Diabetes Mellitus

1. Diabetes Mellitus Presented by Rebecca Clyde

2. Normal Organ Function • Our bodies need glucose for energy to function • Glucose needs to be able to enter the cell so it can be metabolized into energy. • Insulin is needed for glucose to be transported into the cell…….

3. Normal Organ Function • Actions of Insulin: • Affects glucose uptake into cells • cardiac muscle • Skeletal muscle • Fat cells Insulin dependent glucose uptake requires GLUT4 transporter. In absence of insulin: GLUT4 is inside cell & cannot transport glucose into cell

4. http://www.jbc.org/content/277/46/43545.full

5. Figure 1: insulin release and action. Glucose enters beta cells via the glucose transporter (GLUT2) and ATP is generated by glycolysis. This results in closure of ATP-sensitive K+ channels, depolarization of the plasma membrane, and opening of voltage-dependent Ca2+ channels. The influx of Ca2+ leads to the release of insulin (1), which is carried in the bloodstream to cells throughout the body where it binds to insulin receptors. This results in autophosphorylation of insulin receptors and phosphorylation of tyrosines on a variety of cellular proteins including members of the insulin receptor substrate (IRS) family and Cbl-CAP (2). The phosphorylated proteins provide docking sites for SH2 domains of several proteins (e.g. phosphatidylinositol 3-kinase (PI(3)K); Grb2 and SHP2; and Crk) that activate different signaling pathways (dashed lines). This results in translocation of the glucose transporter (GLUT4) and uptake of glucose by the cell; alterations in glucose, lipid, and protein metabolism; and changes in gene expression and cell growth. Immunologic and Genetic Factors in Type 1 Diabetes* Abner Louis Notkins‡ journal bio chemistry, 2002

6. Normal Organ Function • Regulation of blood glucose (how it gets into the cell) • Blood glucose levels are regulated by the pancreas (via insulin and glucagon) • Insulin: allows glucose to enter cell • Stimulated by glucose & glucagon, plasma free fatty acids (inhibiting insulin-mediated suppression of glycogenolysis) & ketones • Glucagon: stimulates glucose to be in blood stream • Inhibited by glucose, plasma free fatty acids & ketones, stimulated by low blood glucose levels.

7. Blood Glucose Regulation

8. Pathophysiology • Diabetes mellitus: • syndrome characterized by • chronic hyperglycemia & other disturbances of • CHO • Fat • protein metabolism.

9. Complications • Heart disease • Hypertension • Blindness • Kidney disease • Nerve damage • Amputations • Dental disease • Pregnancy complications • Hypoglycemia • DKA

10. Link between DM & Cardiovascular Disease • http://online.liebertpub.com.erl.lib.byu.edu/doi/full/10.1089/dia.2012.0031 • Snell-Bergeon J, Wadwa R. Hypoglycemia, diabetes, and cardiovascular disease. Diabetes Technology & Therapeutics [serial online]. June 2012;14 Suppl 1:S51-S58. • How does this research affect the recommendations to tightly control blood sugars? • Where’s that 55% CHO recommendation???

11. Etiology of Type 1 DM • Absolute insulin deficiency • Result of autoimmune-mediated specific loss of beta cells in pancreatic islets • 2 types of T1 DM -Autoimmune mediated -Non-autoimmune mediated

12. Etiology of Type 1 DM • Autoimmune mediated diabetes: • Environmental-genetic factors are thought to trigger cell mediated destruction of pancreatic beta cells • Environmental factors: • Some types of viral infections • Stress (stimulates secretion of counter-regulatory hormones, affects immune responses) • Genetic Factors • Poorly understood

13. Etiology of Type 1 DM • Non-autoimmune mediated • Occurs secondary to other diseases (that would cause destruction of the pancreatic beta cells) • Pancreatitis • Idiopathic (T 1B) diabetes

14. Pathophysiology of Type 1 DM • Stages of beta cell destruction • Lymphocyte & macrophage infiltration of islets -Results in inflammation & islet beta cell death • Production of autoantibodies against islet cells, insulin, other cytoplasmic proteins

