February 1, 2024

A biomarker for early Type 2 diabetes

Genetic analyses suggest that branched chain amino acids may be a sensitive biomarker of early or subclinical Type 2 diabetes and could be used to identify risk and implement preventive measures.

Levels of the essential, branched-chain amino acids, valine, leucine and isoleucine, are involved in the regulation of lipid, glucose and protein metabolism.

Levels of these amino acids are elevated in individuals with impaired insulin secretion and obesity, and genetic studies have suggested that they may play a causative role in insulin resistance and metabolic disease, including Type 2 diabetes.

However, these studies examined a small number of genetic loci, or positions on the chromosome associated with these branched chain amino acids (BCAA), limiting the strength of evidence for a causal connection to Type 2 diabetes.

Using data derived from large-scale genome-wide association studies that have identified considerably more loci, Jonathan Mosley, MD, PhD, Jane Ferguson, PhD, and colleagues developed genetic instruments to identify BCAA-linked candidate genes and genetic variations and used an analysis known as reverse Mendelian randomization to test the causality hypothesis.

The results of their analysis, reported Jan. 25 in the journal Obesity, suggest that higher BCAA levels are the consequence of diabetes-related pathophysiology, including insulin resistance, and not a driver or mediator of disease.

The good news is that BCAA levels are a sensitive biomarker of early or subclinical Type 2 diabetes and thus may help identify risk so that measures can be taken to prevent the disease before it develops.

Co-authors of the paper are Mingjian Shi, MD, PhD, David Agamasu, Nataraja Sarma Vaitinadin, MBBS, PhD, MPH, Venkatesh Murthy, MD, PhD, Ravi Shah, MD, and Minoo Bagheri, PhD, MSc. The study was supported by National Institutes of Health grants R01DK117144, R01GM130791, R01HL142856 and K01HL165020.