Diabetes Pathophysiology Flashcards
1
Q
What are signs and symptoms of hyperglycemia (6)
PPP GB
A
- Glycosuria (excess sugar in urine)
- Polyuria (void more)
- Polydipsia (thirst)
- Blurred Vision
- Polyphagia (hunger)
- Ketogenesis –> Ketosis –> DKA
(breaking down fat for energy due to lack of insulin to break down sugars)
2
Q
What does ketogenesis lead to in total absence of insulin?
A
Diabetic Ketoacidosis
- Ketone buildup causes blood to become acidic
3
Q
What are the heart disease consequences for hyperglycemia?
A
- Risk of stroke
- Risk of heart disease
- Damaged blood vessels
4
Q
What are the eye disease consequences for hyperglycemia
A
- Visual disturbances
- Risk of cataracts and glaucoma
5
Q
What are other consequences of hyperglycemia?
A
- Loss of concioussness
- Risk of stroke
- Visual disturbances
- Risk of Cataracts and glaucauma
- Extreme thirst
- Sweet-smellling breath
- Risk of heart disease
- Fatigue and lack of energy (due to kidney and pancreas problems)
- Gastroparesis (poor gastric emptying, bloating, heartburn, nausea)
- Pancreas malfunction
- Excessive urination
- Protein in the urine (kidney damage)
- Ketoacidosis (lack of insulin, uses other hormones to turn fat into energy = high toxic ketone levels)
- Damaged blood vessels (restrict blood flow)
- Nerve damage “pins and needles” (alter perception of pain, heat)
- High blood pressure
- Risk of infections (esp feet)
- Foot problems calluses, ulcers, infections (from nerve damage from circulation to feet)
- Dry, cracked skin (body loses fluid at faster rate)
6
Q
What is some of the first noticeable symptoms of diabetes?
A
Extreme thirst
excessive urination
7
Q
What is the major cause of death for diabetic patients?
A
Heart disease and stroke
8
Q
What is the life expectancy difference in people with diabetes and no diabetes?
A
6 years
9
Q
Which condition were diabetic patients hospitalized for the most?
A) Stroke
B) hypertension/HF
C) CKD
D) Stroke
E) MI
F) Lower limb amputation
A
F) lower limb amputation
10
Q
Which condition is a strain on out-patient resources
A
Obesity
11
Q
What age did the sharpest increase of diabetes occur?
What age group was the highest prevalence?
A
40
75-79
12
Q
Which is more prevalent in the following factors:
Sex
Income
Education
Indigenous identity
Cultural/racial background
A
Sex: Male
Income: lowest
Education: less than high school
Indigenous identity: First nations living off-reserve
Cultural/racial background: South asian
13
Q
What are the diagnostic tests are used to diagnose diabetes and levels (4)
A
- Fasting plasma glucose 7.0+ mmol/L (8 hours)
- A1C 6.5%+ (in adults) (long-term BG levels since RBC lasts 120 days)
- Test PG 2H after a 75g OGToleranceTest , 11.1+ mmol/L (ideally fasting 8 hours before)
- Random PG 11.1+ mmol/L
14
Q
What is the A1C test? Bias towards what?
A
measure of glycated hemoglobin (glucose irreversibly attached to hemoglobin)
- Tests the average for the last 3 months (average life span of RBC)
- Bias towards the last 30 days of glucose level which accounts for 50% of the A1C value
15
Q
What is the consideration when using A1C diagnosis?
A
Must repeat it if patient is asymptomatic
16
Q
When is A1C testing not used? (5)
A
- Diagnosis in children
- Adolescents (as the sole diagnostic test, could be type 2)
- Pregnant women as part of routine screening for gestational diabetes
- cystic fibrosis
- With suspected type 1 diabetes
17
Q
What does the effect of B12/Fe deficiency have on A1C? What factor does it affect
A
Decrease Erythropoiesis
Increase A1C
18
Q
What does the effect of chronic renal failure have on A1C when it alters glycation
A
decreases blood pH
Increase A1C
19
Q
What affect does ASA, Vit C/E, sickle cell disease have on A1C? What factor does it effect?
A
Altered glycation, increase erythrocyte pH
Decrease A1C
20
Q
What effect does use of EPO, Fe, or B12 reticulocytosis, chronic liver Dx have on A1C?
