Diabetes Mellitus: “Not So Sweet”

1. Diabetes Mellitus: “Not So Sweet” Prutha Dave, RN, BSN davep@alverno.edu MSN 621 Spring 2009 Alverno College

2. Let’s Learn About Type II Diabetes: Home Page Click Below For Instructions On Navigating the Tutorial: Tutorial Objectives Navigation Quick Facts Patho & Genetics Mini Quiz Click Below To Take The Pre-Test: Signs & Symptoms Mini Quiz Pre - Test Tests & Diagnosis Mini Quiz Click Below To Start The Tutorial: Treatment & Medications Mini Quiz Tutorial Patient Education Mini Quiz Image retrieved with permission from:http://www.fredscorner.nl/animations.html

3. Navigation • Click on to go to next slide. • Click on to go back to previous slide. • Click on to go to the home page. • Click on to return back to where you were. • Click on to learn more about the topic. • Role the mouse over or click underlined words to learn more about them. • Click on to take a quick quiz after each section. Mini Quiz Note: An incorrect answer page will ONLY allow you to return BACK to the QUESTION.

4. Objectives of this Tutorial • After completion of this tutorial the participant will gain a better understanding of Diabetes Mellitus, also known as Type II Diabetes. • Also the participant will be able to care for a patient with the disease more effectively. • Topics Covered include: • Pathology & Causes. • Symptoms & Treatment. • Labs/Diagnosis & Patient Education.

5. Quick Facts • In type 2 diabetes, either the body does not produce enough insulin or the cells ignore the insulin. • There are 23.6 million children and adults in the United States, or 7.8% of the population, who have diabetes. • Significant risk factor for coronary heart disease and stroke. • Leading cause of blindness and end stage renal disease. • Major contributor to lower extremity amputations. • Can be successfully managed with the right patient education. • Usually affects older adults but becoming common in obese adolescents. Image retrieved with permission from: http://www.india-shopping.net/india-ayurveda-products/image/diabetes.gif

6. 1. How is Diabetes diagnosed? a. Two separate fasting glucose measurements of 126 mg/dL or higher b. Using symptoms such as polydypsia, polyphagia, and polyuria • c. A hemoglobin A1C level of 6.5%

7. Correct! Yay! Great Job! Two measurements are required to ensure reproducibility and therefore decrease false positives and increase specificity. Image retrieved from: Prutha Dave`Family Photos

8. Oops! Try Again! Click On The Question To Return To It: Question 1 Question 2 Question 3 Question 4 Question 5 Image retrieved from: Prutha Dave`Family Photos

9. 2. A deficiency in which of the following results in hyperglycemia? a. Glucagon b. Insulin c. Ketones d. Cortisol

10. Correct! Yay! INSULIN helps to LOWER blood glucose concentration by MOVING GLUCOSE into BODY TISSUES for energy Image retrieved with permission from:http://www.fredscorner.nl/animations.html

11. 3. What is the Metabolic Syndrome? • Seen in patients with very slow metabolism b. Seen in patients who lack growth hormone, insulin, and cortisol c. Seen in patients with the following cluster of abnormalities: obesity, hyperlipidemia, hypertension, and glucose intolerance

12. Correct! Yay! Metabolic syndrome is a combination of abnormalities including high triglycerides, low HDL’s, HTN, and inflammation. Image retrieved from: Prutha Dave`Family Photos

13. 4. Which of the following class of oral hypoglycemic medications can cause excessive hypoglycemia? a. Biguanides (Metformin) b. ACE inhibitors (Lisinopril, Captopril) c. Sulfonylureas (Glyburide, Glipizide) d. Statins (Lipitor, Crestor)

14. Correct! Yay! Sulfonylureas increase insulin levels and the rate at which glucose is removed from the blood, it is important to know that they can cause hypoglycemic reactions. Image retrieved from: Prutha Dave`Family Photos

15. 5. What are the most common signs of Type II Diabetes? a. Palpitations, restlessness, and diarrhea b. Dehydration, hypotension, and fatigue c. Excessive laughter, bad body odor, and hair loss d. Weight gain, blurred vision, and excessive thirst

16. Correct! Yay! Image retrieved from: Prutha Dave`Family Photos

17. Can be due to absolute insulin deficiency or insulin resistance A metabolic disorder which is characterized by disturbances in carbohydrate, lipid, and protein metabolism caused by an imbalance between insulin availability and insulin need Pathophysiology • Results in an inability to transport glucose into the cells of the body, • thus causing a breakdown of fat and muscle protein (Porth, 2005) Image retrieved with permission from:http://professional.diabetes.org/Multimedia_Display.aspx?TYP=8&CID=53310

18. Video: What Happens in Type II Diabetes? Click On Video To View Video retrieved from with permission from: http://professional.diabetes.org/ResourcesForProfessionals.aspx?typ=17&cid=60425

