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Recent advances in the management of diabetic distal symmetrical polyneuropathy.

Tesfaye S - J Diabetes Investig (2011)

Bottom Line: Furthermore, traditional cardiovascular risk factors for macrovascular disease appear to be associated with an increased risk of DPN.The only compounds found to be efficacious in human diabetic neuropathy, and are in clinical use, are the anti-oxidant, α-lipoic acid and the aldose reductase inhibitor, epalrestat.Management of the patient with DPNP must be tailored to individual requirements and will depend on the presence of other comorbidities. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00083.x).

View Article: PubMed Central - PubMed

Affiliation: Royal Hallamshire Hospital, Sheffield, UK.

ABSTRACT
There is now little doubt that poor blood glucose control is an important risk factor for the development of diabetic peripheral neuropathy (DPN). Furthermore, traditional cardiovascular risk factors for macrovascular disease appear to be associated with an increased risk of DPN. The recently established International Expert Group on Diabetic Neuropathy has recommended new criteria for the diagnosis of DPN in the context of clinical and research settings. Studies in experimental diabetes examining the pathogenesis of DPN have identified a number of metabolic abnormalities including polyol pathway hyperactivity, increased advanced glycation end-point formation, alterations in the protein kinase C beta pathway through diacylglycerol and oxidative stress. There is now strong evidence implicating nerve ischemia as the cause of DPN. Studies in human and animal models have shown reduced nerve perfusion and endoneurial hypoxia. These endoneurial microvascular changes strongly correlate with clinical severity and the degree of nerve-fiber pathology. Unfortunately, many compounds that have been effective in animal models of neuropathy have not been successful in human diabetic neuropathy. The only compounds found to be efficacious in human diabetic neuropathy, and are in clinical use, are the anti-oxidant, α-lipoic acid and the aldose reductase inhibitor, epalrestat. Overall, the evidence emphasizes the importance of vascular dysfunction, driven by metabolic change, in the etiology of DPN, and highlights potential therapeutic approaches. Epidemiological data on diabetic painful neuropathic pain (DPNP) are limited. In one population-based study, the prevalence of DPNP, as assessed by a structured questionnaire and examination, was estimated at 16%. It was notable that, of these patients, 12.5% had never reported symptoms to their doctor and 39% had never received treatment for their pain. Thus, despite being common, DPNP continues to be underdiagnosed and undertreated. Pharmacological treatment of DPNP include tricyclic compounds, serotonin noradrenalin reuptake inhibitors, the anti-oxidant α-lipoic acid, anticonvulsants, opiates, membrane stabilizers, topical capsaicin and so on. Management of the patient with DPNP must be tailored to individual requirements and will depend on the presence of other comorbidities. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00083.x).

No MeSH data available.


Related in: MedlinePlus

 Risk factors for incident neuropathy. The EURODIAB Prospective Complications Study showing odds ratios for the various risk factors for distal symmetrical polyneuropathy in a cohort of 1101 type 1 diabetes mellitus patients followed for 7.3 ± 0.6 years. Adapted from Reference 16. BMI, body mass index; CVD, cardiovascular disease.
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f2:  Risk factors for incident neuropathy. The EURODIAB Prospective Complications Study showing odds ratios for the various risk factors for distal symmetrical polyneuropathy in a cohort of 1101 type 1 diabetes mellitus patients followed for 7.3 ± 0.6 years. Adapted from Reference 16. BMI, body mass index; CVD, cardiovascular disease.

Mentions: In the Rochester Diabetic Neuropathy Study cohort, where clinical parameters and NC tests were used, the prevalence of DSPN was 54% in patients with type 1 diabetes mellitus and 45% in patients with type 2 diabetes mellitus1. Where NC tests were not used, clinic‐ and population‐based studies showed surprisingly similar prevalence rates for DSPN, affecting approximately 30% of all diabetic people14. The EURODIAB Prospective Complications Study, which involved the examination of 3250 type 1 patients from 16 European countries, found a prevalence rate of 28% for DSPN at baseline15, very strongly related to poor glycemic control. The follow‐up study also showed that over a 7‐year period, approximately one‐quarter of type 1 diabetic patients developed DSPN; with age, duration of diabetes and poor glycemic control being major factors16. The development of neuropathy was also associated with potentially modifiable cardiovascular risk factors, such as hypertension, hyperlipidemia, obesity and cigarette smoking (Figure 2)16. Recently, other studies have also implicated cardiovascular risk factors, such as obesity17 and triglycerides18 in the pathogenesis of DSPN. In a cohort of participants with mild to moderate diabetic neuropathy, Wiggin et al.19 also found that elevated triglycerides correlated with myelinated fiber loss independent of disease duration, age, diabetes control or other variables. These data support the evolving concept that hyperlipidemia might be instrumental in the progression of diabetic neuropathy.


