Etiology of diabetes mellitus
Beta cells autoimmune destruction of the pancreas causes T1DM and includes both environmental and genetic factors. Due to genetic factors, the complicated nature of type 1 DM, various genes are involved, and the risk of a high sibling is relatively high (Schwartz et al., 2016, 179). The dizygotic twins have a type 1 DM concordance rate of between 5 and 6 percent. In contrast, monozygotic twins share diagnosis over half the percentage of time when the patient reach the age of 40 (Regnell and Lernmark, 2017, 1373). Extragenetic factors associated with the environment also have the potential of contributing to type 1 DM. Possible beta cells’ immunologically mediated destruction includes viruses like coxsackievirus, rubella, mumps, enterovirus, cytotoxins, cow milk exposure, when the child is still an infant, and toxic chemicals (Atkinson et al., 2014, 76).
The etiology attributed to type 2 DM tends to involve complicated exchanges between the factors between genetic and environmental factors. The existing presumption is that type 2 DM forms when a diabetogenic lifestyle superimposes on a susceptible genotype (Galicia-Garcia, 2020, 14). From a 2016 study by Cameron et al. between 2013 and 2016 in the United States, 41 percent of the adults with diabetes attributed their condition to obesity (Galicia-Garcia, 2020, 14). The highest attributable obesity-related diabetes was 53 percent among Caucasian women and 30 percent among African American men.
The similarity between type 1 and type 2 diabetes is that both occur when the body becomes incapable of properly storing and using glucose that is necessary for energy. The sugar then collects within the blood and fails to reach the cells that need it (American Diabetes Association, 2014, 64). This results in serious health complications. However, type 1 diabetes mellitus (T1DM) is an autoimmune health condition where the body weakens due to the absence of insulin. The health condition originates within the immune system when the antibodies meant to combat infections are changed into auto-antibodies and attack some of the body’s cells (American Diabetes Association, 2014, 65). Type 2 diabetes mellitus (T2DM) comprises a dysfunctional array resulting from insulin action resistance and characterized by hyperglycemia, inadequate secretion of insulin, and inappropriate or excessive glucagon secretion (Galicia-Garcia et al., 2014, 6). Therefore, when poorly controlled, T2DM becomes associated with neuropathic, macro as well as microvascular complications.
Characteristics that predispose one to diabetes
Genetically, type 2 DM is both complicated and non-complicated in how it is understood. Evidence has shown that multiple genes are involved in insulin resistance and beta cells’ pancreatic failure (Grarup et al., 2014, 1528). An associated study by Gruber (2015, 45) shows that the enhanced risk attributed to type 2 diabetes is identified from common dozens of genetic variants due to a wide genome association. The identified genetic variants are responsible for nearly 10 percent of the heritable components found in the majority of type 2 diabetes cases. The MODY (maturity-onset diabetes of youth), which is historically referred to has been recently understood to be a defect variety of beta cells age functions (Shields et al., 2012, 1268). MODY accounts for 2-5 percent of individuals with mild disease and type two diabetes at a young age (Shields et al., 2012, 1268). The trait can be screened through commercial laboratories and is autosomal dominant.
Studies have shown that environmental pollutants also contribute to the progression and development of T2 DM. To fully explore the extent of environmental pollutants, a planned and structured platform is required. In the case of secondary diabetes, occurrences take place when patients suffer from conditions antagonizing insulin action or among patients who take glucocorticoids.
Type 1 diabetes is an autoimmune condition where the immune system is activated to destroy pancreatic cells producing insulin. The cause of autoimmune reaction remains unknown and T1DM is not associated with modifiable lifestyle factors (Reddy, 2017, 45). T2DM is subject to modifiable lifestyle factors like excessive alcohol, smoking, and insufficient sleep. Since T2DM takes time to occur, it can be contributed to by intake of diet with high fat and low fresh fruits and therefore blood pressure levels and normal cholesterol maintenance have ability to minimize pre-diabetes and diabetes onset (Reddy, 2017, 46). In both T1DM and T2DM, ethnicity plays a significant role in their development (Reddy, 2017, 48). Some ethnic groups have been found to carry higher diabetes developing risks compared to others.