19. Insulin • A polypeptide which has a direct effect in lowering blood glucose level • Three actions: • Promotes glucose uptake by target cells and provides for storage as glycogen • Prevents fat and glycogen breakdown • Increases protein synthesis by inhibiting gluconeogenesis

20. Insulin Production • Made by the beta cells of the pancreas (islets of Langerhans) • Composed of two polypeptide chains: A and B • Initially made as a larger molecule: proinsulin and then cleaved to the active form of insulin • Other cleavage product is the inactive C-peptide

21. Insulin Release • Glucose enters cell • Glycolysis makes ATP • ATP production causes K+ channel to close and depolarize the cell • Depolarization opens voltage sensitive Ca2+ channels (Ca2+ enters cell) • Ca2+ influx causes insulin release by exocytosis Image retrieved with permission from http://professional.diabetes.org/Multimedia_Display.aspx?TYP=8&CID=53313

22. Insulin Action • Travels through the portal circulation to the liver • Binds to membrane receptor • Activates intracellular enzymes to increase protein, glycogen, and fat synthesis, as well as increasing glucose transporters Image received with permission from: http://upload.wikimedia.org/wikipedia/commons/thumb/8/8c/Insulin_glucose_metabolism.jpg/400px-Insulin_glucose_metabolism.jpg

23. Glucagon: Another Polypeptide • Antagonist of Insulin • Released during periods of fasting to maintain blood glucose • Released by pancreatic alpha cells • Causes glycogen breakdown, gluconeogenesis, protein degradation, all resulting in elevation of blood glucose • In diabetes, can have a negative effect as glucagon production goes unchecked as cells are starved of glucose resulting in exacerbation of hyperglycemia Image retrieved with permission from: http://www.endocrineweb.com/insulin.html

24. Pathogenesis • Genetic and Environmental factors can lead to insulin resistance & decreased release. • This causes decreased glucose uptake and increased glucose output resulting in hyperglycemia and Type II Diabetes. Image received with permission from:http://professional.diabetes.org/Multimedia_Display.aspx?TYP=8&CID=53319

25. Initial decrease in beta cell mass. Increased apoptosis of cell and decreased regeneration. Long standing insulin resistance – causing the beta cells to get TIRED. Glucotoxicity, Lipotoxicity. Amyloid disposition causing dysfuction. Beta Cell Dysfuntion: Another Sign (Porth, 2005) Image retrieved with permission from: http://www.bodyclinicindonesia.com/library/beta_cell.jpg

26. Genetics and Diabetes Mellitus • There is a strong inheritance pattern for Type II Diabetes and it is a heterogeneous condition. • Two major sets of factors play a role in the development of Diabetes Mellitus: Genetic Factors Environmental Factors

27. Genetic Factors • Research shows that Diabetes Mellitus is polygenic  • Meaning that it has different combinations of gene defects. • Multiple “diabetogenic genes” or polymorphisms, each insufficient in themselves, must be present in order to cause diabetes. Click to Learn about Specific Candidate Genes Associated with DM • These genetic polymorphisms can affect the • utilization of blood glucose. (Radha et al, 2003)

28. Polymorphic Genes : Defects to Diabetes Mutations in the following “candidate” genes are seen in persons with Type II Diabetes and may directly contribute to the onset of the disease: *Click To Learn About Specific Genes Genes Related to Insulin Secretion Genes Related to Insulin Resistance Genes Related to Obesity

29. Insulin Secretion Genes Human Insulin Gene (INS) –transcription of the insulin gene is the restricting step for insulin synthesis and secretion. Beta Cell Genes (SUR/KIR 6.2) – these genes encode components of the B-Cell K ATP channel which mediate glucose metabolism and membrane depolaration to cause insulin realease. Pancreatic Duodenal Homedomain Gene (PDX 1) – a transcription factor gene which regulates pancreatic devleopment and islet cell function. (Radha et al, 2003) Images retrieved from: Microsoft Word Clipart 2003

30. Insulin Resistance Genes Glucose Transporter Gene (GLUT) – acts as a sensor to the B-cell and as a major signaling molecule. Peroxisome Proliferator Activated Receptor Gene y (PPAR-y) – a transcription factor gene associated in the regulation of adipocyte gene expression and glucose metabolism. Insulin Receptor Substrate Gene (IRS) – this gene is shown to be associated with decreased insulin sensitivity. (Radha et al, 2003) Images retrieved from: Microsoft Word Clipart 2003

31. Obesity Related Genes • Research has shown that variations in obesity genes have resulted in insulin resistance followed with the onset of Diabetes Mellitus. (Radha et al, 2003) AdiponectinGenes CLICK TO DISCOVER MORE Single nucleotide polymorphisms within this gene have been associated with a risk for Type II Diabetes. Leptin Receptor Genes CLICK TO DISCOVER MORE Mutations of this gene have been associated with hyperglycemia. Uncoupling Protein 2 Genes CLICK TO DISCOVER MORE Studies with these genes have shown to be associated with obesity and DM. Mutations may also cause interference with glucose homeostasis.

