The Effects of Intensive Glycemic Control on Neuropathy in the VA Cooperative Study on Type II Diabetes Mellitus (VA CSDM)

Azad, Nasrin; Emanuele, Nicholas V.; Abraira, Carlos; Henderson, William G.; Colwell, John A.; Levin, S.; Nuttall, Frank Q.; Comstock, John P.; Sawin, Clark T.; Silbert, Cynthia K.; Rubino, Frank A.

doi:10.1016/s1056-8727(99)00062-8

Cited by 114 publications

(71 citation statements)

References 11 publications

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“…This goal was achieved (3). As another essential part of the study, we obtained data assessing the progress of eye (4), neurological (20), macrovascular (5), and renal disease. The current study, in which completed data for 2 years are available, focused on renal disease.…”

Section: Conclusion -mentioning

confidence: 99%

Effect of intensive glycemic control on microalbuminuria in type 2 diabetes. Veterans Affairs Cooperative Study on Glycemic Control and Complications in Type 2 Diabetes Feasibility Trial Investigators.

et al. 2000

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OBJECTIVE -Microalbuminuria can reflect the progress of microvascular complications and may be predictive of macrovascular disease in type 2 diabetes. The effect of intensive glycemic control on microalbuminuria in patients in the U.S. who have had type 2 diabetes for several years has not previously been evaluated. RESEARCH DESIGN AND METHODS-We randomly assigned 153 male patients to either intensive treatment (INT) (goal HbA 1c 7.1%) or to standard treatment (ST) (goal HbA 1c 9.1%; P = 0.001), and data were obtained during a 2-year period. Mean duration of known diabetes was 8 years, mean age of the patients was 60 years, and patients were well matched at baseline. We obtained 3-h urine samples for each patient at baseline and annually and defined microalbuminuria as an albumin:creatinine ratio of 0.03-0.30. All patients were treated with insulin and received instructions regarding diet and exercise. Hypertension and dyslipidemia were treated with similar goals in each group.RESULTS -A total of 38% of patients had microalbuminuria at entry and were evenly assigned to both treatment groups. INT retarded the progression of microalbuminuria during the 2-year period: the changes in albumin:creatinine ratio from baseline to 2 years of INT versus ST were 0.045 vs. 0.141, respectively (P = 0.046). Retardation of progressive urinary albumin excretion was most pronounced in those patients who entered the study with microalbuminuria and were randomized to INT. Patients entering with microalbuminuria had a deterioration in creatinine clearance at 2 years regardless of the intensity of glycemic control. In the group entering without microalbuminuria, the subgroup receiving ST had a lower percentage of patients with a macrovascular event (17%) than the subgroup receiving INT (36%) (P = 0.03). Use of ACE inhibitors or calcium-channel blockers was similarly distributed among the groups.CONCLUSIONS -Intensive glycemic control retards microalbuminuria in patients who have had type 2 diabetes for several years but may not lessen the progressive deterioration of glomerular function. Increases in macrovascular event rates in the subgroup entering without albuminuria who received INT remain unexplained but could reflect early worsening, as observed with microvascular disease in the Diabetes Control and Complications Trial.

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Section: Conclusion -mentioning

confidence: 99%

Effect of intensive glycemic control on microalbuminuria in type 2 diabetes. Veterans Affairs Cooperative Study on Glycemic Control and Complications in Type 2 Diabetes Feasibility Trial Investigators.

et al. 2000

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“…The treatment of DPN has traditionally focused on the control of hyperglycaemia (15). The impact of intensive glycaemic control on DPN has been widely evaluated (16)(17)(18). Good glycaemic control is the only way to minimize the risk of neuropathy in patients with diabetes (15).…”

Section: Discussionmentioning

confidence: 99%

Muscle NT-3 levels increased by exercise training contribute to the improvement in caudal nerve conduction velocity in diabetic rats

