DIABETES MELLITUS
Maria Cristina Morales Rodríguez
Advanced Pathophysiology Analysis
MRU University (2025)
DIABETES:
A chronic metabolic disorder that appears when blood sugar (glucose) is too high and persists due to the insufficiency of the pancreas to produce insulin or when the body does not react adequately to the effects of insulin. This condition affects millions of people around the world and of any age. It is a chronic disease that can be managed with medication and lifestyle changes, representing a compromise in its stability by the health system because, in the long term, it could bring complications such as nephropathy, neuropathy, retinopathy, cardiovascular disease, which would worsen the health of patients, endocrine metabolic disease. Diabetes describes a metabolic disorder of multiple etiologies characterized by chronic hyperglycemia with disorders in the metabolism of carbohydrates, fats, and proteins due to defects in the secretion and/or action of insulin or both.
The molecular mechanism underlying diabetes
Diabetes is due to a disorder of insulin: a 5.8 KDa peptide hormone secreted by the pancreatic islets of Langerhans in response to elevated levels of nutrients in the blood. Its main function is to maintain blood glucose concentrations within a normal range. Concomitant hyperglycemia can cause irreversible changes in the chemical composition of molecules such as non-enzymatic glycosylation that favors oxidative stress. Knowledge of the relationship between the molecular basis of DM and non-enzymatic glycolysis and oxidative stress leads to a better interpretation of this entity such as insulin resistance and its chronic complications.
Diabetes is classified into two main types Type 1 Diabetes: is when the pancreas produces little or no insulin, which causes an increase in blood glucose, it is autoimmune, caused by the destruction of beta-pancreatic cells by the immune system, the presence of autoantibodies (anti-GAD, anti-IA2) have appeared, which help as markers of the progress of the disease. The lack of insulin due to its deficiency causes an inability in the blood glucose regulatory mechanism, which leads to an increase in this in the blood, hyperglycemia, and ketosis.
Type 2 Diabetes: It begins as insulin resistance, meaning that the body cannot use insulin properly, causing the pancreas to produce more insulin until it can no longer meet the demand. This insulin resistance occurs in peripheral tissues (liver, muscle, adipose tissue). The exact cause of type 2 diabetes is unknown, but some factors may contribute: genetics, sedentary lifestyle, excessive weight gain, these factors: chronic inflammation, oxidative stress, and mitochondrial dysfunction.
Molecular pathways: PI3K / AKT / regulates glucose uptake by insulin, endoplasmic reticulocyte (ER) stress, associated with alterations in fasting glycemia and/or glucose tolerance ( TGA), together with a state of insulin resistance (IR) that induces the overload of functions in b cells and the consequent activation of the ER (endoplasmic reticulum), this stress contributes to complications such as retinopathy and nephropathy through the MAPK pathway, related to inflammation and insulin resistance, the enormous capacity of beta cells to synthesize and secrete insulin is also what makes it vulnerable to chronic exposure to high levels of glucose and fatty acids, agents that contribute to beta cell failure in type 2 Diabetes.
3- Latest findings in Diabetes research
– Identification of a new risk factor for type 1 diabetes: Although it is known that type 1 diabetes is caused by an autoimmune attack on beta cells, which are responsible for insulin production, it has been discovered that proteins called hybrid insulin peptides (HIP) are found in the beta cells of people with type 1 diabetes and are recognized as foreign by their immune cells.
