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Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
Diabetes and Glucose Metabolism
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Diabetes and Glucose Metabolism

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  • Why would a patient secrete less insulin?? Type 1 autoimmune disease where the islet cells in the pancreas have been destroyed by antibodies and no longer produce insulin. Type II the body has been exposed to high levels of blood glucose for so long that it is desensitized to elevated sugar and produces less insulin. Also, for the same reason, the pancreas wears out from producing increased insulin for an extended period of time and therefore no longer can produce insulin in sufficient levels.
  • Transcript

    • 1. Diabetes Mellitus andGlucose Metabolism
      Elizabeth Bunting, MS, PA-C
      Clinical Medicine I
      March 28, 2010
    • 2. Objectives
      Describe normal glucose metabolism
      Describe the pathophysiology of Type I and Type II DM
      Describe the two major types of diabetes with reference to genetics, the age incidence, and diagnosis
      Describe the following therapies for control of blood glucose.
      Diet
      Insulin
      Name and describe the major types of insulin available
      Describe situations in which the use of insulin in Type II Diabetes is clinically correct.
      Describe how to start a patient on insulin and how to counsel a patient
    • 3. Objectives
      Distinguish the features of DM Type II from Type I
      List the classes of antidiabetic agents and discuss their mode of action
      Describe the pathophysiology, signs, symptoms, dignostic features and treatment of
      Diabetic Ketoacidosis and coma
      Hypoglycemia and insulin shock
      Lactic acidosis
      Hyperosmolar coma
      Discuss the dawn phenomenonandSymogyi effect, including their pathophysiology and management.
    • 4. Objectives
      List and describe the following chronic complications of diabetes
      Retinal disease leading to blindness
      Renal disease
      Vascular disease
      Cardiac disease
      Dermatologic disorders
      Gastrointestinal disease
      Discuss the epidemiology of diabetes in the U.S. and explain its socio-economic impact.
    • 5. Objectives
      Discuss the impact of diabetes on pregnancy and include the unique risks and management
      Explain short and ling term monitoring of diabetes.
      Describe patient education principles that may help diabetic patients adhere to their prescribed treatment plan
    • 6. Pancreatic Anatomy
    • 7. Pancreatic Physiology
      Endocrine Gland Secretes:
      Insulin
      Glucagon
      Somatostatin (SS)
      Pancreatic Polypeptide (PP)
      Exocrine Gland Secretes
    • 8. Ketones
      Triglycerides
      Fatty Liver
    • 9. Pancreatic Physiology
      Endocrine and Exocrine activity
      Exocrine:
      Pancreatic Acini cells produce digestive juices
      Duct cells produce NaHCO3
      Endocrinetissue contained inIslets of Langerhans
      Endocrine:
      ALPHA CELLS secrete Glucagon (25%)
      BETA CELLS produce Insulin (60%)
      DELTA CELLS produce Somatostatin (15%)
    • 10. Primary Pancreatic Hormone Activity
      GLUCAGON
      Stimulates breakdown of glycogen in the liver
      Activates hepatic gluconeogenesis (makes sugar)
      INSULIN
      Anabolic hormone
      Facilitates entry of glucose into cells
      Stimulates the liver to store glucose in the form of glycogen
      Promotes the storage of carbohydrate and fat and protein synthesis
    • 11. Insulin
      Biosynthesis, secretion and action
      Mature insulin molecule and C peptide are stored together and cosecreted from secretory granules in the beta cells
      Because the C peptide is cleared more slowly than insulin, it’s a useful marker of insulin secretion
      Glucose is the key regulator of insulin secretion
      Glucose levels >70 mg/dL stimulate insulin synthesis
    • 12. Insulin
      Biosynthesis, secretion and action
      Insulin is secreted in a pulsatile pattern
      Small secretory bursts occur about every 10 minutes
      Superimposed upon greater amplitude oscillations of about 80-150 minutes
      Incretins also play a role in insulin secretion
      Released from GI tract neuroendocrine cells following food ingestion and amplify glucose-stimulated insulin secretion and suppress glucoagon secretion
    • 13. Insulin
      Biosynthesis, secretion and action
      50% is degraded in the liver after entering the portal venous system
      Unextracted insulin enters the systemic circulation where it binds to receptors in target sites
    • 14. Somogyi Effect and Dawn Phenonemon
      Somogyi Effect: nocturnal hypoglycemia (from fasting) leads to a surge of counterregulatory hormones (glucagon and epinephrine) that produce hyperglycemia at around 7 AM
      Dawn Phenomenon: reduced tissue sensitivity to insulin between 5 and 8 AM
    • 15. Diabetes Mellitus
      Syndrome with disordered metabolism and inappropriate hyperglycemia due to a deficiency of insulin secretion or to a combination of insulin resistance and inadequate insulin secretion to compensate.
