Possible Management of Diabetic Neuropathy in Childhood
Authors:
J. Vojtková; P. Ďurdík; M. Čiljaková; L. Vojarová; Peter Bánovčin
Authors‘ workplace:
Klinika detí a dorastu, Jesseniova lekárska fakulta Univerzity Komenského a Martinská fakultná nemocnica, Martin
prednosta prof. MUDr. P. Bánovčin, CSc.
Published in:
Čes-slov Pediat 2010; 65 (4): 186-194.
Category:
Review
Overview
Diabetic neuropathy (DN) presents one of the most common chronic complications of diabetes mellitus (DM). Incidence of DN depends on metabolic control and duration of diabetes, however genetic and other factors are very important, too. Several pathways of neuropathy onset and development have been found – polyol pathway, non-enzymatic glycation of proteins, oxidative stress, decreased function of trans-membrane pump Na+K+ATP-ase, lower concentration of neural growth factor (NGF), activation of protein-kinase C and others. These processes lead to functional or structural damage of nerves either directly or through vasa nervorum microangiopathy.
In childhood, subclinical forms and cardiovascular autonomic neuropathy are often met. The therapy of DN is despite of extensive trials still insufficient. Diabetes control is regarded as the only proved therapeutic intervention improving chronic diabetic complications. Using of thioctic acid and vitamins group B is quite frequent however the beneficial effect is controversial. Other possible interventions are in experimental trials, till now. Recent studies have proved beneficial influence of C-peptide substitution which can increase Na+K+ATP-ase function and prevent development of microangiopathy vasa nervorum by induction of NO-synthetase. Inhibitors of aldose-reductase (epalrestat, fidarestat) inhibit the rate-limiting enzyme in polyol pathway. Low amount of NGF can be influenced by its substitution or stimulation by all-trans retinoic acid. Capturers of carbonyl groups (pyridoxamine, aminoguanidine) act in prevention of advanced glycation end products origin. Protein-kinase C activity can be influenced by its inhibitors (ruboxistaurin). New possibility in future therapy presents therapy “made-to-measure” according to known gene polymorphisms for certain enzymes.
Unfortunately, despite extensive theoretical knowledge, practical possibilities with proved beneficial effect on DN consist in optimal diabetes control. Thioctacid and vitamins have only supportive effect. Additional clinic studies are necessary to confirm the benefit of other methods.
Key words:
diabetic neuropathy, glycemic control, pathogenesis, therapy
Sources
1. Mokáň M, Rozborilová E, Galajda P, et al. Vnútorné lekárstvo. 3. diel. 1. vyd. Bratislava: Vydavatelstvo UK, 2005: 9-46.
2. Rybka J. Diabetes mellitus – komplikace a přidružená onemocnění. Diagnostické a léčebné postupy. 1. vyd. Praha: Grada Publishing, 2007: 91–116.
3. Nordwall M, Hyllienmark L, Ludvigsson J. Early diabetic complications in a population of young patients with type 1 diabetes mellitus despite intensive treatment. J. Pediatr. Endocrinol. Metab. 2006; 19(1): 45–54.
4. Donaghue KC, Craig ME, Chan AK. Prevalence of diabetes complications 6 years after diagnosis in a incident cohort of childhood diabetes. Diabet. Med. 2005; 22(6): 711–718.
5. Eppens MC, Craig ME, Cusumano J, et al. Prevalence of diabetes complications in adolescents with type 2 compared with type 1 diabetes. Diabetes Care 2006; 29(6): 1300–1306.
6. Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes 2005; 54: 1615–1625.
7. Donaghue KC, Margan SH, Chan AKF, et al. The association of aldose reductase gene (AKR1B1) polymorphisms with diabetic neuropathy in adolescents. Diabetic Medicine 2005; 12(10): 1315–1320.
8. DCCT Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes. N. Engl. J. Med. 1993; 329: 977–986.
9. Javorka M, Javorkova J, Tonhajzerova I, et al. Parasympathetic versus sympathetic control of the cardiovascular system in young patients with diabetes mellitus type 1. Clin. Physiol. Funct. Imaging 2005; 25: 270–274.
10. EURODIAB IDDM Complications Study Group. Microvascular and acute complications in IDDM patients: the EURODIAB IDDM Complication Study. Diabetologia 1994; 37(3): 278–285.
11. Scaramuzza A, Salvucci F, Leuzzi S, et al. Cardiovascular autonomic testing in adolescents with type 1 diabetes mellitus: an 18 month follow up study. Clin. Sci. 1998; 94: 615–621.