-a molecule to improve glucose monitoring: Dr. Wang has created a molecule that uses a different, non-enzymatic approach to continuously monitor blood glucose levels (this molecule is stable over long periods and can be easily integrated into miniaturized systems) -use of stem cells: for the regeneration of pancreatic beta cells -genetic therapies: aimed at improving insulin expression -addressing family inheritance: the importance of early intervention in the disease and its A1C results to improve the evolution and its complications
-use of immunotherapy to prevent immune cells from attacking beta cells and reduce the inflammatory process and personalize the treatment for each patient -intestinal microbiota and its role in insulin resistance -determination of BPA (a chemical substance present in many products of daily use), this has been found in many studies to have an immediate and direct effect on glucose levels -age, as one age there is a greater risk of contracting the disease, so a relationship is being established between these factors to improve disease prevention
4- Genetic, Environmental and Immunological Factors in Diabetes
Genetic factors: the risk of a child doubles if the patient developed diabetes before 11 years of age, however, if the mother and father have type 1 diabetes, the risk is 1/10, in many people, it can take years to develop the disease, however, type 2 diabetes has a greater link with family history, but may be closely related to environmental factors and lifestyle.
Environmental factors: Studies confirm that an increased risk of diabetes has been found in urban areas with poor air quality or changes in air quality, which could increase insulin resistance, quality of sociodemographic factors that influence family income, education if we add genetic predisposition, diet, and insufficient physical activity could explain the increase in the disease, the high rate of consumption of sugars and fat causes an increase in insulin resistance, sedentary lifestyle reduces insulin sensitivity, stress and lack of sleep impact on insulin secretion and glucose metabolism
Immunological factors: Type 1 diabetes (autoimmune disease) Infiltration of the target organ by mononuclear cells, humoral and cellular autoreactivity: autoantibodies and autoreactive T cells, the possibility of transfer by immune effects, the possibility of immune effects, the possibility of immunotherapy, HLA association (a protein found on the surface of nucleated cells and responsible for identifying self and foreign in the body) and association with other autoimmune diseases. In conclusion, it has been shown that autoreactive T cells attack beta cells.
Type 2 diabetes there is a low-grade inflammation both in subjects at risk and in subjects already carrying DM2, different alleles of genes that encode immune/inflammatory mediators, direct impact on the levels of these immune mediators of the main environmental factors involved in the pathogenesis of the disease: diet and physical activity, that is, chronic inflammation in DM2 is mediated by proinflammatory cytokines.
5- Therapeutic Implications and Evidence-Based Treatments
Conventional Treatment: is the medical management to control blood sugar levels, which includes lifestyle changes, such as weight loss or dietary changes and moderate exercise, the use of medications, the use of insulin in daily injections, and others may require the use of oral hypoglycemic agents, a complex carbohydrate diet (brown rice and cereals), fruits, vegetables, mature proteins and dairy products, the use of insulin for DM 1 and Metformin as first lines for DM 2
New evidence-based therapies: SGLT2 inhibitors (and other types of drugs that can be used for DM 2) that improve renal glucose excretion, GLP-1 receptor agonists, drugs such as Semiglutide, which not only helps control glucose but also weight loss, Latest generation DPP-4 inhibitors, these drugs act on the incretin system, improving insulin production and reducing glucose production in the liver, Personalized medicine to improve response, according to genetic, environmental and immunological profiles, use of long-acting insulin, combined therapies and cell-based genetic therapies, looking for ways to replace or protect pancreatic cells, encapsulated beta cell implants, coated with a protective membrane that isolates them from the immune system, allowing them to produce insulin without being attacked, stem cells, with the goal of creating insulin-producing cells from stem cells, genetic therapy and gene editing for diabetes prevention, the use of advances in glucose monitoring without punctures, use of devices such as the Freestyle Libre and the Dexcom G6, which maintain glucose in the interstitial fluid and provide painless readings. Pancreatic islet transplantation
6 – Conclusions
Diabetes Mellitus is a chronic, complex, endocrine-metabolic disease with multiple pathophysiological factors and a close genetic, environmental, and immunological interaction, which can cause damage to different organs and tissues such as the kidney, brain, nerves, retina, heart, and arteries. These changes in blood sugar in the body can cause death. It is one of the leading causes of blindness, kidney failure, heart attacks, brain stagnation, and amputations of the lower limbs, which is why it is important to advance research to develop therapeutic strategies that focus on organ protection and cell regeneration, with the hope of improving the quality of life of all patients and minimizing the complications associated with this disease.
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