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Patho Test 4 > Diabetes > Flashcards

Diabetes Flashcards

1
Q

What is insulin’s action on the cell?

A
  • Insulin binds to receptor (dimer) → activate dimers

Signals cell to:

  • Moves GLUT4 transporters to cell surface → glucose entry into cell
    • Normally: inside cell close to 0
  • Glucose (in cell) → phosphorylate → Gucose-6-phosphate → *glycolysis pathway* → ATP
    • Limiting factor: Glucose transported until GLUT4 off cell membrane
  • Options for glucose:
    • *Burn for fuel
    • *Store for later (glucogenesis)
      • Storage examples:
        • Glycogen
        • Lipids
        • Pentose (RNA/DNA synthesis for later)
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2
Q

What are some of insulin’s functions?

A
  • Regulate DNA/gene expression via insulin regulatory elements (growth factor) → upregulate protein synthesis for cellular repair Rest and repair
  • Uptake: ­ increase increase transport into cell
    • AA uptake → ­ protein synthesis
    • Phos
    • K
    • Mag
  • ­ increase ATP production
    • Na/K ATPase (pumps Na out, K in) → DEPENDENT on ATP []
      • ­ increase ATP [] = increase ­ fx pump
        • Hyperkalemia: use insulin to shift K into cell → decrease K levels
        • Tx increased ­ K: Insulin + Glucose
          • Insulin → increase ­ ATP → ­ increase rate Na/K ATPase pump → increase­ K in cell → decrease serum K
          • Glucose → ensure no hypoglycemia
      • Uptake: amino acids, Phos, K, Mag
      • Glycosylate proteins
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3
Q

Insulin effect on body processes?

A
  • decrease Appetite
    • Ex: diabetics continue to eat d/t no appetite suppression
  • decrease Glucagon
  • ­ increase Glucose uptake by muscle/fat, etc
  • increase­ Glycolysis – burn for fuel
  • ­ increase Glycogen synthesis – store for later
  • ­ increase Triglyceride synthesis- store for later
  • ­ increaseAmino acid uptake (modest)
  • increase *­Protein synthesis*
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4
Q

Effects of lack of insulin in the body?

A

(Primarily mediated by Glucagon) = ­ Glucagon fx

  • ­increase Appetite
  • ­ increase Glucagon
  • ­increase Blood glucose
      1. Not taking up glucose
      1. Glucagon ­ increase glucose- tries to make more glucose for cells that don’t see it
  • ­ increase Gluconeogenesis- liver
  • ­ increase Lipolysis- fat
  • increase ­ Protein breakdown (ketones - ketoacidosis)
    • ~AA can go back to liver → make glucose
  • ­ increase Glycogenolysis- glycogen breakdown
    • Storage from liver
  • increase­ Ketone body production → ketoacidosis
    • Take fat released from fat cells → ketone bodies
      • Normal: Okay (happens between meals)
      • DM: Ketoacidosis (typically DMI)

Decrase:

  • decrease Glucose uptake by muscle/fat/etc​
  • decrease Protein synthesis
    • Summary: No insulin → ­ glucagon → ¯ Protein synthesis → ­ Protein breakdown → wt loss
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5
Q

What is the process blood glucose control by insulin and glucagon?

A

(left) FOOD → ­ increase BG → pancreas → ­increase insulin → release in circulation

  • Insulin:
    • Liver uptake: glycogen synthesis (glucose → glycogen)
    • Fat: glucose → lipids/fat (fatty acid and triglyceride synthesis)
    • Muscle: protein synthesis (AA → protein)

(right) Used up glucose → decrease BG → pancreas → ­incresae glucagon

  • Glucagon:
    • Liver: glycogenolysis (glycogen → glucose)
    • Fat: lipolysis (lipids → FFA)
    • Muscle: Proteolysis (protein → AA)
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6
Q

What is the anatomy of the pancreas?