      Several types exist and are caused by a complex interaction of genetics and environmental factors
      Factors that contribute to hyperglycemia include
      Reduced insulin secretion
      Decreased glucose utilization
      Increased glucose production
    • 16. Diabetes Mellitus
      Metabolic dysregulation associated with DM causes secondary pathophysiologic changes in multiple organ systems that impose a tremendous burden on the individual and the health care system
      DM is the leading cause of ESRD, nontraumatic lower extremity amputations, and adult blindness
    • 17. Diabetes Mellitus
      Classification
      Based on the pathogenic process that leads to hyperglycemia
      Two broad categories
      Type 1 – results from complete or near-total insulin deficiency
      Type 2 – heterogeneous group of disorders characterized by variable degrees of insulin resistance, impaired insulin secretion and increased glucose production
    • 18. Types of Diabetes
      Type 1 Diabetes - previously known as
      Insulin Dependent Diabetes Mellitus (IDDM)
      Juvenile Diabetes
      Type 2 Diabetes – previously known as
      • Non-Insulin Dependent Diabetes Mellitus (NIDDM)
      • 19. Insulin Resistant Diabetes
      • 20. Adult Onset Diabetes
    • Diabetes Mellitus
      Epidemiology
      Prevalence of type 2 diabetes is rising more rapidly than type 1 due to increasing obesity and reduced activity levels
      In 2007 it was estimated that 23.6 million people in the US
      ~1 million have type 1 diabetes
      Incidence increases with age
    • 21. Diabetes
      Epidemiology
      7th leading cause of death in 2007
      Prevalence of 20.9% in individuals >60 years
      Prevalence is similar in men and women
    • 22. Diagnosis of Diabetes
      1Give 75 g of glucose dissolved in 300 mL of water after an overnight fast in persons who have been receiving at least 150–200 g of carbohydrate daily for 3 days before the test.
      2A fasting plasma glucose  126 mg/dL is diagnostic of diabetes if confirmed on a subsequent day.
    • 23. Diagnosis of Diabetes
      Person may have IFG and IGT
      They are at substantial risk of developing diabetes and have an increased risk of cardiovascular disease
      25-40% risk of overt diabetes over next 5 years
      Fasting glucose – the most reliable and convenient test for identifying DM in asymptomatic individuals
    • 24. Type 1 Diabetes
    • 25. Type 1 Diabetes
      General Considerations
      Caused by pancreatic islet B-cell destruction that leads to insulin deficiency
      Destruction is immune-mediated in > 90% of cases and idiopathic in the remainder
      Individuals with genetic susceptibility have normal beta cell mass at birth but begin to lose beta cells secondary to autoimmune destruction that occurs over months to years
      Autoimmune process is thought to be triggered by an infectious or environmental stimulus
    • 26. Type 1 Diabetes
      Susceptibility involves multiple genes
      Major gene is located in the HLA region on chromosome 6
      The rate of pancreatic B-cell destruction ranges from rapid to slow and varies among individuals
      Features of diabetes do not become evident until ~80% of beta cells are destroyed
      Prone to ketoacidosis
      Serum C-peptide negative 1–5 years after diagnosis; plasma glucagon is elevated
    • 27. Type 1 Diabetes
      Immunologic markers
      Islet cell autoantibodies (ICAs) – present in >75% of those diagnosed with new-onset type 1 DM
      Testing for these can be useful in classifying type of DM and identifying nondiabetic individuals at risk of developing type 1 DM
      Environmental factors
      None have been conclusively linked to diabetes
    • 28. Type 1 Diabetes
      Prevention
      No interventions have been proven successful in preventing type 1 DM in humans
      Demographics
      Typically onset of disease is prior to age 30 (10-14 most commonly)
      Suspect especially when hyperglycemia first appears in the nonobese or elderly
    • 29. Type 1 Diabetes
      Incidence
