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ERM2- Obesity and Diabetes

  1. Overweight
    • -excess amount of body weight
    • -may be from muscle, bone, fat, body water

    BMI = 25-29.9
  2. Obese
    -presence of an abnormal amount or relative proportion of body fat

    BMI > 30
  3. BMI Calculation
    BMI = weight(kg)/Height2(m)

    BMI = (weight(lbs)/Height(in))703
  4. Association of obesity with risk of DM2
    • -overweight --> increased risk of 3-4x
    • -obese --> increased risk of 18x
  5. Android vs Gynoid Obesity
    • Android: central abdominal (increase CV risk)
    • Gynoid: hips, thighs buttocks (NO increase CV risk)

    Waist to Hip ratio < 0.8 is good!
  6. Waist Circumference
    • male > 40 in
    • female > 35 in
  7. Metabolic Syndrome
    • -cluster of CV risk factors associated with low cardiorespiratory fitness
    • -increased lifetime risk for developing DM2 and CV disease

    • Diagnosis:
    • -abdominal obesity
    • -hypertriglyceridemia
    • -low HDL
    • -HTN
    • -Hyperglycemia
  8. Carbs and Obesity
    • -storage pool for carbs is small (glycogen in muscle)
    • -excess carbs are converted to fat
  9. Genes associated with obesity
    • -FTO region: explains about 1% of BMI heritability
    • -homozygous adults have 2-3kg higher weight
    • -genetic factors are important in obesity but aren't the only factor
    • -epigenetics may play a role
    • -along with permissive environment
  10. Obesity: Medications for Treatment
    • 1. Orlistat (xenical)
    • 2. Phentermine and topiramate (Qsymia)
    • 3. Lorcaserin (Belviq)
  11. Orlistat (xenical)
    • -binds pancreatic lipase and inhibits its function
    • -fats (TGs) leave intestines without being degraded
    • -take with meals

    • Adverse Effects
    • -cramping
    • -passing gas
    • -leakage of oily stool

    sx worse with fatty meals --> encourages healtier eating

    avg weight loss = 5-7lbs
  12. Qysmia
    • -Phentermine: sympathomimetic amine anorectic
    •      -amphetamines stimulate breakdown of fat from adipocytes, increase metabolism and decrease appetite

    • -Topiramate: anti-epileptic
    •      -appetite suppression, satiety enhancement

    • Adverse Effects:
    • -HTN

    -avg weight loss = 12lbs
  13. Lorcaserin
    • -selective 5HT2CR agonist (in brain)
    • -satiety enhancement
    • -longer studies on CV outcomes in progress

    avg weight loss = 7lbs
  14. Obesity: Surgical Treatment
    • 1. Restrictive (AGB, Sleeve gastrectomy)
    • 2. Malabsorptive (biliopancreatic diversion, jujunoileal bypass)
    • 3. Combined (gastric bypass)
  15. Gastric Bypass
    • PROs:
    • -rapid initial weight loss (can resolve diabetes)

    • CONs:
    • -more operative complications
    • -reduced absorption of intestinal nutrients
    • -complications due to malabsorption
    • -non-adjustable
    • -higher mortality than AGB
  16. Adjustable Gastric Band
    • PROs:
    • -least invasive approach
    • -adjustable
    • -reversible
    • -lowest mortality rate
    • -low malnutrition risk
    • -fewer food intolerances

    • CONs:
    • -slower initial weight loss
    • -regular F/U required
    • -slips/erosions
  17. Sleeve Gastrectomy
    • PROs:
    • -fewer food intolerances
    • -faster weight loss than AGB
    • -no slips/erosions
    • -decreased risk vs bypass with equal weight loss
    • -less intense F/U

    • CONs:
    • -less time tested
    • -not adjustable/ non-reversible
    • -slightly higher riks of complication
    • -annecdotal weight gain over years
  18. When to Start Medical Therapy
    -BMI 27 - 29.9 with comorbidities

    -BMI 30+ without comorbidities
  19. When to do surgery
    • AGB
    • -BMI 30-34.9 with comorbidities

    • Any
    • -BMI 35-39.9 with comorbidities
    • -BMI 40+ withoutcomorbidites
  20. DM1: Epidemiology
    • -relative risk in general pop = 0.3%
    • -relative risk with affected sibling = 4%
    • -affected mother = 3%
    • -affected father = 7%
    • -both affected parents = 50%
  21. DM1: natural history
    • 1. Genetic Predisposition
    • -putative trigger (cocksackie virus, stress, environment)
    • -can happen at any age