A

~ fx distributed throughout organ~

Exocrine Function (head)

  • Released into pancreatic duct → duodenum

Endocrine Function (tail)

  • Released into blood → circulated throughout body
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7
Q

Cells in pancreatic islet of langerhans?

A
  • a cells = glucagon
    • increase­ Insulin cuases decrease Glucagon secretion
      • Glucagon SUPPRESSED/inhibited by Insulin!!!
        • NOT by glucose
          • ~issue w/ DMI (never have insulin)
  • b cells = insulin
    • increase glucose causes ­increase Insulin ­
      • (Insulin secretion is stimulated by glucose)
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8
Q

How is insulin secreted from beta cells?

A

b cells:

  • 1. GLUT2 on surface of cell (ALWAYS)
  • 2. Glucose → GLUT2 → glucose into cell
    • Limiting/controlling factor: [] glucose outside cell
      • (increase­ glucose → ­ increasegradient → increase ­ flow inside cell )
    1. Glycolysis → ATP
      * Glycolysis:
      • Glucose + Glucokinase → Glucose-6- phosphate
      • Glucose-6- phosphate (+ oxidation) → ATP
        * ­ increase glucose into cell → increase­ ATP can be produced
  • 4. ATP → binds to ATP-sensitive K channel → CLOSE CHANNEL → ­ increase K intracell
    • ATP is ligand to channel
    • As ­increase ATP → CLOSE ATP/K channels → K not leaving cell
      • K+ ions accumulate → leads to depolarization
  1. Depolarization → VGCC open → Ca comes in (increase) → synthesize/release of insulin from vesicles in β cell

FYI: secretagogues operate by stimulating ATP sensitive K channels to close → leading to insulin release from beta cells

PIC:

  • b cells: Insulin secretion triggered by ­ blood glucose levels.
  • Glucose uptake by the GLUT2 transporter leading to cell depolarization, calcium influx leading to the exocytotic release of insulin from their storage granule
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9
Q

Relationship between insulin, glucagon and blood glucose?

A

Blue: glucagon

Pink: insulin

~80 BG Baseline/goal

  • > 80 → ­increase insulin release (try to decrease BG)
  • < 80 → increase ­ glucagon (try to ­ increase BG)
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10
Q

What is this graph showing?

A

What happens during “feast and famine”

X axis- hrs starvation

Y axis- relative change

  • ­ increase BG
    • increase­ Insulin → SUPPRESSING Glucagon (causing decrease)
      • stimulate glucose uptake by fat, muscle, etc
      • increase­ liver glycogen stores
  • decreeaseBG (taken up)
    • decrease Insulin → ALLOWING increase ­ Glucagon
      • ­ increase Glucagon → breakdown FFA → ­ increase ketones from liver → fuel
      • decrease liver glycogen stores
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11
Q

What are common types of diabetes?

A
  • Type 1 DM (IDDM)
  • Type 2 DM (NIDDM)
  • Other
    • maturity onset diabetes of youth (MODY)
    • gestational DM (GDM)
    • Various other endocrine d/o
      • cushing
      • acromegaly
      • pheochromocytoma
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12
Q

What is Type 1 DM?

A
  • Type 1 diabetes mellitus (IDDM) [~10%]
    • Autoimmune destruction of β-cells
      • No β-cells → no insulin
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13
Q

What is T2DM?

A
  • Type 2 diabetes mellitus (NIDDM) [~90%]
    • Insulin resistance
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14
Q

What is maturity-onset diabetes of youth?

A

Maturity-onset diabetes of youth (MODY)

  • Genetic defect in b-cell insulin production or release
    • Defective/mutated gene associated with uptake of glucose, K channel depolarization, Ca etc
    • NO insulin production (look like Type 1) ~pancreas not work properly
  • ~2% of young (ex: < 15 yo) diabetics
    • SCREEN pts if developed DM young!!
  • Tx:
    • Insulin
    • *Secretagogues (better) → fixes insulin P/R issue
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15
Q

What is gestational diabetes mellitus?

