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UNIT 15 Disorders of Glucose Metabolism Originally developed by: Frank MacDonald RN, MN, Former Clinical Nurse Specialist, Diabetes Clinic, Foothills Hospital Revised (2000) by: Lorraine Anderson, PhD in consultation with Alison Husband RN, MN Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary Unit 17 Disorders of Glucose Metabolism 1 Unit 15 Table of Contents Overview ...................................................................................................................... 4 Aim ............................................................................................................................. 4 Objectives .................................................................................................................. 4 Resources ................................................................................................................... 4 Web Links.................................................................................................................. 5 Pre-test for Glucose Metabolism.............................................................................. 6 Section 1: Type 1 Diabetes ...................................................................................... 10 Learning Activity #1 .............................................................................................. 10 Pathophysiology .................................................................................................... 11 Clinical Manifestations .......................................................................................... 12 Evaluation and Treatment .................................................................................... 12 Section 2: Type 2 diabetes ....................................................................................... 16 Pathophysiology .................................................................................................... 16 Etiology.................................................................................................................... 16 Clinical Manifestations .......................................................................................... 17 Evaluation and Treatment .................................................................................... 17 Learning Activity #2 .............................................................................................. 17 Section 3: Acute Complications of Diabetes Mellitus ....................................... 19 Hypoglycemia ........................................................................................................ 19 Diabetic Ketoacidosis ............................................................................................ 20 Hyperosmolar Hyperglycemic NonKetotic Syndrome (HHNKS) ................. 20 Section 4: Chronic Complications of Diabetes Mellitus ................................... 21 Microvascular Disease ........................................................................................... 21 Macrovascular Disease .......................................................................................... 21 Preventing Long Term Complications—The Diabetes Control and Complications Trial (DCCT)................................................................................. 22 Learning Activity #3 .............................................................................................. 23 Section 5: Gestational Diabetes Mellitus (GDM) ............................................... 24 Final Thoughts........................................................................................................... 25 References .................................................................................................................. 26 Glossary ...................................................................................................................... 27 Acronym List .............................................................................................................. 27 Checklist of Requirements ...................................................................................... 28 Required Readings ................................................................................................. 28 Learning Activities ................................................................................................. 28 Answers to Learning Activities .............................................................................. 29 Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary 2 Unit 17 Disorders of Glucose Metabolism Answers to the Pretest ........................................................................................... 29 Answers to Learning Activity #1......................................................................... 29 Answers to Learning Activity #2......................................................................... 30 Answers to Learning Activity #3......................................................................... 