Early identification of metabolic syndrome risk: A review of reviews and proposal for defining pre-metabolic syndrome status

Nutr Metab Cardiovasc Dis. 2021 Aug 26;31(9):2557-2574. doi: 10.1016/j.numecd.2021.05.022. Epub 2021 May 27.


Aims: a) To analyze the relationship of known and emerging biomarkers/indicators for early risk identification of cardiometabolic health risk; b) to identify early risk markers to be used in both clinical and nonclinical settings; and c) to propose a definition of early risk identification in terms of pre-metabolic syndrome (PreMetSyn).

Data synthesis: Pubmed/Medline, Web of Science, Embase, and Cochrane were searched for Systematic Reviews and Meta-analysis. Selected studies were evaluated, and relevant data were extracted and synthesized.

Conclusions: Serum uric acid is a good predictive biomarker of metabolic syndrome (MetSyn) and has been associated with non-alcoholic liver fat disease (NAFLD) and type 2 diabetes. NAFLD emerges as an early risk indicator of PreMetSyn by itself. Muscle strength should also be included as an early risk marker of cardiometabolic health. High serum triglycerides and waist circumference confirm their predictive value regarding MetSyn. Indicators related to an inflammatory/pro-inflammatory status usually linked to MetSyn showed limited evidence as robust biomarkers for PreMetSyn. Authors suggest defining PreMetSyn related to cardiometabolic risk. It is also necessary to determine how close people are to the cut-off point of MetSyn components, including emerging indicators proposed by our review. Some biomarkers could be used as indicators of PreMetSyn, before any of the MetSyn components appear, allowing early health interventions to prevent its development. Defining a PreMetSyn status might consider both emerging indicators and those variables already included in the definition of MetSyn. New indicators should be considered to create a new risk score specifically meant for PreMetSyn.

Keywords: Biomarkers; Cardiometabolic health risk; Indicators; Metabolic syndrome components; Review; Risk score.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Biomarkers / blood
  • Cardiometabolic Risk Factors
  • Early Diagnosis
  • Health Status Indicators*
  • Humans
  • Metabolic Syndrome / blood
  • Metabolic Syndrome / classification
  • Metabolic Syndrome / diagnosis*
  • Metabolic Syndrome / epidemiology
  • Predictive Value of Tests
  • Prognosis
  • Risk Assessment
  • Terminology as Topic*


  • Biomarkers