A

Gestational diabetes mellitus (GDM) → Identified DURING pregnancy

  • Any diabetes identified during pregnancy
    • DMI dx before pregnant → still DM1
    • No dx DM and now pregnant with DM → Gestational diabetes
      • Goes away after pregnancy
      • Still present after pregnancy → Dx DM1/2
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16
Q

How do cushings, acromegaly and pheochromocytoma cause increase blood glucose?

A
  • Cushing’s: ­ increase Cortisol → ­ increase glucose
  • Acromegaly: ­ increase GH → increase ­ glucose
  • Pheochromocytoma: ­ increase NE/Epi → increase ­ glucose
    • Normal release of mediators: ­ increase BG → good if need energy for various functions
      • Modest effect compared to glucagon
    • ELEVATED hormone diseases ^: increase­ BG (~150’s range vs. 400’s DM)
      • Summary: ~ slightly ­increase BG → check for neuroendocrine dx***
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17
Q

Type 1 Diabetes progression?

A
  • Autoimmune: Type IV hypersensitivity disease
    • Immune system kills pancreatic β-cells → until β-cells gone
    • Trigger of destruction not yet unknown.
  • Type 1 Diabetes Progression
      1. Start 100% β-cells mass → immune cells kills → decrease mass
      1. Variable insulitis/β-cells sensitivity to injury
        * β-cells still producing insulin (unaffected)
      1. Progressive loss of insulin release
        * Keeps killing β-cells
      1. Loss of normal glucose tolerance
        * Not enough β-cell mass to control BG
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18
Q

Clinical symptoms of T1DM?

A
  • Do not arise until sufficient destruction has occurred → typically years after the initial trigger.
    • Previously healthy
      • Effects Men/Women- 1:1
        • ~ 90% < 20 yo
    • High UO with glucose
    • High BG
    • Lethargic
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19
Q

Characteristics of T2DM?

A
  • Progressive loss of insulin sensitivity
    • *Insulin: signal for cells to take up glucose BUT cell hasn’t used glucose from before! → cells become insensitive to signal
      • Ex: Cells (muscle and fat) become less responsive to the action of insulin → ­ INCREASE insulin production by pancreas.
        • Maintains normal serum glucose, but with resulting hyperinsulinemia.
      • As decrease insulin sensitivity → hyperinsulinemia not sufficient to maintain normal glycemia/hyperglycemia
  • Preventable & reversible
    • Tx: exercise → then insulin
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20
Q

Progression of T2DM?

A

Blue: Insulin resistance

Red: Insulin production

    1. Muscle/fat full
    1. ­increase insulin production → stimulate little more uptake into muscle/fat
    1. ­increase insulin production not work anymore → increase fasting BG ­
      * Fasting BG increase ­ → destroys β-cell (glucotoxicity) → decrease insulin production!
      • Ex: GLUT2 glucose transporter on B-cell reliant on glucose GRADIENT → kills cell
    1. Insulin “dependent” Type 2 diabetics
      * Result of increase­ insulin resistance AND decrease insulin production (from β-cell destruction)
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21
Q

What happens with chronic hyperglycemia in T2DM?

A
  • β-cell destruction and loss of insulin production with consequently elevated hyperglycemia.
  • The entire progression typically requires > 10 years.
22
Q

Clinical signs, genetics, pathogenesis, and islet cell condition in T1DM?

A
  • Clinical
    • Onset < 20 years old
    • Normal weight- skinny
    • decrease blood insulin - DECREAES C-peptide (long ½ life)
    • Anti-islet cell antibodies
    • Ketoacidosis common – d/t increase ­ glucagon
  • Genetics
    • < 50% concordance in twins
    • HLA-D linked (AI Dx)
  • Pathogenesis
    • Autoimmunity, immunopathic mech.
    • Severe insulin deficiency
  • Islet Cells
    • Insulitis early (disease of the pancreas caused by the infiltration of lymphocytes)
    • Marked atrophy and fibrosis
    • b-cell depletion –Ab against them
23
Q

Clnical, Genetics, pathogenesis, islet ells of T2DM?

