This document provides an overview of diabetes mellitus and glucose metabolism. It describes normal glucose metabolism and the pathophysiology of Type I and Type II diabetes. Type I diabetes results from a lack of insulin production, while Type II involves insulin resistance and impaired insulin secretion. The document discusses insulin therapy and medications for controlling blood glucose levels, as well as complications, management during pregnancy, and principles of patient education.

1. Diabetes Mellitus andGlucose MetabolismElizabeth Bunting, MS, PA-CClinical Medicine IMarch 28, 2010

2. ObjectivesDescribe normal glucose metabolismDescribe the pathophysiology of Type I and Type II DMDescribe the two major types of diabetes with reference to genetics, the age incidence, and diagnosisDescribe the following therapies for control of blood glucose.DietInsulinName and describe the major types of insulin availableDescribe 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. ObjectivesDistinguish the features of DM Type II from Type IList the classes of antidiabetic agents and discuss their mode of actionDescribe the pathophysiology, signs, symptoms, dignostic features and treatment of Diabetic Ketoacidosis and comaHypoglycemia and insulin shockLactic acidosisHyperosmolar comaDiscuss the dawn phenomenonandSymogyi effect, including their pathophysiology and management.

4. ObjectivesList and describe the following chronic complications of diabetes Retinal disease leading to blindnessRenal diseaseVascular diseaseCardiac diseaseDermatologic disordersGastrointestinal diseaseDiscuss the epidemiology of diabetes in the U.S. and explain its socio-economic impact.

5. ObjectivesDiscuss the impact of diabetes on pregnancy and include the unique risks and managementExplain 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 PhysiologyEndocrine Gland Secretes: Insulin Glucagon Somatostatin (SS) Pancreatic Polypeptide (PP)Exocrine Gland Secretes

8. KetonesTriglyceridesFatty Liver

9. Pancreatic PhysiologyEndocrine and Exocrine activityExocrine:Pancreatic Acini cells produce digestive juicesDuct cells produce NaHCO3Endocrinetissue contained inIslets of LangerhansEndocrine:ALPHA CELLS secrete Glucagon (25%)BETA CELLS produce Insulin (60%)DELTA CELLS produce Somatostatin (15%)

10. Primary Pancreatic Hormone ActivityGLUCAGONStimulates breakdown of glycogen in the liverActivates hepatic gluconeogenesis (makes sugar)INSULINAnabolic hormoneFacilitates entry of glucose into cellsStimulates the liver to store glucose in the form of glycogenPromotes the storage of carbohydrate and fat and protein synthesis

11. InsulinBiosynthesis, secretion and actionMature insulin molecule and C peptide are stored together and cosecreted from secretory granules in the beta cellsBecause the C peptide is cleared more slowly than insulin, it’s a useful marker of insulin secretion Glucose is the key regulator of insulin secretionGlucose levels >70 mg/dL stimulate insulin synthesis

12. InsulinBiosynthesis, secretion and actionInsulin is secreted in a pulsatile patternSmall secretory bursts occur about every 10 minutesSuperimposed upon greater amplitude oscillations of about 80-150 minutesIncretins also play a role in insulin secretionReleased from GI tract neuroendocrine cells following food ingestion and amplify glucose-stimulated insulin secretion and suppress glucoagon secretion

13. InsulinBiosynthesis, secretion and action50% is degraded in the liver after entering the portal venous systemUnextracted insulin enters the systemic circulation where it binds to receptors in target sites

14. Somogyi Effect and Dawn PhenonemonSomogyi Effect: nocturnal hypoglycemia (from fasting) leads to a surge of counterregulatory hormones (glucagon and epinephrine) that produce hyperglycemia at around 7 AMDawn Phenomenon: reduced tissue sensitivity to insulin between 5 and 8 AM

15. Diabetes MellitusSyndrome 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 factorsFactors that contribute to hyperglycemia includeReduced insulin secretionDecreased glucose utilizationIncreased glucose production

16. Diabetes MellitusMetabolic dysregulation associated with DM causes secondary pathophysiologic changes in multiple organ systems that impose a tremendous burden on the individual and the health care systemDM is the leading cause of ESRD, nontraumatic lower extremity amputations, and adult blindness

