Diabetes PATHO Flashcards

1
Q

Type 1 DM
Prevalence

A

Canada has one of the highest prevalence’s in the world

Men = women

10% of all diabetes diagnoses

Most common chronic paediatric illness

Diagnosis 11-13 years (rare < 1 years, > 30 years)

White people 2x > than ethnic minorities

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Type 1 DM
Risk Factors

A
  • virus
  • formulae feeding
  • cow milk allergies
  • genetics (family history, 50% twins)
  • HLA-DR (autoimmune disorders: thyroid (graves, hashimoto), adrenal (addisons), ceilac disease)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Type 1 DM
Pathophysiology

A
  1. Auto-immune
  2. Idiopathic

Genetic predisposition x environment

  • formation auto-antibodies against
    1. Islet antigen 2 antibodies (IA-2A)
    2. anti-glutamic acid decarboxylase (GADA) antibodies
  • Activation macrophages, cytotoxic T cells, humoral immune response (antibody production)
  • Destruction of beta cells (insulin producing cells)
  • No insulin released
  • No GLUT4, no uptake of glucose in fat/muscle/liver
  • No inhibition of glucagon
  • No amylin release
  • No inhibition glucagon, gastric emptying is not slowed, saiety is not supressed
  • removed inhibition glucagon
  • increase blood glucose (counter-regulatory hormone)
  • liver breaks down glycogen, makes glucose from a.a and FFA
  • adipose tissue breaks down fat
  • muscle breaks down protein
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Type I DM
Onset & Screening

A

Slow onset

80-90% beta cell destroyed before detected

No screening for T 1 DM
- cannot prevent / delay diagnosis

If diagnosed screen for other auto-immune diseases (HLA-DL)
- Thyroid (graves, hashimoto)
- Celiac
- Addison’s disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Type 1 DM
Clinical Signs and Symptoms

A

Polyuria
- osmotic diuresis
- glucosuria pulls water out of body

Polydipsia
- Hyperosmolarity of blood
- low blood volume
- triggers hypothalamus thirst center

Polyphagia
- breakdown of glycogen, muscle, fat stores

Underweight

Diabetic ketoacidosis:
- ketones detected in urine, breath, and blood
- liver oxidizing FFA for energy produces ketone bodies
- metabolic acidosis (hyperventilation, lethargy, coma)

Electrolyte imbalances:
- hyponatremia
- hypokalemia

Cellular dehydration
- seizures

No C-Peptide
- no endogenous insulin production

+/-
- IA-2A antibodies
- GADA antibodies

Blurred vision
- hyperglycemia in lens of eye, pulls water in

Genital Pruritis

Infection, poor wound healing
- hyperglycemia
- micro/macrovasular damage from hyperglycemia

Cardiovascular complications
- parasethesias
- chest pain
- extremity pain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Type 1 DM
Etiology

A
  1. Idiopathic
  2. Auto-immune *HLADR
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Type 2 DM
Prevalence

A

90% Type 2 DM

> 40 years of age

ethnic minorities > white
(indigenous > african, hispanic, asian)

Obesity * (and metabolic syndrome)

men > women

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Type 2 DM
Risk Factors

A

Age
> 40 years

obesity* (primary driver)

metabolic syndrome (dylipidemia, hypertension, abdominal girth, hyperglycemia)
- BP > 130
- TG > 1.7
- Waist circumference > 102cm males, > 88cm females

pre-diabetes (impaired FG, impaired GTT, elevated A1C)
- IFG 6.1-6.9mmol/L
- IGTT 7.8-11.0mmol/L
- 6.0-6.4% A1C

ethnic minorities

Males > females

PCOS

Sleep apnea

NAFLD

neuropsychiatric medications

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Insulin Receptor Sensitivity
Modulating factors

A
  • age
  • weight
  • HTN
  • dyslipidemia
  • stress
  • exercise
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Type 2 DM
Clinical Signs and Symptoms

A
  1. Silent hyperglycemia
    - hyperinsulinemia results in silent hyperglycemia
  2. Symptomatic hyperglycemia (HHS)
  • Polyuria (osmotic diuresis)
  • polydipsia
  • polyphagia
  • fatigue
  • glucosuria
  • albuminuria
  • hyperglycemia
  • blurred vision
  • hyperosmolarity blood
  • cellular dehydration, seizures
  • electrolyte imabalances: hypokalemia, hyponatremia
  • infections, impaired wound healing, genital pruritis
  • microvascular and macrovascular complications: CVE, MI, paraesthesias, retinopathy, nephropathy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Type 2 DM
Pathophysiology