    • 2. Damage to cells of pancreas
    • -immune system dysfunction leads to circulating autoantibodies (ICA, GAD)

    • 3. Prediabetes
    • -overtime the number of viable beta cells declines

    • 4. Diabetes
    • -symptoms occur with onset of full diabetes
    • -<20% functional beta cells
  22. DM1: Autoimmune Attack
    • -mainly due to autoreactive T cells (autoantibodies are markers)
    • -trigger causes break in tolerance
  23. ICA
    • -islet cell antibodies
    • -produced in early stages (2-3 years before diabetes)
    • -titres go away after diagnosis
  24. GAD
    • -glutamic acid decarboxylase antibodies
    • -titres stay elevated long term
  25. DM1: Screening
    • -screen immediate family members
    • -screen extended family if diagnosed before 20
    • -screen blood for autoantibodies
  26. DM1: Prevention
    -doesn't exist

    • Primary: with genetic predisposition
    • Secondary: after beta cell injury begins
    • Tertiary: within three months of diagnosis to slow or reverse beta cell dysfunction
  27. Physiologic Insulin and Amylin Delivery
    • -both secreted by beta cells
    • -secreted into portal vein (work within sec-min)

    Image Upload 1
  28. Amylin Functions
    • -has CNS effects
    • 1. reduces appetite
    • 2. suppresses glucagon in glucose dependent manner
    • 3. normalizes stomach motility
  29. DM1: gastric motility
    • -faster gastric and peristaltic motility
    • -leads to faster absorption of nutrients
    • -causes high post meal glucose
  30. Basal Insulin
    • (50%)
    • -necessary to control hepatic glucose output independent of meals
    • -nearly constant level
  31. Bolus Insulin
    • (50%)
    • -limites hyperglycemia after meals
    • -immediate rise and sharp peak at 1 hour
  32. Bolus Options with pump therapy
    • 1. standard (quickly absorbed foods)
    • 2. square wave (gasroparesis, fatty meals)
    • 3. dual wave
  33. Insulin to Carb ratio calculation
    start with 1:15 (DM1) or 1:10 (DM2)
  34. Correction Factor
    • -estimate how much blood sugar will drop with 1U of fast acting insulin
    • -usually 1:50 (DM1) 1:25 (DM2)

    -1800 rule (divide total daily insulin dose into 1800)
  35. Latent Autoimmune Diabetes in Adults (LADA)
    • -DM1 later in life
    • -often misdiagnosed
    • -oral meds not very effective
    • -thin (don't look like DM2)
    • -need insulin tx
  36. ______________________________________________
  37. Impaired Fasting Glucose
    • Normal < 100
    • Prediabetes = 100-125
    • Diabetes > 126
  38. Impaired Glucose Tolerance
    * test with OGTT

    • Normal < 140
    • Prediabetes = 140-199
    • Diabets > 200
  39. A1c value
    • Normal < 5.7
    • Prediabetes = 5.7-6.4
    • Diabetes > 6.5
  40. DM2: causes of hyperglycemia
    • 1. insulin resistance (big genetic component)
    • 2. defects in pancreas (decreased insulin production)
    • 3. increased HGO
    • 4. Adipose tissue may contribute to impaired insulin secretion
  41. Insulin Sensitivity
    • -ability of insulin to lower circulating glucose concentration
    • -upregulate glut4 on muscle and fat
    • -suppress HGO
  42. DM2: Insulin Dysregulation
    • -decreased production
    • -impaired response (insulin resistance)
  43. DM2: Glucagon Dysregulation
    Image Upload 2

    • -decreased postprandial suppression
    • -increases postprandial HGO

    • -tends to be elevated
    • -increases after meal (vs normal, declines)
  44. DM2: Incretin Dysregulation
    • -decreased production
    • -impaired response
    • -not in all patients
  45. DM2: Insulin profile overtime
    • -early see hypersecretory response
    • -disease progression to the point where insulin can no longer stay high
  46. DM2: Insulin Secretion Phases
    • 1. Quick Peak (release of Pre-formed)
    • 2. Second peak (long)