A

Clinical

  • Onset > 30 years (usually)
  • Obese → ppl can ­increase fat cells and not have DM2
  • ­increase blood insulin
  • No anti-islet cell antibodies
  • Ketoacidosis rare – d/t ­ increase insulin/decrease glucagon

Genetics

  • > 90% concordance in twins – d/t lifestyle habits (?)
  • No HLA associations- not a gene!

Pathogenesis

  • Insulin resistance
  • Relative insulin deficiency (relative to NEED, more than normal)

Islet Cells

  • No insulitis
  • Focal atrophy and amyloid deposits
  • Mild b-cell depletion (glucotoxicity)- no Ab destruction
24
Q

What is gestational diabetes?

A
  • Previously undiagnosed diabetes that presents during pregnancy
    • Although gestational diabetes usually resolves after parturition, the patient has an increased risk of subsequent gestational diabetes and type 2 (or type 1) diabetes.
  • Probable cause:
    • Chorionic somatomammotropin – hormone from fetus that increases blood glucose
      • *GH analog → stimulates GH for fetus and mom → tries to increase ­ BG for energy
      • If prediabetic before → pushes mom over limit → GD
25
Q

What is diabetes insipidue?

A
  • defect in water reabsorption in the kidney- problem with ADH synthesis/utilization
    • increase­ UO (diluted urine- tasteless)
    • not associated with DM
26
Q

What is C peptide useful for in diagnosis?

A

Determine Type 2 vs Type 1

If C peptide is not present/low, then it is Type 1 DM

27
Q

Cause of hyperglycemia in type1 vs type 2 dm?

A

Type 1:

  • ­increase BG: insulin production inhibited

Type 2:

  • ­ increase BG: insulin use inhibited → insulin not used by cells
28
Q

What is used to clinically diagnose DM?

A

Clinical diagnosis of diabetes mellitus: (know these numbers)

Typically these tests will be done multiple times

  1. Fasting plasma glucose level (before AM meal)
    1. >126mg/dL (7mmol/L).
    2. Normal levels < 100mg/dL (5.6mmol/L)

or

  1. Plasma glucose levels in excess
    1. >200mg/dL (11mmol/L) after 2 hours during an OGTT

or

  1. Random glucose level (eaten w/ cortisol)
    1. >200mg/dl and diabetic symptoms.

Normal Person:

  • Start: 90
  • Take glucose → Glucose levels increase→ decrease
  • ~2 hrs after: lower than start (hungrier than started)

Diabetic:

  • Start: HIGHER
  • Take glucose → levels increase → stay higher longer
29
Q

Diagnosis of gestational diabetes?

A
  • During pregnancy, hormonal changes can cause increase­ BG (fetus wants the glucose)
  • Diagnosed if woman has: (don’t need to know numbers, just that they are lower)
    • Fasting blood glucose level > 95 mg/dL
    • 1-hour level > 180 mg/dL (OGTT)
    • 2-hour level > 155 mg/dL

or

  • 3-hour level > 140 mg/dL
    • Glucose levels are normally lower during pregnancy → cutoff levels for dx in pregnancy are lower.
30
Q

Pathology of gestational diabetes? Consequences of poorly controlled gestational diabetes?

A
  • Pathology:
    • Typically between 24-28 weeks of pregnancy
      • fetus growing big/fast → needs more glucose/energy! → tells mom to ­ increase BG
  • Poorly controlled gestational diabetes: ~400 BG
    • Glucose crosses placenta → giving baby hyperglycemia
    • Consequences → Unhealthy baby (­ increase risk developing):
      • Short-term:
        • Hypoglycemia at birth (d/t sudden decrease in glucose supply) → PREVENT
      • Long-term:
        • HTN
        • CV dx
31
Q

What happens to gestational diabetes after baby dlievered?