      Highest in Scandinavia
      Lowest in China and parts of South America
      In the United States, average is 15 per 100,000
      Incidences are higher in states densely populated with persons of Scandinavian descent such as Minnesota
      The global incidence is increasing, with an annual increase of ~3%
    • 30. Type 1 Diabetes
      Symptoms and Signs
      Lean body habitus
      Increased thirst (polydipsia)
      Increased urination (polyuria)
      Increased appetite (polyphagia) with weight loss
      Ketoacidosis
      Paresthesias
      Recurrent blurred vision
      Vulvovaginitis or pruritus
      Nocturnal enuresis
      Postural hypotension from lowered plasma volume
    • 31. Type I Diabetes
      Laboratory Tests
      Fasting plasma glucose ≥ 126 mg/dL or > 200 mg/dL 2 h after glucose load
      Ketonemia, ketonuria, or both
      Glucosuria
      Assess degree of glycemic control with glycosylated hemoglobin (hemoglobin A1c)
      reflects glycemic control over preceding 8–12 weeks
      Serum fructosamine
      Reflects glycemic control over preceding 2 weeks
      Helpful in presence of abnormal hemoglobins or in ascertaining glycemic control at time of conception among diabetic women
    • 32. Type 1 Diabetes
      Laboratory tests
      Serum insulin or C-peptide
      Forms when proinsulin is broken down to form insulin and C-peptide
      C-peptide has a longer half life than insulin
      Islet cell antibodies
      Insulin autoantibody
      Screen for DM-associated conditions
      Microalbuminuria
      Dyslipidemia
      Thyroid function
    • 33. Type 1 Diabetes
      Pharmaceutical treatment
      Insulin
      Goal is to design insulin regimens that mimic physiologic insulin secretion
      Insulin regimens usually include multiple-component insulin regimens, multiple daily injections or insulin infusion devices
      Most patients will require 0.5-1 U/kg/day of insulin divided into multiple doses, with ~50% of the insulin given as basal insulin
    • 34. Insulin Preparations
    • 35. A multiple-component insulin regimen consisting of long-acting insulin,one shot of glargine to provide basal insulin coverage and three shots of lispro, or insulin aspart to provide glycemic coverage for each meal.
      The injection of two shots of long-acting insulin, NPH or detemir and short-acting insulin, lispro, insulin aspart (solid red line), or regular (green dashed line)
      B= breakfast
      L= lunch
      S= supper
      HS= bedtime
      = time of insulin injection
      Infusion pump which uses lispro or aspart
    • 36. Diet/Nutrition
      Carbohydrate counting or exchange systems to estimate the nutrient content of a meal or snack
      Estimate of the carb content of a meal determines the bolus insulin dose for a meal or snack
      Want to coordinate and match caloric intake with the appropriate amount of insulin
      A common ratio is 1-1.5 units/10g of carb, but this must be individualized
    • 37. Type 1 Diabetes
      Other agents that improve glucose control
      Amylin (pramlintide)
      Usually cosecreted from pancreatic beta cells with insulin
      Pts who are insulin deficient are also amylin deficient
      SC injection before each meal - reduces postprandial glycemic excursion in type 1 and 2 diabetic pts
      Slows gastric emptying and suppresses glucagon
      Will decrease amount of short-acting insulin needed before the meal
    • 38. Type 1 Diabetes
      Surgery
      Patients receiving simultaneous pancreas and kidney transplants have 85% chance of pancreatic graft survival and 92% chance of renal graft survival after 1 year
      Islet transplantation is minimally invasive
      Plagued by limitations and remains an area of investigation
    • 39. Type 2 Diabetes
    • 40. Type 2 Diabetes
      General considerations
      Typically > 40 years of age
      Fasting plasma glucose ≥ 126 mg/dL more than once
      OGTT > 200 mg/dL 2 h after the oral glucose
      Often associated with hypertension, dyslipidemia, and atherosclerosis
    • 41. Type 2 Diabetes
