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Metabolic disharmony and mortality.

D B Allison¹, K R Fontaine, L J Cheskin

¹Obesity Research Center, St. Luke's/Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, NY 10025, USA. dba8@columbia.edu

Medical Hypotheses

|June 5, 2001

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Metabolic disharmony, a measure of unusual metabolic variable profiles, significantly predicts increased mortality risk. Higher disharmony levels correlate with a greater hazard of death, independent of individual metabolic factors.

Area of Science:

Metabolic Health
Biostatistics
Epidemiology

Background:

Metabolic harmony is defined as metabolic indices achieving expected values.
Metabolic disharmony quantifies joint unusualness of metabolic profiles.
Existing metrics do not fully capture the combined metabolic state.

Purpose of the Study:

Introduce and operationalize 'metabolic disharmony' (MD).
Investigate the association between MD and hazard of death.
Determine if MD predicts mortality independently of known risk factors.

Main Methods:

Defined metabolic harmony and disharmony.
Operationalized MD using Mahalanobis' D(2) statistic on metabolic indices, age, and sex.
Analyzed a large longitudinal cohort (N=5209, 32 years) using survival analysis.

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Main Results:

Metabolic disharmony index (DI) strongly predicted hazard of death (chi(2)(1) = 20.05, P < 0.00005).
A 10 percentile increase in DI associated with a 6.9% increase in hazard rate.
Association remained significant after adjusting for confounders and imputing missing data.

Conclusions:

Metabolic disharmony is a significant predictor of mortality.
MD may represent a novel, independent risk factor for death.
This metric offers a new perspective on metabolic health assessment.