A
Inc erythropoiesis, liver disease= less glucose,
Decrease A1C
21
Q
What effect does a splenectomy have on A1C?
A
Increase A1C
22
Q
What affect does sickle cell, autoimmune diseases, splenomegaly have on A1C
A
Decreased A1C
Auto-immune diseases = insulin resistance = less sugar being bound to Hb
23
Q
What effect does acute or chronic blood loss have on A1C
A
falsely decrease A1C
- all blood in body decreases
24
Q
What effect does hypertriglyceridemia have on A1C
A
Decrease A1C
25
What effect does hyperbilirubinemia, carbamylated Hb, ETOH, chronic opiates have on A1C
Increase A1C
26
When is a confirmatory test required? What kind of test?
In ASYMPTOMATIC hyperglycemia A1C
- repeat any test (could be same or different)
In asymptomatic random PG test
- repeat an alternative test (not the same)
27
When is a confirmatory test NOT required (3)
1. In symptomatic hyperglycemia
2. if 2 different tests are available and above threshold
3. When type 1 diabetes is likely (younger or lean or symptomatic) esp with ketonuria, ketonemia
- no confirmatory test required to avoid delay in treatment to avoid rapid metabolic deterioration
28
What are the diagnostic thresholds based on?
Development of retionpathy
29
What factors favour type 2 diabetes
family history
BMI
Age
ethnic
disease
Cholesterol
Family history type 2
No family history of type 1
BMI 28+
Age 45+
Non-white
Dyslipidemia HDL below 1.0
30
What factors favour type 1 diabetes
family history
BMI
Age
ethnic
disease
Cholesterol
No family history of type 2
1st or 2nd degree relative with type 1 diabetes
BMI under 28
Age under 45
White european
Any autoimmune disease
HDL over 1.5
31
Define type 1 diabetes
- Pancreatic beta cell destruction
- leading to absolute insulin deficiency
- Either immune mediated or idiopathic (unknown reason)
32
Define type 2 diabetes
May range from mostly insulin resistance insulin deficiency to a mostly secretory defect with insulin resistance
-insulin deficiency (impaired secretion)
- insulin resistance (impaired action)
or both
- progressive loss of beta-cell function
- Loss of first phase insulin response to glucose
33
Define gestational diabetes
- Glucose intolerance with onset or first recognition in pregnancy
- usually week 24-28 insulin resistance is high or decreased insulin sensitivity
- usually asymptomatic
34
Define pregestational diabetes
Pregnancy in pre-existing diabetes
- type 1 or type 2 diabetes
35
What is the checklist for preconception for women with pregestational diabetes?
1. Use reliable birth control method until glucose controlled (progestin-only)
2. Preconception A1C of 7.0 (stricter once pregnant)
3. Can remain on metformin and glyburide until pregnancy, otherwise switch to insulin
4. Folic acid 1mg 3 months before and 3 months after
5. D/C Ace/ARB + Statins
36
What is the PREGNANCY management of diabetes targets
A1C
Fasting
1h post-meal
2h- post meal
A1C 6.5% or under (6.1% if possible)
- lower late stillbirth and infant death)
Fasting: Under 5.3mmol/L
1h post-meal: Under 7.8 mmol/L
2h- post meal: 6.7 mmol/L
** individualize targets with severe hypoglycemia
37
What are the risk factors for gestational diabetes?
- 35+ or higher
- High risk ethnic group
- corticosteroids
- Obesity 30+ BMI
- birthed baby that weighed 4kg+, previous GDM
- direct family history of type 2 diabetes
- Polycistic ovary syndrome (PCOS) or acanthosis nigricans (darkened patches of skin)
38
What are the implications for mother and baby of GDM if not treated or controlled
Risks for mom
- pre-eclampsia (high BP)
- preterm delivery
- C-section
- Birth trauma, shoulder dystocia (unusual fetal position and small maternal pelvis)
- post-partum hemorrhage (bleed)
Risks for Baby
- congenital malformations
- macrosomia (high birth weight)
- neonatal hyperglycemia
- NICU admission
- Jaundice
39
When do you screen for gestational diabetes
24-28 weeks pregnant
or any time if there are risk factors for diabetes
40
What is the screening for GDM and what is the preferred approach with targets?
