi.org/10.1016/j.diabres.2016.11.010

  41. 41.

    Kanazawa I, Yamaguchi T, Yano S et al (2008) Metformin enhances the differentiation and mineralization of osteoblastic MC3T3-E1 cells via AMP kinase activation as well as eNOS and BMP-2 expression. Biochem Biophys Res Commun 24;375(3):414–419. https://doi.org/10.1016/j.bbrc.2008.08.034

  42. 42.

    Knox C, Law V, Jewison T, et al (2011) Drug Info/Drug Targets: DrugBank 3.0: a comprehensive resource for ‘omics’ research on drugs. In: Database issue. Nucleic Acids Res 39(Database issue):D1035–D1041 http://www.rcsb.org/ligand/RE2. Accessed 13 Jan 2019

  43. 43.

    Knox C, Law V, Jewison T, et al (2011) Drug Info/Drug Targets: DrugBank 3.0: a comprehensive resource for ‘omics’ research on drugs. In: Database issue. Nucleic Acids Res 39(Database issue):D1035–D1041; http://www.rcsb.org/ligand/08Y. Accessed 13 Jan 2019

  44. 44.

    Knox C, Law V, Jewison T, et al (2011) Drug Info/Drug Targets: DrugBank 3.0: a comprehensive resource for ‘omics’ research on drugs. In: Database issue. Nucleic Acids Res 39(Database issue):D1035–D1041; http://www.rcsb.org/ligand/MF8. Accessed 13 Jan 2019

  45. 45.

    Kohan DE, Fioretto P, Tang W et al (2013) Long-term study of patients with type 2 diabetes and moderate renal impairment shows that dapagliflozin reduces weight and blood pressure but does not improve glycemic control. Kidney Int 85(4):962–971. https://doi.org/10.1038/ki.2013.356

  46. 46.

    Lazarenko OP, Rzonca SO, Suva LJ et al (2006) Netoglitazone is a PPAR-gamma ligand with selective effects on bone and fat. Bone 38(1):74–84. https://doi.org/10.1016/j.bone.2005.07.008

  47. 47.

    Lecka-Czernik B, Moerman EJ, Grant DF et al (2002) Divergent effects of selective peroxisome proliferator-activated receptor-gamma 2 ligands on adipocyte versus osteoblast differentiation. Endocrinology 143(6):2376–2384. https://doi.org/10.1210/endo.143.6.8834

  48. 48.

    Lecka-Czernik B (2013) Safety of anti-diabetic therapies on bone. Clin Rev Bone Miner Metab 11(1):49–58. https://doi.org/10.1007/s12018-012-9129-7

  49. 49.

    Leslie WD, Rubin MR, Schwartz AV et al (2012) Type 2 diabetes and bone. J Bone Miner Res 27(11):2231–2237. https://doi.org/10.1002/jbmr.1759

  50. 50.

    Lin DPL, Dass CR (2018) Weak bones in diabetes mellitus—an update on pharmaceutical treatment options. J Pharm Pharmacol 70(1):1–17. https://doi.org/10.1111/jphp.12808

  51. 51.

    Loscalzo J (2001) Nitric oxide insufficiency, platelet activation, and arterial thrombosis. Circ Res 88:756–762. https://doi.org/10.1161/hh0801.08986

  52. 52.

    Mabilleau G, Mieczkowska A, Chappard D (2014) Use of glucagon-like peptide-1 receptor agonists and bone fractures: a meta-analysis of randomized clinical trials. J Diabetes 6(3):260–266. https://doi.org/10.1111/1753-0407.12102

  53. 53.

    Manigrasso MB, Juranek J, Ramasamy R et al (2014) Unlocking the biology of RAGE in diabetic microvascular complications. Trends Endocrinol Metab 25(1):15–22. https://doi.org/10.1016/j.tem.2013.08.002

  54. 54.

    Marrazzo G, Barbagallo I, Galvano F et al (2014) Role of dietary and endogenous antioxidants in diabetes. Crit Rev Food Sci Nutr 54(12):1599–1616. https://doi.org/10.1080/10408398.2011.644874

  55. 55.