      Pathophysiology
      Characterized by impaired insulin secretion, insulin resistance, excessive hepatic glucose production and abnormal fat metabolism
      Obesity, especially central (hip-waist ratio) is very common (present in 80%)
      Early stages – glucose tolerance remains near normal, despite insulin resistance, because the beta cells increase their insulin output
    • 42. Type 2 Diabetes
      Pathophysiology (cont’d)
      As the disease progresses, islets are unable to sustain the hyperinsulinemic state
      IGT develops, characterized by elevations in postprandial glucose
      Further decline in insulin secretion and increase in hepatic glucose production lead to overt diabetes with fasting hyperglycemia
      Ultimately, beta cell failure may ensue
    • 43. Type 2 Diabetes
      Genetic considerations
      Strong genetic component
      Concordance in identical twins is between 70-90%
      If both parents have type 2, the risk approaches 40% for the offspring
      General considerations
      Prevalence of obesity in type 2 diabetes mellitus
      30% in Chinese and Japanese
      60–70% in North Americans, Europeans, and Africans
      Nearly 100% in Pima Indians and Pacific Islanders from Nauru or Samoa
    • 44. Type 2 Diabetes
      General Considerations
      Enhancers of insulin resistance are aging, sedentary lifestyle, and abdominal-visceral obesity
      Both the tissue resistance to insulin and the impaired B-cell response to glucose are further aggravated by increased hyperglycemia, and both defects improve with decreased hyperglycemia
    • 45. Type 2 Diabetes
      Demographics
      > 90% of all diabetics in the United States have type 2 diabetes (>18 million)
      Traditionally develops after age 40, but now more frequently at younger ages due to increased rates of obesity
      No gender predominance
    • 46. Type 2 Diabetes
      Screening
      ADA recommends screening all individuals >45 years q3 years and earlier if they are overweight and have one additional risk factor for diabetes
      Many are asymptomatic and unaware they have the disease
      Type 2 DM may be present for up to a decade before diagnosis
      Treatment of type 2 DM may favorably alter the natural history of DM
    • 47. Risk Factors for Type 2 Diabetes
      FH of diabetes (parent or sibling with type 2)
      Obesity (BMI >25)
      Habitual physical inactivity
      Race/ethnicity – AA, Latino, Native Amer, Asian or Pacific Islander
      Previously identified with IFG or IGT
      History of GDM or delivery of baby >9 lbs
      HTN (BP >140/90)
      PCOS or acanthosisnigricans
    • 48. Type 2 Diabetes
      History
      Be sure to ask about DM relevant aspects such a weight, FH of DM, risk factors for CV disease, exercise, smoking and ethanol use
      If previously diagnosed with DM ask about type of therapy, prior HgbA1C levels, self-monitoring BG results, frequency of hypoglycemia, assessment of pt’s knowledge about diabetes, exercise and nutrition
    • 49. Type 2 Diabetes
      Symptoms and Signs
      Often asymptomatic
      Obesity
      Polyuria
      Polydipsia
      Weakness or fatigue
      Recurrent blurred vision
      Vulvovaginitis or pruritus
      Slow wound healing
      Peripheral neuropathy
      Acanthosisnigricans
    • 50. Acanthosisnigricans (AN) is a brown to black, poorly defined, velvety hyperpigmentation of the skin, usually present in the posterior and lateral folds of the neck, the axilla, groin, umbilicus, and other areas
    • 51. Type 2 Diabetes
      PE
      Special attention should be given to DM-relevant aspects such as
      Weight or BMI
      Retinal examination
      Yearly evaluation by ophthalmologist
      BP
      >130/80 mmHg is considered HTN
    • 52. Type 2 Diabetes
      PE
      Foot examination
      Peripheral neuropathy – vibratory sensation and light touch sensation with monofilament
      Calluses
      Foot deformities
      Peripheral pulses
      Insulin injection sites
    • 53. Type 2 Diabetes
      Associated conditions
      Insulin resistance