17. Diabetes MellitusClassificationBased on the pathogenic process that leads to hyperglycemiaTwo broad categoriesType 1 – results from complete or near-total insulin deficiencyType 2 – heterogeneous group of disorders characterized by variable degrees of insulin resistance, impaired insulin secretion and increased glucose production

18. Types of DiabetesType 1 Diabetes - previously known asInsulin Dependent Diabetes Mellitus (IDDM)Juvenile DiabetesType 2 Diabetes – previously known asNon-Insulin Dependent Diabetes Mellitus (NIDDM)

19. Insulin Resistant Diabetes

20. Adult Onset DiabetesDiabetes MellitusEpidemiologyPrevalence of type 2 diabetes is rising more rapidly than type 1 due to increasing obesity and reduced activity levelsIn 2007 it was estimated that 23.6 million people in the US ~1 million have type 1 diabetesIncidence increases with age

21. DiabetesEpidemiology7th leading cause of death in 2007Prevalence of 20.9% in individuals >60 yearsPrevalence is similar in men and women

22. Diagnosis of Diabetes1Give 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 DiabetesPerson may have IFG and IGTThey are at substantial risk of developing diabetes and have an increased risk of cardiovascular disease25-40% risk of overt diabetes over next 5 yearsFasting glucose – the most reliable and convenient test for identifying DM in asymptomatic individuals

24. Type 1 Diabetes

25. Type 1 DiabetesGeneral ConsiderationsCaused by pancreatic islet B-cell destruction that leads to insulin deficiencyDestruction is immune-mediated in > 90% of cases and idiopathic in the remainderIndividuals 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 yearsAutoimmune process is thought to be triggered by an infectious or environmental stimulus

26. Type 1 DiabetesSusceptibility involves multiple genesMajor gene is located in the HLA region on chromosome 6The rate of pancreatic B-cell destruction ranges from rapid to slow and varies among individualsFeatures of diabetes do not become evident until ~80% of beta cells are destroyedProne to ketoacidosisSerum C-peptide negative 1–5 years after diagnosis; plasma glucagon is elevated

27. Type 1 DiabetesImmunologic markersIslet cell autoantibodies (ICAs) – present in >75% of those diagnosed with new-onset type 1 DMTesting for these can be useful in classifying type of DM and identifying nondiabetic individuals at risk of developing type 1 DMEnvironmental factorsNone have been conclusively linked to diabetes

28. Type 1 DiabetesPreventionNo interventions have been proven successful in preventing type 1 DM in humansDemographicsTypically 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 DiabetesIncidence Highest in ScandinaviaLowest in China and parts of South AmericaIn the United States, average is 15 per 100,000Incidences are higher in states densely populated with persons of Scandinavian descent such as MinnesotaThe global incidence is increasing, with an annual increase of ~3%

30. Type 1 DiabetesSymptoms and SignsLean body habitusIncreased thirst (polydipsia)Increased urination (polyuria)Increased appetite (polyphagia) with weight lossKetoacidosisParesthesiasRecurrent blurred visionVulvovaginitis or pruritusNocturnal enuresisPostural hypotension from lowered plasma volume

31. Type I DiabetesLaboratory TestsFasting plasma glucose ≥ 126 mg/dL or > 200 mg/dL 2 h after glucose loadKetonemia, ketonuria, or bothGlucosuria Assess degree of glycemic control with glycosylated hemoglobin (hemoglobin A1c) reflects glycemic control over preceding 8–12 weeksSerum fructosamine Reflects glycemic control over preceding 2 weeksHelpful in presence of abnormal hemoglobins or in ascertaining glycemic control at time of conception among diabetic women

32. Type 1 DiabetesLaboratory testsSerum insulin or C-peptideForms when proinsulin is broken down to form insulin and C-peptideC-peptide has a longer half life than insulinIslet cell antibodiesInsulin autoantibodyScreen for DM-associated conditionsMicroalbuminuriaDyslipidemiaThyroid function