    Martin MA, Goya L, Ramos S (2016) Antidiabetic actions of cocoa flavanols. Mol Nutr Food Res 60:1956–1969. https://doi.org/10.1002/mnfr.201500961

  56. 56.

    Martin MA, Goya L, Ramos S (2017) Protective effects of tea, red wine and cocoa in diabetes. Evidences from human studies. Food Chem Toxicol 109:302–314. https://doi.org/10.1016/j.fct.2017.09.015

  57. 57.

    McCabe LR (2007) Understanding the pathology and mechanisms of type I diabetic bone loss. J Cell Biochem 102(6):1343–1357. https://doi.org/10.1002/jcb.21573

  58. 58.

    Monnier VM, Sell DR, Nagaraj RH et al (1992) Maillard reaction-mediated molecular damage to extracellular matrix and other tissue proteins in diabetes, aging, and uremia. Diabetes 41(Suppl 2):36–41. https://doi.org/10.2337/diab.41.2.S36

  59. 59.

    Morgan PE, Sheahan PJ, Davies MJ (2014) Perturbation of human coronary artery endothelial cell redox state and NADPH generation by methylglyoxal. PLoS One 9(1):e86564. https://doi.org/10.1371/journal.pone.0086564

  60. 60.

    Nieland TJ, Chroni A, Fitzgerald ML et al (2004) Cross-inhibition of SR-BI- and ABCA1-mediated cholesterol transport by the small molecules BLT-4 and glyburide. J Lipid Res 45(7):1256–1265. https://doi.org/10.1194/jlr.M300358-JLR200

  61. 61.

    Nobécourt E, Tabet F, Lambert G et al (2010) Nonenzymatic glycation impairs the antiinflammatory properties of apolipoprotein A-I. Arterioscler Thromb Vasc Biol 30(4):766–772. https://doi.org/10.1161/ATVBAHA.109.201715

  62. 62.

    Nuche-Berenguer B, Moreno P, Esbrit P et al (2009) Effect of GLP-1 treatment on bone turnover in normal, type 2 diabetic, and insulin-resistant states. Calcif Tissue Int 84(6):453–461. https://doi.org/10.1007/s00223-009-9220-3

  63. 63.

    Oates PJ, Mylari BL (1999) Aldose reductase inhibitors: therapeutic implications for diabetic complications. Expert Opin Investig Drugs 8(12):2095–2119. https://doi.org/10.1517/13543784.8.12.2095

  64. 64.

    Qiu J, Zhao J, Li J et al (2017) Apocynin attenuates left ventricular remodeling in diabetic rabbits. Oncotarget 8(24):38482–38490. https://doi.org/10.18632/oncotarget.16599

  65. 65.

    Rahelić D, Javor E, Lucijanić T et al (2017) Effects of antidiabetic drugs on the incidence of macrovascular complications and mortality in type 2 diabetes mellitus: a new perspective on sodium–glucose co-transporter 2 inhibitors. Ann Med 49(1):51–62. https://doi.org/10.1080/07853890.2016.1226514

  66. 66.

    Rajpathak SN, Fu C, Brodovicz KG et al (2015) Sulfonylurea use and risk of hip fractures among elderly men and women with type 2 diabetes. Drugs Aging 32(4):321–327. https://doi.org/10.1007/s40266-015-0254-0

  67. 67.

    Riche DM, King ST (2010) Bone loss and fracture risk associated with thiazolidinedione therapy. Pharmacotherapy 30(7):716–727. https://doi.org/10.1592/phco.30.7.716

  68. 68.

    Roy S, Trudeau K, Roy S et al (2010) New insights into hyperglycemia-induced molecular changes in microvascular cells. J Dent Res 89(2):116–127. https://doi.org/10.1177/0022034509355765

  69. 69.

    Rzonca SO, Suva LJ, Gaddy D et al (2004) Bone is a target for the antidiabetic compound rosiglitazone. Endocrinology 145(1):401–406. https://doi.org/10.1210/en.2003-0746

  70. 70.

    Santana RB, Lei X, Chase HB et al (2003) A role for advanced glycation end products in diminished bone healing in type 1 diabetes. Diabetes 52(6):1502–1510. https://doi.org/10.2337/diabetes.52.6.1502

  71. 71.

