Diabetes Flashcards
Which type of diabetes is more common?
Type 2
What is the function of insulin?
- Stimulates GLUT4 to transport glucose
- Inhibits LPL from converting fatty acids to acetyl-CoA
What is the difference between Type 1 and Type 2 Diabetes?
Type 1:
Severe insulin deficiency secondary to destruction of beta cells of the pancreas
Type 2:
Disease of insulin resistance and relative insulin deficiency from beta cell dysfunction
What are the risk factors for diabetes?
Type 1:
1. Family history
2. Being younger at diagnosis
Type 2:
1. Having a close family member with DM2
2. High blood pressure, cholesterol
3. Being overweight
How is the heritability of DM1 compared to DM2?
Type 1
Variable heritability - if identical twin gets DM1, twin has less than 100% chance of getting DM1 but higher than general population
Type 2
1. If parent has DM2 - child has 40% lifetime risk of developing DM2
2. If identical twin has DM2 - twin has 70-80% risk of developing DM2
3. Environmental factors play a role - diet, physical activity
What is the
a) age of onset
b) onset
c) body habitus
d) insulin production
e) C-peptide
f) family history of diabetes
g) ketosis prone
in DM1 compared to DM2?
a) DM1 - childhood/young adult
DM2 - middle age/elderly, but incidence increasing in teens
b) DM1 - acute, presents with DKA
DM2 - gradual
c) DM1 - lean
DM2 - overweight
d) DM1 - absent
DM2 - present
e) DM1 - absent/low
DM2 - present/increased
f) DM1 - not common
DM2 - common
g) DM1 - usually
DM2 - usually not
What are the clinical features of acute diabetes?
- DKA
- Abdominal pain, nausea, vomiting
- Dehydration
- High glucose concentrations
- Increased ketones
- Low arterial/venous pH
What are the clinical features of insidious diabetes?
- Polyuria
- Polydipsia
- Polyphagia
Pee more, drink more, eat more
How is DM2 screened?
Screen every 3 yrs in patients who are > 40 yo or earlier/more frequently in high risk patients
How is diabetes defined?
- Fasting plasma glucose > 7 mmol/L
- HbA1c in adults > 6.5%
- OGTT > 11.1 mmol/L
- Random blood glucose > 11.1 mmol/L
If a patient has symptoms of diabetes, a single test is sufficient. If not, repeat test again on a different day.
How do we test for gestational diabetes?
50 g OGTT, if result inconclusive 75 g OGTT
Who to screen for gestational diabetes?
All pregnant women between GA 24-28 wk
What are the reference ranges for
a) Impaired fasting glucose
b) 2 hour OGTT (75g)
c) HbA1c
in “pre-diabetes”
a) 6.1-6.9 mmol/L
b) 7.8-11 mmol/L
c) 6-6.4%
What is the lab’s role in the diagnosis and management of diabetes?
Diagnosis
1. Fasting plasma glucose
2. Random glucose
3. OGTT
4. A1c
Management
1. POC glucometer
2. Albumin to creatinine ratio
3. B-hydroxybutyrate
4. Cholesterol panel
How to measure blood glucose?
- POC
- personal devices and hospital POC meters
- use capillary whole blood sample
- glucose oxidase/glucose dehydrogenase - Plasma/Serum/Whole blood
Glucose oxidase
Hexokinase
Glucose dehydrogenase
What are the disadvantages of measuring fasting plasma glucose?
- Patient has to fast for 8 hours
- Less sensitive than OGTT
- A large amount of variability exists
- Intraindividual CVs 4.6-8.3%
- Interindividual CVs 7.5-12.5%
What are the cautions when measuring glucose?
- Plasma/serum glucose is 10-15% higher than whole blood glucose due to higher water content
- Need to analyze sample promptly
- Cell metabolize glucose at 0.4 mm/L/hr
What is HbA1c?
HbA1c = glycated Hb
Formed by non-enzymatic linkage of glucose to b chain terminal Valine residue of Hb
How do you measure HbA1c?
Ion exchange chromatography
- Hb fractions are separated based on interactions w/ column, then eluted and absorbance measured at 415 nm
Electrophoresis
Hb fractions have different mobility on capillary electrophoresis
Isoelectric focusing
Separates by pI
Affinity chromatography
Glucose on HbA1c interacts with immobilized boronic acid
Immunoassay
Ab detected against glycated valine
How does A1c relate to average blood glucose concentration?