      CV disease
      HTN
      Dyslipidemia
      PCOS
    • 54. Type 2 Diabetes
      Laboratory Tests
      Fasting plasma glucose  ≥126 mg/dL or >200 mg/dL 2 h after glucose load
      Glucosuria
      Ketonuria on occasion without ketonemia
      Assess the degree of glycemic control with glycosylated hemoglobin (HbA1c)
      reflects glycemic control over preceding 8–12 weeks
    • 55. Type 2 Diabetes
      Laboratory testing
      Screen for DM-associated conditions
      Microalbuminuria
      Dyslipidemia
      Lipoprotein abnormalities in obese persons with type 2 diabetes include
      High serum triglyceride (300–400 mg/dL)
      Low high-density lipoprotein (HDL) cholesterol (< 30 mg/dL)
      A qualitative change in low-density lipoprotein (LDL) particles
      Thyroid function
    • 56. Type 2 Diabetes Management
    • 57. Long Term Treatment
      Goals
      Eliminate symptoms related to hyperglycemia
      Symptoms usually resolve when BG <200 mg/dL
      Reduce or eliminate the long-term microvascular and macrovascular complications
      Allow the pt to achieve as normal a lifestyle as possible
    • 58. Long Term Treatment
      How to achieve these goals
      Pt education about DM, nutrition and exercise
      Provider education at every office visit + the use of a diabetes educator and dietician
      Nutritional recommendations
      Diet that includes fruits, vegetables, fiber-containing foods and low-fat milk
      Glycemic index – estimate of the postprandial rise in the BG when amount of that food is consumed
    • 59. Glycemic Index
      Low glycemic index appears to reduce postprandial glucose excursions and improve glycemic control
      Short grain White Rice 72
      White Bread 70
      Graham Crackers 74
      Broccoli 10
      Corn 55
      Potato (baked) 93
      Sweet Potato 54
      Apple 38
      Watermelon 103
      Honey 58
      Fructose 23
      Walnuts 15
      Corn Chips 72
      Milk (whole) 22
      Yogurt (low-fat) 33
    • 60. Diabetes
      Dietary Recommendations
      Cholesterol to 200 mg QD
      Protein intake to 10–35% of total calories
      Saturated fats to <7% of total calories
      Remainder of diet to consist of monounsaturated fats and carbohydrates with 20–35 g of dietary fiber
    • 61. Long Term Treatment
      Exercise
      ADA recommends 150min/week (distributed over at least 3 days) of aerobic activity
      Reduces CV risk
      Reduces BP
      Maintains muscle mass
      Reduction in body fat and weight loss
      Lowers plasma glucose – during and following exercise
      Increases insulin sensitivity
      Formal exercise tolerance testing (stress test) is warranted in individuals prior to the start of an exercise program with any of the following: age>35 years, diabetes duration >10 years, microvascular complications, neuropathy, PAD
    • 62. Long Term Treatment
      Monitoring of BG
      Patient’s measurements provide you with a picture of short-term glycemic control
      HbA1C reflects average glycemic control over the previous 3 months
      Self-monitoring of BG
      Frequency must be individualized
      Type 1 or type 2 on insulin - ≥3 times a day
      Type 2 on oral meds – 1-2 times a day with decreasing frequency as DM becomes controlled
      Monitor prior to a meal and supplemented with postprandial measurements
    • 63. Type 2 Diabetes
      Pharmaceutical treatment
      Any therapy that improves glycemic control reduces “glucose toxicity” to the islet cells and improves endogenous insulin secretion
      However, type 2 DM is a progressive disorder and ultimately requires multiple therapeutic agents and often insulin
    • 64. Classifications of glucose lowering agents
      Insulin secretagogues
      Drugs that stimulate insulin secretion
      Most effective in pt with relatively recent onset of DM (<5 years)
      Sulfonylureas (glyburide, glipizide, glimepiride)
      Meglitinide analogs (Prandin/repaglinide)
      D-phenylalanine derivative (Starlix/nateglinide)
      Side effects
      Can cause hypoglycemia, especially in the elderly
