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Why Do South Asians Have A Higher Risk Of Developing Type 2 Diabetes And Heart Disease Than White Europids?

More and more people are suffering from type 2 diabetes and cardiovascular disease. These metabolic diseases are typically associated with being overweight or obese, but it has become evident that besides high body mass, ethnicity determines the risk of developing both type 2 diabetes and cardiovascular disease as well. For example, South Asians, who originate from the Indian subcontinent and compose 20% of the world population, have a higher risk of developing type 2 diabetes and cardiovascular disease compared to white Europids. Not only the presence of these diseases is more common in South Asians, they also develop the disorders at a lower age and have a higher chance to decrease as a result.

To be able to develop targeted treatments for type 2 diabetes and cardiovascular disease in South Asians, more insight into the pathophysiology of their increased risk is urgently needed. Previous research has focussed on finding differences in “classical” risk factors for these diseases between South Asians and white Europids. Classical risk factors include obesity, high blood pressure and elevated blood glucose and dyslipidemia (including elevated LDL-cholesterol). Indeed, South Asians have higher blood glucose and LDL-cholesterol levels. Interestingly, on average South Asians also have an unfavorable fat distribution pattern with relatively thin arms and legs and much abdominal fat. Besides, at a similar BMI, body fat percentage is higher in South Asians. Since fat in general and especially abdominal fat is known to contribute to the development of type 2 diabetes and heart disease, these classical risk factors explain at least part of the increased risk that South Asians have.

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Despite the presence of these predisposing classical risk factors in South Asians, they do not fully explain their excess risk of developing a cardiometabolic disease. Another factor that probably plays a role in type 2 diabetes and heart disease is inflammation. This is supported by many observations, like the fact that in white fat tissue many immune cells can be found interspersed between the white fat cells. And during the development of obesity, many more immune cells are attracted towards the white fat tissue that leads to inflammation of the fat. Thus, excessive activation of the immune system, as seen in obese people, could contribute to the development of type 2 diabetes and heart disease.

It was therefore investigated whether inflammation may differ between South Asians and white Europids. In the study, ten South Asian men and ten white men (all from the Netherlands) were compared. All subjects gave blood, a muscle biopsy, and a subcutaneous fat tissue biopsy. In these samples, gene expression of a large panel of immunological factors was measured. These factors are all indicators of specific immune cell types or other components of the immune system. In the blood, several immunological genes were differentially expressed between South Asians and white men, but it did not follow a specific pattern for which it could not be concluded that inflammation is specifically higher or lower in the blood of South Asians. In muscle and fat, however, especially the expression of the type 1 interferon signaling genes was lower in South Asians. Type 1 interferons are components of the immune system that have anti-inflammatory properties. This suggests that South Asians have less dampening of inflammation in metabolic tissues such as muscle and fat, which in turn may contribute to their increased risk of developing type 2 diabetes and heart disease.

The findings described in this article are described in the article entitled South Asian men have lower expression of IFN signaling genes in white adipose tissue and skeletal muscle compared with white men, published in the journal Diabetologia. The study was led by Patrick Rensen and Mariëtte Boon from the Einthoven Laboratory for Experimental Vascular Medicine in Leiden, the Netherlands.

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