Higher body fat percentage is associated with enhanced temperature perception in NAFLD: results from the randomised Wessex Evaluation of fatty Liver and Cardiovascular markers in NAFLD with OMacor thErapy trial (WELCOME) trial

Diabetologia. 2016 Jul;59(7):1422-1429. doi: 10.1007/s00125-016-3966-8. Epub 2016 Apr 22.


Aims/hypothesis: The effect of n-3 fatty acid treatment on temperature perception as a sensory nerve function modality is uncertain. In patients with non-alcoholic fatty liver disease (NAFLD) both with and without type 2 diabetes, we: (1) tested whether 15-18 months' treatment with 4 g/day of docosahexaenoic plus eicosapentaenoic acid (DHA+EPA) improved hot (HPT) and cold (CPT) temperature perception thresholds and (2) explored factors associated with HPT and CPT, in a randomised, double-blind, placebo-controlled trial.

Methods: The effect of treatment (n = 44) on HPT, CPT and temperature perception index (TPI: difference between HPT and CPT) was measured at the big toe in 90 individuals without neuropathy (type 2 diabetes; n = 30). Participants were randomised 1:1, using sequential numbering, by personnel independent from the trial team. All participants and all members of the research team were blinded to group assignment. Data were collected in the Southampton National Institute for Health Research Biomedical Research Centre. Treatment effects and the independence of associations were testing by regression modelling.

Results: Mean ± SD age was 50.9 ± 10.6 years. In men (n = 53) and women (n = 37), HPTs (°C) were 46.1 ± 5.1 and 43.1 ± 6.4 (p = 0.02), CPTs (°C) were 22.7 ± 3.4 and 24.5 ± 3.6 (p = 0.07) and TPIs (°C) were 23.4 ± 7.4 and 18.7 ± 9.5 (p = 0.008), respectively. In univariate analyses, total body fat percentage (measured by dual-energy x-ray absorptiometry [DXA]) was associated with HPT (r = -0.36 p = 0.001), CPT (r = 0.35 p = 0.001) and TPI (r = 0.39 p = 0.0001). In multivariable-adjusted regression models, adjusting for age, sex and other potential confounders, only body fat percentage was independently associated with HPT, CPT or TPI (p = 0.006, p = 0.006 and p = 0.002, respectively). DHA+EPA treatment did not modify HPT, CPT or TPI (p = 0.93, p = 0.44 and p = 0.67, respectively). There were no important adverse effects or side effects reported.

Conclusions/interpretation: Higher body fat percentage is associated with enhanced temperature perception. There was no benefit of treatment with high-dose n-3 fatty acids on the thresholds to detect hot or cold stimuli.

Trial registration: ClinicalTrials.gov NCT00760513 FUNDING: This work was supported by the National Institute for Health Research through the NIHR Southampton Biomedical Research Unit grant and by a Diabetes UK allied health research training fellowship awarded to KMcC (Diabetes UK. BDA 09/0003937).

Keywords: Insulin resistance; Microcirculation; Non-alcoholic fatty liver disease; Omacor/Lovaza; Small sensory nerves; Temperature perception threshold; Type 2 diabetes; n-3 Fatty acid.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Cardiovascular System / metabolism
  • Diabetes Mellitus, Type 2 / physiopathology
  • Docosahexaenoic Acids / pharmacology
  • Double-Blind Method
  • Drug Combinations
  • Eicosapentaenoic Acid / pharmacology
  • Fatty Liver / metabolism
  • Fatty Liver / physiopathology*
  • Female
  • Humans
  • Insulin Resistance
  • Male
  • Microcirculation / drug effects
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / physiopathology*
  • Temperature*


  • Drug Combinations
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid
  • Omacor

Associated data

  • ClinicalTrials.gov/NCT00760513