A1c of 6.7% corresponds to average blood glucose of 9 mmol/L
Each 1% change = average blood glucose change of 2 mmol/L
What is the cons of measuring A1c?
- Assumes a normal RBC lifespan
- Cannot be used in patients who has undergone a transfusion
- Sickle cell anemia
- Enlarged spleen
What are other tests that can be used for diabetes?
GAD65 - glutamic acid decarboxylase 65
- An autoimmune marker than can be present in DM1
- If there is a confusion between DM1 and DM2, GAD65 can point to DM1
- Levels can decrease over time
C peptide
- Can be absent/low in DM1 from little to no insulin production
- But not that useful
What is a test used for hypoglycemia?
Insulin
- NOT useful in the diagnosis of diabetes
- Used in the investigation of hypoglycemia
- When measuring insulin, need to know what forms of insulin the IA detects
What test is useful in the investigation of insulin resistance?
Insulin autoAb
- Forms in patients exposed to exogenous insulin
What hormones can raise blood glucose?
Glucagon, cortisol, epinephrine
What are ways to manage diabetes?
- Diabetes education
- Diet
- Exercise
- Medications for blood glucose
- Medications for other related conditions
What are the classes of oral antihyperglycemics?
- Metformin
- Sulfonylureas
- Incretins
- Acarbose
- SGLT2 Inhibitors
What is the mainstay of treatment for DM1?
Insulin
What is the A1c lowering of insulin? What are the side effects of insulin?
0.9-1.2% +
Weight gain
What are the complications of chronic diabetes?
- Microvascular - retinopathy, neuropathy
- Macrovascular - stroke, heart attack
- Non-vascular - increased infections
What is the metabolic syndrome?
Often, diabetes is found along with other conditions in the same patient = metabolic syndrome
Puts patients at high risk of CV disease
What are the clinical features of the metabolic syndrome?
- Increased weight circumference
- Increased triglycerides
- Decreased HDL
- Hypertension
- Fasting plasma glucose > 5.6 mmol/L
How to maintain the ACR?
Aim to keep it less than 2 mg/mmol
Treat with ACE inhibitors (Ramipril)
What is the leading cause of mortality in diabetics?
Heart disease
What is the relationship between A1c and CV events?
Reduction in A1c in DM1 leads to 42% decrease in CV events
What are the acute complications of diabetes?
- Hypoglycaemia
- Patients need to carry glucose tablets with them in case of hypoglycemic episodes
What are the complications of severe hyperglycemia?
Diabetic ketoacidosis
Hyperglycemic Hyperosmolar State
When is DKA and HHS observed? What is the difference between the two?
DKA - DM1
HHS - DM2
DKA - ketosis and acidosis
HHS - NO ketosis and acidosis
What is the pathophysiology of DKA and HHS?
DKA
1. Completely lack of insulin
2. Cells enter state of starvation
3. Glycogenolysis, gluconeogenesis upregulated, increasing glucose concentrations
4. Leads to osmotic diuresis
5. Lack of insulin also stimulates LPL = ketosis
HHS
1. Insulin deficient
2. Cells enter state of starvation
3. Glycogenolysis, gluconeogenesis, increasing glucose conc
4. Leads to osmotic diuresis
5. Still insulin present so no/very little LPL activity = no ketosis
What are two similarities and two differences in the lab values of DKA and HHS?
Similarities
1. High glucose
2. High serum osmolality
3. Acute kidney injury
4. Low K
Differences
1. DKA has low arterial/venous pH, HHS has normal arterial/venous pH
2. DKA has low bicarbonate, HHS has normal bicarbonate
3. DKA has presence of ketone (beta-hydroxybutyrate), HHS has none
Treatment for DKA and HHS?
- Fluids for dehydration
- K and other electrolytes that were lost from osmotic diuresis
- Insulin to stop ketosis and acidosis
What ketones are produced in ketosis? Which ketone is the one measured?
- Acetone
- Acetoacetate
- Beta-hydroxybutyrate
Beta-hydroxybutyrate is the one measured. It reacts with NAD to form NADH. NADH reacts with a dye to produce NAD and a reduced dye.
How is osmolality measured? Is it increased/normal/decreased in DKA and HHS?
Osmometer, freezing pt depression
Increased in DKA and HHS secondary to elevated glucose