31 Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary Unit 17 Disorders of Glucose Metabolism 3 UNIT 15 Disorders of Glucose Metabolism Diabetes mellitus is a metabolic disease characterized by the presence of hyperglycemia due to defective insulin secretion, insulin action or both. Diabetes mellitus is a serious health problem affecting 5% of Canadians. American data indicates that diagnosis of diabetes may be underestimated by almost half, which may mean that up to 10% of Canadians are diabetic. In the United States, in 1995, diabetes mellitus was the seventh leading cause of death. There is no available data on the cost of the disease in Canada, but American costs per year are about $98.2 billion—$44.1 billion in direct costs and approximately $54.1 in indirect costs such as work loss, disability and premature mortality. For further statistical information on diabetes mellitus statistics go to: Intelihealth.com http://www.intelihealth.com/IH/ihtIH?d=dmtContent&c=203032&p=~br,IHW |~st,21054|~r,WSIHW000|~b,| - cost Although the means for controlling the primary metabolic derangement, hyperglycemia, are available, the continual balancing of blood glucose levels by patients over a lifetime is problematic. Nurses are part of the multidisciplinary team who care for people with diabetes. An understanding of the pathophysiologic mechanisms and therapeutic interventions will enhance your ability to help people with diabetes to learn techniques and problem-solving that will improve their health outcomes. Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary 4 Unit 17 Disorders of Glucose Metabolism Overview This unit contains five parts: 1. 2. 3. 4. 5. Type 1 diabetes mellitus Type 2 diabetes mellitus Acute complications of diabetes mellitus Chronic complications of diabetes mellitus Gestational diabetes Note: Insulin dependent diabetes mellitus (IDDM) is now referred to as Type 1 diabetes and non-insulin dependent diabetes (NIDDM) is now referred to as Type 2 diabetes. Aim The general aim of this unit is to facilitate your understanding of the pathophysiology of the different types of diabetes mellitus, as well as the clinical manifestations, treatment, and complications. Objectives On completion of this unit, you will be able to: 1. Classify diabetes mellitus according to type. 2. For Type 1 and 2 diabetes mellitus: explain the underlying pathophysiological processes. describe the clinical manifestations. describe the evaluation and treatment. identify the acute complications which may develop. identify the long-term complications which may develop, including the value of intensive treatment 3. Define gestational diabetes mellitus and describe the clinical manifestations, evaluation and treatment. Resources Required Harris, S.B., & Lank C.N., (1998). 1998 Clinical Practice Guidelines for the Management of Diabetes in Canada. Canadian Diabetes, 12(1), 3-10. Canadian Diabetes Association, Guidelines for the Nutritional Management of Diabetes Mellitus in the Millennium. Retrieved October 26, 2000 from the World Wide Web http://www.diabetes.ca/prof/index.html, pages 3-6. Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary Unit 17 Disorders of Glucose Metabolism 5 Porth, C. M. (2005). Pathophysiology-Concepts of Altered Health States (7th ed). Philadelphia: Lippincott. Chapter 43. Print Companion: Disorders of Glucose Metabolism Learning Activities Activities for this unit include: 1. Pre-test 2. Learning Activities 1, 2, and 3 Supplemental Materials Supplemental materials include: Canadian Diabetes Association, Clinical practice guidelines for the management of diabetes in Canada. 1998. Retrieved October 26, 2000 from the World Wide Web http://www.diabetes.ca/prof/publications/cpg98eng.pdf (Note that this is a more complete version of the guidelines than the publication indicated in the required reading section.) Canadian Diabetes Association, CDA Position Statement Regarding the UKPDS and Revision of Diabetes Clinical Practice Guidelines Accounting for the UKPDS Results, Retrieved October 26, 2000 from the World Wide Web http://www.diabetes.ca/prof/cpg_ukpdsposition.html Web Links All web links in this unit can be accessed through the Web CT system. Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary 6 Unit 17 Disorders of Glucose Metabolism Pre-test for Glucose Metabolism This unit presumes that you have a basic understanding of the normal physiology of insulin secretion and blood glucose regulation. Please take the following PRE-TEST. This test is NOT consistent with the content or style of the course exams and is a pretest only. If you have difficulty with the pretest, you should review a standard physiology text before commencing the unit. The pre-test answers are at the end of this unit. 1. Glycogenolysis is stimulated by a. human growth hormone b. steroids and glucagon c. glucagon and epinephrine d. insulin and norepinephrine e. none of the above 2. Which of the following hormones increases the heart rate and raises blood sugar levels? a. epinephrine b. aldosterone c. oxytocin d. prolactin e. none of the above 3. Which one of the following