Recent advances in the management of diabetic distal symmetrical polyneuropathy.

Tesfaye S - J Diabetes Investig (2011)

 Risk factors for incident neuropathy. The EURODIAB Prospective Complications Study showing odds ratios for the various risk factors for distal symmetrical polyneuropathy in a cohort of 1101 type 1 diabetes mellitus patients followed for 7.3 ± 0.6 years. Adapted from Reference 16. BMI, body mass index; CVD, cardiovascular disease.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4008012&req=5

f2:  Risk factors for incident neuropathy. The EURODIAB Prospective Complications Study showing odds ratios for the various risk factors for distal symmetrical polyneuropathy in a cohort of 1101 type 1 diabetes mellitus patients followed for 7.3 ± 0.6 years. Adapted from Reference 16. BMI, body mass index; CVD, cardiovascular disease.
Mentions: In the Rochester Diabetic Neuropathy Study cohort, where clinical parameters and NC tests were used, the prevalence of DSPN was 54% in patients with type 1 diabetes mellitus and 45% in patients with type 2 diabetes mellitus1. Where NC tests were not used, clinic‐ and population‐based studies showed surprisingly similar prevalence rates for DSPN, affecting approximately 30% of all diabetic people14. The EURODIAB Prospective Complications Study, which involved the examination of 3250 type 1 patients from 16 European countries, found a prevalence rate of 28% for DSPN at baseline15, very strongly related to poor glycemic control. The follow‐up study also showed that over a 7‐year period, approximately one‐quarter of type 1 diabetic patients developed DSPN; with age, duration of diabetes and poor glycemic control being major factors16. The development of neuropathy was also associated with potentially modifiable cardiovascular risk factors, such as hypertension, hyperlipidemia, obesity and cigarette smoking (Figure 2)16. Recently, other studies have also implicated cardiovascular risk factors, such as obesity17 and triglycerides18 in the pathogenesis of DSPN. In a cohort of participants with mild to moderate diabetic neuropathy, Wiggin et al.19 also found that elevated triglycerides correlated with myelinated fiber loss independent of disease duration, age, diabetes control or other variables. These data support the evolving concept that hyperlipidemia might be instrumental in the progression of diabetic neuropathy.

Bottom Line: Furthermore, traditional cardiovascular risk factors for macrovascular disease appear to be associated with an increased risk of DPN.The only compounds found to be efficacious in human diabetic neuropathy, and are in clinical use, are the anti-oxidant, α-lipoic acid and the aldose reductase inhibitor, epalrestat.Management of the patient with DPNP must be tailored to individual requirements and will depend on the presence of other comorbidities. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00083.x).

View Article: PubMed Central - PubMed

Affiliation: Royal Hallamshire Hospital, Sheffield, UK.

ABSTRACT
There is now little doubt that poor blood glucose control is an important risk factor for the development of diabetic peripheral neuropathy (DPN). Furthermore, traditional cardiovascular risk factors for macrovascular disease appear to be associated with an increased risk of DPN. The recently established International Expert Group on Diabetic Neuropathy has recommended new criteria for the diagnosis of DPN in the context of clinical and research settings. Studies in experimental diabetes examining the pathogenesis of DPN have identified a number of metabolic abnormalities including polyol pathway hyperactivity, increased advanced glycation end-point formation, alterations in the protein kinase C beta pathway through diacylglycerol and oxidative stress. There is now strong evidence implicating nerve ischemia as the cause of DPN. Studies in human and animal models have shown reduced nerve perfusion and endoneurial hypoxia. These endoneurial microvascular changes strongly correlate with clinical severity and the degree of nerve-fiber pathology. Unfortunately, many compounds that have been effective in animal models of neuropathy have not been successful in human diabetic neuropathy. The only compounds found to be efficacious in human diabetic neuropathy, and are in clinical use, are the anti-oxidant, α-lipoic acid and the aldose reductase inhibitor, epalrestat. Overall, the evidence emphasizes the importance of vascular dysfunction, driven by metabolic change, in the etiology of DPN, and highlights potential therapeutic approaches. Epidemiological data on diabetic painful neuropathic pain (DPNP) are limited. In one population-based study, the prevalence of DPNP, as assessed by a structured questionnaire and examination, was estimated at 16%. It was notable that, of these patients, 12.5% had never reported symptoms to their doctor and 39% had never received treatment for their pain. Thus, despite being common, DPNP continues to be underdiagnosed and undertreated. Pharmacological treatment of DPNP include tricyclic compounds, serotonin noradrenalin reuptake inhibitors, the anti-oxidant α-lipoic acid, anticonvulsants, opiates, membrane stabilizers, topical capsaicin and so on. Management of the patient with DPNP must be tailored to individual requirements and will depend on the presence of other comorbidities. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00083.x).

No MeSH data available.


Related in: MedlinePlus