      Weight gain
    • 65. Classifications of glucose lowering agents
      Biguanides
      Reduces hepatic glucose production and improves peripheral glucose utilization slightly
      Metformin (glucophage)
      Promotes modest weight loss
      Side Effects
      GI disturbances – nausea, bloating, diarrhea
      Lactic acidosis – can be prevented by avoiding use in renal insufficiency (creatinine >1.5 mg/dL)
      Must discontinue prior to radiographic contrast material
    • 66. Classifications of glucose lowering agents
      αglucosidase inhibitors
      Reduce glucose absorption from the GI tract
      Reduce postprandial hyperglycemia
      acarbose, miglitol
      Not as potent as other oral agents at lowering the A1C
      Side effects
      Diarrhea, flatulence, abdominal distention (due to increased carbs/sugars in the large bowel)
    • 67. Classifications of glucose lowering agents
      Thiazolidinediones (TZDs)
      Reduce insulin resistance
      Promote redistribution of fat from central to peripheral locations
      Circulating insulin levels decrease
      Pioglitazone (Avandia), rosiglitazone (Actos)
      Must measure LFTs prior to initiating therapy and q2 months for the 1st year of therapy
      Side effects
      Weight gain
      Peripheral edema and CHF – don’t use in CHF class III or IV
    • 68. Classifications of glucose lowering agents
      GLP-1 receptor signaling
      “Incretins”
      Amplify glucose-stimulated insulin secretion
      Exenatide (Byetta)
      Suppresses glucagon and slows gastric emptying
      Most experience modest weight loss
      Suppresses appetite
      SC injection before morning and evening meal
      Only approved for adjunct or combo therapy with metformin, TZD or sulfonylurea
      Sitagliptin (Januvia)
      DPP-IV inhibitor, enhance incretin effect
      Promote insulin secretion and have a preferential effect on postprandial BG
      Oral medication and can be used in combination with metformin or a TZD
    • 69. Classifications of glucose lowering agents
      Insulin therapy
      Can consider as initial therapy especially in lean individuals or those with severe weight loss, in those with underlying renal or hepatic disease, or those hospitalized or acutely ill
      Insulin is usually initiated as a single dose of long-acting insulin (determir (Levemir), glargine (Lantus)) and is most often started at bedtime
      Can use in combination with oral glucose-lowering agents (biguanides, αglucosidaseinhib, TZDs)
      As the disease progress the pt will often need prandial insulin coverage also
    • 70. Classifications of glucose lowering agents
      Choice of initial glucose-lowering agent
      Level of hyperglycemia
      If FPG <200-250 mg/dL pts often respond to a single oral agent
      If FPG >250mg/dL pts often need >1 agent to reach goal
      Consider insulin if FPG >250-300mg/dL or in those who are symptomatic from hyperglycemia
      All oral agents except the αglucosidase inhibitors improve glycemic control to a similar degree (1-2% reduction in A1C)
    • 71. Glycemic management
    • 72. Classifications of glucose lowering agents
      Combination therapy with oral agents
      Mechanisms of action are different so the effect on glycemic control is additive
      several drug combinations of TZD + metformin or sulfonylurea; metformin + sulfonylurea; DPP-IV with metformin are available
    • 73. Diabetes
      Guidelines for ongoing medical care
      Self-monitoring of blood sugar
      HbA1c (2-4 times/year)
      Screen for microalbuminuria annually
      Serum lipids annually
      Feet examination by provider 1-2 times a year, daily by pt
      Diabetic eye examination annually
    • 74. Treatment Goals
    • 75. Diabetes
      Hemoglobin A1C
      There is an equation
      A 1% increase in A1C translates into a 35mg/dL increase in the mean glucose
    • 76. Diabetes
      Complications
      May be present in up to 20-50% of newly diagnosed individuals with type 2
      Retinopathy
      CV disease
      Nephropathy