statements about glucagon is NOT true? It a. is a polypeptide b. stimulates glycogenolysis c. promotes hypoglycemia d. stimulates gluconeogenesis 4. The hormone insulin promotes a. the formation of glucose from glycogen b. the formation of glycogen from glucose c. the actions of epinephrine d. the deamination of amino acids 5. The major action of the hormone glucagon is to a. evoke vasoconstriction b. cause uterine contractions c. lower blood calcium ion levels d. decrease liver glycogen levels Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary Unit 17 Disorders of Glucose Metabolism 7 6. When blood sugar levels are high a. alpha islet cells release insulin b. beta islet cells release insulin c. alpha islet cells release glucagon d. beta islet cells release glucagon e. none of the above 7. Glucagon is produced by the ______ cells in the pancreatic islets a. beta b. delta c. alpha d. chromaffin e. oxyphilic 8. Which of the following metabolic processes would result in lowered blood sugar levels? a. glycolysis b. gluconeogenesis c. glycogenesis d. glycogenolysis 9. After all of the different kinds of cells have stored all the glucose they can, any excess glucose present is converted into a. fat b. glycogen c. keto acids d. amino acids e. urea 10. During the post-absorptive state, nerve cells utilize __________ as their major energy source a. glucose b. amino acids c. glycerol d. keto acids e. fatty acids 11. Which one of the following metabolic processes will DECREASE when insulin is present in the blood? a. glycogen formation b. amino acid transport c. keto acid formation d. lipogenesis Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary 8 Unit 17 Disorders of Glucose Metabolism 12. Which one of the following hormones is NOT secreted in response to stress? a. cortisol b. epinephrine c. vasopressin d. renin-angiotensin-aldosterone e. insulin 13. The actions of insulin include a. the insertion of additional glucose transporters onto the plasma membrane of insulin-dependent cells b. the stimulation of glycogenesis and the inhibition of glycogenolysis c. increased insulin secretion in response to a drop in the blood glucose concentration d. both A and B are correct e. all of the above are correct 14. Which one of the following is a metabolic effect of insulin? a. increased glucose uptake by the cells b. increased breakdown of fat by the cells c. decreased uptake of amino acids by the cells d. both A and B are correct 15. Which one of the following does NOT stimulate insulin secretion? a. elevated blood amino acid concentration b. gastrointestinal hormones c. starvation d. elevated blood glucose concentration 16. Increased levels of which of the following hormones will NOT result in increased blood fatty acid levels? a. glucagon b. human growth hormone c. insulin d. epinephrine 17. The actions of glucagon include a. decreased blood glucose levels b. increased breakdown of fat c. increased hepatic glucose production d. increased amino acid uptake by the cells e. increased calcium ion reabsorption by the renal tubules Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary Unit 17 Disorders of Glucose Metabolism 9 18. Excessive growth hormone levels could cause hyperglycemia a. TRUE b. FALSE 19. The formation of glycogen from glucose is known as gluconeogenesis a. TRUE b. FALSE 20. Both glucagon and epinephrine will increase lipolysis and ketogenesis a. TRUE b. FALSE 21. The effects of insulin, together with epinephrine, produce a “stress hyperglycemia” when the sympathoadrenal axis is activated a. TRUE b. FALSE Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary 10 Unit 17 Disorders of Glucose Metabolism Section 1: Type 1 Diabetes . Read Porth – pp. 987- 994. Type 1 diabetes is diabetes that is primarily a result of pancreatic beta-cell destruction and thus these patients are prone to ketoacidosis. It is due to an autoimmune process. The etiology of beta cell destruction is under active investigation. Future Possibilities: Santamaria and his colleagues found that treating mice predisposed to diabetes with a small protein reduced the production of the problematic T-cells, and halted the progression from inflammation to diabetes. This means that a VACCINE against Type 1 diabetes may be possible in the future. For more information, go to University of Calgary Website http://www.ucalgary.ca/unicomm/newsrelease/diatype1.htm Note: The fasting plasma glucose diagnostic level for the standard oral glucose tolerance test OGTT has been lowered from 7.8 mmol/L (140 mg/dl) to 7 mmol/L Note: First Nation people are three to five times more likely than the general population to have or develop diabetes. Two thirds of First Nation people with diabetes are women. For more information, go to The Canadian Diabetes Association Website http://www.diabetes.ca/about_diabetes/globe/aboriginal.html Learning Activity #1 Answers are at the back of this unit. 1. Which of the following lab results are diagnostic of diabetes mellitus: a. Serial fasting blood glucose values of 6.7, 7.9, 5.4, and 8.1 mmol/L in one individual. b. A random blood glucose of 15.3 mmol/L with symptoms of polydipsia, polyuria, and fatigue. c. A random blood glucose of 11.1 mmol/L with no symptoms. 