33. Type 1 DiabetesPharmaceutical treatment InsulinGoal is to design insulin regimens that mimic physiologic insulin secretionInsulin regimens usually include multiple-component insulin regimens, multiple daily injections or insulin infusion devicesMost 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= breakfastL= lunchS= supperHS= bedtime = time of insulin injectionInfusion pump which uses lispro or aspart

36. Diet/NutritionCarbohydrate counting or exchange systems to estimate the nutrient content of a meal or snackEstimate of the carb content of a meal determines the bolus insulin dose for a meal or snackWant to coordinate and match caloric intake with the appropriate amount of insulinA common ratio is 1-1.5 units/10g of carb, but this must be individualized

37. Type 1 DiabetesOther agents that improve glucose controlAmylin (pramlintide)Usually cosecreted from pancreatic beta cells with insulinPts who are insulin deficient are also amylin deficientSC injection before each meal - reduces postprandial glycemic excursion in type 1 and 2 diabetic ptsSlows gastric emptying and suppresses glucagon Will decrease amount of short-acting insulin needed before the meal

38. Type 1 DiabetesSurgeryPatients receiving simultaneous pancreas and kidney transplants have 85% chance of pancreatic graft survival and 92% chance of renal graft survival after 1 yearIslet transplantation is minimally invasivePlagued by limitations and remains an area of investigation

39. Type 2 Diabetes

40. Type 2 DiabetesGeneral considerationsTypically > 40 years of ageFasting plasma glucose ≥ 126 mg/dL more than onceOGTT > 200 mg/dL 2 h after the oral glucoseOften associated with hypertension, dyslipidemia, and atherosclerosis

41. Type 2 DiabetesPathophysiologyCharacterized by impaired insulin secretion, insulin resistance, excessive hepatic glucose production and abnormal fat metabolismObesity, 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 DiabetesPathophysiology (cont’d)As the disease progresses, islets are unable to sustain the hyperinsulinemic stateIGT develops, characterized by elevations in postprandial glucoseFurther decline in insulin secretion and increase in hepatic glucose production lead to overt diabetes with fasting hyperglycemiaUltimately, beta cell failure may ensue

43. Type 2 DiabetesGenetic considerationsStrong genetic componentConcordance in identical twins is between 70-90%If both parents have type 2, the risk approaches 40% for the offspringGeneral considerationsPrevalence of obesity in type 2 diabetes mellitus 30% in Chinese and Japanese60–70% in North Americans, Europeans, and AfricansNearly 100% in Pima Indians and Pacific Islanders from Nauru or Samoa

44. Type 2 DiabetesGeneral ConsiderationsEnhancers of insulin resistance are aging, sedentary lifestyle, and abdominal-visceral obesityBoth 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 DiabetesDemographics> 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 obesityNo gender predominance

46. Type 2 DiabetesScreeningADA recommends screening all individuals >45 years q3 years and earlier if they are overweight and have one additional risk factor for diabetesMany are asymptomatic and unaware they have the diseaseType 2 DM may be present for up to a decade before diagnosisTreatment of type 2 DM may favorably alter the natural history of DM

47. Risk Factors for Type 2 DiabetesFH of diabetes (parent or sibling with type 2)Obesity (BMI >25)Habitual physical inactivityRace/ethnicity – AA, Latino, Native Amer, Asian or Pacific IslanderPreviously identified with IFG or IGTHistory of GDM or delivery of baby >9 lbsHTN (BP >140/90)PCOS or acanthosisnigricans

48. Type 2 DiabetesHistoryBe sure to ask about DM relevant aspects such a weight, FH of DM, risk factors for CV disease, exercise, smoking and ethanol useIf 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 DiabetesSymptoms and SignsOften asymptomaticObesityPolyuriaPolydipsiaWeakness or fatigueRecurrent blurred visionVulvovaginitis or pruritusSlow wound healingPeripheral neuropathyAcanthosisnigricans

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 DiabetesPESpecial attention should be given to DM-relevant aspects such asWeight or BMIRetinal examinationYearly evaluation by ophthalmologist BP>130/80 mmHg is considered HTN

52. Type 2 DiabetesPEFoot examinationPeripheral neuropathy – vibratory sensation and light touch sensation with monofilamentCallusesFoot deformitiesPeripheral pulsesInsulin injection sites

