The human body is made of molecules that store its genetic information. This is Deoxyribonucleic acid (DNA). The function of DNA is to, generally, store this information safe as it is essential for when the organism is required to procreate and reproduce. During reproduction, part of the DNA from the parent organism is transferred to the offspring. Hence, beneficial traits get transferred to the offspring also. When the DNA undergoes any form of damage, it results in mutations. Mutations can occur from a wide range of causes ranging from errors by DNA polymerase II, which proofread new strands of DNA to correct any mismatch parings, to radiation poisoning, to exposure to carcinogenic substances like Ethidium Bromide and Aflatoxins. (EtBr). These mutations can lead to epigenetic disorders such as Sickle Cell disease and Cockayne's Syndrome. Diabetes Mellitus II or type II diabetes mellitus (T2DM) is connected to alterations at the genetic level. DNA methylation decreases the accessibility of DNA, which reduces or halts the transcription by blocking the binding od transcription factors. This directly affects gene expression (Ponnaluri et al., 2017).
Pathophysiology of Diabetes Mellitus II
90% of diabetes cases are type 2 diabetes mellitus. The disease involves a diminished response to insulin, referred to as insulin resistance. Insulin, during this stage, becomes ineffective, to which the body first responds by releasing excessive amounts of insulin in a bid to maintain glucose homeostasis in the blood. The levels then gradually reduce to below standard levels and resulting in Type 2 Diabetes Mellitus. Generally, the pathophysiology will involve the impaired regulation of the blood glucose by the liver, reducing the functionality of B-cells and their eventual failure. DNA Methylation has been shown to play a significant role in the development of Type 2 Diabetes Mellitus because it affects the ability of the pancreatic B-cells to secrete insulin. DNA methylation in tissues has been widely studied. However, it was a challenge to assess some tissues in humans, such as the pancreatic islets, skeletal muscle, liver, and adipose tissues without getting invasive.
Studies have found that increased DNA methylation in the NDUFB6 promoter results in a negative correlation with how it was expressed in skeletal muscle in Type 2 Diabetes Mellitus subjects. It directly influenced their insulin sensitivity. DNA methylation is a process that results in a methyl group being added to DNA. Pancreatic islets mainly secrete glucagon and insulin from its alpha and beta cells, respectively. The pancreatic B-cells are of more importance because they regulate glycemic episodes in the development of type 2 diabetes mellitus. In some studies, increased methylation levels of the promoter of the peroxisome proliferative activated receptor gamma coactivator 1 alpha (PPARGC1A), which is a coactivator encoding PGC1a, a key regulator of energy metabolism, was associated with its decreased expression in the pancreatic islets of patients with Type 2 Diabetes Mellitus. This was found to affect the insulin secretion stimulated by insulin secretion.
Systems Affected and their Association to Diabetes Mellitus II
The genetic alterations leading up to Type 2 Diabetes Mellitus affect several other organ systems and processes. The hepatic regulation of glucose levels in the blood and the renal system. The pancreatic b-cells work to reduce blood glucose concentration. However, in Type 2 Diabetes Mellitus, they are defective, and hence insulin shots have to be taken intravenously to keep the level of glucose concentration in the blood at moderate levels.
Hepatic System. Due to increased levels of glucose in the blood, the liver is overworked as it tries to remove the excess glucose. Due to the way the glucose in the blood is poorly regulated, Type 2 Diabetes Mellitus patients often suffer from hypoglycemic episodes or high blood sugar. These episodes can leave them fatigued.
Renal System. When there is excess glucose in the blood, the renal system ramps up its workload in trying to remove the excess glucose from the body through the urine (Cydulk, 2018). After blood passes through the nephron, the glomerular filtrate enters the tubules. Much of the water is reabsorbed back into the body to try and balance the glucose-water levels in the blood. This happens very frequently as the kidneys work double-time to remove the excess glucose. This results in frequent urination. The frequent urination also poses a risk of urinary tract infections (UTIs) for both men and women with Type 2 Diabetes Mellitus.
Metabolic System. Due to the always soring blood sugar levels, the glucose does not enter the cells because of the abnormally low levels of insulin hormone produced from the pancreatic b-cells. The body lacks the necessary means to convert the diet food into energy, which is usually through oxidative metabolism. This results in a lack of energy and an acute increase in the feeling of hunger.