    Saoud A, Akowuah GA, Fatokun O et al (2017) Determination of acarbose in tablets by attenuated total reflectance Fourier transform infrared spectroscopy. Arch Ind Biotechnol 1:20–26

  72. 72.

    Sarnoski-Brocavich S, Hilas O (2013) Canagliflozin (invokana), a novel oral agent for type-2 diabetes. Pharm Ther 38:656–666

  73. 73.

    Shah M, Kola B, Bataveljic A et al (2010) AMP-activated protein kinase (AMPK) activation regulates in vitro bone formation and bone mass. Bone 47(2):309–319. https://doi.org/10.1016/j.bone.2010.04.596

  74. 74.

    Shi GJ, Shi GR, Zhou JY et al (2018) Involvement of growth factors in diabetes mellitus and its complications: a general review. Biomed Pharmacother 10(1):510–527. https://doi.org/10.1016/j.biopha.2018.02.105

  75. 75.

    Sottero B, Gargiulo S, Russo I et al (2015) Postprandial dysmetabolism and oxidative stress in type 2 diabetes: pathogenetic mechanisms and therapeutic strategies. Med Res Rev 35(5):968–1031. https://doi.org/10.1002/med.21349

  76. 76.

    Sugimoto K, Murakawa Y, Sima AA (2000) Diabetic neuropathy—a continuing enigma. Diabetes Metab Res Rev 16:408–433

  77. 77.

    Sun C, Shang J, Yao Y et al (2016) O-GlcNAcylation: a bridge between glucose and cell differentiation. J Cell Mol Med 20(5):769–781. https://doi.org/10.1111/jcmm.12807

  78. 78.

    Takayanagi R, Inoguchi T, Ohnaka K (2011) Clinical and experimental evidence for oxidative stress as an exacerbating factor of diabetes mellitus. J Clin Biochem Nutr 48(1):72–77. https://doi.org/10.3164/jcbn.11-014FR

  79. 79.

    Taniguchi N, Takahashi M, Kizuka Y et al (2016) Glycation vs. glycosylation: a tale of two different chemistries and biology in Alzheimer’s disease. Glycoconj 33:487–497. https://doi.org/10.1007/s10719-016-9690-2

  80. 80.

    Thrailkill KM, Lumpkin CK Jr, Bunn RC et al (2005) Is insulin an anabolic agent in bone? Dissecting the diabetic bone for clues. Am J Physiol Endocrinol Metab 289(5):E735–E7345. https://doi.org/10.1152/ajpendo.00159.2005

  81. 81.

    Tilton RG (2002) Diabetic vascular dysfunction: links to glucose-induced reductive stress and VEGF. Microsc Res Tech 57(5):390–407. https://doi.org/10.1002/jemt.10092

  82. 82.

    Tsentidis C, Gourgiotis D, Kossiva L et al (2016) Higher levels of s-RANKL and osteoprotegerin in children and adolescents with type 1 diabetes mellitus may indicate increased osteoclast signaling and predisposition to lower bone mass: a multivariate cross-sectional analysis. Osteoporos Int 27(4):1631–1643. https://doi.org/10.1007/s00198-015-3422-5

  83. 83.

    Vestergaard P, Rejnmark L, Mosekilde L (2005) Relative fracture risk in patients with diabetes mellitus, and the impact of insulin and oral antidiabetic medication on relative fracture risk. Diabetologia 48(7):1292–1299. https://doi.org/10.1007/s00125-005-1786-3

  84. 84.

    Vlassara H, Striker GE (2011) AGE restriction in diabetes mellitus: a paradigm shift. Nat Rev Endocrinol 7(9):526–539. https://doi.org/10.1038/nrendo.2011.74

  85. 85.

    Wang T, Wang Y, Menendez A et al (2015) Osteoblast-specific loss of IGF1R signaling results in impaired endochondral bone formation during fracture healing. J Bone Miner Res 30(9):1572–1584. https://doi.org/10.1002/jbmr.2510

  86. 86.

    Watson JD (2014) Type 2 diabetes as a redox disease. Lancet 383:841–843. https://doi.org/10.1016/S0140-6736(13)62365-X

  87. 87.

