Author(s): Arno Kumagai, M.D., 2009License: Unless otherwise noted, this material is made available under the terms ofthe ...
Citation Key                       for more information see: http://open.umich.edu/wiki/CitationPolicyUse + Share + Adapt ...
DIABETES MELLITUS                    Part 2:              COMPLICATIONS          M2 - Endocrine Sequence                A....
DIABETES MELLITUS                Acute Metabolic                 Complications   Diabetic Ketoacidosis      Hyperglycemic ...
DIABETIC KETOACIDOSIS (DKA)   Definition: A life-threatening state that results   from a relative or absolute deficiency o...
DIABETIC KETOACIDOSIS (DKA)   Definition: A life-threatening state that results   from a relative or absolute deficiency o...
DIABETIC KETOACIDOSIS (DKA)   PRECIPITATING FACTORS (VERY IMPORTANT):   •  Insufficient or no insulin.    •  Physical stre...
Diabetic Ketoacidosis:                           Pathophysiology                               HEPATIC GLUCOSE            ...
Diabetic Ketoacidosis:                           Pathophysiology                               HEPATIC GLUCOSE            ...
Insulin-regulated carbohydrate metabolism: adipocyte Facilitated                   Glycogen synthase glucose transport!   ...
Diabetic Ketoacidosis:                           Pathophysiology                               HEPATIC GLUCOSE            ...
Diabetic Ketoacidosis:                        Ketoacids             ACETOACETATE!                   !-HYDROXYBUTYRATE!    ...
Diabetic Ketoacidosis:            Signs & Symptoms                     •  Polyuria and polydipsia                     •  S...
Diabetic Ketoacidosis:             Clinical Course (Worst Case Scenario)                 Doing Well                       ...
Diabetic Ketoacidosis:             Effects on Mental Status   Factors leading to impairment of CNS function:              ...
Diabetic Ketoacidosis:             Effects on Mental Status   Factors leading to impairment of CNS function:              ...
Diabetic Ketoacidosis:             Effects on Mental Status   Factors leading to impairment of CNS function:              ...
Diabetic Ketoacidosis:             Effects on Mental Status   Factors leading to impairment of CNS function:              ...
Diabetic Ketoacidosis:                             Diagnosis                  The Diagnostic Triad of DKA:                ...
Diabetic Ketoacidosis:                       Diagnosis   The Anion Gap represents the presence of             unmeasured a...
Diagnosis of Diabetic KetoacidosisSigns and symptoms of DKA may be accompanied by    those of the underlying precipitating...
Diabetic Ketoacidosis:                      Treatment1. Intravenous insulin.2. IV Fluids: Initially rapid because of sever...
Treatment of Diabetic Ketoacidosis:                  Don t Let an Elevated K+ Fool You!       Bottom Line:              As...
Treatment of Diabetic Ketoacidosis:                       Mind the Gap             ACETOACETATE!                          ...
Treatment of Diabetic Ketoacidosis:       NC Márcio Cabral de Moura (Flickr)
Treatment of Diabetic Ketoacidosis            Finally, Diagnose and treat the underlying precipitating          event!
DIABETES MELLITUS                Acute Metabolic                 Complications   Diabetic Ketoacidosis      Hyperglycemic ...
Hyperglycemic Hyperosmolar State•  Life-threatening metabolic disorder of extreme   hyperglycemia without ketosis.•  Typic...
Hyperglycemic Hyperosmolar State                           PathogenesisRelative Insulin  Deficiency                       ...
Hyperglycemic Hyperosmolar State              Clinical AspectsIncreasing volume depletion and hemo-concentration may resul...
Hyperglycemic Hyperosmolar State                  Treatment       Similar to the treatment of DKA:•    Volume correction w...
Diabetes MellitusChronic Complications
Diabetes Mellitus: Chronic Complications                              Diabetes                                     !      ...
Diabetes: Chronic Complications                      Microvascular                      Complications        Diabetic     ...
Diabetic RetinopathyRetinal Fundus Photographs      Retinal     capillaries                   Macula                      ...
Diabetic Retinopathy                  Retinal Fundus Photographs Retinalcapillaries                          Macular edema...
