Diabetes (commonly used to refer to type 2 diabetes mellitus), is a chronic condition that affects how the body processes glucose, has long been understood to have a genetic component. The risk of developing diabetes is influenced by a blend of genetic predispositions and environmental factors, including diet and lifestyle choices. The other forms of diabetes such as type 1 diabetes, MODY (mature-onset diabetes in young), gestational diabetes etc. are also influenced by genetic factors, though there are specific mechanisms and risks vary. The relationship between genetics and diabetes is multigenic and complex.
The recent ICMR (Indian Council of Medical Research) report indicates that the prevalence of diabetes in India has increased by nearly 50% over the past decade, with an estimated 90 million people expected to be living with diabetes by 2030. Over half of these individuals are unaware of their diabetic condition, which could lead to serious health issues if not identified and treated.
Type 1 Diabetes typically manifests in childhood or early adulthood and is characterized by an autoimmune attack on the insulin-producing beta cells in the pancreas. While Type 1 diabetes was previously known as juvenile diabetes, it can develop at any age. Genetics play a significant role, but the exact cause can be multifaceted. Certain genetic markers, particularly within the HLA (human leukocyte antigen) gene complex, are associated with an increased risk. However, having the genetic predisposition does not guarantee the development of the disease. Autoantibodies that target pancreatic cells can be present years before symptoms arise, but not everyone with these autoantibodies will develop Type 1 diabetes. Environmental factors, such as viral infections and infant nutrition, also contribute.
Type 2 Diabetes, which usually develops in adults over 45 but increasingly affects younger individuals, is primarily linked to insulin resistance. Variants in several genes, including TCF7L2 KCNQ1 etc. have been strongly associated with an increased risk of type 2 diabetes. Family history is a significant risk factor, as individuals with relatives who have type 2 diabetes are more likely to develop the condition themselves. Lifestyle factors, such as obesity and sedentary lifestyle, interact with these genetic predispositions to increase risk. With urbanization and the rise of digital technology, many young people lead increasingly sedentary lives, spending long hours in front of screens with little physical activity. This lack of exercise contributes to weight gain and insulin resistance, key factors in the development of type 2 diabetes.
Gestational Diabetes occurs during pregnancy and is characterized by high blood sugar levels that can affect both the mother and the baby. Women who develop gestational diabetes often have a family history of diabetes, either Type 2 or gestational diabetes itself. This condition is associated with complications such as high birth weight and an increased risk of developing type 2 diabetes later in life. The prevalence of gestational diabetes is rising, influenced by increasing maternal age and weight.
By identifying specific genetic markers and variations, healthcare providers can develop customized management plans. Polygenic Risk Score (PRS) based screening tests analyze millions of genetic markers to determine an individual’s susceptibility to type 2 Diabetes and is typically a once in a lifetime screening test that can guide long-term lifestyle choices. Such screening tests provide information on one’s genetic predisposition to diabetes and empower individuals to make informed lifestyle and health decisions.
Dr Ramesh Menon is an Associate Director of Genomic Medicine & Personal Genomics Divisions at Bioinformatics Department, MedGenome Labs.