12. Donaghue KC, Chiarelli F, Trotta D, et al. Microvascular and macrovascular complications associated with diabetes in children and adolescents. ISPAD Clinical Practice Consensus Guidelines 2009 Compendium. Pediatric Diabetes 2009; 10(Suppl 12): 195–203.
13. Maguire A, Chan A, Cusumano J, et al. The case for biennial retinopathy screening in children and adolescents. Diabetes Care 2005; 28(3): 509–513.
14. Court JM, Cameron FJ, Berg-Kelly K, et al. Diabetes in adolescence. Pediatric Diabetes 2008; 9(3): 255–262.
15. Edwards JL, Vincent AM, Cheng HT, et al. Diabetic neuropathy: Mechanisms to management. Pharmacol. Ther. 2008; 120(1): 1–34.
16. Consensus Statement. Report and recommendations of the San Antonio Conference on Diabetic neuropathy: American Diabetes Association/American Academy of Neurology. Diabetes Care 1988; 11: 592–98.
17. Česká diabetologická společnost. Standardy diagnostiky a léčby diabetické neuropatie. Diabetologie, metabolismus, endokrinologie, výživa 2007; 10: 215–220.
18. Boulton AJM, Vinik AI, Arezzo JC, et al. Diabetic neuropathies. A statement by the American Diabetes Association. Diabetes Care 2005; 28(4): 956–962.
19. Rasli MH, Zacharin MR. Foot problems and effectiveness of foot care education in children and adolescents with diabetes mellitus. Pediatr. Diabetes 2008; 9(6): 602–608.
20. Javorka M, Javorková J, Tonhajzerová I, et al. Heart rate variability in young patients with diabetes mellitus and healthy subjects explored by Poincaré and sequence plots. Clin. Physiol. Funct. Imaging 2005; 25(2): 119–127.
21. Tonhajzerová I, Javorka K, Petrášková M. Vývoj parametrov variability frekvencie srdca u mladých jedincov vo veku 15–19 rokov. Čes.-slov. Pediat. 1999; 8: 421–424.
22. Javorka K, Javorka M, Javorková J. Variabilita frekvencie srdca a diabetes mellitus. In: Javorka K, et al. Variabitila frekvencie srdca. 1. vyd. Martin: Osveta, 2008: 124–133.
23. Mokáň M, Martinka E., Galajda P, et al. Diabetes mellitus a vybrané metabolické ochorenia. 1. vyd. Turany: Vydavateľstvo P+M, 2009: 1–1003.
24. Klenovicsová K, Saavedra G, Zumpe C, et al. Význam produktov Maillardovej reakcie v strave dojčiat. Čes.-slov. Pediat. 2008; 63(10): 565–573.
25. Ziegler D. Thioctic acid for patients with symptomatic diabetic polyneuropathy: a critical review. Treat. Endocrinol. 2004; 3(3): 173–189.
26. Ziegler D, Ametov A, Barinov A. Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy. The SYDNEY 2 Trial. Diabetes Care 2006; 29: 2365–2370.
27. Huang EA, Gitelman SE. The effect of oral alpha-lipoic acid on oxidative stress in adolescents with type 1 diabetes mellitus. Pediatric Diabetes 2008; 9: 69–73.
28. Uzun N, Sarikava S, Uluduz D, et al. Peripheric and autonomic neuropathy in children with type 1 diabetes mellitus: the effect of L-carnitine treatment on the peripheral and autonomic nervous system. Electromyogr. Clin. Neurophysiol. 2005; 45(6): 343–351.
29. Haupt E, Ledermann H, Kopcke W. Benfotiamine in the treatment of diabetic polyneuropathy – a three-week randomized, controlled pilot study (BEDIP study). Int. J. Clin. Pharmacol. Ther. 2005; 43: 71–77.
30. Scott JA, King GL. Oxidative stress and antioxidant treatment in diabetes. Ann. N. Y. Acad. Sci. 2004; 1031: 204–213.
31. Thornalley PJ. Use of aminoguanidine (Pimagedine) to prevent the formation of advanced glycation endproducts. Arch. Biochem. Biophys. 2003; 419: 31–40.
32. Bolton WK, Cattran DC, Williams ME, et al. Randomized trial of an inhibitor of formation of advenced glycation end products in diabetic nephropathy. Am. J. Nephrol. 2004; 24: 32–40.
33. Birrell AM, Heffernan SJ, Ansselin AD, et al. Functional and structural abnormalities in the nerves of type I diabetic baboons: aminoguanidine treatment does not improve nerve function. Diabetologia 2000; 43(1): 110–116.