The presence of type 1 DM starts when an individual notices the outcome of pancreatic beta cells’ destruction associated with the Langerhans’ islets in the pancreas. With the decline in beta-cell mass, there is a decline in the secreted insulin until the available insulin becomes inadequate and incapable of maintaining normal blood sugar levels (Girard, 2017, 36). Once the beta-cells are destroyed, hyperglycemia forms to an extent ranging between 80 and 90 percent, and then diabetes is diagnosable. The solution to the complication is to use exogenous insulin to stop ketosis, turn around the catabolic condition, lipid metabolism, standardize protein, and decrease hyperglucagonemia (Eiji, 2014, 101). the presence of chronic inflammatory infiltrates the pancreatic islets at type 1 DM symptomatic onset. In patients with longstanding health conditions, the pancreas becomes devoid of insulin-producing cells, while the remaining beta cells become incapable of regenerating.
T2 Mellitus is a characteristic mixture of inadequate secretion of pancreatic beta-cells insulin and resistance in peripheral insulin. Insulin resistance is credited to fatty acids that are freely elevated, pro-inflammatory plasma cytokines, and decreasing sugar movement in the cell’s muscle (Chatterjee, Khunti, Davies, 2017, 2241). Further, insulin resistance increases fat breakdown and elevates hepatic glucose production (Chatterjee et al., 2017, 2241). Initially, type 2 diabetes results in islet paracrinopathy, where there is a loss in the reciprocal relationship between glucagon alpha cells and insulin secretion in beta-cells.
Signs and Symptoms of Diabetes
The significant difference between type 1 and 2 diabetes’ signs and symptoms is growing time. In type 1, symptoms begin to quickly show when the condition develops, in a couple of weeks, while in type 2, it might take up to several years before the symptoms begin to show. With many people with type 2 diabetes live without symptoms until diagnosed with diabetes-related complications, like heart trouble or blurred visions, it is significant to point out the symptoms associated with T2D as those associated with T1D (Gruber, 2015, 47). Therefore, the symptoms of diabetes can be generalized as increased urination and thirst, increased hunger, blurred vision, and fatigue. Others include unintended weight loss, recurrent infections, itchy or deadness on hands or feet, and slow-healing sores (Galicia-Garcia et al., 2020, 16). Warning signs such as enhanced hunger, thirst, and urination relate to the condition’s pathophysiology from increased fats and glucosebreakdown due to insulin resistance. Further, the warning signs are also associated with the inability to maintain blood sugar levels in the body.
How the ADA (American Diabetes Association) diagnoses both type 1 and 2 diabetes comprises of the following: (i) an accidental plasma glucose 11.1 mmol/L or ≥200 mg/dL among clients having a classic hyperglycemic crisis or hyperglycemia symptoms (ADA, 2014, 66). (ii) A 2-hour plasma glucose 11.1 mmol/L or ≥200 mg/dL during a 75-g OGTT (oral glucose tolerance test) (ADA, 2014, 66). (iii) An FPG (fasting plasma glucose) level 7.0 mmol/L or ≥126 mg/dL (ADA, 2014, 66). Further, the ADA (2021, 517) shows that it is not compulsory for T1D screening among asymptomatic low-risk diabetic patients. However, it is appropriate in high-risk patients to carry out an annual screening for anti-islet antibodies before their tenth birthday and one additional screening in the child’s adolescent years.
Metformin is used in treating type 2 DM since it helps prevent its development if the patient has an elevated budding risk of the condition. It helps regulate blood sugar by enhancing how the body handles insulin. When exercise and diet alone are not sufficient, metformin is prescribed to control blood glucose levels (Leslie et al., 2016, 16). In insulin resistance response, exogenous insulin is used in helping the body carry out the mentioned steps. Holst (2021, 2471) shows that in hemoglobin A1c tests, blood amounts are measured in the body concerning hemoglobin. Once diagnosed with diabetes, the test helps monitor patients’ condition and their glucose levels. The test addresses the condition by identifying diabetes or keeping track of how well the condition can be controlled.