A
  1. Obesity results in peripheral insulin resistance
    - adipokines, pro-inflammatory cytokines
    - increased insulin resistance
    - increased demand on beta cells
    - cytotoxic to beta cells
  2. beta cells hyper secrete insulin (hyperinsulinemia)
    - increase beta cell secretion insulin
    - beta cell dysfunction
    - adipokines are also cytotoxic to beta cells
    - silent hyperglycemia
    - microvascular and macrovascular damage continues
  3. beta cells begin to dysfunction
    - adipokines are cytotoxic
    - increased demand, decreased function
    - decrease 1. insulin 2. amylin
    - decrease response to incretins (GLP1 and GIP) which results in decrease insulin secretion
  4. Decreased insulin and amylin removes negative inhibition on glucagon
    - increase gluconeogenesis, and breakdown of fat, protein and glycogen
    - increases blood glucose
  5. decreased function amylin
    - no saeity
    - increased GI motility
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Type 2 DM
Screening

A

Everyone is screened at 40 years, every 3 years

Screen earlier if risk factors present and screen every 6-12 months

*CANRISK calculator

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Gestational DM
Prevalence

A

3-20% of pregnancies

  • all mothers screened at 24 weeks
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Gestational DM
Risk Factors

A

80% have pre-diabetes
1. insulin resistance
2. beta cell dysfunction
at baseline prior to pregnancy

  • advanced maternal age
  • obesity
  • ethnic minorities
  • family history, personal history (genetics)
  • PCOS
  • pre-diabetes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Gestational DM
Clinical Manifestations

A
  1. Silent hyperglycemia
    - asymptomatic
    - all mothers screened at 24 weeks
  2. Symptomatic
    - polyuria, polydipsia, polyphagia, fatigue, hyperglycemia, weight loss
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Gestational DM
Preferred vs. Alternate screening

A

50g OGTT
- 2 hour mark BG > 9.0mmol/L

then

75g OGTT
- 2 hour mark BG > 8.5mmol/L

*lower threshold as fetus eats the glucose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Gestational DM
Complications of hyperglycemia

A
  • still birth
  • spontaneous abortions
  • teratogenic (congenital abnormalities)
  • pre-eclampsia
  • retinopathy

Tighter glycemic control
- A1C < 6.1%
- Hypoglycemia < 3.7mmol/L

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Gestational DM
Pathophysiology

A

Placent causes insulin resistance
- estrogen, progesterone, cortisol, GH, lactogen
- increase maternal resistance to insulin
- increases glucose in blood for the baby

Maternal counter-regulatory hormones released
- glucagon increases blood glucose

beta cell hyperplasia and hypertrophy
- hyperinsulinemia
- increased fetal uptake of glucose

80% of GDM have beta cell dysfunction at baseline along with insulin resistance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Gestational DM
Patient Education Post-Partum

A
  1. breast feed
    - immediately (prevent hypoglycemia)
    - until 4 months (prevent DM in baby and mother)
  2. Re-check FPG at 6 weeks and 6 months
    - type 2DM?
  3. montior thyroid dysfunction
    - higher risk for post partum thyroiditis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Diabetes Mellitus
Immediate Complications

A
  1. Diabetic Ketoacidosis (DKA)
    - diabetic coma syndrome
    - Type I DM
  2. Hyperosmolar Hyperglycemic Syndrome (HHS)
    - Type 2 DM
  3. Hypoglycemic shock
    - Insulin shock
    - Insulin reaction
    - Type 1 or 2 DM
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Diabetic Ketoacidosis (DKA)
Risk factors

A
  1. Undiagnosed Type 1 DM
  2. Trigger - Sick, Trauma, Drug reaction (cocaine, SGLT2, anti-psychotics), thyrotoxicosis
    - release of counter-regulatory hormones (cortisol)
  3. Missed Insulin
  4. Insulin antagonists
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Diabetic Ketoacidosis
Laboratory Results

