Metabolic reasons of diabetes mellitus: An update

Abstract

Diabetes Mellitus (DM) goes beyond just a lack of insulin. Type 2 Diabetes Mellitus (T2DM) is heavily influenced by insulin resistance. Cells become less responsive to insulin’s signal to absorb glucose, leading to high blood sugar levels. Excess body fat, particularly around the abdomen, and a sedentary lifestyle are ley culprits for this resistance. The pancreas struggles to keep up with the demand for insulin in T2DM. Initially, it compensates by producing more, but over time, this ability declines due to factors like genetics and high blood sugar levels. Glucagon, normally working opposite insulin becomes imbalanced in T2DM. Its levels rise, further promoting glucose production and worsening hyperglycemia. The contributing factors include fasting, high protein diet, and pancreatic issues. The liver’s ability to regulate glucose production is impaired in T2DM. This dysregulation leads to the excessive release of glucose into the bloodstream, contributing to chronic hyperglycemia. Certain genetic disorders affecting carbohydrate metabolism can increase the risk of diabetes. These disorders can lead to changes that mimic pre-diabetes, further contributing to insulin resistance. In T2DM, increased lipolysis releases excessive free fatty acids (FFAs) into the blood stream. These FFAs worsen insulin resistance and damage insulin-producing cells, further exacerbating hyperglycemia. Obesity, with its high fat stores and increased lipolysis, is a major risk factor. The kidneys play a crucial role in reabsorbing filtered glucose from the urine. In T2DM, this reabsorption might be heightened contributing to hyperglycemia. Additionally, chronic kidney disease can impair glucose metabolism, potentially impacting diabetes management. While insulin deficiency plays a role, diabetes is a complex interplay of factors. Unravelling the intricate dance between insulin, glucagon, the liver and cellular responses is crucial for effective management and prevention of diabetes-related complications. This review delves into the intricate metabolic reasons behind this condition, focusing in Type 2 Diabetes Mellitus (T2DM).