L28 Diabetes mellitus Flashcards
According to the American Diabetic Association (ADA) diagnostic criteria, what is the normal fasting plasma glucose after fasting for > 10h?
<7.0 mmol/L
According to the American Diabetic Association (ADA) diagnostic criteria, what is the normal 2-hour post-oral glucose tolerance test (OGTT) plasma glucose?
< 11.1 mmol/L
According to the American Diabetic Association (ADA) diagnostic criteria, what is the normal HbA1c level?
<6.5%
What are the procedures for the 2-hour post-oral glucose tolerance test? (4)
Pregnancy?
When to avoid the test?
- Fast overnight
- Check the patient’s plasma glucose at 0 minute
- Ask the patient to drink 75g anhydrous glucose in 300ml of water in 10 mins
- Ask the patient to sit quietly for 120 minutes, then check plasma glucose at 120 minutes
- Pregnancy: additional measurement at 60 mins
- Avoid when initial glucose is high, may induce life-threatening hyperglycemia
What is HbA1c (hemoglobin A1c)?
- Glycated hemoglobin that persists throughout the life of RBC
- reflects the mean blood glucose level over the lifespan of RBC ~120 days
When is HbA1c not useful?
In patients with rapid RBC turnover:
- Pregnancy
- Hemochromatosis, hemolytic anemia
- Thalassaemia major
Some studies used ion-exchange chromatography for the measurement of HbA1c. What is the problem?
This method is interfered by the presence of abnormal hemoglobin (hemoglobinopathies)
(especially in Asia with mosquitoes > spreading Malaria…)
- international standardization: Terminal 6 residues for glycated beta-chain for HbA1c to be measured by LC-MS/MS method (Liquid Chromatography with tandem mass spectrometry)
For random plasma glucose >11.1, diagnosis of DM requires the presence of which classical symptoms of hyperglycemia? (3)
- Polyuria
- Polydipsia
- Unexplained weight loss
If the plasma fasting glucose is 6.3 and the plasma glucose is <7.8, the patient is diagnosed with?
Impaired fasting glucose (IFG)
plasma fasting glucose (5.6-7) (IFG)
plasma glucose <7.8 (normal)
If the plasma fasting glucose is >7 and the plasma glucose is <7.8, what is the diagnosis?
DM
OGTT fasting plasma glucose >7 is already DM (<5.6 is normal)
If the fasting plasma is <5.6 while the plasma glucose is 7.8-11.1, what is the diagnosis?
Impaired glucose tolerance (IGT)
fasting glucose is normal, but plasma glucose is abnormal
How to exclude post-partum DM?
OGTT performed at 6-12 weeks post-partum
The pregnant lady who has 5.1-6.9 fasting plasma glucose at 0min of OGTT, then presented with >10.0 at 60 mins and 8.5-11.0 at 120 minutes.
What is your diagnosis?
The patient has gestational DM.
Pregnant lady has fasting glucose >7 at 0 min of OGTT and >11.1 of plasma glucose at 120 minutes.
What is your diagnosis?
DM in pregnancy
What are the normal firgures at 0, 60 and 120 minutes for pregnant patient?
0 min: <5.1
60 min: <10
120: <8.5
If the patient is suspicious of DM due to his symptoms, positive family history, GDM etc., we first should exclude any secondary causes of DM such as Cushing’s syndrome.
What should be done next?
Take glucose level after 10 hours of fasting +/- HbA1c
if <5.6 > repeat test after 1 year, or refer the patient for OGTT if highly suspicious
if 5.6-7 > OGTT
if greater than 7: OGTT is not necessary, as may impose risk of hyperglycemia
What are the pros and cons of point-of-care POCT glucometry? (hemoglycostix) (2)
in case of doubt, send what tube for laboratory confirmation? (1) Why? (1)
Pros: useful for gross changes
Cons: Poor precision at low BG, not for hypoglycemia
- Fluoride tube (grey), kills enzymes that are involved in the Kreb’s cycle to prevent continuous consumption of blood glucose
In patients with metabolic syndrome as a pre-diabetic condition, what can be seen in the lipid profiles?
- high VLDL
- high TG
- high LDL-cholesterol
- low HDL-cholesterol
There is a cardiovascular risk if there is ApoB glycation in DM patients. Explain why. (5)
ApoB glycation
- Affinity of LDL for LDL receptors reduced
- Reduced LDL catabolism
- Increased LDL in circulation
- LDL particles become sticky and atherogenic
- Atherosclerosis
Describe how protein glycation in DM patients causes diabetic neuropathy.