A

BG > 14mmol/L
anion gap
low bicarbonate
high lactate (low pH)
plasma and urine ketoacids (beta hydroxybutyrate, acetoacetone, acetone)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Diabetic Ketoacidosis
Pathophysiology

A
  1. No insulin (relative insulin deficiency)
  2. Activation counter-regulatory hormones
    - rise in cortisol
    - increase blood glucose
    - site of action: 1. liver 2. muscle 3. fat
    - Liver: breaks down glycogen, gluconeogenesis from oxidation fat
    - Muscle: breakdown protein
    - Fat: lipolysis, FFA
  3. FFA oxidation by liver produces ketoacids
    - beta hydroxybutyrate
    - acetoacetate
    - acetone
  4. Reduction pH leads to metabolic acidosis
    - bicarbonate low, anion gap formation
    - kaussmaul respirations
  5. Hyperglycemia -> clinical signs and symptoms
    - polyuria - osmotic diuresis
    - dehydration
    - hyperosmolality and CNS dehydration
    - polydipsia
    - polyphagia
    - electrolyte imbalances: hyponatremia, hypokalemia
    - N/V/D, arrhythmias, abdominal pain etc.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Hyperosmolar Hyperglycemic non-ketotic Syndrome
Risk Factors

A
  1. Type 2 DM undiagnosed
  2. Insulin antagonists
    - Illness, trauma, drugs (corticosteroids)
  3. Pancreatitis
    - no insulin released
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Hyperosmolar Hyperglycemic (HHS) Laboratory results
BG > 33.5mmol/L Osmolality > 320mmol/L BUN:Cr > 20:1 NO KETONES
26
Hyperosmolar Hyperglycemic Syndrome (HHS) Pathophysiology
Absolute or relative decrease in insulin Hyperglycemia - reduced insulin, blood glucose remains in blood Silent hyperglycemia - onset slow - body has insulin to take up glucose - progresses silently - level hyperglycemia much more severe than DKA Clinical S&S - polyuria - polydipsia - severe dehydration - severe electrolyte imbalances (N/V/abdominal pain, weakness): hyponatremia, hypokalemia - poor skin turgor, dry lips, mucous membranes - hypotensive shock - poor kidney perfusion leads to accumulation BUN:Cr - hypothermia (CNS dysfunction), stupor, coma
27
Higher mortality rate DKA or HHS?
HHS
28
Hypoglycemic Shock Risk Factors
Iatrogenic 1. too much insulin 2. too much insulin secretagogues 3. Combination therapy 4. Impaired awareness hypoglycemia (IAH) multiple hypoglycemic episodes (rapidly fluctuating BG) 5. Exercise 6. To little food with insulin therapy 7. Alcohol 8. Medications - beta blockers (mask hypoglycemia) 9. Decline in insulin need - Chronic kidney disease (decrease insulin degredation) - post partum period (gestational DM)
29
Individuals at high risk for Hypoglycemic shock
- age - longer duration diabetes - more hypoglycemic episodes (threshold hypoglycemia lower) - diabetic neuropathy (ANS not activated) - preschool - cognitive impairment - low health literacy
30
Why are frequent hypoglycemic episodes bad
Re-set glucose counter-regulatory threshold - lower BG required to stimulate SNS response - Neuroglycopenic symptoms are the first signs (Level 3) - too late and require assistance to treat *very dangerous
31
When are Type 1 DM more likely to experience hypoglcyemic shock?
Night time Decreased sympathoadrenal repsonse to hypoglycemia Level 3 *somogyi
32
Clinical Signs and Symptoms Hypoglycemia Adrenergic (Autonomic)
- trembling - sweating - palpitations - pale - anxiety - nausea - tingling - hunger
33
Clinical Signs and Symptoms Hypoglycemia Neuroglycopenic
- Fatigue - confusion - slurred speech - blurred vision - weakness - sensory and motor changes - HA - dizziness - coma - death
34
Classifications of Hypoglycemia
Level 1 BG 3.0-3.9mmol/L (< 4.0mmol/L) Autonomic symptoms Level 2 BG < 3mmol/L Neuroglycopenic symptoms (able to self treat) Level 3 BG < 3mmmol/L neuroglycopenic symptoms unable to self treat
35
Hypoglycemia Laboratory diagnostics
Normal blood glucose adult 4.0-7.0mmol/L Neonate < 1.7mmol/L Adult < 3.9mmol/L Pregnant adult < 3.7mmol/L
36
Hypoglycemic Shock Pathophysiology