Diabetic Retinopathy                       Retinal Fundus Photographs Retinalcapillaries                          Macular ...
Diabetic Retinopathy                                                  Exudates                                            ...
Diabetic Retinopathy        Remember:  Diabetic retinopathy is the  leading cause of new adultblindness in the United Stat...
Diabetic Nephropathy                                    Diabetic glomerulosclerosis                A. Kumagai             ...
Diabetic Nephropathy        Remember: Diabetic nephropathy is theleading cause of renal failure   requiring dialysis in th...
DIABETIC NEUROPATHY:                      Peripheral Sensory Neuropathy                               Symmetrical neuropat...
DIABETIC NEUROPATHY:       Peripheral Sensory NeuropathyOf bottlecaps and bathtubs …                               A. Kuma...
DIABETIC NEUROPATHY:               Autonomic Neuropathy• Gastroparesis              • ERECTILE• Constipation or           ...
Diabetic Neuropathy        Remember: Diabetes is the leading cause of non-traumatic    lower extremityamputations in the U...
DIABETIC COMPLICATIONS        MACROVASCULAR COMPLICATIONSGangrene is 14 times more common in people with diabetes than tho...
DIABETIC COMPLICATIONS:               Diabetes and Pregnancy1. Problems for the Mother:  •  Insulin Requirements increase ...
DIABETIC COMPLICATIONS:          Diabetes and PregnancyHigh blood sugars in pregnancy can lead to…
Hyperglycemia lowers resistance to infection and         interferes with wound healing.                 At BGs of >250 mg/...
DIABETIC COMPLICATIONS•  Complications from influenza are more   common in individuals with diabetes.•  Infections with tu...
Diabetic Complications  Diabetes is a dreadful affliction, the melting down of flesh and limbs into                      W...
Additional Source Information                       for more information see: http://open.umich.edu/wiki/CitationPolicySli...
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03.05.09(b): Complications of Diabetes

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03.05.09(b): Complications of Diabetes

  1. 1. Author(s): Arno Kumagai, M.D., 2009License: Unless otherwise noted, this material is made available under the terms ofthe Creative Commons Attribution–Noncommercial–Share Alike 3.0 License:http://creativecommons.org/licenses/by-nc-sa/3.0/We have reviewed this material in accordance with U.S. Copyright Law and have tried to maximize your ability to use,share, and adapt it. The citation key on the following slide provides information about how you may share and adapt thismaterial.Copyright holders of content included in this material should contact open.michigan@umich.edu with any questions,corrections, or clarification regarding the use of content.For more information about how to cite these materials visit http://open.umich.edu/education/about/terms-of-use.Any medical information in this material is intended to inform and educate and is not a tool for self-diagnosis or areplacement for medical evaluation, advice, diagnosis or treatment by a healthcare professional. Please speak to yourphysician if you have questions about your medical condition.Viewer discretion is advised: Some medical content is graphic and may not be suitable for all viewers.
  2. 2. Citation Key for more information see: http://open.umich.edu/wiki/CitationPolicyUse + Share + Adapt { Content the copyright holder, author, or law permits you to use, share and adapt. } Public Domain – Government: Works that are produced by the U.S. Government. (17 USC § 105) Public Domain – Expired: Works that are no longer protected due to an expired copyright term. Public Domain – Self Dedicated: Works that a copyright holder has dedicated to the public domain. Creative Commons – Zero Waiver Creative Commons – Attribution License Creative Commons – Attribution Share Alike License Creative Commons – Attribution Noncommercial License Creative Commons – Attribution Noncommercial Share Alike License GNU – Free Documentation LicenseMake Your Own Assessment { Content Open.Michigan believes can be used, shared, and adapted because it is ineligible for copyright. } Public Domain – Ineligible: Works that are ineligible for copyright protection in the U.S. (17 USC § 102(b)) *laws in your jurisdiction may differ { Content Open.Michigan has used under a Fair Use determination. } Fair Use: Use of works that is determined to be Fair consistent with the U.S. Copyright Act. (17 USC § 107) *laws in your jurisdiction may differ Our determination DOES NOT mean that all uses of this 3rd-party content are Fair Uses and we DO NOT guarantee that your use of the content is Fair. To use this content you should do your own independent analysis to determine whether or not your use will be Fair.