Protein glycation
- Altered immunogenicity
- Altered protein structure in the glomerular basement membrane
- Loss of -ve charge of the GBM
- Microalbuminuria
Which of the following are the correct ADA therapeutic goals for DM patients with risk factors?
A. HbA1c <7% B. Pre-prandial BG: 5.0-7.2 C. Post-prandial BG: <10 D. SBP <140 E. DBP <80
D should be 130 in patients (with risk factors),
but is 140/90 in patients without risk factors
Also
TG <1.7
LDL-C <1.8
HDL-C >1.1 (M), >1.3 (F)
What is the calculated serum osmolality? (equation)
2x [Na] + urea + glucose
Serum osmolality is one of the markers of DM complications. What does it mean when there is elevated serum osmolality?
Diabetic ketoacidosis (DKA) and hyperosmolar coma/hyperosmolar hyperglycemic state (HOC/HHS)
In DKA, there is reduced insulin/glucagon ratio, less glycolysis, and increased lipolysis (increase beta-oxidation of fatty acids and thus increase ketogenesis)
What ketoacids can be formed? (2) Which can be detected by urine ketostix?
- Acetoacetic acid
- beta-hydroxybutyric acid
only acetoacetic acid can be detected by urine ketostix
Why is urine ketostix not accurate in determining the presence of DKA? What should be measured?
Ketostix only detects acetoacetic acid.
In severe DKA due to increased NADH/NAD+ ratio, acetoacetate is converted into beta-hydroxybutyrate > False-negative > therefore blood ketone measurement is better
What is the change in blood-gas as a complication of DM?
High anion-gap metabolic acidosis (HAGMA) as ketoacids are produced
> respiratory compensation: decreased pCO2 and increase O2
DM can cause both microvascular and macrovascular complications.
Give 2 examples for each.
Microvascular
- retinopathy
- neuropathy
- nephropathy
Macrovascular
- cerebrovascular diseases (e.g. stroke)
- Peripheral vascular disease
- Ischemic heart disease
List 2 precipitating factors that cause DKA and HHS (hyperosmolar hyperglycemic state).
- Stress
- infection
- inflammation
- ischemia - discontinued injection of insulin
HHS (hyperosmolar hyperglucemic state) is a medical emergency.
A. It happens more in T1DM
B. It has a more insidious (gradual) onset than DKA
C. there are more neurological symptoms such as lethargy, focal signs and even coma
D. ABG is normal
E. Glucose level is very high while there is insignificant ketones.
A is incorrect.
More in T2DM!
What is the pathogenesis of HHS?
Partial insulin deficiency in T2DM > sufficiency to inhibit ketogenesis but not glucogenesis.
In HHS, neurological symptoms like lethargy, focal signs, obtundation occur. How about in DKA?
Less neurological symptoms, but mostly hyperventilation, abdominal pain
What would be the change in plasma sodium in patients with DKA and HHS? (same) (4)
- Early hyponatremia (secondary to hyperglycemia > increase osmolality > ECF expansion)
- Late hypernatremia: ongoing osmotic diuresis, increase [Na] and osmolality
Describe the onset and pathogenesis of DKA. What ABG problems would it cause?
Onset: acute onset
Pathogenesis: Lack of insulin in T1DM, unopposed lipolysis > ketone production
High anion-gap metabolic acidosis
What would happen to plasma potassium in DKA and HHS (same)?
Normal or increase, but total K deficit due to
- Osmotic diuresis (DKA and HHS)
- Excretion of potassium ketoacid anion salts (DKA)
- Shift of K from ICF to ECH due to insulin deficiency and hyperosmolality (HHS)
What are the treatments for DKA and HHS? (4)
- Treat the underlying cause (e.g. infection)
- Rehydration by normal saline
- Insulin + KCl
- Monitor glucose and K+
Male patient, 58, previously healthy for routine health screening.
FBG: 5.6
HbA1c: 7.5%
Is he a diabetic?
any further test to suggest?
Not yet proven,results may be due to hemoglobinopathy?
FBG is normal, HbA1c is high (>6.5)
F/45, history of GDM, fasting plasma glucose = 6.9
HbA1c = 6.1%
any further test to suggest?
Both high
HbA1c under good control (<7 %)
OGTT to see real DM or not