15. http://www.jbc.org/content/277/46/43545.full

16. Figure 2 Mechanisms of immune-mediated beta cell killing. A, direct killing of beta cells. Autoantigens that are processed and presented as peptides in a complex with MHC class I molecules on the surface of beta cells are recognized by antigen-specific CD8+ cytotoxic T lymphocytes. This results in up-regulation of a number of co-stimulatory molecules (e.g. FAS/FASL). A cascade of signal transduction events ensues resulting in beta cell death by apoptosis through one or more of several different effector pathways (e.g. FAS/FASL, perforin/granzyme). B, indirect (bystander) killing of beta cells. Autoantigens that are engulfed, processed, and presented as peptides in a complex with MHC class II molecules on the surface of APCs (e.g. macrophages or dendritic cells) are recognized by antigen-specific CD4+ helper T lymphocytes. This up-regulates co-stimulatory molecules (e.g. CD28/CD80) and triggers the release of a variety of cytokines (e.g.interferon γ (INFγ), tumor necrosis factor α (TNFα), and NO) from both CD4+ T cells and APCs resulting in apoptosis of nearby beta cells.

17. Signs/Symptoms of Type 1 DM • Thought to be rapid onset, (destruction of beta cells cannot happen overnight) • involves a long preclinical period with a gradual destruction of beta cells, eventually leading to insulin deficiency & hyperglycemia • Slow decrease in your ability to intake glucose into cells as insulin production is gradually decreased.

18. Signs/Symptoms of Type 1 DM • Polydipsia • 2’ elevated blood sugar levels, water is osmotically attracted from body cells, leading to intracellular dehydration & hypothalamic stimulation of thirst

19. Signs/Symptoms of Type 1 DM • Polyuria • Hyperglycemia acts as an osmotic diuretic • The amt of glc filtered by the glomeruli of the kidneys exceeds the amount that can be reabsorbed by renal tubules (glc transporting molecules become saturated) • Glucosuria results, accompanied by large amounts of water lost in urine

20. Signs/Symptoms of Type 1 DM Polyuria http://courses.washington.edu/conj/bess/polyuria/polyuria.htm

21. Signs/Symptoms of Type 1 DM • Polyphagia • Depletion of cellular stores of CHO, fat, protein results in cellular starvation & corresponding increase in hunger.

22. http://www.elmhurst.edu/~chm/vchembook/624diabetes.html

23. Signs/Symptoms of Type 1 DM • Fatigue • Metabolic changes result in poor use of food products. • Contributing to lethargy & fatigue, sleep loss from severe nocturia

24. ***Diagnosis of Type 1 DM • Symptoms present in fasting and post prandial states • Signs/symptoms of DKA • Acetone is blown off, giving breath a sweet odor

25. Medical Interventions for Type 1 DM • Prevention of autoimmune destruction • immunosuppression w/ antirejection drugs • immunomodulation therapies • oral/intranasal insulin • Tx regimens are to achieve optimal glucose control (as measured by HbA1c) without causing episodes of significant hypoglycemia

26. Medical Interventions for Type 1 DM: Avoiding DKA • Avoiding Diabetic Ketoacidosis • DKA is caused by insufficient availability of insulin, so the body uses fat for fuel. • Ketones are formed in lipolysis and deamination of amino acids • Lowers body pH, bad news.

27. Medical Goals • Glycemic Goals (for nonpregnant adults) Note: postprandial glucose measurements should be taken 1-2 hours after the beginning of a meal (representing peak glucose levels)

28. Medical Goals: Insulin Therapy http://www.joslin.org/info/insulin_action.html

29. Type 2 Diabetes Mellitus

30. Etiology of Type 2 DM • Insulin resistance with insulin secretory deficit • 2’ genetic abnormalities • combined with environmental influences Result in insulin resistance & decreased insulin secretion by beta cells Insulin resistance=suboptimal response of insulin-sensitive tissues to insulin

31. Pathophysiology of Type 2 DM Insulin resistance leads to lipolysis in adipocytes causing elevated levels of free fatty acids Increased FFAs cause decreased insulin sensitivity Impairs pancreatic insulin secretion, augments hepatic glucose production, leading to lipotoxicity (further increasing insulin resistance)

