Alanine tied to diabetes, BP, lipid profile but not CAD

Plasma alanine or factors affecting alanine appear to contribute to an increased risk of diabetes, higher blood glucose, low-density lipoprotein cholesterol (LDL-C), and blood pressure (BP), but not coronary artery disease (CAD), reports a study.

A team of investigators applied single nucleotide polymorphisms that strongly (p<5 x 10^-8) correlated with plasma alanine as genetic instruments to large genome-wide association studies of CAD (63,108 cases, 296,901 controls), diabetes (90,612 cases; 583,493 controls), glucose (515,538 participants), lipids (LDL-C, high-density lipoprotein [HDL]-C, triglycerides, total cholesterol, and apolipoprotein B; >1.1 million participants), BP (757,601 participants), and body mass index (682,137 participants).

Sex-specific analyses were also performed due to the potential sex disparity. Finally, the investigators obtained the Mendelian randomization (MR) estimate per standard deviation increase in alanine concentrations using inverse variance weighting, followed by sensitivity analyses using weighted median, MR-Egger, MR-Pleiotropy RESidual Sum and Outlier, and MR-Robust Adjusted Profile Score.

Overall, genetically predicted plasma alanine correlated with a greater risk of diabetes (odds ratio [OR], 1.35, 95 percent confidence interval [CI], 1.06‒1.72), higher glucose (β, 0.11, 95 percent CI, 0.02‒0.19), LDL-C (β, 0.08, 95 percent CI, 0.04‒0.12), triglycerides (β, 0.25, 95 percent CI, 0.13‒0.38), total cholesterol (β, 0.14, 95 percent CI, 0.08‒0.20), apolipoprotein B (β, 0.12, 95 percent CI, 0.03‒0.21), and BP (β, 1.17, 95 percent CI, 0.31‒2.04 for systolic BP; β, 0.97, 95 percent CI, 0.49‒1.45 for diastolic BP), but not with CAD.

Of note, the positive associations of serum alanine with LDL-C and triglycerides were more noticeable in women than in men.

“Further studies are needed to clarify possible mechanisms,” the investigators said.

“Alanine is an amino acid commonly used as a nutritional supplement and plays a key role in the glucose-alanine cycle,” they noted.