Zhang

et al. 2012

Mol Med Report

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Abstract. The aim of the present study was to explore the role of exercise in diabetic peripheral neuropathy (DPN) and the mechanisms involved. For this purpose, 31 male SpragueDawley rats were used. The rats were assigned to 5 groups: diabetic rats subjected to exercise training (swimming) for 8 weeks (D-Ex1 group), diabetic rats subjected to exercise training for 4 weeks after 4 weeks of being sedentary (D-Ex2 group), diabetic rats which remained sedentary for 8 weeks (D-Sed group), control rats subjected to exercise training for 8 weeks (C-Ex1 group) and control rats which remained sedentary for 8 weeks (C-Sed group). Blood glucose levels and caudal nerve conduction velocity (NCV) were evaluated at 0 (baseline), 28 (4 weeks) and 56 days (8 weeks) after the induction of diabetes. The levels of neurotrophin-3 (NT-3) in skeletal muscle were measured by ELISA at the end of the experiment. Blood glucose levels in the D-Ex1 group rats decreased significantly after 8 weeks of exercise. The caudal NCV markedly decreased in all diabetic rats and significantly increased after 4 or 8 weeks of exercise training. Muscle NT-3 levels were significantly lower in the D-Sed compared to the 4 other groups. Muscle NT-3 levels positively correlated with caudal NCV. In conclusion, swimming training has a beneficial effect on DPN and muscle NT-3 levels, which could help improve caudal NCV in streptozotocin-induced diabetic rats. IntroductionDiabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes and is responsible for 50-75% of non-traumatic amputations in developed countries (1,2). The streptozotocin (STZ) model is widely used to investigate experimental DPN (3). Abnormal nerve conduction is an early feature of diabetic nerve damage (4). Tesfaye et al showed that conduction velocity significantly increased after exercise in normal subjects (5). Selagzi et al found that exercise training significantly increased the compound muscle action potential amplitude and decreased motor latency in diabetic rats (4). However, little is known about the mechanisms involved in exersise improving nerve dysfunction in STZ-induced diabetic rats.Neurotrophin-3 (NT-3) is a type of neurotrophic factor that comprises a heterogeneous group of molecules produced by neurons, Schwann cells and end organs in the central and peripheral nervous system (PNS). In adults, neurotrophins of the PNS are synthesized in and released from target tissues. Skeletal muscles are such target tissues and produce neurotrophins. NT-3 plays a crucial role in mediating central nervous system plasticity and regeneration in the spinal cord and muscle. Short-term STZ-induced diabetes causes a reduction in muscle NT-3 mRNA and protein expression, which leads to a decreased retrograde axonal transport of NT-3 to the neuronal cell body and consequent sub-optimal neurotrophic support (6). Previous studies have shown that the continuous production of NT-3 by the latency-associated promoter 2 (LAP2)-driven expression of the transgene from a herpes simple...

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“…Auch in der VACSDM-Studie ("Veterans Affairs Cooperative Study on Glycemic Control and Complications in NIDDM"), bei der im Gegensatz zur UK-PDS über mehrere Jahre ein beachtlicher Unterschied in der Qualität der Stoffwechseleinstellung zwischen den beiden Therapiearmen aufrechterhalten werden konnte, war nach 2-jähriger Beobachtungsdauer, allerdings in einer nur sehr kleinen Gruppe von Patienten, kein Unterschied in der Progression der Neuropathie nachweisbar [5]. Die auf dem 44.…”