50g glucose with PG 1 hour later
- Under 7.8mmol/L: normal --> reassess 24-28
- 11.1+ mmol/L: GDM
- 7.8 - 11.0 mmol/L: 75g OGTT (measure FPG, 1hPG, 2hPG)
FPG: 5.3 and under
1hPG: 10.6+
2hPG: 9.0+
**if 1 value is met or exceeded = GDM
41
What is the alternative approach for screening for GDM and what are the targets?
75g OGTT (measure FPG, 1hPG, 2hPG)
FPG: 5.1 or under
1hPG: 10.0+
2hPG: 8.5+
**if 1 value is met or exceeded = GDM
42
When do we initiate pharmacological therapy when GDM is confirmed?
When glycemic targets are not achieved within 1-2 weeks
FPG: Under 5.3
1hPG: over 7.8
2hPG: over 6.7
43
What is first-line for GDM therapy
Second line?
3rd line?
1st line: insulin (aspart, lispro, glulisine)
2nd line: Metformin can be used as an alternative or additional to insulin (in 40%)
- less maternal weight gain
- crosses placenta
- data safe in pregnancy and offspring up to 2
3rd line: Glyburide (sulfonylurea)
- refusing insulin and metform not fully controlling
- use WITH metformin
- has higher risk of hypoglycemia
44
What is the post-partum testing for GDM? when is it tested for gestational or diagnosis earlier than 24 weeks?
75g OGTT
6 weeks to 6 months
FPG or OGTT at 6-8 weeks
45
What intervention to do if the postpartum OGTT test is
normal?
Impaired glucose tolerance?
Type 2 diabetes?
normal?
- healthy behaviours
Impaired glucose tolerance?
- healthy behaviours
- +/- metformin
Type 2 diabetes?
- healthy behaviours
- +/- metformin
- +/- insulin
46
Define MODY (mature onset diabetes of the young)
How is it managed
Genetic disorder UNDER 30
Managed with oral meds NOT insulin
47
What are the 4 general mechanisms of drug-induced hyperglycemia
1. Dec insulin production/secretion
2. Destruction of B- cell
3. Inc insulin resistance -> inc glucose output from liver
4. Dec peripheral insulin sensitivity -> dec glucose utilization in the muscle
48
What drugs can contribute to hyperglycemia? (7)
- Atypical antipsychotics (olanzapine, clozapine)
- B-blockers
- Calcium channel blockers
- Thiazide diuretics
- Cyclosporine
- Niacin (statins)
- Glucocorticoids
49
1. What is the diagnosis for impaired fasting glucose (IFG) pre-diabetes
2. What is the diagnosis for impaired glucose tolerance (IGT) pre-diabetes
3. What is the A1C diagnosis for prediabetes
1. FPG: 6.1- 6.9 mmol/L
2. 2hPG OGTT 75g: 7.8-11 mmol/L
3. A1C: 6.0-6.4
50
Define metabolic syndrome
Constellation (pattern) of abnormalities that inc CV risk and T2DM risk
- obesity
- hypertension
- dyslipidemia
- Elevated glucose
51
How often do you screen for diabetes in high risk patients or 40+ years old
Every 3 years
52
What is a normal FPG and A1C when screening a patient
FPG: below 5.6 mmol/L
A1C: below 5.5%
53
What FPG and A1C range indicate a patient at risk for diabetes
FPG: 5.6-6.0 mmol/L
A1C: 5.5- 5.9 %
*If 1 risk factor consider doing 75-OGTT
54
What FPG and A1C range indicate a patient is pre-diabetic
FPG: 6.1-6.9 mmol/L
A1C: 6.0-6.4 %
**Consider doing 75-g OGTT
55
What are the 3 sources of plasma glucose
1. Diet (carbs, protein, fat)
2. Liver via glycogenolysis (breakdown of glycogen into glucose)
3. Liver and kidney via gluconeogenesis (formation of glucose from other carbon compounds like lactate pyruvate etc)
56
What are the 2 main hormones that regulate glucose
Insulin and glucagon
57
T/F adipose tissue use glucose
True
58
Which organ is glucose the main source of energy for
brain
59
What glucose concentration impair cerebral function?
Under 3.0 mmol/L
60
What does the brain do in long periods of fasting and no glucose?
