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New Method to Predict Prediabetes

Aug 24, 2019
Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Amber Satz, PharmD Candidate, LECOM School of Pharmacy

A new study revealed that plasma aspartic acid and asparagine levels predict prediabetes development; histidine plasma levels proved protective of prediabetes risk.  

While many diseases including diabetes are known to be highly genetic, there are no tests available to predict whether an individual will develop a disease. Pharmacogenomics has been developing tremendously and may provide accurate predictions in the future, but currently clinicians are only capable of predicting relative risk of a disease for a patient, based on genetic findings. Measurement of circulating plasma amino acids may serve as a helpful tool to predict patients’ future onset of prediabetes and type 2 diabetes.


Several studies have shown a correlation between certain amino acids and the development of diabetes years later. The mechanism by which elevations in plasma of certain amino acids links to the development of T2DM is currently unclear. The Framingham Heart Study correlated elevated levels of branched-chain amino acids, isoleucine, leucine, and valine, and aromatic amino acids, tyrosine, and phenylalanine, to incident T2DM 12 years later among a predominantly Caucasian cohort. The Malmo Diet and Cancer Study displayed the same results among another Caucasian cohort. The Insulin Resistance Atherosclerosis Study (IRAS) analyzed a multiethnic cohort and found a decreased baseline plasma level of glycine and increased levels of valine, leucine, phenylalanine, and glutamine/glutamate among participants with insulin resistance who later developed T2DM. Significant differences were observed among participants of different ethnic backgrounds.

While several studies have identified the correlation between elevations in amino acids and type 2 diabetes, a new study sought to identify if there is such a relationship between those and prediabetes. The Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study analyzed 70 participants (35 European American, 35 African American) who developed prediabetes, referred to as progressors, and 70 participants (35 European American, 35 African American) who maintained normal glycemic control, or nonprogressors, for 5.5 years. The hyperinsulinemic euglycemic clamp procedure was used to assess insulin sensitivity. Acute insulin secretory response to glucose (AIRg) was measured using the frequently sampled intravenous glucose tolerance test (FSIVGTT). 

Fasting glucose and insulin levels were used for the homeostasis model assessment (HOMA) of insulin resistance (HOMA-IR), an estimate of hepatic insulin sensitivity, and beta-cell function (HOMA-B). Mass spectrometry was used to profile amino acids.

Using a linear regression model and Pearson correlation coefficient, several conclusions were drawn from the results. Glycine levels were positively associated with insulin sensitivity. Alanine, glutamine/glutamic acid, isoleucine/leucine, phenylalanine, proline, tyrosine and valine were each inversely related to insulin sensitivity. Also, citrulline, glutamine/glutamic acid and tyrosine were positively associated with insulin secretion. In comparison to nonprogressors, progressors had higher level of aspartic acid/asparagine, glutamine/glutamic acid and phenylalanine. Progressors also had low levels of histidine. Using a stepwise logistic regression model, adjusting for age, sex and race, the levels of aspartic acid, asparagine, phenylalanine and histidine significantly predicted incident prediabetes.

With the results collected from this study, we can compare to what was seen previously in patients who developed type 2 diabetes. The strongest correlation to prediabetes was seen from plasma levels of asparagine and aspartic acid; histidine levels predicted decreased prediabetes risk. The only amino acid that was present in findings in both the T2DM risk prediction and prediabetes risk prediction was phenylalanine. The differences in these findings may be due to the ethnicity variances between the studies. Further longitudinal studies would be helpful in solidifying these outcomes before using amino acid plasma levels for predictions in practice.


Practice Pearls:

  • Previous trials displayed a correlation between certain plasma amino acids and the development of T2DM; a new study revealed a relationship between a new set of amino acid and prediabetes.
  •   Asparagine and aspartic acid plasma levels were linked to the development of prediabetes; histidine levels predicted decreased prediabetes risk.
  • With further research, amino acids could serve as a relatively easy and affordable method to predict patients’ risk for T2DM.


Reference for “New Method to Predict Prediabetes”:

Owei, Ibiye, et al. “Amino Acid Signature Predictive of Incident Prediabetes: A Case-Control Study Nested within the Longitudinal Pathobiology of Prediabetes in a Biracial Cohort.” Metabolism, vol. 98, 2019, pp. 76–83., doi:10.1016/j.metabol.2019.06.011.


Amber Satz, PharmD Candidate, LECOM School of Pharmacy