Section: Stoffwechseleinstellung Bei Typ-1-diabetesunclassified

Pharmakotherapie der sensomotorischen Neuropathie

Luft¹

2008

Diabetologe

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Ein Drittel aller Diabetespatienten erleidet im Verlauf der Erkrankung eine Nervenschädigung, in den allermeisten Fäl-len in Form einer peripheren sensomotorischen Polyneuropathie [20]. Sie stellt für alle Betroffenen ein prognostisch ungüns-tiges Zeichen quoad vitam dar, ist bei bis zur Hälfte der Patienten mit behandlungsbedürftigen Beschwerden verbunden und hat sehr häufig ein neuropathisches Fuß-syndrom zur Folge.Die seltene, zumeist asymmetrische, motorische Mononeuropathie (diabetische Amyotrophie) führt zwar akut zu sehr beeinträchtigenden Beschwerden (Schmerzen, Muskelschwäche bis zu Läh-mungen und Atrophien), zeichnet sich aber im Langzeitverlauf durch eine güns-tige Prognose aus, sodass sie nicht im Brennpunkt des therapeutischen Interesses der Diabetologen steht.Störungen autonomer Funktionen können apparativ sehr häufig nachgewiesen werden. Symptomatische autonome Neuropathien sind selten und werden symptombezogen behandelt. Beschwerden und Komplikationen der symmetrischen sensomotorischen peripheren Polyneuropathie zwingen den behandelnden Arzt, sich Rechenschaft über die Möglich-keiten der langfristigen Prävention oder Behandlung der Nervenschädigung und der Linderung von akuten Beschwerden zu geben. Die Maßnahmen, die notwendig sind, um langfristig das Auftreten von Komplikationen der manifesten Neuropathie, vor allem des diabetischen neuropathischen Fußsyndroms zu verhindern, werden hier nicht dargestellt. Etwa 3 Jahre nach der letzten Übersicht in dieser Zeitschrift schien eine Aktualisierung gerechtfertigt [24]. Möglichkeiten der medikamentösen Prävention und Behandlung der NeuropathieEine wirksame medikamentöse Präven-tion oder Behandlung würde durch die Kenntnis der zur Nervenschädigung füh-renden Pathomechanismen erleichtert. Einigkeit besteht darin, dass der Hyperglykämie die größte Bedeutung zukommt, aber auch andere Risikofaktoren, die für makro-und mikroangiopathische Komplikationen identifiziert wurden, wie arterielle Hypertonie und Fettstoffwechselstö-rung, von Bedeutung sind. Inwieweit die aus Tiermodellen entwickelten pathophysiologischen Modelle, die diese Noxen in den molekularen Maßstab übertragen, für die menschliche Neuropathie von Bedeutung sind, ist weitgehend unklar.E Die Kenntnisse zur Prophylaxe diabetischer Nervenschädigungen sind begrenzt, beziehen sich ausschließlich auf die Stoffwechselnormalisierung und sind nur bei Typ-1-Diabetes aussagekräftig.Substanzen, die in möglicherweise wichtige pathogenetische Mechanismen der menschlichen diabetischen Neuropathie eingreifen, sind bislang nicht prophylaktisch eingesetzt worden. Stoffwechseleinstellung bei Typ-1-DiabetesDas prophylaktische Potenzial einer normoglykämischen Stoffwechseleinstellung wurde im "Diabetes Control and Complications Trial" (DCCT; [11, 12, 13]) bei Typ-1-Diabetes-Patienten untersucht. Eine über Jahre anhaltend verbesserte Stoffwechseleinstellung reduzierte das relative Risiko für das Auftreten einer Neuropathie -gemessen an den Ergebnissen neurologischer Untersuchungen, autonomer Reflextests und neurophys...

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The Effects of Intensive Glycemic Control on Neuropathy in the VA Cooperative Study on Type II Diabetes Mellitus (VA CSDM)

Cited by 114 publications

References 11 publications

Effect of intensive glycemic control on microalbuminuria in type 2 diabetes. Veterans Affairs Cooperative Study on Glycemic Control and Complications in Type 2 Diabetes Feasibility Trial Investigators.

Effect of intensive glycemic control on microalbuminuria in type 2 diabetes. Veterans Affairs Cooperative Study on Glycemic Control and Complications in Type 2 Diabetes Feasibility Trial Investigators.

Muscle NT-3 levels increased by exercise training contribute to the improvement in caudal nerve conduction velocity in diabetic rats

Pharmakotherapie der sensomotorischen Neuropathie

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