53. Type 2 DiabetesAssociated conditionsInsulin resistanceCV diseaseHTNDyslipidemiaPCOS

54. Type 2 DiabetesLaboratory TestsFasting plasma glucose ≥126 mg/dL or >200 mg/dL 2 h after glucose load GlucosuriaKetonuria on occasion without ketonemiaAssess the degree of glycemic control with glycosylated hemoglobin (HbA1c) reflects glycemic control over preceding 8–12 weeks

55. Type 2 DiabetesLaboratory testingScreen for DM-associated conditionsMicroalbuminuriaDyslipidemiaLipoprotein 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) particlesThyroid function

56. Type 2 Diabetes Management

57. Long Term TreatmentGoalsEliminate symptoms related to hyperglycemiaSymptoms usually resolve when BG <200 mg/dLReduce or eliminate the long-term microvascular and macrovascular complicationsAllow the pt to achieve as normal a lifestyle as possible

58. Long Term TreatmentHow to achieve these goalsPt education about DM, nutrition and exerciseProvider education at every office visit + the use of a diabetes educator and dieticianNutritional recommendationsDiet that includes fruits, vegetables, fiber-containing foods and low-fat milkGlycemic index – estimate of the postprandial rise in the BG when amount of that food is consumed

59. Glycemic IndexLow glycemic index appears to reduce postprandial glucose excursions and improve glycemic controlShort grain White Rice 72White Bread 70Graham Crackers 74 Broccoli 10Corn 55Potato (baked) 93Sweet Potato 54Apple 38Watermelon 103Honey 58Fructose 23Walnuts 15Corn Chips 72Milk (whole) 22Yogurt (low-fat) 33

60. DiabetesDietary RecommendationsCholesterol to 200 mg QDProtein intake to 10–35% of total caloriesSaturated fats to <7% of total caloriesRemainder of diet to consist of monounsaturated fats and carbohydrates with 20–35 g of dietary fiber

61. Long Term TreatmentExerciseADA recommends 150min/week (distributed over at least 3 days) of aerobic activityReduces CV riskReduces BPMaintains muscle massReduction in body fat and weight lossLowers plasma glucose – during and following exerciseIncreases insulin sensitivityFormal 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 TreatmentMonitoring of BGPatient’s measurements provide you with a picture of short-term glycemic controlHbA1C reflects average glycemic control over the previous 3 monthsSelf-monitoring of BGFrequency must be individualizedType 1 or type 2 on insulin - ≥3 times a dayType 2 on oral meds – 1-2 times a day with decreasing frequency as DM becomes controlledMonitor prior to a meal and supplemented with postprandial measurements

63. Type 2 DiabetesPharmaceutical treatment Any therapy that improves glycemic control reduces “glucose toxicity” to the islet cells and improves endogenous insulin secretionHowever, type 2 DM is a progressive disorder and ultimately requires multiple therapeutic agents and often insulin

64. Classifications of glucose lowering agentsInsulin secretagoguesDrugs that stimulate insulin secretionMost 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 effectsCan cause hypoglycemia, especially in the elderlyWeight gain

65. Classifications of glucose lowering agentsBiguanidesReduces hepatic glucose production and improves peripheral glucose utilization slightlyMetformin (glucophage)Promotes modest weight lossSide EffectsGI disturbances – nausea, bloating, diarrheaLactic 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 agentsαglucosidase inhibitorsReduce glucose absorption from the GI tract Reduce postprandial hyperglycemiaacarbose, miglitolNot as potent as other oral agents at lowering the A1CSide effectsDiarrhea, flatulence, abdominal distention (due to increased carbs/sugars in the large bowel)

67. Classifications of glucose lowering agentsThiazolidinediones (TZDs)Reduce insulin resistancePromote redistribution of fat from central to peripheral locationsCirculating insulin levels decreasePioglitazone (Avandia), rosiglitazone (Actos)Must measure LFTs prior to initiating therapy and q2 months for the 1st year of therapySide effectsWeight gainPeripheral edema and CHF – don’t use in CHF class III or IV

