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Tyrosine amino acids potential targets for diabetes treatment in South Asian men
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Levels of tyrosine, along with several other amino acids, are more strongly associated with increased diabetes risk in South Asian men than in European men, according to research published in Diabetologia.
“The study fits another piece in the jigsaw of complicated underlying reasons as to why South Asians are at such high risk of developing type 2 diabetes compared with European origin populations,” Therese Tillin, MSc, MBBS, of the University College London Institute of Cardiovascular Science, London, U.K. told Endocrine Today.
Tillin and colleagues prospectively analyzed a British population-based cohort from the Southall and Brent Revisited Study (SABRE) including 1,279 European man and 1,007 South Asian men aged 40 to 69 years without diabetes; 801 Europeans and 643 South Asians completed 19 years of follow-up.
“This is the first study that has looked at the links between amino acid levels, the building blocks of proteins, and the future development of diabetes in people of both European and South Asian origins living in one geographical area,” Tillen said.
The investigators set out to compare cross-sectional associations between amino acids, metabolic and obesity traits, along with longitudinal associations with incident diabetes.
Through nuclear magnetic resonance spectroscopy, the researchers built a profile of nine amino acids in blood samples collected at baseline, between 1988 and 1991.
“We found that higher levels of some amino acids, in particular tyrosine, were already present in non-diabetic South Asian individuals back then,” Tillin said. “Some of these amino acids, again especially tyrosine, more strongly predicted later development of type 2 diabetes in the South Asian people than in the Europeans in our study, even after adjustment for other risk factors such as obesity and insulin resistance.”
For every standard deviation increment of tyrosine, the adjusted OR for South Asians to develop diabetes was 1.47 (95% CI, 1.17–1.85,) compared with 1.10 for Europeans (95% CI, 0.87–1.39) (P = .045 for ethnicity × tyrosine interaction).
Serum concentrations of isoleucine, phenylalanine and alanine were also higher in South Asians, but cross-sectional correlations of amino acids and glycemia and insulin resistance were similar between ethnic groups. Most amino acids showed weaker correlations with measures of obesity in South Asians.
Diabetes developed in 227 (35%) South Asians and 113 (14%) Europeans, with stronger adverse associations seen between branched chain and aromatic amino acids and incident diabetes in South Asians.
“Although it is thought that increased levels of obesity around the waist level, diet, physical activity levels and genetic factors contribute, no study to date has been able to tease out fully the underlying causes for the markedly greater risk of developing type 2 diabetes experienced by South Asians compared with European origin populations,” Tillin said.
“Our findings suggest that amino acid disturbances, particularly tyrosine, may be a focus for future research, paving the way for better prevention and potentially for targeted treatments in South Asian individuals.”
The study design did not allow for detailed study of metabolism needed to understand why some amino acid levels were higher in South Asians and why they were more strongly linked to the development of diabetes in South Asians.
“Future studies in South Asians and comparable Europeans could examine in each ethnic group the role of different tissues such as liver, kidneys, adipose and muscle, in metabolic pathways which involve amino acids and their associations with impaired insulin sensitivity,” Tillin said. – by Allegra Tiver
For more information:
Therese Tillin, MSc, MBBS, can be reached at UCL Institute of Cardiovascular Science, Fourth Floor, 170 Tottenham Court Road, London W1T 7HA
Disclosure: Some of the researchers report being shareholders of Brainshake Ltd, a startup company offering NMR-based metabolite profiling.
Perspective
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Om Ganda, MD
Compared to people of European descent, South Asians have a higher incidence of developing type 2 diabetes, despite less overweight and obesity. The cause of this paradox remains a mystery.
We do know that South Asians have more insulin resistance, which makes them more susceptible to diabetes. But it is not clear if the insulin resistance is caused by genetic factors or other modifiable factors, such as diet, exercise habits and other lifestyle factors. Currently, there are no definite biomarkers to explain the increased risk of diabetes in any population.
It has also been known for almost 50 years that certain amino acids are elevated in people at increased risk of diabetes, and they correlate strongly with insulin resistance. We now have sophisticated technology to measure each of the 20 amino acids in our body.
In this study, Tillin and colleagues show that five of the amino acids, if elevated, increase the risk of subsequent development of diabetes years later in both Europeans and South Asians. They also show that this relationship was stronger for South Asians, than for Europeans, partly related to greater insulin resistance in South Asians. This was particularly true for tyrosine, one of those five amino acids, because it was a stronger biomarker than other amino acids in South Asians, compared with Europeans, even after accounting for their level of insulin resistance.
How tyrosine or any of the other elevated amino acids mediate the subsequent development of diabetes will require much further work.
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