Type 2 diabetes mellitus: pathogenesis and genetic diagnosis
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REVIEW ARTICLE
Type 2 diabetes mellitus: pathogenesis and genetic diagnosis D. Himanshu 1 & Wahid Ali 2 & Mohd Wamique 2 Received: 29 April 2020 / Accepted: 17 September 2020 # Springer Nature Switzerland AG 2020
Abstract Type 2 diabetes mellitus (T2DM) is a heterogeneous condition that is related to both defective insulin secretion and peripheral insulin resistance. Beta cells are the major organ for secreting insulin hence, it is important to maintain an adequate beta-cell mass in response to various changes. Insulin resistance is a major cause of T2DM leads to elevated free fatty acid (FFA) levels which increases beta-cell mass and insulin secretion to compensate for insulin insensitivity. Chronic increase of plasma FFA levels results in disturbances in lipid metabolism, which contributes to decreased beta-cell function and lipotoxicity thus promoting T2DM. In the present review, we have discussed the process of beta-cell destruction, the role of genes in contributing to the fast increase in the progression of T2DM in detail. More than 130 variants in various T2DM susceptibility and candidate genes have been discovered to be associated with T2DM. Still, these variants elucidate only a small amount of total heritability of T2DM. Further, there is also an inventory of presently used therapeutic tools and a review of novel therapeutic approaches like incretinbased therapies or sodium-glucose transporter-2 inhibitors. Additionally, providing a concise but comprehensive update, this review will be essential to every clinician involved in the treatment of diabetes mellitus. Keywords Genetics . Type 2 diabetes mellitus . Insulin resistance . Obesity . Beta cell
Introduction Type 2 diabetes mellitus (T2DM) persists to be one of the major health problems worldwide. It is a metabolic disorder caused by hyperglycemia, which occurs due to inadequate pancreatic insulin secretion or insulin resistance in peripheral tissues [1]. T2DM is the outcome of a diverse interaction between genetic, epigenetic and environmental factors [2]. Long term defects in β-cells can affect insulin levels and may result in severe glucotoxicity effects on pancreatic cells resulting in impaired insulin secretion [3]. Insulin resistance is a condition in which cells fail to react to insulin appropriately and inhibit the activity of lipoprotein lipase as a consequence of modifying lipids
* Mohd Wamique [email protected] 1
Department of Endocrinology, King George’s Medical University, Lucknow, Uttar Pradesh 226003, India
2
Department of Pathology, King George’s Medical University, Lucknow, Uttar Pradesh 226003, India
and apolipoprotein by altering the catabolism [4]. These changes may contribute to increasing lipolysis and free fatty acid (FFA) into the blood that results in the disease phenotype. Among the different known factors, the most general cause of developing insulin resistance is obesity and overweight [5, 6]. T2DM also shows a strong inheritable genetic association with a family history, where disease risk increases up to 40%
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