68. Classifications of glucose lowering agentsGLP-1 receptor signaling“Incretins”Amplify glucose-stimulated insulin secretionExenatide (Byetta)Suppresses glucagon and slows gastric emptyingMost experience modest weight lossSuppresses appetiteSC injection before morning and evening mealOnly approved for adjunct or combo therapy with metformin, TZD or sulfonylureaSitagliptin (Januvia)DPP-IV inhibitor, enhance incretin effectPromote insulin secretion and have a preferential effect on postprandial BGOral medication and can be used in combination with metformin or a TZD

69. Classifications of glucose lowering agentsInsulin therapyCan 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 illInsulin is usually initiated as a single dose of long-acting insulin (determir (Levemir), glargine (Lantus)) and is most often started at bedtimeCan 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 agentsChoice of initial glucose-lowering agentLevel of hyperglycemiaIf FPG <200-250 mg/dL pts often respond to a single oral agentIf FPG >250mg/dL pts often need >1 agent to reach goalConsider insulin if FPG >250-300mg/dL or in those who are symptomatic from hyperglycemiaAll 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 agentsCombination therapy with oral agentsMechanisms of action are different so the effect on glycemic control is additiveseveral drug combinations of TZD + metformin or sulfonylurea; metformin + sulfonylurea; DPP-IV with metformin are available

73. DiabetesGuidelines for ongoing medical careSelf-monitoring of blood sugarHbA1c (2-4 times/year)Screen for microalbuminuria annuallySerum lipids annuallyFeet examination by provider 1-2 times a year, daily by ptDiabetic eye examination annually

74. Treatment Goals

75. DiabetesHemoglobin A1CThere is an equationA 1% increase in A1C translates into a 35mg/dL increase in the mean glucose

76. DiabetesComplicationsMay be present in up to 20-50% of newly diagnosed individuals with type 2RetinopathyCV diseaseNephropathyNeuropathyDiabetic ketoacidosisHypoglycemia and altered awareness of hypoglycemia

77. DiabetesPreventionGoal of therapy is to prevent acute illness and reduce risk of long-term complicationsType 2 DM is preceded by a period of IGT and a number of lifestyle modifications and pharmacologic agents prevent or delay the onset of DMMaintain a normal BMIDiet and exercise for 30 min/day five times/weekADA 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 AcuteDiabetic ketoacidosisHyperglycemic Hyperosmolar StateChronicDuration and degree of glycemic control are the best predictors of complicationsVascularMicrovascularRetinopathy, neuropathy, nephropathyMacrovascularCAD, PAD, CV diseaseNonvascularGastroparesis, infections, skin changes, sexual dysfunction, cataracts, glaucoma, periodontal disease

80. Ocular ComplicationsDiabetic retinopathyDM is the leading cause of blindness b/t the ages of 20-74 in the USRetinal vascular microaneurysms, blot hemorrhages, cotton wool spots eventually progress in most patients with continued hyperglycemia and lead to retinal ischemiaCan be treated early with laser photocoagulation

81. Retinal Changes

82. Cardiovascular ComplicationsDM major risk factor for cardiovascular disease in the USAnnual incidence of cardiovascular death rate is increased by 3 times in diabetic men and by 4 times in diabetic women Risk factors for cardiovascular diseaseInsulin resistanceElevated urinary protein excretionPoor glycemic controlOverweight or obesityDyslipidemiaHTNSedentary lifestyleSmokingMonitoring of lipid levels and management of hyperlipidemia is essential in the prevention of macrovascular complications

83. Diabetic NephropathyDM is the #1 cause of ESRD in the U.S. Leading cause of DM-related morbidity and mortalityBegins with microalbuminuria defined as 30-300 mg/dAfter 10 years macroalbuminuria develops in 50%Overall risk of developing diabetic nephropathy is 20-40%

84. Diabetic NephropathyTreatmentGlycemic control slows progressionStrict BP controlStart ACE or ARBRestrict protein intake to 0.8g/kg/dayNephrology consultation when GFR is <60 mL/minMore likely to develop in:MalesRelatives have had kidney disease or HTN Poor glycemic controlPatient has HTN