A
  • Normally:
    • Resolves following childbirth
      • But dangerous for both mother and baby → baby becomes hypoglycemic
    • 2/3 chance GD will return in future pregnancies
      • *warning sign that mom was prediabetic before pregnant* → might return to prediabetic or diabetic after birth
32
Q

What is pre-diabetse?

A

Pre-diabetes

  • AKA: impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT)
    • ~Depending on the test used to diagnose it. Some people have both IFG and IGT.
      • IFG: impaired fasting glucose
        • BG level: 100-125 mg/dL after an overnight fast
          • not high enough to be classified as diabetes (~DM >126)
      • IGT: impaired glucose tolerance
        • BG level: 140-199 mg/dL after 2-hour oral glucose tolerance test
          • not high enough to be classified as diabetes (~ DM >200)
    • REVERSIBLE → prevent end organ disease
  • Population: ~40% U.S. adults → ages 40-74
33
Q

What are some acute complications of DM?

A
  • Hypoglycemia → took too much insulin (DM2)
  • Diabetic ketoacidosis (DM1) → not enough insulin
  • Hyperosmolar hyperglycemic nonketotic syndrome (HHNKS or HONKS) (DM2)
    • Osmolarity > 290 (~350-400) → suck H2O out of cells
    • Hyperglycemia: osmolarity ­INCREASE d/t GLUCOSE (osmotic agent)
    • Nonketotic: no ketones in urine
      • MEDICAL EMERGENCIES
34
Q

What are some chronic complicatiosn of DM?

A
  • Hyperglycemia and non enzymatic glycosylation
    • increase glucose–> glucose sticks to proteins
    • AGEs increase with age
  • microvascular disease (RNC is micro…)
    • diabetic retinopathy
    • diabetic neprotpathy
    • diabetic CARDIOMYOPATHY- most CV dx caused by MACROvascular dx
  • Macrovascular disease ** big killers**** (PCS is MACRO… lots of cell towers)
    • PAD
    • CAD
    • Stroke
  • Increase activity of polyol/sorbitol pathway
    • diabetic neuropathy- schwann cells swell–> damage to cells they myelinate
    • cataracts- polyol pathway makes various sugar ETOH
      • increase BG–> increase pathway activity–> too much ETOH sugars–> cause cell to swell
  • other
    • glaucoma–> diabetic blind bc cataracts and diabetic neuropathy
    • infection- poor circulation
35
Q

Hypoglycemia mild s/s and severe s/s?

A
  • Blood glucose = < 70mg/dl
    • ~ Need lower before seeing effects
  • MILD S/S:
    • Hunger
    • Shakiness
    • Paleness
    • Blurry vision
    • Sweating
    • Anxiety
  • SEVERE S/S:
    • Extreme tiredness
    • Confusion
    • Dazed appearance
    • Seizures (~ < 30)
    • Unconsciousness ® COMA® DEATH
      • Tx: conscious → candy bar, bread/unconscious → Dextrose drip
36
Q

What is DKA?

A
  • Diabetic Ketoacidosis
  • Life-threatening HYPERGLYCEMIA
    • → could result in brain damage
    • Breakdown from fat/PRO for energy → KETOSIS
  • Causes: Not getting insulin
    • Untreated or undiagnosed DM (especially IDDM)
      • decrease insulin & ­ increase glucagon → try to ­ increase BG → break down fat → goes liver → makes ketones bodies
    • Non-compliance to DM Rx
    • infection or illness
37
Q

S/S DKA?