  3. 3. DIABETES MELLITUS Part 2: COMPLICATIONS M2 - Endocrine Sequence A. KumagaiWinter 2009
  4. 4. DIABETES MELLITUS Acute Metabolic Complications Diabetic Ketoacidosis Hyperglycemic (DKA) Hyperosmolar State (HHS)A. Kumagai
  5. 5. DIABETIC KETOACIDOSIS (DKA) Definition: A life-threatening state that results from a relative or absolute deficiency of insulin Too Much Too Little Insulin, Insulin Illness or StressHypoglycemia DKAA. Kumagai
  6. 6. DIABETIC KETOACIDOSIS (DKA) Definition: A life-threatening state that results from a relative or absolute deficiency of insulin. •  Usually occurs in individuals with Type 1 diabetes. •  Insulin levels are very low. •  High levels of stress hormones : epinephrine, norepinephrine, growth hormone and cortisol. STRESS INSULIN HORMONES Hypoglycemia Hyperglycemia & DKAA. Kumagai
  7. 7. DIABETIC KETOACIDOSIS (DKA) PRECIPITATING FACTORS (VERY IMPORTANT): •  Insufficient or no insulin. •  Physical stress: dehydration, trauma. •  Surgery, infections, heart attacks, etc. STRESS INSULIN HORMONES Hypoglycemia Hyperglycemia & DKAA. Kumagai
  8. 8. Diabetic Ketoacidosis: Pathophysiology HEPATIC GLUCOSE OUTPUT BLOOD GLUCOSE Liver 80-100 mg/dL INSULIN-STIMULATED GLUCOSE TRANSPORT INSULIN PANCREAS INSULIN FAT MUSCLE INSULIN-MEDIATED INHIBITION OF LIPOLYSISA. Kumagai
  9. 9. Diabetic Ketoacidosis: Pathophysiology HEPATIC GLUCOSE OUTPUT BLOOD Liver GLUCOSE INSULIN-STIMULATED GLUCAGON GLUCOSE TRANSPORT INSULIN PANCREAS INSULIN FAT MUSCLE INSULIN-MEDIATED INHIBITION OF LIPOLYSIS Meanwhile, in the adipocyte…A. Kumagai
  10. 10. Insulin-regulated carbohydrate metabolism: adipocyte Facilitated Glycogen synthase glucose transport! Insulin inhibits lipolysis by GLUT4! stimulating lipoprotein lipase (LPL) and inhibiting hormone-sensitive lipase (HSL) ! Lipogenesis! PDH! ACC Lipolysis Insulin! (-)! HSL (+)! LPL! FFA Glycerol Source Undetermined
  11. 11. Diabetic Ketoacidosis: Pathophysiology HEPATIC GLUCOSE OUTPUT BLOOD GLUCOSE Liver KETONES GLUCAGON INSULIN MUSCLE PANCREAS INSULIN FAT INSULIN-MEDIATED EPINEPHRINE- INHIBITION OF STIMULATED LIPOLYSIS MYOLYSIS EPINEPHRINE, NOREPINEPHRINEA. Kumagai
  12. 12. Diabetic Ketoacidosis: Ketoacids ACETOACETATE! !-HYDROXYBUTYRATE! NADH ! CH3! + H+! NAD! CH3! O=C! CH2COO-! O-C-H! CH2COO-! CH3! O=C! HCO3-! CH3! Acetone! Bicarbonate!A. Kumagai
  13. 13. Diabetic Ketoacidosis: Signs & Symptoms •  Polyuria and polydipsia •  Severe volume depletionHYPERGLYCEMIA •  Electrolyte depletion •  Eventual: renal hypoperfusion, prerenal azotemia, hypotension and shock •  Acidosis KETONES •  Compensatory resp. alkalosis •  Hypotension •  Shock
  14. 14. Diabetic Ketoacidosis: Clinical Course (Worst Case Scenario) Doing Well • Precipitating Event • Polyuria, polydipsia, dehydration • Anorexia, nausea, vomiting, abd. pain •  Kussmal respirations, Juicy Fruit Breath • Altered consciousness • Cardiovascular collapse Coma & Coma & Death" DeathA. Kumagai
