Blood glucose measurement and urinalysis/endocrine worksheet Submission dateline: 3pm on 30th April 2021 Submission method: Via Turnitin submission link on Moodle. Oral glucose tolerance test The OGTT evaluates the efficiency of the body to metabolize glucose and has been regarded as the “gold standard” for diagnosis of diabetes. Diabetes symptoms do not appear until the pathology has become well established, sometimes for years. Glycaemia monitoring remains the best method to detect pre-diabetic states and also make people sensitive to the influence of their lifestyle (BMI, exercise, foods etc.) on the physiology of their body and on their health. The test takes places after an overnight fast (minimum 8 hours). A blood test is taken before the patient is asked to consume a drink containing 75g glucose. Samples of blood are collected at regular intervals (such as 30min, 60min, 90min) or at 120min after glucose ingestion. World Health Organization-defined glucose levels are shown in Table 1. Table 1. 2006 WHO recommendations for diagnostic criteria for diabetes and intermediate hyperglycaemia Normal Fasting < 6.1 mmol/L OGTT (2h) < 7.8 mmol/L Impaired glucose tolerance < 7.0 mmol/L ≥ 7.8 and < 11.1 mmol/L Diabetes mellitus ≥ 7.0 mmol/L ≥ 11.1mmol/L Absorption of a meal rich in carbohydrate (such as in the OGTT) acutely elevate the blood glucose level, and we rely on control systems to monitor such changes and make appropriate adjustments, maintain blood glucose within a relatively narrow range (4 – 8mmol/L). 1. Describe how blood glucose is controlled - which hormones are involved, what processes do they regulate? (300 words) In the absorptive (fed) state, glucose from absorbed nutrients is either used as energy for most cells, while the excess is converted to glycogen and stored in the liver and muscle or glycerol to triglycerides and stored in adipose tissue. This process is anabolic and is governed by the hormone insulin that is released by B cells in the pancreas. Insulin is released to lower BG levels upon intake of food and is monitored by somatostatin. It does so by increasing uptake of glucose via GLUT-4, storage of glucose as glycogen, uptake of amino acids and synthesis of protein and DNA synthesis. On the other hand, in a starved state, a cells in the pancreas release glucagon upon low BG and is inhibited by high BG, insulin and somatostatin. Unlike insulin, it stimulates hepatic glycogenolysis and glycolysis which refers to breakdown of glycogen in the liver and muscle and other cells to glucose respectively. It also stimulates gluconeogenesis which ameans formation of glucose from non carb precursors and lipolysis that converts triglycerides from adipose tissue to glycerol and then glucose. Glucagon and insulin work together automatically as a negative feedback system to keeps BG levels stable. Foods will have different effects on blood glucose both due to the body's state of health and the composition of the food. Glycaemic index (GI) is a measure of how rapidly the carbohydrates in a food lead to an elevation in blood glucose; a food with a high GI (such as chocolate, biscuits) raises blood glucose more than a food with a medium or low GI (wholemeal bread, beans). Glycaemic load (GL) relates to the overall effect a food has on blood sugar, the total amount of digestible carbohydrates in a food. In a study to examine the effects of glycaemic load on postprandial blood glucose, the following data were obtained: Table 2 shows the summary data for each of the “treatments” in normal healthy subjects (aged 20-25 years). Included also is the OGTT of a normal healthy subject and that of a patient with diabetes mellitus in which an OGTT was performed in the diagnosis of her condition. Table 2. Mean blood glucose (mmol/L) for treatment GL groups (n=8), sampling following an overnight fast and at intervals after ingestion of a “meal” OGTT, normal OGTT, diabetes HGL MGL LGL Fasted 4.4 7.2 30 min 7.6 10.8 60 min 8.4 13.4 120 min 6.2 12.8 4.6 4.4 4.5 8.1 6.3 5.2 7.3 6.2 4.8 6.3 5.5 4.5 Treatments groups: OGTT 75g glucose in 250mL water (75g CHO, 300 Kcal) HGL (high GL) Energy drink and pop tart (102g CHO, 521 Kcal) MGL (medium GL) Bagel, peanut butter, banana (89g CHO, 565 Kcal) LGL (low GL) Ham, cheese (12g CHO, 520 Kcal) 2. Using graph plot on Excel, draw a suitable graph to represent the data for the two OGTT test results. Describe the responses to the oral glucose test. (100 words) At 0min (fasted) the OGTT for normal people is at 4.4 while for diabetic people 7.2, whereas after 30 and 60min, the normal ogtt went up to 7.6 then 8.4 while the diabetic ogtt went up to 10.8 then 13.4. lastly, after 120minutes, the normal ogtt dropped to 6.2 while the diabetic ogtt dropped slowly to 12.8. Mean blood glucose (mmol/L) OGTT test results 13,4 12,8 10,8 7,2 8,4 7,6 6,2 4,4 FASTED 30 MIN 60 MIN 120 MIN time OGTT, normal OGTT, diabetes 3. Using the same graph, represent the data for the three GL meals. Attach the generated graph to this document. What conclusions can be drawn? (100 words) Mean blood glucose (mmol/L) OGTT test results 13,4 12,8 10,8 8,1 7,6 6,3 5,2 7,2 4,6 4,5 4,4 FASTED 30 MIN 8,4 7,3 6,2 4,8 6,3 6,2 5,5 4,5 60 MIN 120 MIN time OGTT, normal OGTT, diabetes HGL MGL LGL According to the graph HGL has a faster uptake, but also drops faster than MGL after 60minutes and stays at a higher 6.3 compared to MGL’s 5.5. This could be due to HGL having a higher glycaemic load which stimulates a stronger response and release of glucagon, which further elicits an insulin response to balance the blood glucose levels. 4. Consider the following: how does the physical state of the meal (solid vs. liquid, cooked vs. uncooked, high fibre vs. low fibre) affect digestion and absorption rates (and hence postprandial blood glucose)? (100 words) Solid food is broken down through ingestion and chemically converted into liquid whereas ingested liquid can skip this step suggesting that digestion is faster for liquids. In terms of cooked food, carbs usually soften causing them to digest faster in contrast with protein that hardens after cooking and takes longer than raw meat. Fats also naturally slow digestion. High fiber foods take longer to digest and absorb as it requires the breaking down of polysaccharide linkages. As for postprandial blood glucose, foods with a lower glycaemic index or foods that take longer to digest have a lesser increase in BG levels as slow digesting food release sugar slowly. 5. What are the disadvantages to regularly consuming meals high in fat and low in carbohydrates? (200 words) High fat diets can cause a rise in cholesterol, specifically LDL due to most foods having high amounts of saturated fats. Along with that, in some diets such as keto diets, the consumption of fruits and vegetables is also limited which can lead to nutrient deficiency as the body is deprived of some vitamins and minerals such as fibre which result in a number of bowel complications like constipation. Another risk of such meals is the production of excess ketones by the breakdown of fats in the liver due to short supply of glucose and over time can lead ketoacidosis which refers to high levels of ketones making the blood more acidic and thus causing dehydration. A low carb diet can also result in gluconeogenesis because of shortage of glucose and glycogen which can not only hinder brain functionality as its main source of energy is glucose, but also slow down repair and function of other major organs which can manifest into physical symptoms as lethargy, muscle weakness and nausea. 6. What is the function of fasting a minimum of 8 hours before an OGTT? (50 words) As the measurement at 0min (fasted) is used as a baseline for the test, it is required that the blood contain none or minimal amounts of glucose to prevent the reading coming out as hyperglycaemic. Furthermore, if there is insulin in the blood that was released due to ingestion of glucose prior to testing, it can cause the glucose to be absorbed in the cells which can also lead to a false negative result. Case Studies CASE STUDY 1 A 55-year old woman reports of intense thirst and recurrent vaginal thrush infections. On further questioning, she describes frequent trips to the toilet and blurring of her vision. A physical examination reveal a height of 5'3'' (1.60m), weight of 12 stone 9lbs (80kg), and blood pressure of 160/100mmHg (normal <140/90). A simple "pin-prick" blood test reveals a random blood glucose of 17mmol/ L (normal < 11.1 mmol/ L). A provisional diagnosis of type 2 diabetes is made. 1. Comment on the presenting symptoms, explain the physiological processes that lead to their presentation in this patient. (100 words) Since the blood is high in glucose, the kidneys filter out this glucose into the urine which causes the water molecules to go down the concentration gradient in the kidney and from the cell, which not only causes build-up of fluids that leads to frequent urination but also ultimately dehydration. Along with that high BG levels also lead to thrush, which is a yeast infection that thrives in warm, moist areas of the body. Lastly, hyperglycaemia also affects your vision as the lens inside the eye is swollen. 2. How would you interpret the physical examination and blood test? (BMI = weight (kg)/height (m)2 Ideal 18.5 – 25; overweight 25 – 30; obese 30 – 40) (100 words) the patient has a BMI of 31.2 which falls under the obese range and can also be a cause for the high blood pressure other than type 2 diabetes. The blood test also shows increased levels of glucose which is a defining characteristic of diabetes along with similar symptoms to those of type 2 diabetes. 3. If left untreated, this patient is at increased risk of which of the following (circle all those that are appropriate): nephropathy, hypoglycaemia, retinopathy, myocardial infarction, stroke, neuropathy, diabetic ketoacidosis, muscle-wasting, hyperglycaemia, cold intolerance, postural hypotension 4. How should this patient be managed? (100 words) Some basic diabetes treatments include lifestyle changes such as exercise and healthy eating which includes cutting back on refined carbs and calories and adding fruits and vegetables to your diet along with more fibre. This would also help in weight loss. For medications, drugs that either lower the level of glucose by helping the body respond better/be more sensitive to insulin or making more insulin should be used and may also include taking long lasting insulin shots. CASE STUDY 2 A 50-year old man reports of weight loss, despite increased appetite and more frequent bowel movements over the recent weeks. His resting heart rate is 82bpm and blood pressure is 110/76. He complains of palpitations. The doctor notices that there is also a slight bulging of the eyes and firmness around the front of the neck. 1. What is your initial diagnosis? Hyperthyroidism 2. Which symptoms are consistent with your diagnosis? Explain how these symptoms arise. (100 words) Hyperthyroidism is usually associated with high basal metabolic rate which means that your body burns more energy due to which weight loss with a high appetite is a common issue. Since thyroid hormones also influence the heart, excess of this hormone can increase heart rate and fatigue. Not only that but due to hyperthyroidism causing overactivity of the sympathetic nervous system, the hyperstimulation leads to increased motility in the gut thus causing diarrhoea. Lastly, the bulging of eyes is because of the immune system attacking and damaging the tissues around the eye which causes an inflammatory reaction whereas the firmness is due to the formation of thyroid goitre. 3. Regarding your diagnosis, is this a primary or secondary endocrine disorder? Explain your answer. (50 words) since the patient has limited eye symptoms and a number of CVS complications, it can be safe to conclude that it is secondary hyperthyroidism as it usually affects middle aged people is the product of overstimulation of the thyroid gland by excessive TSH in the circulation. 4. What would you expect the levels of T3, T4 and TSH to be in this patient? The levels of all T3, T4 and TSH are elevated Finally, in a second patient with a lack of iodine in the diet: a) Thyroid hormones: high or low? low b) Is this hypothyroidism or hyperthyroidism? hypothyroidism c) Levels of TSH – low, normal or high? low d) Presence of a goitre? Yes Urine testing The test results for 6 people (6 test samples including a control) are in the sheets below, determine the common or major pathological cause (if appropriate). Test sample 1- Normal Observation of urine: Yellow, clear Test results: x x x x x x x x x What is the purpose of this control (normal) urine sample in this investigation? It is used as a reference for comparison of values with the other samples Test sample 2 Observation of urine: Yellow, clear Test results: x x x x x x x x x x Provide an explanation for the outcomes Indicate a common or major pathological cause (where appropriate) High glucose in urine due to hyperglycaemia as kidney filter out the glucose from blood to urine. Most likely an indicator of diabetes Test sample 3 Observation of urine: Yellow, clear Test results: x x x x x x x x x x x Provide an explanation for the outcomes Indicate a common or major pathological cause (where appropriate) Higher levels of ketones and glucose filtered out of the body by the kidney. Could be due to ketoacidosis and diabetes as body is not able to absorb and metabolize glucose thus causing it to burn down fat and produce ketones as an alternative. This leads to excess ketones and glucose in the blood and then the urine which also lowers the pH. Test sample 4 Observation of urine: Light yellow, clear Test results: x x x x x x x x x x Provide an explanation for the outcomes Indicate a common or major pathological cause (where appropriate) Specific gravity measures the ability of the kidney to concentrate the urine In this result the specific gravity is lower than normal, and the colour of urine is light yellow and since water has a specific gravity of 1.000, the urine is very diluted. This could be due to impaired kidney function due to the tubules being damaged, too much fluid intake due to increased thirst, kidney failure or diabetes insipidus. Test sample 5 Observation of urine: Yellow, slightly turbid Test results: x x x x x x x x x x Provide an explanation for the outcomes Indicate a common or major pathological cause (where appropriate) When the pH of urine is high, which in this case is 9.0 indicated that the urine is very alkaline, it usually signifies gastric suctioning, kidney impairments, pyloric obstruction, respiratory alkalosis or an UTI.The urine test shows a high number of leukocytes in urine which could be due to an inflammation in the tract or kidney which is usually caused by an UTI. Another result that points toward an UTI is the presence of nitrites in urine as urine contains nitrates that are reduced to nitrites by the bacteria through a nitrification process. Test sample 6 Observation of urine: Yellow, turbid Test results: x x x x X X x x x x Provide an explanation for the outcomes Indicate a common or major pathological cause (where appropriate) This result shows turbidity in urine due to leakage of protein and blood in the urine which could be due to insufficient filtering by the glomeruli in the kidney. This condition is called proteinuria and can be attributed to several issues such as dehydration, high blood pressure, diabetes mellitus, inflammation of the glomerulus, CKD, auto immune disease or cancer. Haematuria refers to the presence of blood in the urine which can also be caused by damaged glomerulus or tubules in the kidney and can happen due to kidney diseases, infections, abnormalities or damage/trauma. What are the advantages and disadvantages of the urine dipstick tests? (100 words) The test allows for quick analysis of urine results for different factors such as bilirubin, proteins, ketones, blood etc although these results could be a false positive or negative due to the chemical reactions being affected by oxidizing, reducing, and discolouring substances. This test can also be performed by most people provided that they are not colour blinds and has no discomfort or side effects plus can is reproducible. Though as mentioned before, the accuracy of this test is questionable as it relies on the collection of the sample by the patient and many of the abnormalities can be seen in normal people.