      Neuropathy
      Diabetic ketoacidosis
      Hypoglycemia and altered awareness of hypoglycemia
    • 77. Diabetes
      Prevention
      Goal of therapy is to prevent acute illness and reduce risk of long-term complications
      Type 2 DM is preceded by a period of IGT and a number of lifestyle modifications and pharmacologic agents prevent or delay the onset of DM
      Maintain a normal BMI
      Diet and exercise for 30 min/day five times/week
      ADA recommends consideration of Metformin (glucophage) in individuals with both IFG and IGT who are at high risk of progression to diabetes
      <60 years, BMI >35, +FH 1st degree relative, elevated TGs, reduced HDL, HTN or A1C >6%
    • 78. Comparison of Diabetes S&S
    • 79. Complications
      Acute
      Diabetic ketoacidosis
      Hyperglycemic Hyperosmolar State
      Chronic
      Duration and degree of glycemic control are the best predictors of complications
      Vascular
      Microvascular
      Retinopathy, neuropathy, nephropathy
      Macrovascular
      CAD, PAD, CV disease
      Nonvascular
      Gastroparesis, infections, skin changes, sexual dysfunction, cataracts, glaucoma, periodontal disease
    • 80. Ocular Complications
      Diabetic retinopathy
      DM is the leading cause of blindness b/t the ages of 20-74 in the US
      Retinal vascular microaneurysms, blot hemorrhages, cotton wool spots eventually progress in most patients with continued hyperglycemia and lead to retinal ischemia
      Can be treated early with laser photocoagulation
    • 81. Retinal Changes
    • 82. Cardiovascular Complications
      DM major risk factor for cardiovascular disease in the US
      Annual incidence of cardiovascular death rate is increased by 3 times in diabetic men and by 4 times in diabetic women
      Risk factors for cardiovascular disease
      Insulin resistance
      Elevated urinary protein excretion
      Poor glycemic control
      Overweight or obesity
      Dyslipidemia
      HTN
      Sedentary lifestyle
      Smoking
      Monitoring of lipid levels and management of hyperlipidemia is essential in the prevention of macrovascular complications
    • 83. Diabetic Nephropathy
      DM is the #1 cause of ESRD in the U.S.
      Leading cause of DM-related morbidity and mortality
      Begins with microalbuminuria defined as 30-300 mg/d
      After 10 years macroalbuminuria develops in 50%
      Overall risk of developing diabetic nephropathy is 20-40%
    • 84. Diabetic Nephropathy
      Treatment
      Glycemic control slows progression
      Strict BP control
      Start ACE or ARB
      Restrict protein intake to 0.8g/kg/day
      Nephrology consultation when GFR is <60 mL/min
      More likely to develop in:
      Males
      Relatives have had kidney disease or HTN
      Poor glycemic control
      Patient has HTN
    • 85. Diabetic Neuropathy
      Most common complication of DM Type 2
      Develops in ~50% of individuals with DM
      Peripheral neuropathy
      Most common is distal symmetric polyneuropathy
      Most frequently presents with distal sensory loss but may also have hyperesthesia, paresthesia and dysesthesia
      Begins in feet and spreads proximally, usually present at rest and worsens at night
    • 86. Diabetic Neuropathy
      Autonomic neuropathy
      Involves the cholinergic, noradrenergic, and peptidergic
      Can involve multiple systems
      CV, GI, GU
      Postural hypotension and decreased CV response
      Gastroparesis
      Urine retention
      ED
      Treatment
      Check feet daily and take precautions (footwear)
      TCAs, anticonvulsants, duloxetine (Cymbalta) and pregabalin (Lyrica), gabapentin (Neurontin)
    • 87. PV Disease of the Feet
      Screening and referral to footcare clinic for people with diabetes who are at high risk of developing foot ulcers reduces the risk of foot ulcers and major amputation
    • 88. Foot structure
      Foot appearance
      Vascular status
      Neurosensory
      128 Hz tuning fork base at great toe nail
      Monofilaments
      Deep tendon reflexes