Breaks down fat and uses ketone bodies for energy
- toxic --> can lead to DKA
Brain cannot store or make glucose
61
Define the fed state. How is glucose used in this state
Fed state = postprandial or absorptive
- after meal for about 4h
- Glucose is supplied by the meal and endogenous glucose is suppressed by 80%
- insulin is released and inhibits lipolysis and gluconeogenesis
62
Define the fasting state. How is glucose used from the liver and kidneys
post-absorptive = after supper/sleeping
- food is been digested, absorbed and stored
- overnight or skipping meals
Liver: 80-85% total
50% is glycogenolysis 30% gluconeogenesis
proportion of GLUCONEOGENESIS increases with duration of fasting
Kidney: 15-20%
- 100% gluconeogenesis
63
Define starvation state. What does body rely for energy
Body is deprived of glucose for 2-3 days
Body relys on fats and protein for energy
- gluconeogenesis from amino acids and free fatty acids FFA
64
What does the brain use for energy in the starvation state
BBB blocks free fatty acids
- uses ketones for energy
- ketones are a by-product of breaking down FFA for energy
65
In overnight fasting is ketone still used in the brain for energy
Yes
66
What are the main 2 functions of the pancreas
1. Producing and secreting digestive enzyme
2. Producing and secreting hormones for glucose regulation
67
Explain how insulin is produced
B-cells in pancreas produce proinsulin --> C-peptide cleaved --> Insulin + C-peptide
68
Explain how insulin regulates glucose via direct and indirect mechanisms (4)
1. Suppresses glucose release from liver and kidney
2. Increase glucose uptake in muscle and adipose tissue
3. Inhibits release of FFA --> reduce gluconeogenesis and glucose transport into cells
4. promotes glucose storage as glycogen via inhibition of glycogenolysis
69
What levels of glucose will stimulate insulin synthesis
3.9
70
Explain how glucagon counterregulates glucose
1. Stimulates hepatic glycogenolysis to breakdown and release stored glycogen in muscle and liver tissue
2. Release of amino acids from muscle, which are used by the liver as a substrate in making glucose --> gluconeogenesis
3. Conversion of FFAs into ketone bodies in prolonged starvation
70
What are 2 other counterregulatory hormones other than glucagon.
Explain
- fast or slow acting?
Catecholamines - epinephrine and norepinephrine
- fast acting
- inc glucose via glycogenolysis, gluconeogenesis, and lipolysis
Growth hormone and cortisol
- slow acting
- inc glucose by gluconeogenesis and red of glucose transport
- cortisol impairs insulin secretion
71
Which organs are exceptions that do not use FFA as fuel (3)
- Brain
- Renal medulla
- blood cells
72
How does FFA work in our body (2)
Gluconeogenesis (stimulate glucose production in liver and kidney)
Impair glucose transport
73
What are regulators of FFA (4)
- SNS
- Growth hormone
- Insulin
- Hyperglycemia
74
How are incretin hormones made
Secreted by the gut (intestinal musoca) that stimulate insulin release from pancreas
- only released upon ORAL glucose not IV
75
What are the 2 incretin hormones. Explain them
GIP: Gastric inhibitory polypeptide
GLP-1: glucagon-like peptide 1
- inhibits glucagon secretion
- delays gastric emptying
- Promotes satiety
- deficient in T2D
76
When do symptoms start to show in type 1 diabetic?
when 70%+ of beta cells are destroyed
77
What autoimmune markers are present in type 1 diabetes (2)
GAD: anti-glutamic acid
ICA: anti-islet cell autoantibodies
insulin autoantibodies
78
What do low and high levels of C-peptide indicate? What does the test measure? When is it most useful?
Measures endogenous insulin secretion
Most useful 3-5 years after diagnosis
High = T2DM = insulin sensitivity issue
Low = T1DM = absolute insulin requirement
Normal - 0.66
79
LADA = Latent autoimmune diabetes in adults
Typical age
BMI
progression to insulin dependance
Autoantibodies?
Insulin resistance
Family history?
Typical age: 30-50
BMI: Under 25 (lean)
progression to insulin dependance: within 6 years
Autoantibodies? Yes islet antibodies
Insulin resistance? Some
Family history? Of autoimmune disease
80
If a level below the cut-off point and a level above the cut-off point is present, which test do you repeat?
Repeat the test that was above the diagnostic cutpoint
