Natural History of Peripheral Neuropathy in Patients with Non-Insulin-Dependent Diabetes Mellitus

Partanen, Juhani; Niskanen, Leo; Lehtinen, Janne; Mervaala, Esa; Siitonen, Onni; Uusitupa, Matti

doi:10.1056/nejm199507133330203

Cited by 578 publications

(398 citation statements)

References 17 publications

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“…We have shown that neuropathy progressed electrophysiologically at a rate comparable with other studies in patients with type 1 [28] and type 2 diabetes [29]. Alterations in nerve conduction velocity and amplitude have been considered to reflect underlying structural pathology of the myelinated fibres [30].…”

Section: Discussionsupporting

confidence: 80%

Sural nerve pathology in diabetic patients with minimal but progressive neuropathy

et al. 2005

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Aims/hypothesis: The early pathological features of human diabetic neuropathy are not clearly defined. Therefore we quantified nerve fibre and microvascular pathology in sural nerve biopsies from diabetic patients with minimal neuropathy. Methods: Twelve diabetic patients underwent detailed assessment of neuropathy and fascicular sural nerve biopsy at baseline, with repeat assessment of neuropathy 8.7±0.6 years later. Results: At baseline, neuropathic symptoms, neurological deficits, quantitative sensory testing, cardiac autonomic function and peripheral nerve electrophysiology showed minimal abnormality, which deteriorated at follow-up. Myelinated fibre density, fibre and axonal area, and g-ratio were normal but teased fibre studies showed paranodal abnormalities (p<0.001), segmental demyelination (p<0.01) and remyelination (p<0.01) without axonal degeneration. Unassociated Schwann cell profile density (p<0.04) and unmyelinated axon density (p<0.001) were increased and axon diameter was decreased (p<0.007). Endoneurial capillaries demonstrated basement membrane thickening (p<0.006), endothelial cell hyperplasia (p<0.004) and a reduction in luminal area (p<0.007). Conclusions/interpretation: The early pathological features of human diabetic neuropathy include an abnormality of the myelinated fibre Schwann cell and unmyelinated fibre degeneration with regeneration. These changes are accompanied by a significant endoneurial microangiopathy.

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Section: Discussionsupporting

confidence: 80%

Sural nerve pathology in diabetic patients with minimal but progressive neuropathy

et al. 2005

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“…Electrophysiological studies showed that muscle strength in diabetic patients correlated with fiber density and amplitude of the macromotor unit potential, suggesting incomplete reinnervation after axonal loss (32). Longitudinal studies suggest an average loss of compound muscle action potential amplitude at a rate of ϳ3%/year in patients with type 2 diabetes over a 10-year period (33). Further research should identify the role of the decrease in motor amplitudes on skeletal muscle strength and quality in subjects with diabetes.…”

Section: Statistical Analysesmentioning

confidence: 99%

Accelerated Loss of Skeletal Muscle Strength in Older Adults With Type 2 Diabetes

Park

Goodpaster²,

Strotmeyer³

et al. 2007

Diabetes Care

644

481

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OBJECTIVE -It has been shown that adults with either long-standing type 1 or type 2 diabetes had lower skeletal muscle strength than nondiabetic adults in cross-sectional studies. The aim of the study was to investigate longitudinal changes of muscle mass and strength in community-dwelling older adults with and without type 2 diabetes.RESEARCH DESIGN AND METHODS -We examined leg and arm muscle mass and strength at baseline and 3 years later in 1,840 older adults aged 70 -79 years in the Health, Aging, and Body Composition Study. Regional muscle mass was measured by dual energy X-ray absorptiometry, and muscle strength was measured using isokinetic and isometric dynamometers.RESULTS -Older adults with type 2 diabetes (n ϭ 305) showed greater declines in the leg muscle mass (Ϫ0.29 Ϯ 0.03 vs. Ϫ0.23 Ϯ 0.01 kg, P Ͻ 0.05) and strength (Ϫ16.5 Ϯ 1.2 vs. Ϫ12.4 Ϯ 0.5 Nm, P ϭ 0.001) compared with older adults without diabetes. Leg muscle quality, expressed as maximal strength per unit of muscle mass (Newton meters per kilogram), also declined more rapidly in older adults with diabetes (Ϫ1.6 Ϯ 0.2 vs. Ϫ1.2 Ϯ 0.1 Nm/kg, P Ͻ 0.05). Changes in arm muscle strength and quality were not different between those with and without diabetes. Rapid declines in leg muscle strength and quality were attenuated but remained significant after controlling for demographics, body composition, physical activity, combined chronic diseases, interleukin-6, and tumor necrosis factor-␣.CONCLUSIONS -In older adults, type 2 diabetes is associated with accelerated loss of leg muscle strength and quality. Diabetes Care 30