34. Little WC, Zile MR, Kitzman DW. The effect of alagebrium chloride (ALT-711), a novel glucose cross-link breaker, in the treatment of elderly patients with diastolic heart failure. J. Card. Fail. 2005; 11: 191–195.
35. Kass DA, Shapiro EP, Kawaguchi M, et al. Improved arterial compliance by a novel advanced glycation end-product crosslink breaker. Circulation 2001; 104(13): 1464–1470.
36. Peppa M, Brem H, Cai W, et al. Prevention and reversal of diabetic nephropathy in db/db mice treated with alagebrium (ALT-711). Am. J. Nephrol. 2006; 26(5): 430–436.
37. Ekberg K, Brismar T, Johansson BL, et al. C-Peptide replacement therapy and sensory nerve function in type 1 diabetic neuropathy. Diabetes Care 2007; 30(1): 71–76.
38. Bril V, Buchanan RA. Long-term effects of ranirestat (AS-3201) on peripheral nerve function in patients with diabetic sensorimotor polyneuropathy. Diabetes Care 2006; 29: 68–72.
39. Drel VR, Pachem P, Ali TK, et al. Aldose reductase inhibitor fidarestat counteracts diabetes-associated cataract formation, retina oxidative-nitrosative stress, glial activation, and apoptosis. Int. J. Mol. Med. 2008; 21(6): 667–676.
40. Hotta N, Akanuma Y, Kawamori R, et al. Long-term clinical effects of epalrestat, an aldose reductase inhibitor, on diabetic peripheral neuropathy: the 3-year, multicenter, comparative Aldose Reductase Inhibitor-Diabetes Complications Trial. Diabetes Care 2006; 29: 1538–1544.
41. Aiello LP, Clermont A, Arora V, et al. Inhibition of PKC beta by oral administration of ruboxistaurin is well tolerated and ameliorates diabetes-induced retinal hemodynamic abnormalities in patients. Invest. Ophthalmol. Vis. Sci. 2006; 47: 86–92.
42. Casellini CM, Barlow PM, Rice AL, et al. A 6-month, randomized, double-masked, placebo-controlled study evaluating the effects of the protein kinase C-beta inhibitor ruboxistaurin on skin microvascular blood flow and other measures of diabetic peripheral neuropathy. Diabetes Care 2007; 30(4): 896–902.
43. Apfel SC, Schwartz S, Adornato BT, et al. Efficacy and safety of recombinant human nerve growth factor in patients with diabetic polyneuropathy: A randomized controlled trial. JAMA 2000; 284: 2215–2221.
44. Hernandez-Pedro N, Ordonez G, Ortiz-Plata A, et al. All-trans retinoic acid induces nerve regeneration and increases serum and nerve contents of neural growth factor in experimental diabetic neuropathy. Transl. Res. 2008; 152(1): 31–37.
45. Vieira KP, De Almeina E, Lima Zollner AR, et al. Ganglioside GM1 effects on the expression of nerve growth factor (NGF), Trk-A receptor, proinflammatory cytokines and on autoimmune diabetes onset in non-obese diabetic (NOD) mice. Cytokine 2008; 42(1): 92–104.
46. Chattopadhyay M, Wolfe DP, Krisky DM, et al. Gene therapy of diabetic neuropathy using HSV-mediated transfer of erythropoetin to dorsal root ganglion in vivo. Molecular Therapy 2005; 11: 249.
47. Schratzberger P, Walter DH, Rittig K, et al. Reversal of experimental diabetic neuropathy by VEGF gene transfer. J. Clin. Invest. 2001; 107(9): 1083–1092.
48. Avery RL, Pearlman J, Pieramici DJ, et al. Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic retinopathy. Ophthalmology 2006; 113: 1–15.
49. Weintraub MI, Wolfe GI, Barohn RA, et al. Static magnetic field therapy for symptomatic diabetic neuropathy: A randomized, double-blind, placebo-controlled trial. Arch. Phys. Med. Rehabil. 2008; 84(5): 736–746.
50. Nikolaeva NV, Bolotova V, Lukianov VF, et al. Non-pharmacological treatment of microcirculation disturbance in children with diabetic polyneuropathy. Zh. Nevrol. Psikhiatr. Im. S. S. Korsakova 2008; 108(11): 43–46.
Labels
Neonatology Paediatrics General practitioner for children and adolescentsArticle was published in
Czech-Slovak Pediatrics
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