Too much insulin - Trigger: too much insulin, combination therapy, excerise, alcohol, not enough food, sleep - uptake of BG into cells Counter-regulatory hormones released - Cortisol increases: gluconeogenesis, glycogenolysis, lipolysis, proteolysis - SNS activated: adrenergic symptoms Insufficient counter-regulatory response - neuroglycopenic symptoms: CNS depression, confusion, HA, coma, death
37
Long term Hypoglycemia Complications
Hypoglycemia is pro-inflammatory - platelet aggregation - fibrosis Long term consequences of hypoglycemia - Fear of hypoglycemia (keep blood glucose high increase micro and macrovascular complications) - IAH (impaired awareness hypoglycemia) - Scaring of the brain (intellectual development, alzheimer's disease, pontine dysfunction, hemiparesis)
38
Treatment of Hypoglycemia
1. switch from intermediate to long acting insulin - degludec > glargine > detemir 2. check insulin regularly at night (impaired awareness hypoglycemia) 3. continuous glucose monitoring and continuous subcutaneous insulin infusions 4. Increase glucose target for 3 months - re-sets the adrenergic hypoglycemic set point - avoidance hypoglycemia for 2 days or 3 months 5. Avoid drinking 6. Exercise - reduce pre-prandial insulin - reduce basal insulin at night - increase carbohydrate intake before exercise - weights before cardio - sprints in between cardio 7. patient and family education *prevention is easier than treatment
39
Laboratory Values Predict what chronic complications
A1C - CVD, CVE, progression to T2DM FPG and OGTT - microvascular complications
40
Chronic complications of DM
Microvascular complications (capillaries) 1. neuropathy 2. retinopathy 3. nephropathy Macrovascular complications (major arteries, cerebral arteries) 1. Cardiovascular disease 2. Cerebrovascular disease 3. Peripheral vascular disease
41
Microvascular complications Pathophysiology
Hyperglycemia -> glycation end products -> inflammation -> atheroscelerosis -> scaring, narrowing -> ischemia -> necrosis
42
Retinopathy & DM
DM leading cause of blindness world wide 1. non-proliferative stage - inflammation, increased premeability retina capillaries 2. pre-proliferative stage - ischemia, infarcts 3. proliferative stage - neovascularization, retinal detachment, blindness Other: - blurred vision (lens swelling) - cataracts - glaucoma
43
Nephropathy & DM
DM leading cause of ESRD 50% individuals with DM 1. Glomeruloscelerosis - hyperglycemia damages the glomerular membrane - inflammation -> scaring -> loss of negative charge and filtration slits - proteinuria 2. Acute tubular necrosis - hyperglycemia damages the epithelium of the nephron tubulse - cannot reabsorb or secrete (perform functions)
44
Neuropathy & DM
Most common complication of DM DM leading cause of nephropathy in the west demylination of nerves slows conduction 1. sensory nerves - loss sensation, pain, temperature, vibration, pressure, etc. 2. motor nerves - loss of motor funciton - Charcot Arthropathy - degeneration joints in foot 3. Autonomic nerves - gastric paresis - insensible hypoglycemia - silent MI - etc.
45
Macrovascular Complications DM
1. Cerebrovascular disease (strokes) 2. cardiovascular disease (CAD, MI, etc.) 3. peripheral vascular disease (ex. gangrene and amputations)
46
Cardiovascular disease (CAD) and DM
1. CAD 2. HF 1. CAD Coronary Artery disease leading cause of morbidity and mortality in DM Hyperglycemia --> glycated end products --> inflammation endothelial lining --> recruitment neutrophils and macrophages -> oxidative damage LDL --> engluphed --> fatty streak / atheroscelerotic plaque --> unstable plaque --> thrombosis narrow lumen --> ischemia --> infarct --> necrosis 2. HF Atheroscelerosis increases BP Increase pressure heart pumps against L ventricular remodelling Diastolic compliance decreases HFpEF - heart failure preserved ejection fraction
47
Peripheral artery disease and DM
Hyperglycemia -> demylination nerves -> slow/no conduction -> injury -> ulceration -> infection -> amputation
