Comparison of Peripheral Nerve Damages According to Glucose Control Timing in Experimental Diabetes

H. Y. Jin; S. M. Kang; W. Y. Liu; C. H. Song; K. A. Lee; H. S. Baek; T. S. Park

doi:10.1055/s-0032-1306350

Experimental and Clinical Endocrinology & Diabetes, Inhaltsverzeichnis

Exp Clin Endocrinol Diabetes 2012; 120(08): 451-459
DOI: 10.1055/s-0032-1306350

Article

Comparison of Peripheral Nerve Damages According to Glucose Control Timing in Experimental Diabetes

H. Y. Jin^*

¹Department of Internal Medicine, Division of Endocrinology and Metabolism, Research Institute of Clinical Medicine of Chonbuk National University-chonbuk National University Hospital, Jeonju, South Korea

,

S. M. Kang^*

² Department of Internal Medicine, Division of Endocrinology and Metabolism, Seoul National University Bundang Hospital, Seongnam, South Korea

,

W. Y. Liu

¹Department of Internal Medicine, Division of Endocrinology and Metabolism, Research Institute of Clinical Medicine of Chonbuk National University-chonbuk National University Hospital, Jeonju, South Korea

,

C. H. Song

³ Department of Anatomy, Chonbuk National University Medical School, Jeonju, South Korea

,

K. A. Lee

¹Department of Internal Medicine, Division of Endocrinology and Metabolism, Research Institute of Clinical Medicine of Chonbuk National University-chonbuk National University Hospital, Jeonju, South Korea

,

H. S. Baek

¹Department of Internal Medicine, Division of Endocrinology and Metabolism, Research Institute of Clinical Medicine of Chonbuk National University-chonbuk National University Hospital, Jeonju, South Korea

,

T. S. Park

¹Department of Internal Medicine, Division of Endocrinology and Metabolism, Research Institute of Clinical Medicine of Chonbuk National University-chonbuk National University Hospital, Jeonju, South Korea

› Institutsangaben

Abstract

Objective:

In addition to tight glucose control, early intensive therapy has been reported to be more important for the prevention of diabetic micro- and macro-vascular complications. What is not known exactly is the quantitative difference according to timing delay in glucose control and whether early period control is really better than late control in terms of diabetic peripheral neuropathy. In this study, we investigated the effect of timing differences in glucose control on the peripheral nerves in an experimental diabetic model.

Methods:

5 groups (6–8 rats in each group) were comprised of normal glucose rats (designated control), rats with hyperglycemia (designated DM), rats with glucose control for the entire 28-week study period (designated DM + INS [W0–28]), rats with glucose control for the early 14-week period followed by hyperglycemia for the late 14-week period (designated DM + INS [W0–14]), and rats with hyperglycemia for the early 14-week period followed by glucose control in the late 14-week period (designated DM + INS [W15–28]).

Results:

We found that the current perception threshold (CPT) was lower in the DM + INS (W0–28) and DM + INS (W15–28) groups than in the DM + INS (W0–14) or DM groups (P<0.05). The mean myelinated fiber area of the sciatic nerve was significantly greater in the DM + INS (W0–28) and DM + INS (W15–28) groups (63.5±2.32 and 60.1±2.14 um, respectively) than in the DM + INS (W0–14) or DM groups (55.5±2.81 or 51.5±2.64 um, respectively) (P<0.05), and the intraepidermal nerve fiber (IENF) density was significantly higher in the DM + INS (W0–28) and DM + INS (W15–28) groups (6.9±0.46 and 6.8±0.11, respectively) than in the DM + INS (W0–14) or DM groups (59.5±0.32 and 5.3±0.39/mm, respectively) (P<0.05).

Conclusion:

Our results indicate that continuous glucose control is necessary to alleviate peripheral nerve damage and that glycemic control during the later period may be more important than early period management. The importance of continuous glucose control, including the later period of diabetes, should therefore be emphasized in diabetic peripheral neuropathy.