Cellular Basis of Diabetes
The genetic contribution to T1D also reflects within the essential variances in the disease’s frequency. At chromosome 11p15.5, the insulin gene (INS) that encodes the pre-proinsulin peptide is next to the variable number of tandem repeats (VNTR) polymorphism (Oram et al., 2016, 338). Variations in VNTR alleles promote either susceptibility or resistance to T1DM through the impact associated with INS transcription within the thymus. Other genes involved in type 1 diabetes mechanism comprise PTPN22, which produces the negative T-cell kinase signaling regulator LYP and UBASH3A, and their involvement increases risk of type 1 diabetes (Regnell and Lernmark A. (2017, 1378). The other genes constitute CTLA4, an effective T-cell activator, IL2RA, involved in T-cell function regulation, SH2B3, PTPN2, and CLEC16A, to list a few.
T2D, the most familiar diabetic type, makes up most of the cases associated with the disease. The condition mainly appears in adulthood; however, younger generations are increasingly being identified with it. In T2D, while the pancreas exists and continues to produce insulin, the tissues fail to respond immediately due to insulin resistance (Chatterjee et al., 2017, 2245). With time, insulin levels decline; however, this is not the principal effect attributed to T2D. The main challenge with T2D, as already established, is that a majority of its patients do not realize they have it until when diagnosed with cancer-related complications.
Several genetic variants have been associated with insulin resistance and the functioning of the beta-cell role, including the single-nucleotide polymorphisms (SNPs), which appear to enhance the risk of acquiring T2D (Galicia-Garcia et al., 2020, 17). More than 40 independent loci demonstrate a relationship with an increase in type 2 diabetes risks. Some of the most potent subsets of the loci include; FSADS, which alters unsaturated fatty acids metabolism, TCF7L2, PPARG, HHEX, MTNR1B, among others (Chatterjee et al., 2017, 2245). del et al. (2021, 1225) argue that the susceptibility attributed to T2D likewise tends to be affected by genetic variants, which involve incretin hormones released from endocrine cells within the gut. The vulnerability also stimulates insulin secretion as a response to food digestion.
Epigenetic is the mitotically heritable changes in gene expression that indirectly alters DNA sequence. By implication, the epigenetic changes are non-genetically determined and they can be impact by inherited variations in the genes. In T1DM, non-genetic effects can alter gene translation and transcription resulting in diabetic risk and insulin secretion. The key biological processes like apoptosis in pancreatic beta cells are affected through gene expression (Rose et al., 2018, 1926). In T2DM, with the epigenetic mechanisms being responsible in a decline in beta cell proliferation, the decline is enhanced with age (Rose et al., 2018, 1927). From genome-wide DNA maps, methylation pattern in beta cells affect beta cells function via epigenome modulation where the enhancers near the proproliferative gene loci involved in metabolism of glucose undergo demethylation.
Immunity and Wound Healing
The immune system’s role is to keep the body free from infections caused by viruses, bacteria, and tumors. Problems with the immune system, like other organ systems, can lead to the development of chronic conditions like diabetes. In several ways, the immune system combats the infections. In the etiology of T1DM, an organ-specific autoimmune disease affects how the pancreatic beta cells produce insulin (Eiji, 2014, 99). The condition is characterized through pancreatic beta cells selective destruction and defined by a decline in the cell’s mass with mononuclear cells infiltration into the Langerhans islets (Regnell and Lernmark, 2017, 1379). Cell-mediated immunity, therefore, highly likely plays an essential role in T1D’s pathogenesis.
According to Gruber (2015, 54), LADA (latent autoimmune diabetes in adults) is a disorder where despite islet antibodies being present at diabetes diagnosis, there is a slow progression of autoimmune beta cells failure. Based on Carry et al. (2021, 1595), the first six months after diagnosis has taken place, and patients do not have to use insulin for at least six months. However, the features offered in both T1D and T2D differ. This classic autoimmune condition is frequent in type 1 patients, who are over thirty years when diagnosed.
Diabetic foot ulcers are diabetic progression components that are devastating and result from glycemic control loss, immunosuppression, peripheral vascular disease, and peripheral neuropathy. Peripheral neuropathy, secondary to diabetes, is a factor associated with diabetic foot ulcer etiology resulting in the amputation of 84 percent of the patients with the condition (Wade and Harry, 2015, 28). Reperfusion is blood flow restoration to tissues or an organ. Once a heart attack occurs, an immediate objective is to quickly open the arteries blocked and reperfuse the heart’s muscles.
