Large-fiber dysfunction in diabetic peripheral neuropathy is predicted by cardiovascular risk factors.
OBJECTIVE
Diabetic large-nerve fiber dysfunction, as measured by vibration perception threshold (VPT), predicts foot ulceration, amputation, and mortality. Thus, determination of modifiable risk factors is of great clinical importance.


METHODS
We assessed 1,407 patients with type 1 diabetes and a normal VPT participating in the EURODIAB Prospective Complications Study, at baseline mean +/- SD age of 32.7 +/- 10.2 years with diabetes duration of 14.7 +/- 9.3 years and follow-up of 7.3 +/- 0.6 years. VPT was measured using biothesiometry on the right big toe and medial malleolus. An abnormal result was defined as >2 SD from the predicted mean for the patient s age.


RESULTS
An abnormal VPT was associated with an increased incidence of gangrene, amputation, foot ulceration, leg bypass or angioplasty, and mortality (P < OR = 0.02). The incidence of abnormal VPT was 24% over the 7.3-year follow-up. Duration of diabetes and A1C significantly influenced the incidence of abnormal VPT (P < 0.0001). After correction for these, established risk factors for cardiovascular disease (CVD), including male sex (P = 0.0004), hypertension (P < 0.0001), total cholesterol (P = 0.002), LDL cholesterol (P = 0.01), smoking (P < 0.0001), weight (P < 0.0001), and diabetes complications (retinopathy [P = 0.0001], nephropathy [P = 0.01], and autonomic neuropathy [P = 0.001]), were all found to be significant risk factors. A previous history of CVD doubled the incidence of abnormal VPT.


CONCLUSIONS
This prospective study indicates that cardiovascular risk factors predict development of large-fiber dysfunction, which may account for the high mortality rate in patients with an abnormal VPT, and emphasizes the importance of early determination of VPT to detect subclinical neuropathy and to address cardiovascular risk factors.
Elliott
Jackie
J
Diabetes Research Unit, Royal Hallamshire Hospital, Sheffield, UK. jackie.elliott@sth.nhs.uk
Tesfaye
Solomon
S
Chaturvedi
Nish
N
Gandhi
Rajiv A
RA
Stevens
Lynda K
LK
Emery
Celia
C
Fuller
John H
JH
D000328:Adult; D002318:Cardiovascular Diseases / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D048909:Diabetes Complications; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000150:complications; D003929:Diabetic Neuropathies / Q000209:etiology* / Q000378:metabolism; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications; D008297:Male; D010465:Perception / Q000502:physiology*; D010523:Peripheral Nervous System Diseases / Q000209:etiology* / Q000378:metabolism; D011446:Prospective Studies; D012307:Risk Factors; D012684:Sensory Thresholds / Q000502:physiology; D012737:Sex Factors; D012907:Smoking; D055815:Young Adult
D008078:Cholesterol, LDL; D002784:Cholesterol