Longitudinal assessment of diabetic polyneuropathy using a composite score in the Rochester Diabetic Neuropathy Study cohort

Abstract

Because there are little satisfactory data on change in severity of diabetic polyneuropathy (DP) over time from study of population-based cohorts of diabetic patients in epidemiologic surveys of DP, it is difficult to predict outcome or morbidity or to identify risk factors; it is also difficult to estimate statistical power for use in controlled clinical trials. In this longitudinal study of almost 200 patients from the Rochester Diabetic Neuropathy Study (RDNS) cohort, we assess which symptoms, clinical examinations, tests, or combinations of examinations and tests (composite scores) are best used as minimal criteria for the diagnosis of DP and as a quantitative measure of severity of DP. An abnormality (> or = 97.5th percentile) of a composite score that included the Neuropathy Impairment Score of the lower limbs plus seven tests (NIS(LL)+7 tests), was a better minimal criteria for DP than clinical judgment alone or previously published minimal criteria. First, it provided a more comprehensive assessment of neuropathic impairment. Second, it avoided the overestimated frequency of DP when the minimal criteria for DP was any one or two abnormalities from multiple measurements. Minimal criteria using nerve conduction and reduced heart beat response to deep breathing identified approximately twice as many patients with DP than did clinical examination and vibration detection threshold using CASE IV. This difference could be used to subclassify state 1 DP. Although various individual measures of DP, for example, vibration detection threshold (as evaluated by CASE IV and the 4, 2, and 1 stepping algorithm [see text]), were good measures of worsening, the composite score NIS(LL)+7 tests (assessing neuropathic impairment) was much better at showing monotone worsening. Using this composite score, the average diabetic patient in the RDNS worsened by 0.34 points per year, whereas patients with diabetic polyneuropathy worsened by 0.85 points per year. On the assumption that a therapeutic agent may prevent worsening of DP but not cause improvement, controlled clinical trials of patients with DP would need to be conducted for a period of 3 years to achieve a meaningful change of 2 NIS points (the level of abnormality considered by a Peripheral Nerve Society consensus group to be clinically meaningful).

Accelerated atrophy of lower leg and foot muscles—a follow-up study of long-term diabetic polyneuropathy using magnetic resonance imaging (MRI)

“…The present follow-up studies provide new insights into the progression of muscle dysfunction in diabetes in relation to neuropathy. Nerve function declines with diabetes duration [22] leading to denervation and loss of muscle strength in patients with neuropathy [7]. In the present study we have shown that muscle volume in the lower leg was more than halved during an observational period of 13 years in type 1 diabetic patients with severe neuropathy and that in patients with a milder degree of neuropathy one fifth of the foot muscle volume was lost over a decade.…”

“…Progressive deterioration of nerve conduction variables, autonomic tests, sensory detection thresholds and clinical examination scores can be slowed or prevented by tight glycaemic control [22,33,34]. To our knowledge, there is only one follow-up study on diabetic muscle mass and strength including older type 2 diabetic patients, but the participants were not characterised with respect to degree of neuropathy [27].…”

Long‐term Phase 1/2 intraspinal stem cell transplantation outcomes in ALS

“…While not applied previously in ALS to our knowledge, ALS/SURV is similar to the CAFS and composite statistics used in studies where endpoints involved nerve conductions 23, 24. When there is high mortality, combining functional status with survival duration has greater comparative power and provides additional insight into potential efficacy.…”

Standing balance and trunk position sense in impaired glucose tolerance (IGT)-related peripheral neuropathy

“…Our investigation was approved by the Institutional Review Board of the University of Michigan Medical School, and participants were consented according to the Declaration of Helsinki. The criteria for inclusion within this study cohort were evidence of symptomatic clinical peripheral neuropathy based on the Michigan Neuropathy Symptom Instrument (MNSI), Michigan Diabetic Neuropathy Score (MDNS) [24][25][26] and an abnormality in at least one of the following: (1) nerve conduction studies (NCS) of the median motor and sensory responses, tibial and peroneal motor responses and sural sensory response on the left sides, (2) CASE IV quantitative sensory testing (QST) (≥95 th percentile compared to gender and age matched controls for cold detection threshold (CDT) in the dorsal foot or vibration detection threshold (VDT) at the great toe) [27,28] or (3) quantitative sudomotor axon reflex testing (QSART) sweat volume (≤5 th % at one of four sites: medial forearm 75% of the distance from the ulnar epicondyle to the pisiform bone, the proximal leg, medial distal leg, and proximal foot [29,30]. Participants also required glucose measurements consistent with either IGT or impaired fasting glucose (IFG) on at least two separate tests of IGT or IFG, using current definitions for these disorders of glucose regulation [31].…”