48
Impaired fasting glucose Pathophysiological changes
6.1-6.9mmol/L Impaired fasting glucose *Predicts microvascular complications PRO - fast - easy - predicts microvascular complications CON - variable - one point in time - fasting 8 hours
49
Impaired oral glucose tolerance Pathophysiological changes
7.8-11.0mmol/L *predicts microvascular complications PRO - fast - easy - measure any time of day CON - unpalitable - high cost - high variability - one time point
50
Impaired A1C Pathophysiology changes
A1C 6.1-6.4% *predicts microvascular changes *predicts type 2 DM *predicts CVD and all cause mortality PRO - predictor micro and macrovascular changes - Predictor type 2 DM advancement - reflects 120 days glucose management CON - not for diagnosis in children or adolescents - altered values in hemoglobinopathies, age, ethnicity, liver and kidney disease
51
Pre-Diabetes Diagnostic Classification
Impaired fasting glucose 6.1-6.9mmol/L impaired oral glucose tolerance 7.8-11.0mmol/L impaired A1C 6.1-6.4%
52
Goal of Treatment DM
Maintain A1C in target range - Tight control is not recommended (<6.5%) as associated with higher mortality, no CV benefit (only microvascular benefit) Individualized based on age: children, adolescent, adult, pregnant, elderly ; and health status Minimize fluctuations in BG Minimize hypoglycemic episodes - more episodes = higher mortality, cardiovascular complications, and IAH Multifactorial treatment - BG - HTN - dyslipidemia - exercise - smoking cessation
53
Glycemic Targets Adults
Fasting plasma glucose 4.0-7.0mmol/L 2 hour post prandial glucose 5.0-10mmol/L A1C < 7%
54
Glycemic Targets Pregnancy
A1C < 7% (at minimum) A1C < 6.5% (goal) A1C < 6.1% (third trimester) Prevention - miscarriage, still birth, spontaneous abortion - congenital abnormalities - pre-eclampsia - retinopathy
55
Glycemic Targets Children and Adolescents
A1C < 7.5% - prevention hypoglycemia (inflammatory scarring of brain and negative impact congitive development and IQ) - prevention IAH development Fasting plasma glucose 4.0mmol/L - 8.0mmol/L 2 hour post prandial glucose 5.0mmol/L-10mmol/L
56
Glycemic Targets Functional dependence, IAH, frailty, palliative care
A1C 7.1-8.5% Functional dependence - unable to notify S&S of hypoglycemia - IAH and high risk death Frailty and palliative care - hypoglycemia = degredation of glycogen, muscle, fat stores - decreased implication of CV and microvascular damage IAH - loosen glycemic control - re-set counter-regulatory threshold
57
Laboratory screening DM
- A1C - urinalysis (nephropathy) - retinopathy - neuropathy - dyslipidemia - blood pressure - vaccinations yearly (influenzae, COVID19) - smoking, alcohol cessation - pregnancy planning - autoimmune disorders (thyroid, celiac, addisons)
58
Self Monitoring DM
Blood glucose at minimum TID A1C levels for glycemic control over 120 days Ketone monitoring when sick, stressed, trauma
59
Initiation insulin therapy Children T2 DM
A1C > 9 % - insulin and metformin 9% > A1C > 7% - metformin - diet, exercise
60
Nonpharmacological Management DM
1. Exercise (weight loss) 2. Diet
61
Dietary Considerations DM
- portion control (40-60% carbs, 15-20% protein, 20-35% fat) - DASH, Mediterranean, Nordic, Vegetarian diets - whole wheat, nuts, legums/beans/pulses, omega fats, fish, vegetable proteins, vegetables, fruits, high fibre - low glycemic index carbohydrates - regular spacing of meals throughout the day - physical activity - weight loss
62
Physical activity DM
150minutes per week moderate-high intensity aerobic exercise 3x per week resistance training No more than 2 days rest
63
Physical exercise induced Hypoglycemia vs. hyperglycemia
PE induced hypoglycemia - reduce bolus insulin - eat before exercise - reduce basal insulin 20% (exercise long lasting effect) - cardio before weights - sprints between weights PE induced hyperglycemia - weights and sprints induce counter-regulatory hormones which breakdown lipids, muscle, and glycogen stores to raise glucose levels