Loss or lack of insulin is primary to type 1 diabetes and occurs when there is damage to the cells reproducing insulin. The importance of insulin within the body is to move blood sugar into cells. The deficiency resulting from the loss or destruction leaves too much glucose in the blood but insufficient cells (Leslie et al., 2016, 17). Insulin resistance, on the other hand, primary to T2D, occurs when insulin is generally produced in the body. However, the body cannot move the sugar into the cells for energy (Girard, 2017, 39). Primarily, the pancreas creates more insulin to overcome resistance in the body, and eventually, the cells wear out.
Incretins are secreted gut hormones, from the enteroendocrine cells, into the blood several minutes after eating. Holst (2021, 2272) shows the role of physiological incretins in regulating insulin secretion after eating. Two incretins exist; the GLP-1 glucagon-like peptide) and the GLP (glucose-dependent insulinotropic peptide) (Leslie et al., 2016, 19). In T2DM, GIP no longer modulates how the glucose-dependent insulin is secreted. When T2DM causes GIP to secrete insulin incompletely, it becomes detrimental to the function of beta cells.
The role of the liver in fuel metabolism revolves around maintaining blood sugar levels. During food consumption, excess glucose can be stored in the liver as glycogen. Gestational diabetes is the glucose intolerance resulting from variable severity with first or onset recognition at the time of pregnancy. The risk associated with gestational diabetes to the fetus and the mother is that insulin requirements are very high during pregnancy and cannot be met because of diabetes (Leslie et al., 2016, 19). The outcome causes beta cells dysfunction responsible for stimulating glucose disposal and suppressing fatty acids and glucose productions.
Diabetic neuropathy is the damage that occurs to the nerve when people have diabetes. In time, elevated blood glucose levels and elevated fat levels in the blood result from diabetes damages nerves. With several types, symptoms of diabetic neuropathy vary among patients. Concerning diabetes, uncontrolled high blood glucose interferes and damages nerves with their inability to send signals resulting in diabetic neuropathy (Gruber, 2015, 56). The clinical risk associated with diabetic neuropathy is that the potential to cause various chronic complications is high. The potential complications include hypoglycemia unawareness, sharp drops in blood pressure, urinary incontinence, and tract infections.
Kussmaul respirations are deep and rapid breathing at consistent paces that indicate metabolic acidosis or an accumulation of too much acid. The ADA (2021, 523) argues that when it comes to diabetes, insufficient insulin levels, relative to fats and lipids, produce acidic molecules, referred to as ketone bodies, when broken down. The upsurge of the ketone bodies within the blood brings out diabetic ketoacidosis, whose increase may lead to the development of Kussmaul respirations (Shields et al., 2012, 1271). Diabetic ketoacidosis (DKA) is characterized by metabolic acidosis, moderate hyperglycemia, and serum ketones presence with high anion gaps (Garro de Morales et al., 2019, 17). The risk associated with DKA is an increase in respiratory failure that results in mortality and morbidity.
Polyuria is a term that is associated with a condition where a patient passes too much urine. When levels of glucose are too elevated, the body tries to eliminate the surplus glucose through urination. The kidney filters out the excess water and resulting in an increased urination need. Polydipsia relates to a term that describes the condition coming from excess thirst. Polydipsia results from a boost in blood sugar levels. When the levels are elevated, kidneys generate more urine to eradicate extra sugar from the body. The typical role of SGLT2 (sodium-glucose cotransporter 2) is to reduce blood sugar levels by increasing urinary sugar excretion (Galicia-Garcia et al., 2020, 56). In diabetes mellitus, SGLT2 factors are involved in the management of selection for persistent hyperglycemia management. The use of its inhibitors is necessary for diabetic nephropathy treatment and heart failure management.
Vascular alterations associated with diabetes comprise functional, structural, and anatomic changes resulting in multi-organ dysfunction. Diabetic macro and microvascular alterations are differentiated by the size of vessels since, in macrovascular alterations, the dimensions of vessels like capillaries are big. The modifications in diabetic microvascular vessels, on the other hand, are slight. The risks associated with diabetic vascular complications affect the peripheral retina, peripheral neuropathy, congestive heart failure, and death.
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