A
  • Fruity acetone breath
    • Acetone- types of ketone body (finger-nail polish remover)
      • Acetone: LOW boiling point → can exhale it!
  • Kussmaul’s breathing (deep, rapid, gasping)
    • Ex: Have metabolic acidosis → tx by ­ RR
  • Dehydration
    • ­INCREASE osmolarity → H2O sucked out of cells → ­ increase UO (cells dried out)
  • N/V, abdominal pain
  • Altered LOC
    • Combo from metabolic acidosis & ­increase osmolarity
  • Weakness, paresthesia
38
Q

Labs seen in DKA?

A
  • Severe hyperglycemia
  • electrolyte imbalance
  • Metabolic acidosis → electrolyte imbalances
  • + ketones in urine (from hyperketonemia)
39
Q

How do you calculate gluocse excretion in the urine?

Example one: BG 80 mg/dL, GFR 125 mL/min

Example 2: Blood glucose= 300 mg/dL; GFR= 125 mL/min

How much glucose will be in the urine? What is the filtered load of each example?

A

GFR = 125 ml/min

Tmax = 300 mg/min

  • Filtered load= BG x GFR (CHANGE UNITS TO MATCH)
    • 1 dL = 1 x 10-1 (0.1) L, =100 mL

Example 1:

  • Blood glucose = 80 mg/dl
  • Filtered load = 80 mg/dl * 125 ml/min
    • change to 0.8 mg/mL*125mL/min

= 100 mg/min (all glucose reabsorbed, none in urine)

Example 2:

  • Blood glucose = 300 mg/dl
  • Filtered load = 300 mg/dl * 125 ml/min
    • change to 3 mg/mL*125mL/min

= 375 mg/min filtered load

  • 375 mg/min – 300 mg/min (Tmax) = 75 mg/min (not reabsorbed → Glucose in urine)

Note: 1 mM of glucose = 18 mg/dL (mg % = mg/dL)

40
Q

What is the pathway of ketogenesis from acetyl-CoA?

A

​

  • Fast/no food → BG decrease → liver mobilize glycogen → glucose (lasts ~1 day)
  • ­ increase Glucagon → fat cells mobilize FFA→ FFA in blood → go to liver → beta-oxidation of fat → ­ increase ketones released
  • Liver: makes Acetyl-CoA
    • Acetyl-CoA + HMG-CoA synthase → acetoacetate
  • Acetoacetate: MAJOR ketone “ketone acid”
    • Released from liver as: “Ketone Bodies/Ketone Acids”
      • Acetone- Ketone (not an acid)
      • B-hydroxybutyrate- Acid (not a ketone)
    • Body (& brain) use ketones as FUEL → takes longer for liver to ­ ketone production
  • Normal person:
    • Ketones → stimulate insulin secretion in b-cells
      • Glucagon will be controlled/modulated (enough to keep FFA release sufficient to keep ketone body production sufficient) ~ wont be hungry after fast after few days
    • No fxing b-cells → glucagon ­­­ (DM1)
  • Depletion of oxaloacetate via high rates of gluconeogenesis slows entry of acetyl-CoA into Krebs Cycle.
  • Under these conditions, acetyl-CoA is converted into ketone bodies for use by:
    • Brain
    • Heart
    • Kidney
    • Liver
  • Ketone bodies include: acetoacetate, acetone, and β-hydroxybutyrate.
  • Cannot make glucose from fat – you can make acetoacetate which can be used as fuel
  • Ketogenesis generates ketone bodies from acetyl-CoA, releasing the CoA to participate in β-oxidation. The enzymes involved, HMG-CoA synthase and lyase, are unique to hepatocytes; mitochondrial HMG-CoA is an essential intermediate. The initial product is acetoacetic acid, which may be enzymatically reduced to β-hydroxybutyrate by β-hydroxybutyrate dehydrogenase, or may spontaneously (nonenzymatically) decompose to acetone, which is excreted in urine or expired by the lungs.
41
Q

Comparison of HHNKS vs DKA?

Glucose elevation, osmolarity, pH, Bicarb, c-peptide, anion gap?

