This assignment will be looking at the pathophysiology of Type 1 diabetes, the effects this has upon Carol in terms of symptoms and how it may affect the developing embryo and foetus.
What is Type 1 Diabetes?
Diabetes type 1 is an organ specific autoimmune disease which develops in the pancreas and islet cell antibodies when the body’s immune system attacks and destroys insulin producing beta cells (Nelson-Piercy, 2005). This affects the metabolism of fats, proteins and carbohydrates as insulin facilitates the transformation of glucose to glycogen, changes glucose to fat and stimulates the oxidation of glucose for ATP production (Marieb and Hoehn, 2008). Insulin helps to maintain the homeostasis of blood sugar levels, increasing when levels are high and decreasing when low. This works by the insulin signaling pathway which includes an insulin receptor that is made up of two receptor subunits that are located on the outside of the cell membrane and two subunits that penetrate through the membrane. The extracellular subunits contain a binding site for insulin. When insulin binds to the extracellular subunits, it activates a chemical reaction that travels through the linked subunits into the cell. This sends chemical signals to proteins within the cell and causes them to alter their activity, which initiates the movement of glucose transporters to the cell membrane. Glucose transporters are the cells ' method for transferring glucose through the cell membrane from the blood and into the cell. The glucose transporters are ever present inside organelles however, they are useless to transport glucose without activation from insulin. The binding of insulin to the cell leads to a rapid movement of the vesicles to the cell membrane, where they fuse with it and insert the glucose transporters. This gives the cell the ability to open itself to the transfer of glucose from the blood. When blood glucose levels decline, insulin ceases to bind to the cell receptors and the glucose transporters are moved back into the cell 's cytoplasm.
Diabetes causes an imbalance to this natural process which has serious physiological and psychological effects on the individual with the condition.
Evidence suggests that type 1 diabetes may be triggered in predisposed individuals by genetic and environmental factors. Research has identified the MHC (major histocompatibility complex) on chromosome 6 as being connected to autoimmune diseases and has traced type 1 to MHC class II genes within the leukocyte antigen region HLA-DQB1 and HLA-DRB1 (Nejentsev and Howson, 2007). However research is continuing as genetics doesn’t fully explain the development of type 1 diabetes as not everyone with diabetic parents will necessarily contract the disease. Other researchers have suggested that viral infections may trigger the disease such as Coxsackie B and rubella (Wylie and Bryce, 2008) as they can cause strong immune responses possibly infecting and damaging beta cells. This could lead on to and explain why beta cell antigens are produced, resulting in beta cells being attacked by the immune system.
The pancreas contains the islets of Langerhans which produce many pancreatic hormones; through the beta cells it produces insulin. The immune system is designed to destroy foreign bodies however in type 1 diabetics the immune system attacks beta cells due to the antigens on the cell surface. Macrophages, dendritic and APC cells process beta cells and present the antigen to CD4+ T cells; this stimulates the secretion of cytokines activating beta cell-specific cytoxic CD8+ T cells which destroy the insulin producing cells (Joon and Yun, 2005).
The secretion of insulin is controlled by the glucose concentrations in the blood stream. As the level of glucose rises in the blood, the insulin levels also increase. Insulin accelerates the transport of glucose from the blood into the cells, decreasing the blood glucose level, accelerating glycogenesis (glucose to glycogen conversion) and stimulating protein and fat synthesis (Wylie and Bryce, 2008). When beta cells have been destroyed there is no, or a lack of, insulin in order to facilitate the metabolism of glucose into the body; as a result of this there is an increasing blood glucose level as the glucose cannot be moved into the cells. Untreated this can cause serious damage to all of the organ systems in the body and lead to death.
