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The American Heart Association now describes cardiovascular-kidney-metabolic (CKM) syndrome
as a continuum that starts with no risk factors, move through dysfunctional adiposity and metabolic
risk, and end at clinical disease. South Asian ancestry is named as a factor that pushes people
along it faster (Circulation 2023;148:1606). What that progression looks like at the level of circulating
metabolites, in Indians specifically, is largely unknown. Most metabolomic biomarker work has been
done elsewhere.
We set out to fill that gap with untargeted LC-MS plasma metabolomics in 261 Asian Indians
recruited across multiple centres: non-diabetic controls, prediabetes, type 2 diabetes (T2D), diabetic
kidney disease (DKD) and diabetic cardiovascular disease (DCD).
Of 214 annotated metabolites, 31, 33 and 30 were altered in T2D, DKD and DCD respectively, after
adjusting for age, sex and site. Ten of these, including cholic acid and several
lysophosphatidylcholines (LPCs), were already off in prediabetes and kept drifting as disease
progressed. the derangement starts well before anyone gets a diagnosis. Once complications set in,
the picture splits. DCD is a lipid story: LPCs, sphingosine-1-phosphate. DKD is a gut story:
microbiome-derived uremic toxins such as N,N,N-trimethylalanyl-proline betaine,
phenylacetylglutamine and indoxyl sulfate dominate, and a 12-metabolite panel built from them
separates DKD stages and tracks where serum creatinine goes next. What the two share is a drop
in carnitine, valine and short-chain LPCs, mitochondrial fatty-acid oxidation under strain, and with it,
loss of metabolic flexibility.
Put together, this gives us a compact, India-specific panel for catching CKM risk early. I'll close by
talking about how we're trying to make this kind of study less of a one-off: Emzing (formerly MSOne),
which automates annotation and statistics on LC-MS data, and Vault, where we're pooling studies
like this one so we can keep going back and asking it new questions. |