A
  • Glucose elevation: Osmotic agent
    • HHS: increase­ 58.1 (in osmolarity → just from glucose)
    • DKA: increase­ 38.5
  • Osmolarity
    • HHS: 380 (90 mOsm > normal osmolarity) ­­­increase
      • Sucks H2O out of cells (brain) → cause coma → death
    • DKA: 323 ( DKA > normal)
      • Not as much as HHS
  • pH
    • HHS: 7.3 (barely acidotic)
    • DKA: 7.12 (severely acidotic)
  • Bicarb (follow with degree of acidosis)
    • HHS: 18
    • DKA: 9.4
  • C-peptide → insulin should be increased­ so should see ­ increase C-Peptide if making insulin
    • HHS: 1.14 (­ increased x 5 > normal)
    • DKA: 0.21 (LOW- B-cell depletion)
  • Anion Gab
    • HHS: normal (11)
    • DKA: increase­ → d/t metabolic acidosis
  • *HHNKS not that big of acidosis, but increase ­­­osmolarity, due to excessive glucose, dehydrating the cells

Both: increase­ in BG, osmolarity

Different: C peptide, pH, Bicarb, and anion gap

42
Q

Implications of HHNKS?

A

EMERGENCY

  • Higher BG → worse outcome for HHNKS
  • Mortality rate is function of BG
    • >1000 BG → Mortality rate ~10-30%
    • Tx: LARGE dose of insulin
  • dka is easier to manage…
43
Q

What are AGEs?

A

Advanced Glycosylation of End-products (AGEs)

  • More glucose = more protein cross linking, (remember hgb is protein)
  • these also are why the proteins are rigid and lose flexibility (stiff joints)
  • AGE receptors – finding these and macrophaging/destroys them=== inflammation (atherosclerosis, retinopathy, neuropathy)

Glucose binds to sidechains of proteins

  • ­ increase glucose have → ­ increase binding
    • Shifts, happens quickly
  • Over time: irreversible binding → Amadori product
    • Amadori product → *crosslinks* → crosslinked protein
    • Crosslinked protein:
      • Useless, problematic
  • Macrophages: have receptor → Receptor for Advanced Glycosylation End Products (RAGE)
    • Finds proteins that have been crosslinked → destroys them
  • Higher BG → faster the reaction
    • Ex: BG 100 → can keep up with rate
    • Ex: BG 400 → 4x faster buildup:
      • Cant clear glycosylated end products fast enough (AGEs)
      • ­ Activated macrophages trying to clear AGEs → ­ chronic inflammation in body
44
Q

What is HbA1C? Normal values?

A

HbA1c – glycosylated Hemoglobin

Hemaglobin: most common glycocylated end protein (AGE)

  • HbA1c = measure of how much glycocylation of Hgb in blood
    • Average over the last 1-2 weeks (sources say 90 days)

GOAL: 7% → 170 (mean plasma glucose)
A1c Test:

  • Normal: < 5.7
  • Pre-diabetes: 5.7- 6.4%
  • Diabetes: > 6.5%
    • DM dx: GOAL < 7
45
Q

What happens when HBA1C is reduced? What type of diabetic benefits most from HBA1C reduction?

A

DCCT was a trial with DM1 linking relationship of HbA1c to risk of microvascular complications

GOAL: ¯decreaseBG → see what happened

*See: decrease BG (HbA1C %) → complications decrease

Ex: HbA1C 6% → no complications

HbA1C 11%:

  • 13 X RELATIVE RISK of retinopathy
  • 11 X realative risk of nephropathy (compared normal)
    • Problem: Study done on DM1
    • DM2 → meds don’t decrease complication risks like DM1 meds (insulin) does

(curve not applicable for DM2 pts)

46
Q

What is diabetic retinopathy?