85. Diabetic NeuropathyMost common complication of DM Type 2Develops in ~50% of individuals with DMPeripheral neuropathyMost common is distal symmetric polyneuropathyMost frequently presents with distal sensory loss but may also have hyperesthesia, paresthesia and dysesthesiaBegins in feet and spreads proximally, usually present at rest and worsens at night

86. Diabetic NeuropathyAutonomic neuropathyInvolves the cholinergic, noradrenergic, and peptidergicCan involve multiple systemsCV, GI, GUPostural hypotension and decreased CV responseGastroparesisUrine retentionEDTreatmentCheck feet daily and take precautions (footwear)TCAs, anticonvulsants, duloxetine (Cymbalta) and pregabalin (Lyrica), gabapentin (Neurontin)

87. PV Disease of the FeetScreening 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 structureFoot appearanceVascular statusNeurosensory 128 Hz tuning fork base at great toe nailMonofilamentsDeep tendon reflexes

89. Skin & Mucous Membrane Complications Protracted wound healing and skin ulcerationsShin spots – pigmented pretibial papulesGranulomaannulare – erythematous plaques on the extremities or trunkRepetitive candidainfection

90. InfectionsMany common infections are more frequent and severe in the diabetic population“malignant” or invasive otitisexternaPneumoniaUTISkin and soft tissue infections

91. HypoglycemiaGlucose level <55 mg/dL with symptoms that are relieved promptly after the glucose level is raisedMost convincingly documented by Whipple’s triadSymptoms consistent with hypoglycemiaLow 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. HypoglycemiaEtiology and pathophysiologyMost commonly a result of the treatment of diabetesHypoglycemia in diabetesImpact and frequencyMore common in type 1 DMPts suffer an average of twice a week with symptomatic hypoglycemia and once a year with a severe episode2-4% die as a result of hypoglycemiaOccurs in type 2 DM with sulfonylureas or insulin

94. HypoglycemiaHypoglycemia in diabetesConventional risk factorsRelative or absolute insulin excessInsulin dose is excessive, ill-timed or the wrong typeInflux 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. HypoglycemiaHypoglycemia in diabetesHypoglycemic-associated autonomic failureDefective glucose counterregulationHypoglycemia unawarenessFasting (postabsorptive) hypoglycemiaCausesDrugs – insulin, sulfonylureas, ethanolCritical illness – hepatic, renal or cardiac failure, sepsisEndogenous hyperinsulinism – insulinoma, autoimmune, ectopic insulin secretion

96. HypoglycemiaPostprandial (reactive) hypoglycemiaOccurs exclusively after mealsDiagnosis requires documentation of Whipple’s triad after a mixed mealEarly - rapid discharge of ingested carbohydrate into the small bowel followed by rapid glucose absorption and hyperinsulinismParticularly associated with dumping syndrome after gastrectomy

97. HypoglycemiaSymptomsNeuroglycopenic – CNS glucose deprivationBehavioral changes, confusion, fatigue, seizures, LOCNeurogenicAdrenergic – norepi releasePalpitations, tremor and anxietyCholinergic – acetylcholine releaseSweating, hunger, paresthias

98. HypoglycemiaSignsDiaphoresisPallorTachycardiaIncreased systolic BPTransient focal neuro deficits

99. HypoglycemiaLaboratory TestsIf history suggests prior hypoglycemia and a potential mechanism isn’t apparentObtain plasma glucose, insulin, C-peptide under conditions when hypoglycemia would be expected, typically during fastingTreatment3 glucose tablets (20g), 4 oz of juice, 6 oz of soda, or 7 lifesavers – if pt is able and willing25g IV glucose or 1mg SC or IM glucagon - if pt is unable or unwilling to take orally

100. HypoglycemiaTreatmentFasting (postabsorptive) hypoglycemiaChange dose of medication, no alcoholEndocrine tumor – surgical removal Reactive (postprandial) HypoglycemiaDietary manipulation is an adjunct: reduce proportion of carbohydrates in the diet, increase the frequency and reduce the size of the meals

101. HyperglycemiaWill be covered in your Emergency Medicine class in the Fall

102. Any Questions ???