  15. 15. Diabetic Ketoacidosis: Effects on Mental Status Factors leading to impairment of CNS function: BRAINA. Kumagai
  16. 16. Diabetic Ketoacidosis: Effects on Mental Status Factors leading to impairment of CNS function: HYPEROSMOLALITY BRAINA. Kumagai
  17. 17. Diabetic Ketoacidosis: Effects on Mental Status Factors leading to impairment of CNS function: HYPOTENSION HYPEROSMOLALITY BRAINA. Kumagai
  18. 18. Diabetic Ketoacidosis: Effects on Mental Status Factors leading to impairment of CNS function: ACIDOSIS HYPOTENSION OUCH HYPEROSMOLALITYA. Kumagai
  19. 19. Diabetic Ketoacidosis: Diagnosis The Diagnostic Triad of DKA: DKA Serum Blood Ketones Glucose Gap Metabolic AcidosisA. Kumagai
  20. 20. Diabetic Ketoacidosis: Diagnosis The Anion Gap represents the presence of unmeasured anions. Na+ Cl- K+ HCO3- Anion Gap = Na+ - (Cl- + HCO3-) (Normal = 12) Organic acids, such as acetoacetate and "- hydroxybutyrate, decrease the HCO3- (which is a biologic buffer) and aren t measured in the gap. Therefore, the gap increases.A. Kumagai
  21. 21. Diagnosis of Diabetic KetoacidosisSigns and symptoms of DKA may be accompanied by those of the underlying precipitating disorder; HOWEVER, DKA per se DOES NOT CAUSE FEVER. Therefore, if a fever is present, assume there is an infection until proven otherwise!!
  22. 22. Diabetic Ketoacidosis: Treatment1. Intravenous insulin.2. IV Fluids: Initially rapid because of severe volume depletion - loss of 7-10 L of total body water.3. Electrolyte replacement: esp. Na, K, Mg, and PO4.4. Carbohydrate replacement (5-10% dextrose) once serum glucose is below 250 mg/dL5. Administration of bicarbonate for acidosis is NOT recommended.6. Diagnose and treat PRECIPITATING EVENT!
  23. 23. Treatment of Diabetic Ketoacidosis: Don t Let an Elevated K+ Fool You! Bottom Line: As soon as you see pee, give K+! ACIDOSIS INSULIN Rx H+ INSULIN K+ K+ K+ SERUM SERUM K+ K+ MUSCLE During acidosis, H+ shifts into cells to Treatment with insulin causes K+ to be buffered by intracellular buffers. K shift back into cells, and serum K+ + shifts out of cells in exchange. may drop like a rock during therapy. Consequently, serum K+ is usuallyelevated DESPITE total body K+ depletion. A. Kumagai
  24. 24. Treatment of Diabetic Ketoacidosis: Mind the Gap ACETOACETATE! !-HYDROXYBUTYRATE! CH3! NADH ! CH3! + H+! NAD! O=C! O-C-H! CH2COO-! CH2COO-! Therefore, during management of DKA, don t watchCH ! ketones; MIND THE GAP! the 3 O=C! HCO3-! CH3! Acetone! Bicarbonate! IMPORTANT! Acetone is produced during the normal regeneration of bicarbonate and is detected by most serum ketone assays. Therefore, the serum ketones normally increase during recovery from DKA.A. Kumagai
  25. 25. Treatment of Diabetic Ketoacidosis: NC Márcio Cabral de Moura (Flickr)
  26. 26. Treatment of Diabetic Ketoacidosis Finally, Diagnose and treat the underlying precipitating event!