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“…1,2 The most common forms are autonomic neuropathy and distal symmetrical polyneuropathy (DSPN) the latter being the most diagnosed in patients with diabetes mellitus (DM). 1,[3][4][5] Its prevalence fluctuates between 8 and 40% according to the clinical criteria or laboratory tests used for its diagnosis. [3][4][5][6] Most DM patients with DSPN are asymptomatic 3,7 and are symptomatic only in 15% of type 1 and 4-13% of type 2 (T2DM) patients.…”

Section: Introductionmentioning

confidence: 99%

“…1,[3][4][5] Its prevalence fluctuates between 8 and 40% according to the clinical criteria or laboratory tests used for its diagnosis. [3][4][5][6] Most DM patients with DSPN are asymptomatic 3,7 and are symptomatic only in 15% of type 1 and 4-13% of type 2 (T2DM) patients. 6,8,9 Early diagnosis and treatment are of great importance because (1) DSPN is the chief risk factor for trophic lesions and lower limb amputations in DM patients, 6,8,10,11 and around 85-96% of patients with DSPN are asymptomatic; (2) on occasion, neuropathies due to other aetiologies occur, requiring differential diagnosis; and (3) treatment at an earlier stage should improve prognosis.…”

Section: Introductionmentioning

confidence: 99%

Thermal Threshold: Research Study on Small Fiber Dysfunction in Distal Diabetic Polyneuropathy

Jiménez-Cohl

Grekin

Leyton

et al. 2012

J Diabetes Sci Technol

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Abbreviations: (CI) confidence interval, (DM) diabetes mellitus, (DN) diabetic neuropathy, (DSPN) distal symmetrical polyneuropathy, (EMG) electromyography, (NC) nervous conduction, (SD) standard deviation, (SFN) subclinical small fiber neuropathy, (T2DM) type 2 diabetes mellitus, (TT) thermal threshold Keywords: diabetic neuropathy, thermal threshold, nervous conduction The most commonly used technique for diagnosis of diabetic neuropathy (DN) is nervous conduction (NC). Our hypothesis is that the use of the thermal threshold (TT) technique to evaluate small fiber damage, which precedes large fiber damage, could enable earlier diagnosis and diminish false negatives. Research Design and Methods:The study involved 70 asymptomatic patients with type 2 diabetes mellitus (T2DM) all being treated with oral hypoglycemic medication, and having negative metabolic control levels with glycosylated hemoglobin A1c greater than 7% and less than 8%. Diabetic neuropathy was their only evident complication. All other complications or other causes of neuropathy were discarded. Their time of evolution was 1 to 48 months since date of diagnosis of diabetes. Both thermal threshold and sensory and motor nervous conduction were determined in upper and lower limbs. Results:Nervous conduction was found normal in 81% and altered in 19% of patients (large fiber neuropathy). Thermal threshold was normal in 57% and altered in 43% of patients (small fiber neuropathy). In those with normal TTs, no case with an altered NC was found (p < 0.001). Patients with altered TTs could have normal (57%) or altered NC (43%). Thus, NC showed a high frequency of false negatives for DN (57% of 30 cases).The frequency of small fiber neuropathy found with the TT test was higher than that of large fiber neuropathy found with the NC test (p < 0.001) and was found at an earlier age. Conclusions:The TT test demonstrated a higher frequency of neuropathy than the NC test in clinically asymptomatic T2DM patients. We suggest that small fiber should be studied before large fiber function to diagnosis distal and symmetrical DN.

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Natural History of Peripheral Neuropathy in Patients with Non-Insulin-Dependent Diabetes Mellitus

Abstract: The prevalence of polyneuropathy among patients with NIDDM increases with time, and the increase may be greater in patients with hypoinsulinemia.

Cited by 578 publications

References 17 publications

Sural nerve pathology in diabetic patients with minimal but progressive neuropathy

Sural nerve pathology in diabetic patients with minimal but progressive neuropathy

Accelerated Loss of Skeletal Muscle Strength in Older Adults With Type 2 Diabetes

Thermal Threshold: Research Study on Small Fiber Dysfunction in Distal Diabetic Polyneuropathy

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