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Research paper
Metabolic syndrome is related to polyneuropathy and impaired peripheral nerve function: a prospective population-based cohort study
  1. Rens Hanewinckel1,2,
  2. Judith Drenthen2,3,
  3. Symen Ligthart1,
  4. Abbas Dehghan1,
  5. Oscar H Franco1,
  6. Albert Hofman1,4,
  7. M Arfan Ikram1,
  8. Pieter A van Doorn2
  1. 1Department of Epidemiology, Erasmus University Medical Centre Rotterdam, Rotterdam, The Netherlands
  2. 2Department of Neurology, Erasmus University Medical Centre Rotterdam, Rotterdam, The Netherlands
  3. 3Department of Neurophysiology, Erasmus University Medical Centre Rotterdam, Rotterdam, The Netherlands
  4. 4Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA
  1. Correspondence to Dr M Arfan Ikram, Department of Epidemiology, Erasmus University Medical Centre, P.O. Box 2040, Rotterdam 3000 CA, The Netherlands; m.a.ikram{at}


Objective Diabetes mellitus is a known risk factor for polyneuropathy, but the role of pre-diabetes and metabolic syndrome remains unclear. We aimed to investigate the role of these factors in a community-dwelling middle-aged and elderly population.

Methods 1256 participants of the population-based Rotterdam Study (mean age 70.0, 54.5% females) were screened for polyneuropathy with a questionnaire, neurological examination and nerve conduction studies. Data on type 2 diabetes and components of metabolic syndrome were also collected. Logistic regression was used to investigate associations of diabetes, pre-diabetes and metabolic syndrome and its separate components with polyneuropathy. Linear regression was used to investigate associations with nerve conduction parameters in participants without polyneuropathy.

Findings Diabetes was associated with polyneuropathy (OR 3.01, 95% CI 1.60 to 5.65), while impaired fasting glucose was not (OR 1.55, 95% CI 0.70 to 3.44). Metabolic syndrome was associated with polyneuropathy (OR 1.92, 95% CI 1.09 to 3.38), with a stronger association when more components of the syndrome were present. Analysing separate components of metabolic syndrome revealed associations for elevated waist circumference (OR 2.84, 95% CI 1.35 to 5.99) and elevated triglycerides (OR 2.01, 95% CI 1.11 to 3.62). Similar associations were found after excluding participants with diabetes. In participants without polyneuropathy, metabolic syndrome associated with lower sural sensory nerve action potential amplitudes.

Conclusions Metabolic syndrome, abdominal obesity and dyslipidaemia, are strongly associated with polyneuropathy, irrespective of the presence of diabetes. Metabolic syndrome also associates with impaired nerve function in people without polyneuropathy. Our study therefore suggests that cardiometabolic disturbances have an impact on peripheral nerve function that extends beyond clinically manifest disease.

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  • Contributors RH, JD, OHF, AH, MAI and PAvD have made substantial intellectual contributions to conceptualisation and design of the study. RH, JD, SL and AD were involved in acquisition of data. RH, JD, MAI and PAvD were involved in analysis and interpretation of data. RH drafted the article. JD, SL, AD, OHF, AH, MAI and PAvD revised the manuscript critically for important intellectual content. All authors gave final approval of the version to be published. RH has full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

  • Funding The Rotterdam Study is funded by Erasmus Medical Centre and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The current study was funded by the Prinses Beatrix Spierfonds for neuromuscular diseases (grant number W.OR12-08) and a grant from the Janivo Foundation.

  • Competing interests AD is supported by Netherlands Organization for Scientific Research (NWO) grant (veni, 916.12.154) and the EUR Fellowship. OHF works in ErasmusAGE, a centre for ageing research across the life course, which is funded by Nestlé Nutrition (Nestec); Metagenics; and AXA. AH received grants from the Netherlands Organization for Scientific Research, the Netherlands Genomics Initiative, the Netherlands Ministry of Health and the European Commission; and remuneration as editor of the European Journal of Epidemiology. MAI received grants from the Netherlands Heart Foundation (2009B102 and 2012T008), Netherlands Organization for Health Research and Development (ZonMW: 916.13.054), Internationaal Parkinson Fonds, and Internationale Stichting Alzheimer Onderzoek (number 12533). PAvD received a grant from the Prinses Beatrix Spierfonds for neuromuscular diseases (grant number W.OR12-08) and a grant from the Janivo Foundation to conduct this study. Other, non-related, grants include grants from the Prinses Beatrix Spierfonds, Baxalta, Grifols and from Sanguin Blood Supply (for the conduct of prospective studies into treatment of GBS, CIDP and Pompe Disease).

  • Ethics approval The Medical Ethics Committee of the Erasmus Medical Centre and the Ministry of Health, Welfare and Sport of the Netherlands.

  • Provenance and peer review Not commissioned; externally peer reviewed.