  27. 27. DIABETES MELLITUS Acute Metabolic Complications Diabetic Ketoacidosis Hyperglycemic (DKA) Hyperosmolar State (HHS)A. Kumagai
  28. 28. Hyperglycemic Hyperosmolar State•  Life-threatening metabolic disorder of extreme hyperglycemia without ketosis.•  Typically seen in elderly with type 2 diabetes, some 30% of whom are previously not diagnosed with diabetes.•  Common precipitating events: myocardial infarction, stroke, sepsis.•  Potentially deadly: mortality may exceed 40%.
  29. 29. Hyperglycemic Hyperosmolar State PathogenesisRelative Insulin Deficiency HYPERGLYCEMIA THE VICIOUS CYCLE OF HEMO- CONCENTRATION HHS POLYURIA VOLUME DEPLETION A. Kumagai
  30. 30. Hyperglycemic Hyperosmolar State Clinical AspectsIncreasing volume depletion and hemo-concentration may result in:•  Hyperviscosity and increased risk of thrombosis•  Disturbed mentation and obtundation•  Neurologic signs •  Focal signs, e.g., sensory or motor deficits or focal seizures •  Motor abnormalities, e.g., flacidity, depressed reflexes, tremor or fasciculations. Ultimately, without treatment, coma and death
  31. 31. Hyperglycemic Hyperosmolar State Treatment Similar to the treatment of DKA:•  Volume correction with normal saline.•  Replacement of electrolytes.•  IV insulin.•  Diagnosis and treatment of underlying cause.
  32. 32. Diabetes MellitusChronic Complications
  33. 33. Diabetes Mellitus: Chronic Complications Diabetes ! Mellitus HEART,! RETINA! BRAIN & ! LARGE KIDNEYS ! NERVES VESSELS! Microvascular Complications Macrovascular ComplicationsA. Kumagai
  34. 34. Diabetes: Chronic Complications Microvascular Complications Diabetic Diabetic Retinopathy Diabetic Neuropathy NephropathyA. Kumagai
  35. 35. Diabetic RetinopathyRetinal Fundus Photographs Retinal capillaries Macula Optic nerve NORMAL RETINA Source Undetermined
  36. 36. Diabetic Retinopathy Retinal Fundus Photographs Retinalcapillaries Macular edema Macula Optic nerve Exudates NORMAL RETINA NON-PROLIFERATIVE OR BACKGROUND RETINOPATHY Disease Progression Source Undetermined (Both Images)
  37. 37. Diabetic Retinopathy Retinal Fundus Photographs Retinalcapillaries Macular edema New Vessel Macula Optic nerve Exudates Formation PROLIFERATIVE NORMAL RETINA NON-PROLIFERATIVE OR RETINOPATHY BACKGROUND RETINOPATHY Disease Progression Source Undetermined (All Images)
  38. 38. Diabetic Retinopathy Exudates • leakage of plasma proteins into neuroretina. Microaneurysms EM Photograph of Plastic Cast of Retinal Capillaries from Diabetic Retina Source UndeterminedLater stages of retinopathy involve death of endothelial cells and capillary drop out, progressive ischemia and proliferative neovascular changes.
  39. 39. Diabetic Retinopathy Remember: Diabetic retinopathy is the leading cause of new adultblindness in the United States.
  40. 40. Diabetic Nephropathy Diabetic glomerulosclerosis A. Kumagai Source Undetermined This is EXTREMELYDiabetic glomerulosclerosis is characterized by basement important! membrane thickening and mesangial cell proliferation. Diabetic nephropathy may be diagnosed in its earliest--and potentially, reversible--stages by detection of extremely small amounts of albumin in the urine, so-called microalbuminuria.
  41. 41. Diabetic Nephropathy Remember: Diabetic nephropathy is theleading cause of renal failure requiring dialysis in the United States.