2. Which of the following glucose tolerance test results are diagnostic of diabetes? Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary Unit 17 Disorders of Glucose Metabolism Fasting 30 min. 60 min. 90 min. 120 min. 11 A 5.7 mmol/L 8.9 11.0 10.2 9.1 B 7.4 mmol/L 10.7 12.2 12.9 11.3 C 4.3 mmol/l 7.9 10.0 12.6 15.9 Pathophysiology . Note: There is strong evidence suggesting that genetic susceptibility is not a sufficient condition for the development of IDDM; only 50% of genetically identical twins of Type 1 siblings will develop diabetes. Breaking News: Another note of Canadian pride is some exciting research being done here at the University of Calgary by Pere Santamaria. For further information please go to University of Calgary Website http://www.ucalgary.ca/unicomm/NewsReleases/diabtype1.htm The white blood cells referred to here are T lymphocytes specific for beta pancreatic cells. The reference for the complete article is: Amrani, A., Verdguer, J., Serra, P. et al 2000. Progression of autoimmune diabetes driven by avidity maturation of a T-cell population. Nature. 406(6796), 739-42. Controversy: The cow milk controversy. Some studies suggest that exposure to cow's milk at an early age may predispose a susceptible individual to Type 1 diabetes. This remains controversial. For a website that supports the cow milk controversy see: Science News Online http://www.sciencenews.org/sn_arc99/6_26_99/fob2.htm Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary 12 Unit 17 Disorders of Glucose Metabolism Controversy: Another, possibly more serious controversy, is the view that vaccinations are an environmental trigger for Type 1 diabetes. Some parents are resisting vaccinating their children for fear it may trigger diabetes. For a website that examines this controversy go to Science News Online http://www.sciam.com/2000/0300issue/0300infocus.html Future Possibilities: As discussed above it is possible a vaccine for Type 1 diabetes may be developed. This group is looking at EDIBLE vaccines: Scientific American Magazine http://www.sciam.com/2000/0900issue/0900langridge.html Clinical Manifestations Note: The main and most important clinical manifestation of Type 1 diabetes is hyperglycemia which occurs whenever normal blood glucose levels are exceeded. However osmotic fluid shifting and diuresis are not common until blood glucose levels typically exceed 12 –16 mmol/L. Evaluation and Treatment Know what is meant by glycated hemoglobin – see page 1000. Harris, SB, & Lank, C.N. (1998). 1998 Clinical Practice Guidelines for the Management of Diabetes in Canada. Canadian Diabetes, 12(1), 4-8. Canadian Diabetes Association, Guidelines for the Nutritional Management of Diabetes Mellitus in the Millennium (pages 3-6). Retrieved October 26, 2000 from the World Wide Web http://www.diabetes.ca/prof/index.html Insulin Note: Insulin effectiveness depends on: Location of injection site. Consistency of timing of injection. Age or temperature of insulin. Vascular dilation/constriction. Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary Unit 17 Disorders of Glucose Metabolism 13 Insulin action times vary. Rapid-acting insulin (Lispro) reaches the blood within 15 minutes after injection. It peaks 30 to 90 minutes later and may last as long as 5 hours. Short-acting (regular) insulin usually reaches the blood within 30 minutes after injection. It peaks 2 to 4 hours later and stays in the blood for about 4 to 8 hours. Intermediate-acting (NPH and lente) insulins reach the blood 2 to 6 hours after injection. They peak 4 to 14 hours later and stay in the blood for about 14 to 20 hours. Long-acting (ultralente) insulin takes 6 to 14 hours to start working. It has no peak or a very small peak 10 to 16 hours after injection. It stays in the blood between 20 and 24 hours. History: Our American textbook has left out an important historical matter and one of great Canadian pride, namely the discovery of insulin in 1922 at the University of Toronto by Banting and Best. Banting and the supervisor of the laboratory MacLeod were awarded the Nobel Prize for the critical discovery. Banting shared his prize with his assistant Best. See the web page on Banting and Best by going to The Public Broadcasting System Website http://www.pbs.org/wgbh/aso/databank/entries/dm22in.html Note: Since the publication of the textbook a large study on the intensive blood glucose control and/or blood pressure control, called the United Kingdom Prospective Diabetes Study or UKPDS. This study was published in September 1998, after the Canadian Clinical Practice Guidelines were developed. To see more information about this study and how it lead to slight revisions in the 1998 CPG please go to The Canadian Diabetes Association Website http://www.diabetes.ca/prof/cpg_ukpdsposition.html Note: The textbook discusses animal insulin. Most physicians prescribe human recombinant insulin. This is not human insulin but a form of insulin produced using recombinant DNA technology. Recombinant DNA is created when DNA is synthesized in a test tube and transferred into cells where it can be replicated and expressed as a protein. Here the gene for human insulin was transferred into microorganisms. These organisms produce human insulin. Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary 14 Unit 17 Disorders of Glucose Metabolism Meal Planning Note: For your reference the Guidelines for the Nutritional Management of Diabetes Mellitus in the Millennium may be accessed at The Canadian Diabetes Association Website http://www.diabetes.ca/prof/index.html Exercise Note: Physical activity can make balancing insulin dosage and food intake more complicated. The true benefits of exercise in Type 1 diabetes seem to be in the reduction of other cardiovascular risks that work synergistically with diabetes. Exercise has many other benefits including increased energy reserve and an improved outlook on life which are the same with or without diabetes. Exercise is not recommended for insulin dependent individuals when their blood glucose is 16 mmol/L or greater and they are ketonuric. Under these conditions due to inadequate availability of circulating insulin exercise will exacerbate the ketosis. Transplantation Breaking News: Improvements in the isolation and transplantation of beta islet cells has led to the development of a non surgical transplantation procedure which is in clinical trials. The procedure was refined at the University of Alberta and is known as the Edmonton Protocol. For web access go to Alberta Foundation for Diabetes Research Website http://www.afdr.ab.ca/press/100005/main.htm For more information on beta cell transplantation go to Diabetes Research Institute Website http://www.drinet.org/html/islet_cell_transplantation.htm Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary Unit 17 Disorders of Glucose Metabolism 15 Future Possibilities: Genetic engineering may be able to cure Type 1 diabetes by introducing genes for insulin production. Very recently at the University of Calgary researchers have developed a gene that is introduced into diabetic rats via a genetically engineered virus. The gene is for an insulin regulator that will produce insulin when blood glucose levels are too high, normalizing the glucose levels. This will be tested in higher organisms and possibly humans. For further information click here: University of Calgary http://www.ucalgary.ca/unicomm/NewsReleases/diabet4.htm Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary 16 Unit 17 Disorders of Glucose Metabolism Section 2: Type 2 diabetes Type 2 diabetes is a form of diabetes mellitus that may range from insulin resistance with relative insulin deficiency to a predominant secretory defect with insulin resistance. Peripheral insulin resistance may be related to a defective insulin receptor and/or post-receptor defects, and/or hepatic overproduction of glucose. These defects combine to cause hyperglycemia without the ketosis of Type 1 diabetes. Pathophysiology Read: Porth, pp. 995-997 Etiology Note: A clear indication of the importance of genetics in the etiology of Type 2 diabetes is the fact that nearly 100% of monozygotic twins are concordant for the disease. Environmental factors are also important. Obesity is strongly correlated with Type 2 diabetes, particularly truncal obesity. Obesity and a sedentary lifestyle are the major modifiable and independent risk factors for Type 2 diabetes according to the 1998 Clinical Practice Guidelines. The role of environmental factors is demonstrated most clearly by research done with aboriginal peoples throughout the world who have moved from traditional lifestyles to modern urban lifestyles. The incidence of Type 2 diabetes is significantly higher (25 times) in the urban subgroups than in the traditional setting and lifestyle. Breaking News: On the rapid increase in the number of children diagnosed with Type 2 diabetes, go to Intelihealth.com http://www.intelihealth.com/IH/ihtIH/WSIHW000/333/21142/296067.html Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary Unit 17 Disorders of Glucose Metabolism 17 Note: The actual percentage of Type 2 diabetics that are obese varies considerably from 60 to 90 percent depending on the source. This probably reflects different definitions of obesity. Clinical Manifestations Read Porth – pp. 998-999 Note: Type 2 diabetes may be asymptomatic. Evaluation and Treatment Read: Porth – pp.1000 - 1005 Learning Activity #2 Answers are at the back of this unit. 1. For the following, identify each as being characteristic of Type 1 or Type 2 diabetes. a. b. c. d. e. f. Ketosis prone Onset usually over 40 years of age Strong familial pattern Insulin required for survival Occurs in younger people usually Non-ketosis prone Type 1 ______ ______ ______ ______ ______ ______ Type 2 ______ ______ ______ ______ ______ ______ 2. Identify which of the following statements are false, and then rewrite the statement so that it is true. a. Familial inheritance is a bigger risk factor in Type 1 than in Type 2 diabetes. b. Obesity of the legs and hips is closely associated with Type 2 diabetes. c. Nearly 100% of genetically identical twins of a Type 2 sibling will get diabetes. d. Viral destruction of beta cells is the primary cause of Type 1 diabetes Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary 18 Unit 17 Disorders of Glucose Metabolism 3. Identify which of the following statements are false then rewrite the statement so that it is true. a. Type 2 persons often develop much higher blood glucose levels than Type 1 before they are severely ill. b. The symptoms of hyperglycemia are different in Type 1 and Type 2 diabetes. c. Weight loss is the usual treatment of choice in Type 1 diabetes. d. Exercise is important in blood glucose control in both types of diabetes. e. Urine testing is of no use in monitoring either type of diabetes. 