Key words

diabetic peripheral neuropathy - intraepidermal nerve fiber density - timing of glucose control

Volltext

Referenzen

References
1 Aronson D. Hyperglycemia and the pathobiology of diabetic complications. Adv Cardiol 2008; 45: 1-16
2 Ceriello A. Hypothesis: the “metabolic memory”, the new challenge of diabetes. Diabetes Res Clin Pract 2009; 86 (Suppl. 01) S2-S6
3 Ceriello A, Ihnat MA, Thorpe JE. Clinical review 2: The “metabolic memory”: is more than just tight glucose control necessary to prevent diabetic complications?. J Clin Endocrinol Metab 2009; 94: 410-415
4 Chew E, Ambrosius W, Davis M et al. Effects of medical therapies on retinopathy progresion in type 2 diabetes. The New England journal of medicine 2010; 363: 233-244
5 Duckworth W, Abraira C, Moritz T et al. Glucose Control and Vascular Complications in Veterans with Type 2 Diabetes. New England Journal of Medicine 2009; 360: 129-139
6 Edwards JL, Vincent AM, Cheng HT et al. Diabetic neuropathy: mechanisms to management. Pharmacol Ther 2008; 120: 1-34
7 Fard AS, Esmaelzadeh M, Larijani B. Assessment and treatment of diabetic foot ulcer. International journal of clinical practice 2007; 61: 1931-1938
8 Gerstein HC, Riddle MC, Kendall DM et al. Glycemia treatment strategies in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Am J Cardiol 2007; 99: 34i-43i
9 Gimbel J, Richards P, Portenoy R. Controlled-release oxycodone for pain in diabetic neuropathy: a randomized controlled trial. Neurology 2003; 60: 927-934
10 Holman RR, Paul SK, Bethel MA et al. 10-Year Follow-up of Intensive Glucose Control in Type 2 Diabetes. New England Journal of Medicine 2008; 359: 1577-1589
11 Jin HY, Liu WJ, Park JH et al. Effect of Dipeptidyl Peptidase-IV (DPP-IV) Inhibitor (Vildagliptin) on Peripheral Nerves in Streptozotocin-induced Diabetic Rats. Archives of Medical Research 2009; 40: 536-544
12 Jin HY, Lee KA, Song SK et al. Sulodexide prevents peripheral nerve damage in streptozotocin induced diabetic rats. Eur J Pharmacol 2012; 674: 217-226
13 Kowluru RA. Effect of reinstitution of good glycemic control on retinal oxidative stress and nitrative stress in diabetic rats. Diabetes 2003; 52: 818-823
14 Max MB, Lynch SA, Muir J et al. Effects of Desipramine, Amitriptyline, and Fluoxetine on Pain in Diabetic Neuropathy. New England Journal of Medicine 1992; 326: 1250-1256
15 Partanen J, Niskanen L, Lehtinen J et al. Natural history of peripheral neuropathy in patients with non-insulin-dependent diabetes mellitus. The New England journal of medicine 1995; 333: 89-94
16 Patel A. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. The Lancet 2007; 370: 829-840
17 Perkins BA, Greene DA, Bril V. Glycemic Control Is Related to the Morphological Severity of Diabetic Sensorimotor Polyneuropathy. Diabetes Care 2001; 24: 748-752
18 Raskin J, Smith T, Wong K et al. Duloxetine versus routine care in the long-term management of diabetic peripheral neuropathic pain. Journal of palliative medicine 2006; 9: 29-40
19 Richter R, Portenoy R, Sharma U et al. Relief of painful diabetic peripheral neuropathy with pregabalin: a randomized, placebo-controlled trial. The journal of pain 2005; 6: 253-260
20 Vinik AI. Advances in diabetes for the millennium: new treatments for diabetic neuropathies. MedGenMed 2004; 6: 13
21 Vinik AI, Mehrabyan A. Diabetic neuropathies. Med Clin North Am 2004; 88: 947-999 xi
22 Yagihashi S, Yamagishi S-I, Wada R. Pathology and pathogenetic mechanisms of diabetic neuropathy: Correlation with clinical signs and symptoms. Diabetes Research and Clinical Practice 2007; 77: S184-S189
23 Zor T, Selinger Z. Linearization of the Bradford protein assay increases its sensitivity: theoretical and experimental studies. Analytical biochemistry 1996; 236: 302-308