Type 2 diabetes mellitus is indicated as the most significant metabolic illnesses across world and is primarily caused by the interaction of two key factors. These include deficiencies in target tissues’ insulin sensitivity and pancreatic beta-cell production (Galicia-Garcia et al., 2020). The molecular procedures attributed to the production, release, and insulin levels in cells ought to all be tightly controlled for insulin to satisfy the demands. Flaws can cause the aetiology of T2DM in any system at play, which might result in a metabolic imbalance. The paper will explore type II diabetes focusing on relevant pathophysiological factors, causes, risk aspects, possible consequences, treatment modalities, and preventive strategies.
Pathophysiological Factors
Pre-proinsulin is created as a by-product of the production of insulin by beta cells. Various proteins in the ER help pre-proinsulin undergo a conformational change throughout the developmental phase to generate proinsulin. After being moved from the ER to the GA, proinsulin is split into C-peptide and insulin and then enters immature secretory vesicles (Galicia-Garcia et al., 2020). Until it is needed for release, insulin is retained in granule form once it has fully matured. A response to increased glucose levels is the primary reason for insulin secretion. It is crucial to remember that extra factors like hormones can also trigger insulin release. The main way that beta cells absorb sugar as blood glucose levels increase is through the solute transporter protein GLUT2, which also acts as a sensing element. After glucose is consumed, its catabolism begins, and the plasma membrane’s ATP-dependent potassium channels start to close, increasing the intracellular ATP/ADP ratio (Galicia-Garcia et al., 2020). Ca2+ now can enter the cell as a result of the membrane depolarizing and the current Ca2+ channels opening. The secretory insulin which has granules prime and fuse to the plasma membrane, resulting in insulin exocytosis, when the intracellular Ca2+ concentration rises.
Remarkably, unusually high blood glucose levels characterize the pathogenesis of a disease as a result of dysfunctional feedback loops involving insulin production and secretion. When beta cell malfunction occurs, the body’s ability to maintain physiologic glucose levels is limited because less insulin is produced. However, insulin receptor (IR) is also attributed to the decreased consumption of glucose in muscle, adipose tissue, liver and increased glucose synthesis in liver muscles (Galicia-Garcia et al., 2020). Even while both of these occurrences contribute to the pathogenesis of the disease and happen early on, ß-cell dysfunction usually shows up as a more serious state than IR. The development of T2DM, however, is accelerated by hyperglycaemia when both IR and β-cell dysfunction are present.
VLDLs, CMs, and their remnants (CMRs), which are heavy in triglycerides, carbs, and lipids that raise blood sugar, are widely present in the circulation as a result of the high-calorie Western diet (TG). Due to the increase in reactive oxygen species (ROS), inflammatory molecules are abnormally induced. Since oxidative stress is a well-known stimulator of inflammation, following a substantial meal, there will be a synergistic interaction between the two stages that amplifies the adverse effects (Galicia-Garcia et al., 2020). The persistent and dramatic increase in ROS levels significantly contributes to the aetiology of T2DM and IR.
Endoplasmic reticulum (ER) stress and superoxide (O2) production are consequent effects of a pro-oxidant environment. Other adverse outcomes include NADPH oxidase (NOX) activation, mitochondrial malfunction, and ER dysfunction (Galicia-Garcia et al., 2020). The five key mechanisms associated with increase of problems from diabetes are activated by an increase in O2 generation. The polyol process is expanded, the PKC isoform is triggered, the AGEs binding site with its activating ligands are created more frequently, and the hexamine system is overactive (Galicia-Garcia et al., 2020). These methods lead to many pro-inflammatory pathways being activated, ischemia-induced angiogenesis being hindered, and long-lasting epigenetic changes that continue to regulate the expression of pro-inflammatory genes.
Risk Factors and Causes
Notably, it is thought that type 2 diabetes has a substantial genetic component, which explains why it frequently runs in families. A person’s chances of having this disease increase if their parents or siblings have it because several genes are attributed to type II diabetes. Outstandingly, belonging to a racial or ethnic group has a higher risk compared to non-Hispanic whites, of contracting type 2 diabetes mellitus.
The chance of acquiring this disease is likely to increase with age. Around 45 years of age, type 2 diabetes risk starts to increase rapidly, and continues significantly after an age of 65 years (Roden & Shulman, 2019). Organ transplant is another risk factor for developing type 2 diabetes mellitus. To prevent a person’s body from rejecting the donor organ after a transplant, they must take medications for the rest of their life. Although many of these medications, such as tacrolimus or steroids, can either cause diabetes or worsen it, they all contribute to the success of organ transplants. When one is in good health, the pancreas produces insulin to assist the body in storing and utilizing the sugar from food (Roden & Shulman, 2019). Type 2 diabetes develops when one of the following conditions takes place. These include pancreas stops producing insulin, less insulin is being secreted by pancreas, and the body becomes insensitive.
Possible Consequences
Notably, type 2 diabetes mellitus may come along with short and long-term complications such as hypoglycaemia, which entails low blood sugar levels. If an individual uses insulin or a sulfonylurea medication, their blood glucose level could fall. In addition, blood glucose may drop significantly while taking these medications if one eats less than usual or is more active (Yadav et al., 2021). Other potential hypoglycaemia causes include some drugs and excessive alcohol consumption. Nephropathy is a long-term consequence of the type 2 diabetes mellitus. Kidney disease, also known as diabetic nephropathy, can compromise kidney function and necessitate dialysis or kidney transplantation if left untreated (Yadav et al., 2021). The kidneys can stop functioning because they will not be able to effectively clean the blood if the diabetes is uncontrolled (or poorly controlled).
Prevention Strategies
Type 2 diabetes is significantly avoided by adhering to a few simple rules, such as controlling weight, increasing activity, eating a healthy diet, and stopping smoking. However, people cannot bear full responsibility for behavior modification (Yadav et al., 2021). To make healthy choices simple, communities, media, the food industry, workplaces, healthcare professionals, families, schools, and workplaces must collaborate. Minimal alcohol intake and regular physical exercise would be helpful in the prevention of type 2 diabetes.
Treatment Modalities
Metformin is the most common therapy implemented for type 2 diabetes. This treatment may help keep blood sugar at a healthy level. Metformin is offered as pills that can be taken either before or after meal. As a side effect, metformin frequently leads to diarrhoea and general malaise. A person’s body secretes more insulin when they use sulfonylureas. However, glinides enhance stimulation of the pancreas resulting in release of more insulin (Roden & Shulman, 2019). They work more quickly than sulfonylureas and impact the body for a shorter period.
References
Galicia-Garcia, U., Benito-Vicente, A., Jebari, S., Larrea-Sebal, A., Siddiqi, H., Uribe, K. B., Ostolaza, H., & Martín, C. (2020). Pathophysiology of type 2 diabetes mellitus. International Journal of Molecular Sciences, 21(17), 1-34. Web.
Roden, M., & Shulman, G. I. (2019). The integrative biology of type 2 diabetes. Nature, 576(7785), 51-60. Web.
Yadav, R., Jain, N., Raizada, N., Jhamb, R., Rohatgi, J., & Madhu, S. V. (2021). Prevalence of diabetes related vascular complications in subjects with normal glucose tolerance, prediabetes, newly detected diabetes, and known diabetes. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 15(5), 1-7. Web.