4. Which of the following metabolic processes occur due to insulin deficiency? (Answer all that apply) a. glycogenolysis b. gluconeogenesis c. lipogenesis d. increased glucose uptake by muscle cells e. glycogenesis f. lipolysis 5. List the following treatment measures for Type 2 diabetes in the usual order of usage: a. dietary intervention b. oral hypoglycemic agents c. exercise d. human recombinant insulin 6. What is the major pathophysiologic factor in Type 2 diabetes? 7. List the main treatment measures used for Type 1 diabetes. Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary Unit 17 Disorders of Glucose Metabolism 19 Section 3: Acute Complications of Diabetes Mellitus Hypoglycemia Read: Porth – pp. 1007 - 1008 Note: that the textbook gives the glucose values here in mg/dl. Note: Hypoglycemia can be defined as a plasma glucose level less than 3.6 mmol/L. It may occur due to a number of factors including more physical activity and/or less food than usual, resulting in excess insulin availability. Variability in insulin absorption and action as mentioned previously can be responsible for hypoglycemia. As blood glucose drops, counter regulatory hormones are produced to raise the blood glucose. This is not fast enough however, to correct the falling glucose level before symptoms are apparent. In addition, the counter regulation (particularly glucagon secretion) can be impaired in diabetes, particularly diabetes of long duration. Hypoglycemia may lead to insulin shock and eventually to coma if untreated. Point of Interest: The electroencephalogram will indicate isoelectricity at a blood glucose of 1.0 to 0.8 mmol/L. If isoelectricity is longer than 30 minutes permanent brain damage will result, particularly in the hippocampus and caudate (Auer, R.N., Olsson Y., & Siesjo, B.K. (1984). Hypoglycemic brain injury in the rat.. Correlation of density of brain damage with the EEG isoelectric time: A quantitative study. Diabetes 33, 1090 1098). It may result in death if untreated. It has been used in suicides and murder. History: Insulin shock was used as a THERAPY in the last century, primarily in treating the mentally ill. It was also used to ‘treat’ morphine addiction and even acne (Baker, A.B. 1938. Cerebral lesions in hypoglycemia. II. Some possibilities of irrevocable damage from insulin shock. Arch. Pathol. 26, 765-776.). Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary 20 Unit 17 Disorders of Glucose Metabolism Diabetic Ketoacidosis Read: Porth – pp.1006 -1007 The textbook is a little unclear about ketogenesis. Here is a quick review: 1. As insulin levels drop, more fatty acids are converted to ketones (acetoacetate and beta-hydroxybutyrate), and there is decreased ketone use in the periphery. 3. Increasing glucagon levels results in increasing ketone formation. 4. Ketones lose hydrogen ion (H+) as they circulate in the blood, that is they act as an acid in blood. The pH of the blood drops. 5. This contributes to metabolic acidosis. Note: Untreated diabetic ketoacidosis (DKA) eventually causes changes to mentation with eventual stupor and coma. Central nervous system depression seems to be mainly correlated with the level of serum osmolarity. Mortality occurs in 7-8% of cases. Hyperosmolar Hyperglycemic NonKetotic Syndrome (HHNKS) Read: Porth – p. 1007. Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary Unit 17 Disorders of Glucose Metabolism 21 Section 4: Chronic Complications of Diabetes Mellitus Read: Porth – 1008 – 1013. Harris and Lank, pp. 5-6 and 8-9. Microvascular Disease Retinopathy Note: According to the 1998 Clinical Practice Guidelines for the Management of Diabetes in Canada, diabetic retinopathy is THE major cause of adult blindness in North America and is the most feared complication. They recommend that screening and evaluation for retinopathy should be performed annually 5 years after the onset of diabetes in postpubertal patients (age 15 years or over) with Type 1 diabetes and in everyone with Type 2 diabetes at the time of diagnosis. The interval for follow up assessments should be tailored to the severity of the retinopathy. In those with Type 2 diabetes who have no or minimal retinopathy, the recommended interval is 2 years and should not exceed 4 years. Macrovascular Disease Note: Diabetic macrovascular disease is essentially an accelerated form of the atherosclerotic vascular disease found in the non-diabetic population. Uncontrolled hyperglycemia associated with dyslipidemia is thought to be the primary etiologic factor. Review the new target levels for lipids in Table 5 of Harris, S.B., and C.N. Lank, 1998. Also review carefully their recommendations for the control of blood pressure and lipid control on page 5. Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary 22 Unit 17 Disorders of Glucose Metabolism Preventing Long Term Complications—The Diabetes Control and Complications Trial (DCCT). The Diabetes Control and Complications Trial Research Group: The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. 1993. New England Journal of Medicine 329:977. Point of Interest: The DCCT was a prospective, randomized, clinical trial. The general objective was to determine whether tight glycemic control resulting in near euglycemia, that is normal glucose levels, would slow down or prevent long term complications (retinopathy, nephropathy and neuropathy). The DCCT enrolled 1,400 people in 1983-1993 with insulin dependent diabetes (13-39 years old) and was comprised of two cohorts with no complications or minor complications. The study design consisted of two randomized groups. The conventional treatment group received one to two insulin injections and blood glucose tests per day with no predefined target blood glucose values. The intensive treatment group received three or more injections per day, or an insulin pump with frequent blood glucose monitoring. Treatment goals were aimed at achieving near normal glycemia. The results showed that the intensive treatment group had much tighter blood glucose control, and also had a statistically significant reduction in long term complications. Retinopathy 63% reduction Nephropathy 41% reduction Neuropathy 60% reduction Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary Unit 17 Disorders of Glucose Metabolism 23 Learning Activity #3 Answers are at the back of this unit. 1. Briefly list measures thought to aid in preventing diabetic retinopathy. 2. What are three mechanisms by which the person with diabetes may be more susceptible to infection? 3. Why is someone with long duration diabetes more likely to have a ‘silent heart attack’? 4. True or False: a. It is now known that tight blood glucose control will prevent the long-term complications of diabetes. b. Patient education and knowledgeable medical care can ensure early detection and prompt treatment of long-term complications. c. Having diabetes presents continual challenges in controlling the disease and may require repeated adjustments to new losses associated with long-term complications. Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary 24 Unit 17 Disorders of Glucose Metabolism Section 5: Gestational Diabetes Mellitus (GDM) Read: Porth – p. 998 Gestational diabetes mellitus is defined as diabetes that is diagnosed during pregnancy. Because pregnancy itself causes a lower range of ‘normal’ blood glucose, the diagnostic criteria for gestational diabetes are correspondingly lower than for other types of diabetes, i.e., a blood glucose of 7.8 mmol/L or higher one hour after a 50 g glucose drink is considered a positive screen indicating the need for an oral glucose tolerance test. Any two plasma glucose levels exceeding the following during a 100 g oral glucose tolerance test (GTT) are diagnostic of GDM: Fasting 60 min. 120 min. 180 min. 5.8 mmol/L (venous plasma glucose) 10.6 mmol/L 9.2 mmol/L 8.1 mmol/L A screening test for GDM is recommended for all women between 24 and 28 weeks gestation. The third trimester of pregnancy is the usual time of onset due to the diabetogenic effects of increasing placental hormone production. Controversy: There is some controversy over the diagnosis of GDM. Many physicians identify pregnant women with a 2 hour GTT result of 6.7 mmol/L or greater as glucose intolerant and treat them with dietary intervention and surveillance. Parameters for prescribing insulin in GDM vary but typically 2 hours after a meal blood glucose levels in excess of 6.5 mmol/L will be treated with insulin. Oral hypoglycemic medications are contraindicated in pregnancy. Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary Unit 17 Disorders of Glucose Metabolism 25 Final Thoughts The study of glucose metabolism is not only fascinating and important, but an excellent model of the consequences of the deregulation of hormonal control of homeostasis. Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary 26 Unit 17 Disorders of Glucose Metabolism References Auer, R.N., Olsson Y. & Siesjo, B.K. (1984). Hypoglycemic brain injury in the rat. Correlation of density of brain damage with the EEG isoelectric time: A quantitative study. Diabetes, 33, 1090-1098. Baker, A.B. (1938). Cerebral lesions in hypoglycemia. II. Some possibilities of irrevocable damage from insulin shock. Arch. Pathol, 26, 765776. Canadian Diabetes Association, CDA Position Statement Regarding the UKPDS and Revision of Diabetes Clinical Practice Guidelines Accounting for the UKPDS Results, Retrieved October 26, 2000 from the World Wide Web http://www.diabetes.ca/prof/cpg_ukpdsposition.html Canadian Diabetes Association, Clinical practice guidelines for the management of diabetes in Canada. 