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Unlocking the Key: Genetic Links to Diabetes in Asia

Diabetes is a fast-growing epidemic in Asia. With more than 60 percent of people with diabetes in the world living in Asia, it is a public health concern as the number of diabetes cases increases each year. Genetic studies on diabetes in Asian populations could therefore provide answers linking pathophysiology and genes that could pose increased risk of diabetes.

by Deborah Seah

Diabetes, one of the leading causes of deaths worldwide with 463 million adults aged 20 to 79 years having this chronic disease in 2019. This number is projected by the International Diabetes Federation to increase to a staggering 700.2 million by 2045 if current trends still persist. In South East Asia (SEA) alone, 88 million adults (20 – 79 years) are living with diabetes and is estimated to increase to 153 million by 2045. Diabetes-related health expenditure in 2019 was also estimated to be US$ 8 billion within the SEA region and will see an increase as the number of people with diabetes is expected to increase over the next few decades.

The term diabetes encompasses a number of categories depending on the pathophysiology. In general, diabetes is a long-term condition in which the body is unable to produce enough insulin or is unable to effectively use it for the homeostasis of blood glucose level. There are three main types of diabetes, type 1, type 2, and gestational diabetes.

Type 1 diabetes (insulin-dependent) occurs during childhood and is the most common cause of diabetes at that young age, however it still can occur at any age. Type 2 diabetes (non-insulin-dependent) on the other hand accounts for more than 90 percent of all diabetes cases in the world and results from the inability to effectively use insulin in the patient’s body. Gestational diabetes affects pregnancy women and is a result of hyperglycaemia, posing increased risk of complications throughout the pregnancy and during labour. Women with gestational diabetes and their children are at an increased risk of type 2 diabetes in the future.

Pre-diabetic conditions such as impaired glucose tolerance and impaired fasting glycaemia are also present throughout the SEA region, with a 3.1 percent regional prevalence. According to the IDF atlas, in 2019 31 million adults (20 – 79 years) in SEA have impaired glucose tolerance. The pre-diabetes stage is an intermediary condition in which blood glucose levels are between the normal set point and the diabetic level. Those with pre-diabetic conditions are at high risk of progressing to type 2 diabetes, however with proper measures in place and lifestyle changes the condition is still reversible.

Besides the hyperglycaemia, diabetes can also result in a number complication due to the increase in blood glucose or consuming certain types of diabetes medications. Hypoglycaemia is a common result when using insulin or sulphonylureas, a fine balance between sufficient lowering of blood glucose and intake has to be achieved. Other complications of diabetes include; diabetic ketoacidosis, diabetic retinopathy, peripheral neuropathy, vascular damage, and diabetic foot. Diabetes can also lead to an increased risk of diseases such as cardiovascular disease, and kidney disease.

The healthcare cost of treatment of diabetes and its related complication weighs heavy on both the patient and healthcare systems. Based on the report by IDF, treating complications of diabetes itself accounts for more than 50 percent of the direct health cost incurred by diabetics.

With this growing public health problem in Asia and across the world, better understanding of the genetic links to diabetes that is specific to Asian populations could potentially allow for the development of appropriate screening, preventive and therapeutic strategies in tackling the diabetes epidemic in Asia.

Genetic Links to Diabetes in Asian Populations

Published in May 2020, a group of international researchers conducted one of the largest GWAS meta-analyses of East Asian individuals. The study aimed to gain insights to genetic variants associated with type 2 diabetes in East Asians. In the study, a meta-analysis was carried our using GWAS data from 77,418 individuals with type 2 diabetes and 356,122 healthy controls. Results of the study published in Nature found 61 new genetic variants that are associated with type 2 diabetes in the East Asian population.

“We know diabetes is caused by a complex set of risk factors, such as BMI, that have varying effects on the disease across ancestries.” Said Assistant Professor Sim Xueling, of the National University of Singapore, Saw Swee Hock School of Public Health (SSHSPH) one of the co-authors of the study. “These findings expand the number of genetic variants associated with diabetes and highlight the importance of studying different ancestries.”

Another prominent finding from the study was that these genetic variants are able to interact with a number of nearby genes in different tissues to affect the development of type 2 diabetes. Some of these genes include those involved in skeletal muscle and pancreatic functions, alcohol metabolism, as well as genes associated with adipose tissue at the abdominal area.

Research in genetic links specific to Asian populations would serve as a valuable stepping stone towards precision medicine in diabetes. It will also increase understanding of how genes could be targeted for treatment strategy.

“Genetic variants are present in all our genomes, some of which predispose individuals to disease like type 2 diabetes Due to differences in population history, some variants are more common in one population than another. This study emphasizes the importance of including large numbers of individuals from different parts of the world in these studies so that we can better understand the cause of diseases. Singapore, with its multi-ethnic populations from different parts of the work, is an ideal environment for studying this.” Said Professor Tai E Shyong, Senior Consultant of the Division of Endocrinology at the National University Hospital, and Professor at SSHSPH.


Genetic Markers linking Diabetes and other Age-related Diseases

Besides the microvascular and macrovascular complications resulting from diabetes, it has also been found to be genetically linked to other types of age-related diseases. More specifically, type 2 diabetes has been discovered to share certain common genetic markers that could contribute to the development of both diseases.

A study conducted by the Mount Sinai School of Medicine identified through genome wide association study (GWAS) a number of single nucleotide polymorphisms (SNPs) that were associated with higher chance of developing type 2 diabetes and Alzheimer’s disease.

“Many of these SNPs are traced to genes whose anomalies are known to contribute to type 2 diabetes and Alzheimer’s disease, suggesting that certain diabetic patients with these genetic differences are at high risk for developing Alzheimer’s disease. Our data highlights the need for further exploration of genetic susceptibility to Alzheimer’s disease in patients with type 2 diabetes.” Said Dr. Giulio Maria Pasinetti.

Dr Pasinetti is The Saunders Family Chair and Professor of Neurology, currently the Program Director of the NIH funded Mount Sinai Center for Molecular Integrative Neuroresilience and the Chief of the Brain Institute Center of Excellence for Novel Approaches to Neurodiagnostics and Neurotherapeutics.

Development of Alzheimer’s disease is a known long-term complication of type 2 diabetes. Previous studies have also elucidated on this point and provided evidence of a causative role of diabetes for the onset and progression of dementia due to Alzheimer’s disease. With the millions of people suffering from type 2 diabetes worldwide, it puts stress on the individuals having to manage their condition daily as well as healthcare systems for the expenditure of resources. This is likewise for Alzheimer’s disease. Growing evidence suggesting a possibility that Alzheimer’s disease could be genetically linked to common chronic diseases such as type 2 diabetes is critical to propel the development of potential novel therapeutic interventions to target these at-risk groups.

Studies into the genetic link for diabetes in specific Asian populations will no doubt draw clearer insight to the higher number of cases and deaths from diabetes in Asia. These links could be further applied to developing strategies in prevention and treatment of diabetes. However, other issues such as the lack of healthcare resources, specialized services, and skilled health workers in certain parts of Asia would still pose a problem when addressing the diabetes epidemic in Asia. [APBN]


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