A
  • Leaky BV in retina → retinal damage!
    • Arterials/capillaries in retina start leaking/falling apart → BLINDNESS
      • Hemmorage
      • Leaking, etc
  • Leading cause of blindness.
    • Diabetics → more likely to develop eye problems
      • Ex: cataracts, glaucoma
      • Retinal damage → largest cause of blindness.
  • Prevalence:
    • *type 1 (40%) → d/t being diabetic longer
    • type 2 (20%).
47
Q

Cataracts in diabetics?

A
  • Cataracts of the crystalline lens with opacification
    • more frequent in DM
    • *occurs to everyone with age…
      • treatment- cataract replacement but no txmt retinopathy
  • Increased sorbitol and increased proteins in the lens
48
Q

What is diabetic nephropathy? Consequences?

A
  • Leading cause of kidney failure
  • Leakiness of glomerular capillaries
    • microalbuminuria-proteinuria.
  • Leaking in big capillary beds → GLOMERULUS
    • Causes →
      • decreaseGFR
      • ­ increase Protein leaking (microalbuminuria/proteinuria)
  • Leading cause of kidney failure.
    • Type 1 & 2 diabetes at risk
      • ~ 30% pts w/ DM develop diabetic nephropathy
    • Poor control of BP → greatest rate of progression
      • ~ macrovascular damage
  • DAMAGE
    • Proteinuria–> damage to glomerulus
    • damage to proximal tubule too
  • Treatment: once proteinuria dx–>
    • keep BP under control c ACE/ARB
    • Uncontrolled DM–> dialysis
      • afer dialysis or transplantation–> DM pts tend to do worse than those w/o DM
  • Consequences of diabetic nephropathy:
    • Glomerulosclerosis
    • tubulointerstitial fibrosis
    • Arteriolar sclerosis
    • Renal failure
    • Hypertension → exacerbates
      • Tx: ACEI & ARBs → decreaseremodeling from HTN
      • ACE/ARBS great TXMT HTN and reduce risk for diabetic neprhoparthy, even in people that aren’t HTN
    • cardiovascular disease
49
Q

Tissue chanags in diabetic nephpropathy?

A
  • Nodular lesions → large wods of glycocylated proteins
  • Loops have degenerated → become large loop
    • Problems: (2)
      • decrease surface area for filtration and GFR will fall
      • ­increase radius → more likely to rupture
        • Pressure ­ increase in large capillary → cause glomerular membrane/capillary to rupture → bleed → clot → turn to fibrin caps (#4 pic)
        • Fibrin caps → ­ increase SA loss
    • Result → #3 pic
      • Small amount of glomerulus left with functional capillaries
      • Large wods of protein (where mesangial cells were)
      • Large loops (microaneurysma) ~microaneurysms → leak
        • ¯decrease GFR
        • ­increase Protein in urine
50
Q

What is diabetic neuropathy?

A
  • Inability to feel pain in foot (diabetic neuropathy)
  • decrease BF to lower extremities → ¯decrease immune response to infection
  • Peripheral neuropathy
    • causes either pain or loss of feeling in the toes, feet, legs, hands, and arms (schwann cell degeneration)
      • “diabetic foot”
    • Blisters and sores appear on numb areas of foot → pressure or injury goes unnoticed.
    • Not tx injuries promplty→ infection may spread to the bone → lead to amputation
  • Autonomic neuropathy
    • Changes:
      • digestion, bowel and bladder function, sexual response, and perspiration.
      • Affect nerves serving heart and control BP
  • Focal neuropathy
    • results in sudden weakness of one nerve, or a group of nerves, causing muscle weakness or pain.
      • Any nerve in the body may be affected.
      • Ex: Schwann cells innervate the lower neurons of neuromusclar junction
        • Repeated insult → paralysis

Start: Numbness/tingling → progresses…

51
Q

Connection between diabetic gangrene and amputation?

A
  • Diabetics have accelerated atherosclerosis (extensive and involve peripheral vasculature)
    • Predisopose to complication of gangrene → amputation

Patho Test 4 (4 decks)

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