1998. Retrieved October 26, 2000 from the World Wide Web http://www.diabetes.ca/prof/publications/cpg98eng.pdf Diabetes Control and Complications Trial Research Group. (1993): The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. New England Journal of Medicine, 329, 977. Gerstein, H.C., Hanna, A., Rowe, R., Leiter, L., & MacGregor, A. MDCDA position statement regarding the UKPDS and revision of diabetes clinical practice guidelines accounting for the UKPDS results. Retreived Actober 26, 2000 from the World Wide Web http://www.diabetes.ca/prof/cpg_ukpdsposition.html Harris, S.B., & Lank, C.N. (1998). 1998 Clinical practice guidelines for the management of diabetes in Canada. Canadian Diabetes, 12(1), 3-10. Meltzer, S. et.al. (1998). 1998 Clinical practice guidelines for the management of diabetes in Canada. Retrieved October 26, 2000 form the World Wide Web http://www.diabetes.ca/prof/publications/cpg98eng.pdf Porth, C. M. (2005). Pathophysiology – Concepts of Altered Health Staes (7th ed.). Philadelphia: Lippincott. Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary Unit 17 Disorders of Glucose Metabolism 27 Glossary Note: A glossary of diabetes related terms can be accessed at Diabetes Institute of the University of Minnesota http://www.diabetesinstitute.org/glo.htm - B diabetes mellitus: Is a metabolic disease characterized by the presence of hyperglycemia due to defective insulin secretion, insulin action or both. gestational diabetes mellitus: Is diabetes that is diagnosed during pregnancy. type 1 diabetes: Is diabetes that is primarily a result of pancreatic beta-cell destruction and thus these patients are prone to ketoacidosis. type 2 diabetes: Is a form of diabetes mellitus that may range from insulin resistance with relative insulin deficiency to a predominant secretory defect with insulin resistance. Acronym List ACE Angiotensin converting enzyme CAPD Continuous ambulatory peritoneal dialysis DCCT Diabetes Control and Complications Trial DKA Diabetic ketoacidosis FPG Fasting plasma glucose GDM Gestational diabetes mellitus GI Gastrointestinal HHNKS Hyperosmolar HyperglycemicNonKetotic Syndrome HLA Human leukocyte antigens IDDM Insulin dependent diabetes mellitus NIDDM Noninsulin dependent diabetes mellitus OGTT Oral glucose tolerance test PG Plasma glucose UKPDS United Kingdom Prospective Diabetes Study Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary 28 Unit 17 Disorders of Glucose Metabolism Checklist of Requirements Pre-test Required Readings Harris, S.B., & Lank C.N., (1998). 1998 Clinical Practice Guidelines for the Management of Diabetes in Canada. Canadian Diabetes, 12(1), 3-10. Canadian Diabetes Association, Guidelines for the Nutritional Management of Diabetes Mellitus in the Millennium. Retrieved October 26, 2000 from the World Wide Web http://www.diabetes.ca/prof/index.html, pages 3-6. Porth, C. M. (2005). Pathophysiology – Concepts of Altered Health States (7th ed.). Philadelphia: Lippincott. Print Companion: Disorders of Glucose Metabolism Learning Activities Learning Activity #1 Learning Activity #2 Learning Activity #3 Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary Unit 17 Disorders of Glucose Metabolism Answers to Learning Activities Answers to the Pretest 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. c a c b d b c c a a c d a c c b a a a b a Answers to Learning Activity #1 1. a, b. 2. b, c. Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary 29 30 Unit 17 Disorders of Glucose Metabolism Answers to Learning Activity #2 1. a. 1, b. 2, c. 2, d. 1, e. 1, f. 2 2. a. Familial inheritance is a bigger risk factor in Type 2 than in Type 1 diabetes. b. Obesity of the trunk is closely associated with Type 2 diabetes. c. True d. Autoimmune destruction of beta cells is the primary cause of Type 1 diabetes. 3. a. True b. The symptoms of hyperglycemia are the same in Type 1 and Type 2 diabetes c. Weight loss is the usual treatment of choice in Type 2 diabetes. d. Exercise is important in blood glucose control for Type 2 diabetes. e. True 4. a, b, f 5. 1. dietary intervention 2. exercise 3. oral hypoglycemic agents 4. human recombinant insulin 6. Consider the major pathophysiologic factor in Type 2 diabetes. 7. patient education exogenous insulin injections dietary carbohydrate consistency monitoring of condition blood glucose testing urine ketone testing prn Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary Unit 17 Disorders of Glucose Metabolism 31 Answers to Learning Activity #3 1. regular ophthalmologic examination adequate blood glucose control adequate control of any hypertension 2. hyperglycemia causing inadequate chemotaxis vascular insufficiency neuropathic insensitivity 3. parasympathetic damage (autonomic neuropathy) caused by diabetes results in lack of pain during coronary insufficiency as from a myocardial infarction. 4. a. F, b. T, c. T Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary