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15 May 2016
Symptomatic polyneuropathy more common with increasing number of metabolic syndrome components
Data from the Health, Aging, and Body Composition (Health ABC) study show that regardless of glycaemic status, symptomatic polyneuropathy is more common in individuals with additional metabolic syndrome components; low high-density lipoprotein (HDL) cholesterol was implicated as one possible driver.
Callaghan BC, Xia R, Banerjee M, de Rekeneire N, Harris TB, Newman AB, Satterfield S, Schwartz AV, Vinik AI, Feldman EL, Strotmeyer ES; Health ABC study. Metabolic syndrome components are associated with symptomatic polyneuropathy independent of glycemic status. Diabetes Care 2016;39:801–807.
Objective: To determine whether the prevalence of symptomatic distal symmetric polyneuropathy (DSP) increased with increasing number of metabolic syndrome components independent of glycaemic status. The associations between the individual metabolic syndrome components and symptomatic DSP were also investigated.
Study design: Analysis of data from the Health, Aging, and Body Composition (Health ABC) study, a prospective cohort study in subjects aged 70–79 years at baseline.
Study population: 2,382 subjects (mean age 73.5 years, 48% male) had complete neuropathy outcome data and were included in cross-sectional analysis. Of these, 1,263 participants also had complete neuropathy outcome data at year 11 and were included in longitudinal analysis.
Key outcomes:

·       DSP was defined as neuropathic symptoms (questionnaire) plus at least one of three confirmatory tests (heavy monofilament, peroneal conduction velocity, and vibration threshold).

·       Secondary DSP outcomes included the three confirmatory tests, the peroneal compound motor action potential (CMAP) at the ankle and a 1.4-g (light) monofilament at the dorsum of the great toe.


Neuropathic symptoms were collected by questionnaire in response to the following questions: “In the past 12 months, have you ever had numbness, an ‘asleep feeling,’ a prickly feeling or tingling in your legs or feet?” and “In the past 12 months, have you ever had a sudden stabbing or burning pain, or a deep aching in your legs or feet?” The three confirmatory neuropathy tests included a peroneal motor nerve conduction velocity (CV) ,40 m/s, a vibration threshold>131 um, and inability to feel a 10-g (heavy) monofilament at the dorsum of the great toe in three out of four trials.

Multivariable logistic and linear regression evaluated the association of metabolic syndrome components with DSP in cross-sectional and longitudinal analyses.

Main results:

·       In the cohort, 21% had diabetes, 30% prediabetes, and 53% metabolic syndrome. The prevalence of DSP was 11.1%.

·       When stratified by glycaemic status, DSP prevalence increased as the number of metabolic syndrome components increased (p = 0.03).

·       For the primary outcome, diabetes (odds ratio [OR] 1.65 [95% CI 1.18–2.31], cross-sectional analysis) and baseline haemoglobin A1C (OR 1.42 [95% CI 1.15–1.75], longitudinal analysis) were the only metabolic syndrome measures significantly associated with DSP.

·       Waist circumference and low HDL cholesterol were significantly associated with multiple secondary neuropathy outcomes.

Authors’ conclusion: Independent of glycemic status, symptomatic DSP is more common in those with additional metabolic syndrome components. However, the issue of which metabolic syndrome components drive this association, in addition to hyperglycemia, remains unclear. Larger waist circumference and low HDL cholesterol may be associated with DSP, but larger studies with more precise metabolic measures are needed.


Polyneuropathy (DSP) is the most common form of diabetic neuropathy and confers substantial morbidity (1). However, as enhanced glucose control has only a marginal impact in reducing the incidence in patients with type 2 diabetes, the relevance of other metabolic factors warrants investigation.

Previous studies have suggested an association between metabolic syndrome and polyneuropathy (2-5), although data for the individual components of the metabolic syndrome and neuropathy have so far been inconclusive, due to patient criteria (only diabetes patients enrolled) or study methodology (cross-sectional analysis). The current study, one of the largest to date to investigate this association, has attempted to address these deficits by enrolling normoglycaemic, prediabetic and diabetic individuals, as well as undertaking both cross-sectional and longitudinal analyses.  The results indicate that the presence of an increasing number of components of the metabolic syndrome increases the risk of symptomatic polyneuropathy. Information regarding the association with individual components of the metabolic syndrome, however, is less conclusive, although low HDL cholesterol was implicated as one possible driver. Indeed, each 10 mg decrement in HDL cholesterol was associated with a significant increase in neuropathic symptoms (by 9%, p<0.05), as well as a positive light monofilament test (p<0.05).

Given the high prevalence of both the metabolic syndrome and polyneuropathy in older adults, it may be that even small causal effects have substantial clinical impact. Further study is clearly warranted to further investigate the association of metabolic syndrome components, notably low HDL cholesterol, with the development of polyneuropathy.


1. Poncelet AN. Diabetic polyneuropathy. Risk factors, patterns of presentation, diagnosis, and treatment. Geriatrics 2003;58:16-8.

2. Bonadonna R, Cucinotta D, Fedele D, Riccardi G, Tiengo A; Metascreen Writing

Committee. The metabolic syndrome is a risk indicator of microvascular and macrovascular complications in diabetes: results from Metascreen, a multicenter diabetes clinic-based survey. Diabetes Care 2006;29:2701–7.

3. Costa LA, Canani LH, Lisbôa HR, Tres GS, Gross JL. Aggregation of features of the metabolic syndrome is associated with increased prevalence of chronic complications in type 2 diabetes. Diabet Med 2004;21:252–5.

4. Isomaa B, Henricsson M, Almgren P, Tuomi T, Taskinen MR, Groop L. The metabolic syndrome influences the risk of chronic complications in patientswith type II diabetes. Diabetologia 2001;44:1148–54.

5. Ylitalo KR, Sowers M, Heeringa S. Peripheral vascular disease and peripheral neuropathy in individuals with cardiometabolic clustering and obesity: National Health and Nutrition Examination Survey 2001-2004. Diabetes Care 2011;34:1642–7.

Key words symptomatic polyneuropathy, metabolic syndrome, HDL cholesterol