1 research outputs found
Small- and large-fiber neuropathy after 40 years of type 1 diabetes associations with glycemic control and advanced protein glycation: the Oslo Study
OBJECTIVE To study large- and small-nerve fiber function in type 1 diabetes of long
duration and associations with HbA1c and the advanced glycation end products (AGEs)
N-ε-(carboxymethyl)lysine (CML) and methylglyoxal-derived hydroimidazolone.
RESEARCH DESIGN AND METHODS In a long-term follow-up study, 27 persons
with type 1 diabetes of 40 ± 3 years duration underwent large-nerve fiber examinations, with
nerve conduction studies at baseline and years 8, 17, and 27. Small-fiber functions were assessed
by quantitative sensory thresholds (QST) and intraepidermal nerve fiber density (IENFD) at year
27. HbA1cwas measured prospectively through 27 years. Serum CML was measured at year 17 by
immunoassay. Serum hydroimidazolone was measured at year 27 with liquid chromatography–
mass spectrometry.
RESULTS Sixteen patients (59%) had large-fiber neuropathy. Twenty-two (81%) had smallfiber dysfunction by QST. Heat pain thresholds in the foot were associated with hydroimidazolone and HbA1c. IENFD was abnormal in 19 (70%) and significantly lower in diabetic patients
than in age-matched control subjects (4.3 ± 2.3 vs. 11.2 ± 3.5 mm, P , 0.001). IENFD
correlated negatively with HbA1c over 27 years (r = 20.4, P = 0.04) and CML (r = 20.5, P =
0.01). After adjustment for age, height, and BMI in a multiple linear regression model, CML was
still independently associated with IENFD.
CONCLUSIONS Small-fiber sensory neuropathy is a major manifestation in type 1 diabetes
of 40 years duration and more prevalent than large-fiber neuropathy. HbA1c and the AGEs CML
and hydroimidazolone are important risk factors in the development of large- and small-fiber
dysfunction in long-term type 1 diabetes