Diagnostic Studies for Diabetes Mellitus II
The treatment of Type 2 Diabetes Mellitus has been approached from different angles. The currently available diagnostic studies include the plasma glucose specific tests which, often receive most of the recommendations from a majority of medical practitioners since, besides being cheap and easily available, they measure the amount of excess glucose in the blood.
The Fasting Plasma Glucose test. It is a simple diagnostic study of the plasma glucose levels, of which samples are usually obtained after not less than 8 hours of fasting. It is easy and cheap, with a relatively low amount of risk. It has been used for years now to diagnose prediabetes and diabetes. The glucose levels should remain at 100mg/dL for normal persons. Results ranging between 100 -125mg/dL are used diagnose for pre-diabetes (Hepler & Falck, 2018). Measurements of above 125mg/dL are considered diabetic.
The RPG. A diagnostic study that measures the resting or 'casual' plasma glucose. This test does not require fasting and the results can be obtained the same day. RPG measurements of between 140 and 199mg/dL are indicative of prediabetes (Hepler & Falck, 2018). A reading of above 200mg/dL would lead the doctor to diagnose the patient with diabetes. One of the more popular diagnostic studies is the capillary blood glucose measurements. The readings are taken using a meter. The gadget is easy to use and patients can self-monitor themselves using it. It, however, does not give more in-depth insights into a specific type of diabetes. It is recommended that higher than average readings be confirmed by a comprehensive laboratory diagnostic study, such as the one mentioned previously in this paper.
The Hemoglobin A1c. A diagnostic survey that measures blood glucose concentration over 2 or 3 past months. A1c level measurements of 5.7% - 6.4% confirm a prediabetes diagnosis, while anything higher than 6.5% is considered to be diabetic (Hepler & Falck, 2018). The study takes advantage of the fact that the hemoglobin circulates in the blood until the erythrocytes die, which takes about 120 days (approximately three months).
Subsequent Treatment Therapies
Diet therapy. Type 2 diabetes mellitus patients may be subjected to a diet with reduced total and saturated fats. They are advised to take complex carbohydrates instead. Different people have different rates of glucose absorption, and hence this can play in as a factor when type 2 diabetes mellitus patients are practicing diet therapy.
Exercise. Exercise is also a subsequent treatment that helps type 2 diabetes mellitus patients. It is also a recommended prevention method since exercise helps in increasing the GLUT-4 transporters in the muscles, improvement of regulation of glucose levels in the blood, improved blood flow to tissues sensitive to insulin hormone, and also a reduction in free fatty acid levels.
Insulin Therapy. One of the most rampant Type 2 Diabetes Mellitus therapies is insulin therapies. While in the past, this was a last resort, today, it is among the first treatment options for persons with type 2 diabetes mellitus. Since regular digestion influences insulin is taken orally, it has to be injected intravenously (Pippitt, Li, Gurgle, 2016).
Screening and Prevention
Type 2 Diabetes mellitus screening involves checking for abnormal blood sugar levels and also frequently monitoring or screening known type 2 diabetes mellitus adults of 40 - 70 years old. Testing is also recommended for obese people. Typical results warrant a re-check every three years. However, individuals with factors that contribute to Type 2 Diabetes Mellitus should screen more frequently.
Ponnaluri V. K, Ehrlich K. C, Zhang G, Lacey M, Johnston D, Pradhan S, Ehrlich M. (2017). Association of 5-hydroxymethylation and 5-methylation of DNA cytosine with tissue-specific gene expression. Epigenetics. Feb;12(2):123-138. doi: 10.1080/15592294.2016.1265713. Epub 2016 Dec 2.
Pippitt K., Li. M, Gurgle H. E. (2016). Diabetes Mellitus: Screening and Diagnosis. Am Fam Physician. 2016 Jan 15;93(2):103-109. https://www.aafp.org/afp/2016/0115/p103.html
Hepler, L., & Falck, S. (2018). Do I Have Prediabetes or Diabetes? Guide to Diagnosis and Management. Healthline. https://www.healthline.com/health/type-2-diabetes/a1c-fpgt-ogtt-tests
Cydulka R. K, et al., eds. (2018). Type 2 diabetes mellitus. In: Tintinalli's Emergency Medicine Manual. 8th ed. New York, N.Y.: McGraw-Hill Education; 2018. Accessed Nov. 26, 2018.
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