    DM2 lacks first phase and second phase is blunted

    *** insulin levels never 0, vs DM1
  47. DM2: Natural History
    • Image Upload 3
    • -post prandial glucose levels rise earlier than fasting glucose levels
    • -in prediabetes insulin resistance progressively increases but diabetes doesn't develop right away b/c beta cells produce more insulin
    • -at time of diagnosis beta cell function starts to decline
  48. DM2: Incretin Effect
    • -insulin secretion greater with oral glucose than IV glucose
    • -due to L cell secretion of incretins
    • -impaired in DM2
  49. GLP1
    • -stimulates glucose dependent insulin secretion
    • -slows accelerated gastric emptying
    • -associated with satiety and weight loss
    • -inhibits excessive glucagon

    more important in DM2 that GIP
  50. GIP
    • -stimulates glucose dependent insulin secretion
    • -little effect on gastric motility, satiety and glucagon secretion
  51. DM2: GLP1 analogs
    • -improves glycemic control
    • -can normalize PP glucose (w/o hypoglycemia)
    • -delays gastric emptying
    • -decreases food intake and reduces appetite
  52. Metabolism of GLP1 and GIP
    -rapidly cleaved by DPP4
  53. DM2: adipose accumulation
    • -weak association with subcutaneous adipose tissue
    • -strong association with visceral adipose tissue
  54. DM2: Adisopathy
    • -insulin resistance
    • -ectopic lipid accumulation in liver/muscle/beta cells
    • -failure to expand adipose tissue during positive energy balance
  55. DM2: Insulin Secretagogues
    • 1. Sulfonylureas
    •      -Glyburide
    •      -Glimiperide
    •      -Glipizide

    • 2. Meglitinides
    •      -repaglinide
    •      -nateglinide

    • 3. Incretins
    •      -GLP1 agonists (Exenatide, Liraglutide)
    •      -DPP4 inhibitor (Sitagliptin, Saxagliptin, Linagliptin)
  56. Sulfonylureas
    • PROs:
    • -increase insulin secretion
    • -effective glucose lowering

    • CONs:
    • -hypoglycemia
    • -weight gain
    • -secondary failure
  57. Meglitinides
    • PROs:
    • -increase insulin secretion
    • -effective glucose lowering

    • CONs:
    • -hypoglycemia
    • -weight gain
    • -secondary failure
  58. Incretins
    • PROs:
    • -glucose-mediated insulin release
    • -effective glucose lowering
    • -no hypoglycemia
    • -decreased gastric emptying
    • -decreased appetite (weight loss)
    • -trophic effects on beta cell
    • -possible beneficial CV effects

    • CONs:
    • -nausea/vomiting
    • -pancreatitis
    • -thyroid cancer
  59. DM2: Insulin Sensitizers
    • 1. Biguanides
    •      -metformin

    • 2. Thiazolidinediones
    •      -Rosiglitazone
    •      -Pioglitazone
  60. Biguanides
    • PROs:
    • -effective glucose lowering
    • -no hypoglycemia
    • -weight loss
    • -possible beneficial CV effects

    • CONs:
    • -diarrhea, abdominal pain
    • -caution in renal disease (lactic acidosis)
    • -caution in CHF
    • -secondary failure
  61. Thiazolidinediones
    • PROs:
    • -effective glucose lowering
    • -no hypoglycemia
    • -May have trophic effects on beta cells

    • CONs:
    • -weight gain (expands subcu fat)
    • -pedal edema
    • -caution in CHF
    • -CV effects
    • -Bone loss
    • -Bladder tumors

    NOT FREQUENTLY USED
  62. DM2: Other Agents
    • 1. a-glucosidase inhibitors
    •      -acarbose
    •      -miglitol

    • 2. bile acid sequestrants
    •      -colesevelam

    • 3. DA agonists
    •      -cycloset

    • 4. Amylin analog
    •     -Parmlintide
  63. a-glucosidase inhibitors
    -carb blockers (prevent glucose absorption)

    • PROs:
    • -no hypoglycemia
    • -weight neutral

    • CONs:
    • -less glucose lowering
    • -gas
    • -caution in LV disease
  64. Bile Acid Sequestrants
    -lower XOL

    • PROs:
    • -no hypoglycemia
    • -weight neutral
    • -XOL lowering

    • CONs:
    • -less glucose lowering
    • -constipation
  65. DA Agonists
    -acts on circadian rhythm (small effects on A1c)

    • PROs:
    • -no hypoglycemia
    • -weight neutral

    • CONs:
    • -less glucose lowering
    • -nausea
    • -hypotension
  66. Amylin Analog
    • PROs:
    • -decreases postprandial glucose
    • -weight loss

    • CONs:
    • -less glucose lowering
    • -GI side effects
  67. DM2: Starting basal insulin
    • -continue oral agents
    • -add single evening insulin dose
    • -adjust dose by fasting SMBG
    • -increase insulin dose weekly as needed
Author
jknell
ID
184745
Card Set
ERM2- Obesity and Diabetes
Description
Endocrine and Reproductive Pathology
Updated

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