Polyuria - Frequent urination
The high levels of blood glucose circulate through the body including the renal system. Each kidney contains nephrons which uses filtration in order to process urine. The glomerulus which sits on the end of the nephron is very porous so allows large quantities of solute rich fluid to move from the blood to the glomerular capsule. Small molecules such as glucose are able to pass freely through the porous membrane and make up a part of urine filtrate. This then flows through the proximal convoluted tubule (PCT), the loop of Henle, descending and then ascending, then goes through the distal convoluted tubule (DCT) and finally ends in a collecting duct. The cells lining the tubules and indeed the tubules design itself are there to facilitate the reabsorption of rich solutes like glucose. Normally all of the glucose that has been filtered will be reabsorbed which involves transport proteins that require specific binding (Marieb and Hoehn, 2010). In someone with high levels of blood glucose the renal threshold for the reabsorption of glucose is exceeded, resulting in glucose being passed in urine (glycosuria). The impact of high levels of glucose in the vasculature causes an osmotic imbalance with the loss of water from cells and interstitial spaces. As the water is drawn out the cells shrink impairing their function. Intracellular fluid is found inside the bilayered plasma membrane and is the matrix in which cellular organelles are suspended and chemical reactions take place. The intracellular compartment contains on average about 28 liters of fluid and under ordinary circumstances remains in osmotic equilibrium. The increase in glucose increases the amount of urine that will be passed (this process is known as polyuria) and it causes dehydration (Wylie and Bryce, 2008).
Polydipsia - Excessive thirst
As discussed above due to the excessive loss of water symptoms of dehydration occur as the osmotic gradient within the blood has been altered. This results in the individual drinking in response to thirst, known as polydipsia.
Polyphagia - Increased appetite
As the bodies’ requirements for glucose are not being met its response is to convert glycogen back into glucose (glycogenolysis). Glycogen stores are quickly depleted however so there is a breakdown of body fat and protein to produce glucose (gluconeogenesis). Appetite may be aroused – polyphagia, in response to the lack of glucose; however as insulin is absent this only see’s to increase the blood glucose level (Wylie and Bryce, 2008).
The lack of insulin has a domino effect on the body; as there is insufficient insulin, blood glucose levels rise in the blood plasma causing hyperglycaemia and fat metabolism results in ketone bodies being produced. Blood and urine become saturated with these leading to ketonaemia and ketonuria. When the production of ketone bodies exceeds the body’s ability to use them, they build up in the circulation resulting in ketosis. Although acetone is chemically neutral, acetoacetic and beta-hydroxybutyric acids are acidic. Therefore, when these acids accumulate in the blood, they cause the blood pH to decrease, resulting in metabolic acidosis. At the same time, the rising glucose level begins to cause osmotic diuresis. The renal tubular threshold for total reabsorption of ketone bodies and glucose is quickly exceeded, causing them to spill into the urine for excretion. The negative charge of the ketones draws positively charged electrolyte ions, such as sodium and potassium, into the urine to maintain a neutral state. Lack of fluid intake, combines with increased urine production can cause an increased loss of electrolytes and fluid through the urine (Marieb and Hoehn, 2010).
Unexplained weight loss
Weight loss occurs due to the depletion of body fat, muscle, protein and insulin stores, together with cell deprivation of glucose, fluids, and electrolyte imbalance, resulting in muscle weakness and exhaustion (Wylie and Bryce, 2008).
It is the imbalance of blood glucose levels that can cause mood swings such as becoming suddenly irritable and eventually becoming tired and lethargic (Wylie and Bryce, 2008). Prolonged mismanagement of diabetes can result in psychological disorders such as anger, depression and even ante or post natal depression (Snoek and Skinner, 2004). Teenage mothers are also at an increased risk for developing depression during pregnancy and postpartum due to the unique challenges of this developmental period, diabetes aside. Adolescence is already a time of rapid metabolic, hormonal, physiological, and developmental changes and pregnancy adds another layer of complexity with additional physiological and psychological changes (McClanahan, 2009). Compared to adult mothers, teenage mothers tend to be more socially isolated, experience higher levels of parenting stress, have lower self-esteem and confidence, and experience family conflict, all of which have been found to be associated with depressive symptoms among teen mums (Yozwiak, 2009). The physical, emotional and financial demands of motherhood can also impact on a young mum’s academic functioning, career aspirations and her relationships with friends and family, contributing to additional emotional distress during the pregnancy and postpartum period especially when combined with a disease such as diabetes.