    • 89. Skin & Mucous Membrane Complications
      Protracted wound healing and skin ulcerations
      Shin spots – pigmented pretibial papules
      Granulomaannulare – erythematous plaques on the extremities or trunk
      Repetitive candidainfection
    • 90. Infections
      Many common infections are more frequent and severe in the diabetic population
      “malignant” or invasive otitisexterna
      Pneumonia
      UTI
      Skin and soft tissue infections
    • 91. Hypoglycemia
      Glucose level <55 mg/dL with symptoms that are relieved promptly after the glucose level is raised
      Most convincingly documented by Whipple’s triad
      Symptoms consistent with hypoglycemia
      Low plasma glucose concentration measured with a precise method (not a glucose monitor)
      Relief of symptoms after the plasma glucose is raised
    • 92. Physiology of glucose counterregulation
    • 93. Hypoglycemia
      Etiology and pathophysiology
      Most commonly a result of the treatment of diabetes
      Hypoglycemia in diabetes
      Impact and frequency
      More common in type 1 DM
      Pts suffer an average of twice a week with symptomatic hypoglycemia and once a year with a severe episode
      2-4% die as a result of hypoglycemia
      Occurs in type 2 DM with sulfonylureas or insulin
    • 94. Hypoglycemia
      Hypoglycemia in diabetes
      Conventional risk factors
      Relative or absolute insulin excess
      Insulin dose is excessive, ill-timed or the wrong type
      Influx of exogenous glucose is reduced (missed meal)
      Glucose utilization is increased (during exercise)
      Sensitivity to insulin is increased (improved glycemic control, increased fitness or weight loss)
      Endogenous glucose production is reduced (alcohol ingestion)
      Insulin clearance is reduced (renal failure)
    • 95. Hypoglycemia
      Hypoglycemia in diabetes
      Hypoglycemic-associated autonomic failure
      Defective glucose counterregulation
      Hypoglycemia unawareness
      Fasting (postabsorptive) hypoglycemia
      Causes
      Drugs – insulin, sulfonylureas, ethanol
      Critical illness – hepatic, renal or cardiac failure, sepsis
      Endogenous hyperinsulinism – insulinoma, autoimmune, ectopic insulin secretion
    • 96. Hypoglycemia
      Postprandial (reactive) hypoglycemia
      Occurs exclusively after meals
      Diagnosis requires documentation of Whipple’s triad after a mixed meal
      Early - rapid discharge of ingested carbohydrate into the small bowel followed by rapid glucose absorption and hyperinsulinism
      Particularly associated with dumping syndrome after gastrectomy
    • 97. Hypoglycemia
      Symptoms
      Neuroglycopenic – CNS glucose deprivation
      Behavioral changes, confusion, fatigue, seizures, LOC
      Neurogenic
      Adrenergic – norepi release
      Palpitations, tremor and anxiety
      Cholinergic – acetylcholine release
      Sweating, hunger, paresthias
    • 98. Hypoglycemia
      Signs
      Diaphoresis
      Pallor
      Tachycardia
      Increased systolic BP
      Transient focal neuro deficits
    • 99. Hypoglycemia
      Laboratory Tests
      If history suggests prior hypoglycemia and a potential mechanism isn’t apparent
      Obtain plasma glucose, insulin, C-peptide under conditions when hypoglycemia would be expected, typically during fasting
      Treatment
      3 glucose tablets (20g), 4 oz of juice, 6 oz of soda, or 7 lifesavers – if pt is able and willing
      25g IV glucose or 1mg SC or IM glucagon - if pt is unable or unwilling to take orally
    • 100. Hypoglycemia
      Treatment
      Fasting (postabsorptive) hypoglycemia
      Change dose of medication, no alcohol
      Endocrine tumor – surgical removal
      Reactive (postprandial) Hypoglycemia
      Dietary manipulation is an adjunct: reduce proportion of carbohydrates in the diet, increase the frequency and reduce the size of the meals
    • 101. Hyperglycemia
      Will be covered in your Emergency Medicine class in the Fall
    • 102. Any Questions ???

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