32. Environmental Factors • The complex interactions between genes and the environment make it difficult to identify a single factor that leads to Diabetes Mellitus. (Radha et all, 2003) • Environmental Factors Include: Central Obesity Lack of Activity Uncontrolled Diet Viruses Toxins (Smoking)

33. What is one function of insulin? MINI QUIZ: TEST YOUR KNOWLEDGE a. Promote weight loss b. Causes glycogen breakdown c. Increases protein synthesis d. Elevate blood glucose

34. Correct! Great Job! INSULIN promotes glucose uptake, prevents fat and glycogen breakdown, and Increases Protein Synthesis! Good Reading!

35. Oops! Try Again! Image retrieved from: Prutha Dave`Family Photos

36. The release of Glucagon has a positive effect on patients with Type II Diabetes: True or False? TRUE FALSE Image retrieved with permission from:http://www.fredscorner.nl/animations.html

37. Correct! Great Job! Glucagon production can have a NEGATIVE effect if it goes unchecked as cells are starved of glucose resulting in exacerbation of hyperglycemia Image retrieved from: Prutha Dave`Family Photos

38. Sorry! Try Again! Image retrieved from: Prutha Dave`Family Photos

39. Signs & Symptoms • Sneaky onset • Most common signs: The “Polys” • Polyuria • Polydipsia • Blurred Vision • Fatigue • Skin Infections • Paresthesias • Weight loss at first Image retrieved with permission from: http://en.wikipedia.org/wiki/Diabetes

40. MINI QUIZ: TEST YOUR KNOWLEDGE Which symptom is the patient speaking of when she says she is having an abnormal touch sensation? Polyuria Gas Presyncope Paresthesias

41. Correct! Great Job! Image retrieved from: Prutha Dave`Family Photos

42. Uh-oh! Try Again! Image retrieved from: Prutha Dave`Family Photos

43. Tests and Diagnosis TESTS TO KNOW: • Fasting Plasma Glucose: • A blood test that measure the blood glucose level after a person has been fasting for at least eight hours. This is the fastest, most reproducible, and cheapest method to make the diagnosis. • Oral Glucose Tolerance Test: • A test in which a 75g dose of a sugary solution is given and then 2 hours later the blood glucose level is measured. This test is slightly more sensitive than the plasma glucose. • Glycosylated Hemoglobin (HbA1c): • Measures the percentage of red blood cells that have glucose bound to them and is useful in monitoring glycemic control. Not recommended for routine diagnosis. FASTING PLASMA GLUCOSE : CLICK TO LEARN MORE ORAL GLUCOSE TOLERANCE TEST : CLICK TO LEARN MORE HbA1c : CLICK TO LEARN MORE

44. How The Diagnosis is Made Normal Response Fasting Plasma Glucose (FPG) • A fasting blood glucose level less than or equal to 110 mg/dl. This must be confirmed on a separate occasion. Oral Glucose Tolerance Test (OGTT) • 2 hour postload glucose level of less than 140 mg/dl.

45. Impaired Fasting Glucose &Impaired Glucose Tolerance In essence, impaired fasting glucose and impaired glucose tolerance are the same thing, just measured differently. Impaired Fasting Glucose: • A fasting glucose >110 and < 126 mg/dl. This is considered a risk factor diabetes, but by itself, does not make the diagnosis of diabetes. The patient will require close monitoring. Impaired Glucose Tolerance: • 2-hour glucose results from the OGTT that are > 140 and < 200 mg/dl.  This is also considered a risk factor for future diabetes.

46. Diabetes A DIAGNOSIS OF DIABETES IS MADE WHEN: 1. Fasting Plasma Glucose level greater than 126 mg/dl on separate occasions. 2. Random blood glucose > 200 with classic symptoms. 3. Oral glucose tolerance tests show that the blood glucose level at 2 hours is > 200 mg/dl.  This must be confirmed by a second test on another day.

47. MINI QUIZ: TEST YOUR KNOWLEDGE Which of the following tests is not used for a routine diagnosis of Type 2 Diabetes? Fasting Glucose Oral Glucose HbA1c Finger Stick

48. Correct! Great Job! Good Job. The HbA1C test is a measurement of glycosylated hemoglobin and is a useful tool for monitoring glycemic control but is not recommended for diagnostic purposes. Image retrieved from: Prutha Dave`Family Photos

49. Almost! Try Again! Image retrieved from: Prutha Dave`Family Photos

50. True or False: For a diagnosis for Diabetes to be made a person must have a Fasting Plasma Glucose level greater than 126 mg/dl on only one occasion. True False