Effects on the developing embryo and foetus
During pregnancy insulin resistance is increased in order to improve the availability of glucose and amino acid transfer to the foetus. Good glycaemic control is therefore necessary in order to stabilise the mothers’ blood sugar levels, as this can help reduce the risks of miscarriage and congenital malformation and abnormalities (Macdonald and Magill-Cuerdon, 2012). Complications that may affect the foetus is excessive birth weight as extra glucose in the mothers bloodstream crosses the placenta, triggering the foetus’ pancreas to make extra insulin. This can make the foetus grow too large (macrosomia). Very large babies are more likely to become wedged in the birth canal, sustain birth injuries or require a C-section birth, which all have implications and risks for the mother. Sometimes babies of mums with diabetes develop hypoglycemia (low blood sugar) shortly after birth because their own insulin production is high. Severe episodes of hypoglycemia may provoke seizures in the baby. Prompt feedings and sometimes an intravenous glucose solution can return the baby 's blood sugar level to normal.
Explain the argument that there is a relationship between genetic susceptibility, obesity and the development of Type 2 diabetes
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems. People are considered obese when their body mass index (BMI), a measurement obtained by dividing a person 's weight in kilograms by the square of the person 's height in metres, exceeds 30. (WHO, 2012)
Being overweight places extra stress on the body in a variety of ways, including the body’s ability to maintain proper blood glucose levels and can cause resistance to insulin. The prolonged effects of the insulin resistance can eventually cause diabetes to develop (Type 2).
In 1962, Neel hypothesized that diabetes type 2 represented a ‘thrifty genotype’, which had a selective advantage (Neel, 1962). He theorised that in primitive times, individuals who were ‘metabolically thrifty’ and able to store a high proportion of energy as fat when food was plentiful were more likely to survive times of famine. However, in recent years, most populations experience a continuous supply of calorie-dense processed foods, as well as a decrease in physical activity. This likely explains the rise in type 2 diabetes prevalence worldwide. The major environmental risk factors for type 2 are obesity and a sedentary lifestyle (Shaw and Chisholm, 2003). So the dramatic increase in the rates of type 2 in recent years has been attributed primarily, to the rise in obesity worldwide (Zimmet et al, 2001). It has been estimated that approximately 80% of all new type 2 cases are due to obesity (Lean, 2000). This is true for adults and children.
The other major T2D risk factor is physical inactivity. In addition to controlling weight, exercise improves glucose and lipid metabolism, which decreases type 2 risk. Physical activity, such as daily walking or cycling for more than 30 minutes, has been shown to significantly reduce the risk of T2D (Hu et al., 2003). Physical activity has also been inversely related to body mass index and IGT. Recently, intervention studies in China (Pan et al., 1997), Finland (Tuomilehto J et al., 2001) and the US (Diabetes Prevention Program Study Group, 2002) have shown that lifestyle interventions targeting diet and exercise decreased the risk of progression from IGT to T2D by approximately 60% .
It is well established that excess body fat leads to increasing insulin resistance, and insulin resistance predisposes to diabetes.
It has long been known that type 2 is, in part, inherited. Family studies have revealed that first degree relatives of individuals with type 2 are about 3 times more likely to develop the disease than individuals without a positive family history of the disease (Flores et al, 2003).
An increasing number of genetic variants have been consistently found to contribute to the risk of developing Type 2 diabetes. Variants in the TCF7L2 gene appear to be associated with the highest risk of developing Type 2 diabetes, and also can predict the likelihood that a person will convert from a state of pre-diabetes (borderline blood sugar levels) to full-blown type 2 diabetes. Several studies have shown that overweight pre-diabetics who have certain TCF7L2 variants have a 55-70% chance to develop type 2 diabetes within 3 to 5 years after their initial diagnosis. It has been shown by the NIH-sponsored Diabetes Prevention Program Outcome study that weight loss and treatment with metformin can prevent or delay the transition from pre-diabetes to type 2 diabetes in this high-risk group.
Insulin resistance occurs when insulin levels are sufficiently high over a prolonged period of time causing the body’s own sensitivity to the hormone to be reduced. Once the body starts to get resistant to insulin, it can be a difficult process to reverse because of the knock on effect of insulin resistance. Higher circulating levels of insulin in the blood stream and weight gain help to further advance insulin resistance.
Fillipi, C, Estes, E, Oldham, J and Herrath, M, 2009. Immunoregulatory mechanisms triggered by viral infections protect from type 1 diabetes in mice. The Journal of Clinical Investigation, 119 (6), 1515-1523.
Macdonald, S and Magill-Cuerdon, J, 2012. Mayes ' Midwifery. 14th ed. China: Bailliere Tindall Elsevier.
Marieb, E and Hoehn, K, 2010. Human Anatomy and Physiology. 8th ed. San Francisco: Pearson Benjamin Cummings.
McClanahan KK, 2009. Depression in Pregnant Adolescents: Considerations for Treatment. Journal of Pediatric and Adolescent Gynecology.
Nejentsev, S and Howson, J, 2007. Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A. Nature , 450, 887-892.
Nelson-Piercy, C, 2005. Handbook of Obstetric Medicine. 2nd ed. Spain: Taylor and Francis.
Roep, B, 2003. The role of T-cells in the pathogenesis of Type 1 diabetes: From cause to cure. Diabetologia, 46 (3), 305-321.
Schmidt RM, Weimann CM, Rickert VI, O’Brian Smith E, 2006. Moderate to sever depressive symptoms among adolescent mothers followed fours years postpartum. Journal of
Snoek, F and Skinner, C, 2000. Psychology in Diabetes Care. 1st ed. London: John Wiley & Sons.
Stables, D and Rankin, J, 2010. Physiology in Childbearing with Anatomy and Related Biosciences. 3rd ed. China: Bailliere Tindall Elsevier.
University of Maryland Medical Centre. 2009. Diabetes - type 1 - Causes. [ONLINE] Available at: http://www.umm.edu/patiented/articles/what_causes_type_1_diabetes_000009_2.htm. [Accessed 03 October 12].
Wylie, L and Bryce, H, 2008. The Midwives ' Guide to Key Medical Conditions: Pregnancy and Childbirth. 1st ed. Croydon: Churchhill Livingstone Elsevier.
Yozwiak JA, 2009. Postpartum Depression and Adolescent Mothers: A Review of Assessment and Treatment Approaches. Journal of Pediatric and Adolescent Gynecology, online.
References: Fillipi, C, Estes, E, Oldham, J and Herrath, M, 2009. Immunoregulatory mechanisms triggered by viral infections protect from type 1 diabetes in mice. The Journal of Clinical Investigation, 119 (6), 1515-1523. Macdonald, S and Magill-Cuerdon, J, 2012. Mayes ' Midwifery. 14th ed. China: Bailliere Tindall Elsevier. Marieb, E and Hoehn, K, 2010. Human Anatomy and Physiology. 8th ed. San Francisco: Pearson Benjamin Cummings. McClanahan KK, 2009. Depression in Pregnant Adolescents: Considerations for Treatment. Journal of Pediatric and Adolescent Gynecology. Nejentsev, S and Howson, J, 2007 Nelson-Piercy, C, 2005. Handbook of Obstetric Medicine. 2nd ed. Spain: Taylor and Francis. Roep, B, 2003 Schmidt RM, Weimann CM, Rickert VI, O’Brian Smith E, 2006. Moderate to sever depressive symptoms among adolescent mothers followed fours years postpartum. Journal of Adolescent Health Snoek, F and Skinner, C, 2000. Psychology in Diabetes Care. 1st ed. London: John Wiley & Sons. Stables, D and Rankin, J, 2010. Physiology in Childbearing with Anatomy and Related Biosciences. 3rd ed. China: Bailliere Tindall Elsevier. University of Maryland Medical Centre. 2009. Diabetes - type 1 - Causes. [ONLINE] Available at: http://www.umm.edu/patiented/articles/what_causes_type_1_diabetes_000009_2.htm. [Accessed 03 October 12]. Wylie, L and Bryce, H, 2008. The Midwives ' Guide to Key Medical Conditions: Pregnancy and Childbirth. 1st ed. Croydon: Churchhill Livingstone Elsevier. Yozwiak JA, 2009. Postpartum Depression and Adolescent Mothers: A Review of Assessment and Treatment Approaches. Journal of Pediatric and Adolescent Gynecology, online.