32. Signs/Symptoms of Type 2 DM • Often non-specific • Characteristics of a typical Type 2 diabetic • Overweight • Dyslipidemic • Hyperinsulinemic • Hypertensive

33. Signs/Symptoms of Type 2 DM • May also show classic symptoms polyuria, polydipsia • Non-specific symptoms fatigue, pruritis, recurrent infections, vision changes (glucose pulling H2O out of lenses) • Symptoms of neuropathy • Paresthesias: tickling, tingling, burning, numbness • Weakness

34. Diagnosis of Type 2 DM • Similar to Type 1 (signs/symptoms) • Look for recurrent infections, visual changes

35. Medical Interventions for Type 1 DM • Restore near-euglycemia & correct related metabolic disorders. • Dietary measures • Restrict total kcals, as obese pt loses weight, the body’s resistance to insulin often diminishes • Non-obese individuals should consume a consistent CHO diet. • EXERCISE! • Meds may be needed if diet/weight loss cannot control BG levels well enough.

36. Pathophysiology of Gestational Diabetes • Any degree of glucose intolerance with onset or 1st recognition during pregnancy • Insulin resistance and inadequate insulin secretion

37. Diagnosis of Gestational Diabetes • Presence of risk factors • Older age • Family hx • Hx of glc intolerance • Obesity • Ethnicity • Hx of poor obstetric outcomes • Infant weight >9# • And measurement of elevated fasting/casual plasma glucose

38. MNT (presented in the nutrition care process format) • 1. Nutrition assessment • 2. Sample nutrition diagnosis • 3. Typical MNT interventions (including principles of the diet and general education needs) • 4. Desired outcomes • 5. Monitoring tools • 6. Are there evidence based guidelines? If so, how/where do we access them?

39. 1. Nutrition assessment For Type 1 & Type 2 GM • Diet: • Energy Intake (FH 1.1) • Carbohydrate intake (FH 1.5.3) • Diet history (2.1)

40. 1. Nutrition assessment For Type 1 & Type 2 GM • Anthropometric Measurements • Height/length (AD-1.1.1) • Weight (AD1.1.2) • BMI (AD 1.1.5)

41. 1. Nutrition assessment For Type 1 & Type 2 GM • Biochemical data • Glucose, fasting (BD 1.5.1) • HgbA1c (BD 1.5.3)

42. 1. Nutrition assessment For Type 1 & Type 2 GM • Clinical • Nerves & Cognition (PD 1.1.7)

43. 1. Nutrition assessment For Type 1 & Type 2 GM • Client History • living/home situation (CH 3.1.2) • Occupation (CH 3.1.6)

45. 2. Sample nutrition diagnosis • Involuntary weight loss (NC 3.2) • Altered glucose values (NC 2.2) • Inconsistent CHO intake (NI 5.8.5) • Food and nutrition knowledge related deficit (NB 1.1) • Not ready for diet/lifestyle change (NB 1.3) • Inability or lack of desire to manage self care (NB 2.3)

46. 3. Typical MNT interventions (including principles of the diet and general education needs) • Sample PES Statement: • Inconsistent CHO intake related to physiological causes, e.g. type 2 diabetes mellitus as evidenced by fasting blood glucose >126

47. Diabetic Meal Plans • Evaluate current intake to begin • Consistent CHO (use for newly diagnosed T2 because they’re not on insulin yet) evenly space meals, include snacks

48. Diabetic Meal Plans • Practice! Pt on an 1800 kcal diet including 3 meals & 2 snacks (900 kcal/4=225gCHO, 225/4(3meals, 2 snacks)=56g --> 56g per meal & 28g/snack)

49. Teaching Tips • Food label tips: • Pts should ignore g sugar listed, use g CHO to count CHO • CHO from dietary fiber are included in total g CHO • If > 5g dietary fiber in food, - g fiber from total • 3g fat/100kcal= choices

50. Carbohydrate Counting • Who needs it? (***someone willing to test blood glc, newly dx pts***) • Based off 3 meals/d