  42. 42. DIABETIC NEUROPATHY: Peripheral Sensory Neuropathy Symmetrical neuropathy is the most common: •  Primarily involving the distal extremities with stocking-glove distribution. •  Sensory: decreased vibration,Diabetic “Charcot Feet” temperature, proprioception. •  Initially may present with painful paresthesias: burning or pins- and-needles sensation. Eventually leads to complete loss of sensation. •  Predisposed to skin breakdown, ulcer formation and unrecognized Diabetic Foot Ulcer trauma. Source Undetermined
  43. 43. DIABETIC NEUROPATHY: Peripheral Sensory NeuropathyOf bottlecaps and bathtubs … A. Kumagai oparrish (Flickr) "
  44. 44. DIABETIC NEUROPATHY: Autonomic Neuropathy• Gastroparesis • ERECTILE• Constipation or DYSFUNCTION Diarrhea • Urinary retention•  Chronic edema•  Postural Abnormal sweating and hypotension increased callus formation• Cardiac arrhythmias• Sudden Death
  45. 45. Diabetic Neuropathy Remember: Diabetes is the leading cause of non-traumatic lower extremityamputations in the United States.
  46. 46. DIABETIC COMPLICATIONS MACROVASCULAR COMPLICATIONSGangrene is 14 times more common in people with diabetes than those without.Coronary Heart Disease:•  Twice as common in people with diabetes.•  Occurs at an earlier age and places women at equal is This risk EXTREMELY with men. important!•  For MI s: individuals with diabetes have a high initial mortality rate and lower 5-year survival rate.•  MI s often occur WITHOUT CHEST PAIN.Risk of death from stroke is approximately 3 times greater for people with diabetes than for those without.
  47. 47. DIABETIC COMPLICATIONS: Diabetes and Pregnancy1. Problems for the Mother: •  Insulin Requirements increase and metabolic control often worsens during pregnancy. •  Diabetic retinopathy and possibly nephropathy may worsen.2. Problems for the Baby: •  Infant mortality is higher in babies from diabetic mothers. •  Congenital malformations are more frequent. •  Respiratory distress syndrome (RDS) is more common.
  48. 48. DIABETIC COMPLICATIONS: Diabetes and PregnancyHigh blood sugars in pregnancy can lead to…
  49. 49. Hyperglycemia lowers resistance to infection and interferes with wound healing. At BGs of >250 mg/dL, WBC motility and opsinization of bacteria are significantly impaired. (Pacman) Albertsab@cawiki" (bug) A. Kumagai"
  50. 50. DIABETIC COMPLICATIONS•  Complications from influenza are more common in individuals with diabetes.•  Infections with tuberculosis and pneumococcal pneumonia are common.•  Yeast infections are common among diabetes women.•  Wound healing is delayed in poorly controlled diabetes.
  51. 51. Diabetic Complications Diabetes is a dreadful affliction, the melting down of flesh and limbs into What urine…Life is short, can we unpleasant and painful... do???-- Areteus of Capadocia, 2nd C. A.D.
  52. 52. Additional Source Information for more information see: http://open.umich.edu/wiki/CitationPolicySlide 4: Arno KumagaiSlide 5: Arno KumagaiSlide 6: Arno KumagaiSlide 7: Arno KumagaiSlide 9: Arno KumagaiSlide 10: Source UndeterminedSlide 11: Arno KumagaiSlide 12: Arno KumagaiSlide 15: Arno KumagaiSlide 16: Arno KumagaiSlide 17: Arno KumagaiSlide 18: Arno KumagaiSlide 19: Arno KumagaiSlide 20: Arno KumagaiSlide 23: Arno KumagaiSlide 24: Arno KumagaiSlide 25: CC: BY-NC Márcio Cabral de Moura, http://www.flickr.com/photos/mcdemoura/2209204939/, Flickr, http://creativecommons.org/licenses/ by-nc-sa/2.0/deed.enSlide 27: Arno KumagaiSlide 29: Arno KumagaiSlide 33: Arno KumagaiSlide 34: Arno KumagaiSlide 35: Source UndeterminedSlide 36: Source Undetermined (Both Images)Slide 37: Source Undetermined (All Images)Slide 38: Source UndeterminedSlide 40: Arno Kumagai; Source UndeterminedSlide 42: Source UndeterminedSlide 43: CC: BY-NC-SA oparrish, Flickr, http://creativecommons.org/licenses/by-nc-sa/2.0/deed.en; Arno KumagaiSlide 49: (Pacman) Albertsab@cawiki, Wikimedia Commons, http://commons.wikimedia.org/wiki/File:Pac_Man.svg; Arno Kumagai

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