Diabetes Risk in South Asian Men Linked to Tyrosine Levels

Liam Davenport

February 12, 2015

Serum levels of an amino acid are strongly associated with the risk for type 2 diabetes in South Asian men, potentially offering a target for novel treatments and prevention strategies, suggest the results of a new UK study.

The research, which spanned a follow-up period of almost 20 years, showed that increases in serum levels of tyrosine are associated with a 50% increased risk for diabetes in South Asian men, compared with an increase of just 10% among Europeans. Similar patterns were observed for other amino acids, but to a lesser extent.

"These findings suggest that higher branched-chain and aromatic amino acids, particularly tyrosine, may be a focus for identifying novel etiological mechanisms and potential treatment targets for diabetes in South Asian individuals and may contribute to their excess risk of diabetes," the researchers say:

The study was published online in Diabetologia on February 12.

Looking for the Cause of Excess Diabetes in Ethnic Minorities

Explaining the genesis of the investigation, lead author Therese Tillin, MD, from the UCL Institute of Cardiovascular Science, University College London, United Kingdom, told Medscape Medical News: "It goes back 25 years, really, when the migration of South Asians and African Caribbeans to the UK was toward the end of its peak, and all those migrants were reaching their middle years.

"It was becoming very apparent that South Asians and African Caribbean migrants were at markedly excess risk of diabetes and, for the South Asians, coronary heart disease, and that prompted the start of the [Southall and Brent Revisited] SABRE study, in Southall [in West London]."

The original research team looked at adipose tissue and various conventional risk factors known at the time, with the aim of "trying to unpick why there was such an epidemic of diabetes in these ethnic-minority groups," Dr Tillin said.

The current study represents the third wave of clinical follow-up. For this, Dr Tillin and colleagues used nuclear magnetic resonance spectroscopy to measure levels of nine circulating amino acids in serum samples taken in 1988–1991 from 1279 European and 1007 South Asian nondiabetic British men. At baseline, the men were aged 40 to 69 years.

Complete follow-up data for 19 years were available for 801 European and 643 South Asian men, of whom 14% and 35% developed diabetes after a median of 15 and 14 years, respectively.

Correlation, Not Yet Causality

The researchers found that serum concentrations of the amino acids isoleucine, phenylalanine, tyrosine, and alanine were significantly higher in South Asian men than in their European counterparts — the first time such an ethnic-specific association has been shown, although a weaker, but still positive, association between amino acids and diabetes has been reported in Europeans previously.

And while amino-acid levels were correlated with glycemia and insulin resistance to a similar degree in both groups, the strength of correlation between amino acid levels and obesity was weaker in South Asians, suggesting that obesity is not the most indicative risk for future diabetes risk in this patient population.

Overall, serum tyrosine levels were a much stronger indicator of diabetes risk in South Asian men than in European men, even after researchers controlled for risk factors such as obesity and insulin resistance.

For each one-standard-deviation increase in tyrosine levels, the adjusted odds ratio (OR) of developing diabetes among South Asian men was 1.47 ( P = .001), compared with an adjusted OR of 1.10 (P = .4) among European men. Further analysis revealed a significant interaction between ethnicity and tyrosine (P = .045).

A similar pattern was seen for phenylalanine, isoleucine, leucine, and valine, although the strength of association was not as great as with tyrosine.

Dr Tillin noted that the researchers are unsure as to why there is such a large difference in tyrosine-associated diabetes risk between European and South Asian individuals.

Nevertheless, she said that, although their study is population-based and not a detailed metabolic investigation, "it's highlighting something that does appear to be quite different.

"The fact that tyrosine is at such a high level compared with the other amino acids in the South Asians, although some of the other amino acid levels are quite high, does suggest that there's something going on there…[that] there might be a causal role for it," she added.

Targeted Therapies, Aggressive Prevention

The findings suggest that novel targeted therapies and more aggressive preventive strategies could be developed, Dr Tillin suggested. But "I think more research needs to be done at the detailed…tissue level to see what's going on in the muscle."

She said there is particular interest in the "central-obesity" story vs "lean muscle mass" and whether protein turnover is altered in South Asians, as that may be why tyrosine concentrations are higher.

"This is a first step. It's something that hasn't been shown before. It's been shown in European populations, but it hasn't been shown in South Asians alongside a comparable European population."

And while there are obviously some differences between the populations that may go some way to explaining the excess risk for diabetes seen in South Asians, such as diet and genetic makeup, "none of those factors have yet been shown to be causal," she observed.

So, if the study were to be repeated in South Asia, would Dr Tillin expect to see the same results?

"We obviously don't know about the amino-acid profile, but we do know that urbanization in south Asia is producing a very similar picture," she replied. "The migration from rural areas to urban areas is producing an explosion in the rates of [type 2] diabetes in the Indian subcontinent."

She said she believes there has been one small study in an Indian group, "which suggests an amino acid might be implicated, but without a comparator group, it's hard to know how that explains an excess risk. So hopefully we've just put another piece of the jigsaw in there."

The metabolomics analyses were funded by Diabetes UK. The SABRE Study was funded at baseline by the UK Medical Research Council, Diabetes UK, and the British Heart Foundation and at follow-up by the Wellcome Trust and British Heart Foundation. Dr Tillin reports no relevant financial relationships; disclosures for the coauthors are listed in the article.

Diabetologia. Published online February 12, 2015. Article

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