the prevalence of type 2 diabetes mellitus ( t2 dm ) in korea is estimated to be 7.3% ( in those over 20 years of age ) , and it has increased about 5-fold over the past 30 years according to a report of the korea national health and nutrition examination survey ( knhnes iii , 2005 ) . the number of patients with t2 dm is expected to increase dramatically from about 3.2 million in 2011 ( 8.8% of the national population ) to about 4.25 million ( 11.1% ) by 2030 .
this enormous increase in the number of t2 dm patients will inevitably be accompanied by chronic diabetic microvascular or macrovascular complications . among the diabetic complications , diabetic peripheral neuropathy ( dpn )
is the most prevalent and troublesome complication in patients with diabetes mellitus ( dm ) .
diabetic neuropathy ( dn ) , which may be focal or diffuse , is diagnosed when diabetic patients complain of symptoms and/or show signs of peripheral nerve dysfunction after the exclusion of other etiologies .
peripheral neuropathic pain in diabetic patients is defined as pain arising as a direct consequence of abnormalities in the peripheral somatosensory system in people with diabetes .
the symptoms can be present as severe numbness , paresthesia , or hyperesthesia , however , dpn may be asymptomatic in about 50% of patients . as the dpn progresses , the painful symptoms usually disappear .
in addition , dpn is also associated with substantial morbidity , which includes not only a susceptibility to foot or ankle fractures and ischemic ulceration leading to lower - limb amputations , but also depression [ 11 - 13 ] . according to the seattle diabetic foot study , which included 749 diabetic patients
, there were a number of findings that independently increase the risk for dm foot ulcer , including certain foot deformities , reduced foot arterial perfusion , and both sensory and autonomic neuropathy .
diabetic patients with critical limb ischemia have high risks of lower limb amputation and death .
in addition to its influence on morbidity and mortality , painful symptoms in dpn have a significant detrimental impact on quality of life as the condition limits daily activities and interferes with sleep [ 16 - 18 ] .
considering the health - related economic viewpoint , diabetic foot disease significantly increases the health care costs in patients with dm . according to a retrospective study that analyzed insurance costs in the united states ,
the cost of care for patients with a foot ulcer is 5.4 times higher in the year after the first ulcer episode , but 2.8 times higher in the second year compared with that of diabetic patients without foot ulcers .
therefore , early detection and prompt intervention for dpn must be performed for patients with t2 dm .
the prevalence of dpn is generally estimated to be 10% to 50% in patients with t2 dm , and the incidence increases with age and duration of dm . the reported prevalence of dn in korea is variable , from 14.1% to 54.5% depending on the study population and the diagnostic method ( table 1 ) [ 21 - 24 ] . in the diabcare - asia 1998 study , which included 230 dm centers from 12 countries ( n=24,317 ) ,
the frequencies of retinopathy , microalbuminuria , and neuropathy were 21% , 39% , and 34% , respectively .
the prevalence of those complications was significantly higher in those patients with higher hemoglobin a1c ( hba1c ) levels .
a nationwide survey performed in 2006 by the committee of the korean diabetes association on the epidemiology of diabetes mellitus ( n=5,652 ) showed that the prevalence of dpn defined by neurologic symptoms or nerve conduction velocity abnormalities was 44.7% .
this prevalence was higher than the prevalence of microalbuminuria or retinopathy . in a prospective observational study among 508 korean t2 dm patients , diabetic foot disease occurred in 32 patients ( 6.3% ) , and the incidence of diabetic foot disease increased when peripheral neuropathy was present ( odds ratio [ or ] , 2.949 ; 95% confidence interval [ ci ] , 1.075 to 8.090 ) .
while chronic neuropathic pain is present in 13% to 26% of dm patients , it can be found not only in diabetic subjects , but also in impaired glucose tolerance ( igt ) or impaired fasting glucose individuals . according to a community - based cross - sectional study from the united kingdom , chronic dpn is common and often severe but frequently unreported and
interestingly , they showed that 12.5% of patients had never reported their symptoms to their doctors , and 39.3% never received treatment .
there are some studies about the relationships between dpn and other diabetic complications in korean t2 dm patients .
reported that the prevalence of cardiovascular disease ( cvd ) was higher in patients with dpn . in their multivariate analysis ,
dpn was independently associated with cvd ( or , 1.801 ; 95% ci , 1.009 to 3.214 ) in t2 dm patients ( n=1,041 ) , with a 52.8% prevalence determined by neurophysiologically diagnosing peripheral polyneuropathy based on electroneuromyographic findings .
a close relationship between peripheral sensory neuropathy and peripheral vascular disease was also reported independent of glucose level and other microvascular complications , in particular , retinopathy in t2 dm .
the association between cardiovascular risk factors and development of large - fiber nerve dysfunction , which was measured by vibration perception threshold , was reported in type 1 dm patients ( n=1,407 ) in the eurodiab prospective complication study .
hyperglycemia not only activates the sorbitol accumulation with a subsequent increase in cellular osmolarity , but it also shunts to the hexose pathway , producing oxidative stress and the formation of advanced glycation end products ( table 2 ) .
this damage leads to hyperexcitability in central neurons and the generation of spontaneous impulses within the axons as well as the dorsal root ganglion of these peripheral nerves .
most of the clinical practice guidelines , including those from the korean diabetes association , recommend that dpn screening should begin at the initial diagnosis of t2 dm and should be performed at least annually thereafter [ 34 - 36 ] .
the exclusion of non - diabetic causes of neuropathy , including alcoholism , vitamin b12 deficiency , endocrinopathies , vasculitides , heavy metal exposure , drug use , and malignancy , is important because these may account for 10% of the cases of neuropathy in people with dm .
though the symptoms can exist without signs , the severity of painful symptoms can be reliably assessed by the visual analogue scale or the numerical rating scale ( 0 , no pain ; 10 , worst possible pain ) .
in addition , validated scales and questionnaires such as the neuropathic pain symptoms inventory , the brief pain inventory , and the neuropathic pain questionnaires are widely used ( table 3 ) .
however , the nerve conduction study remains the most reliable , accurate , and sensitive method to evaluate peripheral nerve function , and it has been adopted as the gold standard .
this approach is not only time - consuming , expensive , and insensitive for the detection of small - fiber neuropathy , but also it is impractical to perform in an outpatient clinic setting .
however , the semmes - weinstein monofilament ( swmf ) test is simple to use as a screening tool to identify patients at risk for diabetic foot complication in the primary care setting .
the inability to sense the 10 g force pressure is considered as insensate and an independent predictor for higher risk of foot ulceration .
considered the swmf test as a useful screening tool for dpn . the nerve conduction study ( ncs )
was used as a gold standard to compare the sensitivity and the specificity of the swmf test .
the results were considered as abnormal if the patient could not perceive the 5.07/10 g swmf at more than four of ten sites ( 37 t2 dm outpatients ) . the sensitivity and
the specificity at two sites ( the third and fifth metatarsal head sites ) were 93.1% and 100% , the same as at the ten sites .
it is likely that the two - site swmf test is a useful screening test for dpn as is the ten - site test . in a study of 126 diabetic patients ,
41% complained of dpn symptoms , and swmf and vibration perception were more impaired in patients with subjective sensory symptoms . in 82 diabetic patients , the medial plantar sensory ncs provided a more sensitive diagnosis of dpn , even in patients with normal range measurements in the sural nerve .
the medial plantar sensory nerve action potential was abnormal in 46.7% of the symptomatic and 14.3% of the asymptomatic diabetic patients with normal routine ncs in this study .
the medial plantar sensory ncs may be helpful in the diagnosis of subclinical dpn in the asymptomatic diabetic patient .
compared to the single test , the combinations of tests have a greater than 87% sensitivity in detecting dpn .
the aims of dpn treatment are to decrease the painful symptoms , to treat the specific pathogenic mechanism , and to prevent progression or subsequent complications .
most of all , strict diabetic control and correction of metabolic risk factors should be initiated .
the lifestyle intervention that improves glycemic control and decreases blood pressure with lipid profiles improves both the painful neuropathic symptoms and the intra - epidermal nerve fiber density .
these findings suggest that early diagnosis and prompt intervention may be of significant clinical benefit . for pharmacological treatment ,
first line therapy consists of tricyclic antidepressants ( tca ) , duloxetine , pregabalin or oxycodone ( table 4 ) .
if the pain is not controlled with first - line therapy , second - line therapy or combination therapy can be used , for which the potential side effects and possible drug interactions must be considered . topical treatment with a 5% lidocaine plaster or capsaicin is also considered .
randomized controlled trials have been performed for the treatment of dpn in korean patients with t2 dm using alpha - lipoic acid , pregabalin , or tramadol / acetaminophen combination treatment .
the neuropathic symptom score , assessed by the total symptom score , was improved after intravenous alpha - lipoic acid treatment at a dose of 600 mg / day for 14 days in 19 t2 dm patients compared to 13 control subjects ( p<0.05 ) .
open - label study with oral thioctic acid 600 mg once daily for 8 weeks ( n=61 ) also improved dpn symptoms without serious adverse effects in korean diabetic patients . in an open , randomized , comparative study conducted in 163 t2 dm subjects with dpn ,
tramadol / acetaminophen ( ultracet ) treatment ( n=79 ) for 6 weeks was as effective as gabapentin ( n=84 ) for the decrease of pain intensity , an increase in the quality of life , an increase in mood , and a decrease in sleep disturbance in the treatment of painful dn .
ten weeks of pregabalin treatment for patients with neuropathic pain ( dpn [ type 1 or 2 diabetes , n=18 ] , postherpetic neuralgia [ n=146 ] , or posttraumatic neuropathic pain [ n=76 ] ; n=162 pregabalin , n=78 placebo ) showed a significant reduction in the daily pain rating scale score with improvement in anxiety and a decrease in sleep disturbance . despite the improvement in treatment modalities for chronic pain in recent years , patients with dpn still continue to be inadequately treated .
the dramatic increase in the prevalence of t2 dm with its acute or chronic complications are a major health concern in korea .
screening of high risk individuals , early detection , and proper management of dpn in patients with t2 dm is urgently needed .
careful foot examination , active application of outpatient screening tools including the assessment of pedal pulses , and an organized diabetic foot - care program are needed . despite the improvement in treatment modalities for chronic pain in recent years ,
therefore , active pharmacologic treatment should be considered to relieve neuropathic pain and improve the quality of life in patients with t2 dm .
 diabetic peripheral neuropathy ( dpn ) , a common and troublesome complication in patients with type 2 diabetes mellitus ( t2 dm ) , contributes to a higher risk of diabetic foot ulcer and lower limb amputation . 
 these situations can negatively impact the quality of life of affected individuals . despite its high prevalence and clinical importance , most diabetes mellitus patients 
 not only do not recognize the presence of diabetic neuropathy , but also do not report their symptoms to physicians or other health care providers . 
 therefore , dpn is usually under diagnosed and undertreated . for early detection and appropriate intervention for dpn , 
 a careful history , physical with neurologic examination , and prompt treatment are needed in t2 dm patients . 
INTRODUCTION
PREVALENCE OF DPN IN KOREAN PATIENTS WITH T2DM
PATHOGENESIS AND MECHANISM OF DPN
DIAGNOSIS OF DPN
TREATMENT OF DPN
CONCLUSION