    Watts NB, Bilezikian JP, Usiskin K et al (2016) Effects of canagliflozin on fracture risk in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 101(1):157–166. https://doi.org/10.1210/jc.2015-3167

  88. 88.

    Whiting PH, Kalansooriya A, Holbrook I et al (2008) The relationship between chronic glycaemic control and oxidative stress in type 2 diabetes mellitus. Br J Biomed Sci 65:71–74

  89. 89.

    Willerson JT, Ridker PM (2004) Inflammation as a cardiovascular risk factor. Circulation 109(21 Suppl 1):II2–II10. https://doi.org/10.1161/01.CIR.0000129535.04194.38

  90. 90.

    Williamson JR, Chang K, Frangos M et al (1993) Hyperglycemic pseudohypoxia and diabetic complications. Diabetes 42:801–813. https://doi.org/10.2337/diab.42.6.801

  91. 91.

    Wong CY, Martinez J, Dass CR (2016) Oral delivery of insulin for treatment of diabetes: status quo, challenges and opportunities. J Pharm Pharmacol 68:1093–1108. https://doi.org/10.1111/jphp.12607

  92. 92.

    Woodcock J, Sharfstein JM, Hamburg M (2010) Regulatory action on rosiglitazone by the US food and drug administration. N Engl J Med 363(16):1489–1491. https://doi.org/10.1056/NEJMp1010788

  93. 93.

    Yamamoto M, Sugimoto T (2016) Advanced glycation end products, diabetes, and bone strength. Curr Osteoporos Rep 14(6):320–326. https://doi.org/10.1007/s11914-016-0332-1

  94. 94.

    Yan LJ (2014) Pathogenesis of chronic hyperglycemia: from reductive stress to oxidative stress. J Diabetes Res 2014:1–11. https://doi.org/10.1155/2014/137919

  95. 95.

    Zema MJ (2012) Colesevelam hydrochloride: evidence for its use in the treatment of hypercholesterolemia and type 2 diabetes mellitus with insights into mechanism of action. Core Evid 7:61–75. https://doi.org/10.2147/CE.S26725

  96. 96.

    Zheng Y, Ley SH, Hu FB (2018) Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol 14(2):88–98. https://doi.org/10.1038/nrendo.2017.151

  97. 97.

    Zhong Q, Itokawa T, Sridhar S et al (2007) Effects of glucose-dependent insulinotropic peptide on osteoclast function. Am J Physiol Endocrinol Metab 292(2):E543–E548. https://doi.org/10.1152/ajpendo.00364.2006

  98. 98.

    Zhou G, Myers R, Li Y et al (2001) Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 108(8):1167–1174. https://doi.org/10.1172/JCI13505

  99. 99.

    Zoungas S, Woodward M, Li Q et al (2014) Impact of age, age at diagnosis and duration of diabetes on the risk of macrovascular and microvascular complications and death in type 2 diabetes. Diabetologia 57(12):2465–2474. https://doi.org/10.1007/s00125-014-3369-7

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Acknowledgments

The authors thank the Secretaría de Investigación y Posgrado, Instituto Politécnico Nacional (SIP20195079/SIP20195185). Samuel Álvarez-Almazán is grateful for the scholarship from CONACyT (No. 434986).

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Correspondence to Feliciano Tamay-Cach or Jessica Elena Mendieta-Wejebe.

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Key points

• Most molecular alterations of diabetes are based on the overactivation of the protein kinase C pathway.

• Since every diabetes treatment has beneficial and adverse effects, there is no general therapy for all patients.

• Bone weakening is now recognized as a complication of diabetes that also requires attention for treatment.

DM treatments are based on decrease of oxidative stress, inflammation, cardiovascular disorders, and/or bone damage.

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Álvarez-Almazán, S., Filisola-Villaseñor, J.G., Alemán-González-Duhart, D. et al. Current molecular aspects in the development and treatment of diabetes. J Physiol Biochem (2020) doi:10.1007/s13105-019-00717-0

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Keywords

  • Diabetes
  • T1DM
  • T2DM
  • Complications of diabetes
  • Insulin resistance
  • Diabetes treatment