Diabetes Mellitus Flashcards
Diagnostic criteria for DM
HbA1c >=6.5%
or
Fasting plasma glucose >=7.0 mmol/L (normal <5.6)
or
2 hour post-OGTT plasma glucose >=11.1 mmol/L (using WHO 75g anhydrous glucose load); normal <7.8
or
Presence of classical symptoms (polyuria. polydipsia, unexplained weight loss) with a random plasma glucose of >11.1 mmol/L
Cautions in diagnosing DM
Secondary causes should always be excluded e.g. Cushing’s syndrome, thyrotoxicosis
If initial glucose levels very high (>10), don’t send for OGTT!! – may induce life-threatening hyperglycaemia
OGTT should be performed 6-12 wks post partum to exclude any underlying diabetes
Pre-diabetes: Impaired glucose tolerance vs impaired fasting glycaemia
IGT
- fasting plasma glucose <7 mmol/L and 2 hr post OGTT plasma glucose 7.8-11.0 mmol/L
IFG
- fasting plasma glucose 5.6-6.9 mmol/L
Gestational DM criteria and risks
OGTT performed at 24-28 wks gestation
Normal
0 min - <5.1 (accelerated starvation as glucose goes to baby)
60 min - <10
2 hr - <8.5 (expected impaired tolerance due to pregnancy hormones)
GDM
0 min - 5.1-6.9
60 min - >=10
2 hr - 8.5-11.0
DM in pregnancy
0 min - >=7.0
2 hr - >=11.1
Adverse outcomes of GDM
- macrosomia = higher chance of requiring cesarean section (difficult labour) and risk of neonatal hypoglycaemia
Approach to suspected DM
- symptoms, positive FHx, GDM
- exclude any secondary causes of DM
- fasting plasma glucose a+/- HbA1c
- -> <5.6 – FU 1 yr if no symptoms; OGTT if highly suspicious or with symptoms
- -> 5.6-6.9 – OGTT
- -> >7.0 – diagnosis confirmed (OGTT unnecessary) – assess other CVS risk factors e.g. lipid profile and refer for complications assessment/ education
Oral glucose tolerance test patient preparation and procedure
Patient prep
- normal diet/ drugs
- avoid physical activity
- no flu or other acute illness
Procedure
- timing: 8-9 am (fasting sample)
- glucose load: 75g anhydrous into 300 ml warm water (drink within 10 min)
- venepuncture to avoid excessive stress
- blood collection immediately and 2 hrs post OGTT
Pathophysiological changes in DM
Disease of protein glycation
- glomerular BM –> loss of negative charges which normally repel albumin from GBM –> microalbuminuria –> diabetic nephropathy
- apolipoprotein of LDL particles (ApoB) –> LDL particles become “sticky” and more atherogenic; less affinity for LDL-R so less uptake/catabolism –> taken up by macrophages and increase vascular complications
Monitoring DM: HbA1c principle, limitations
- t1/2 of RBC = 60 days
- HbA1c reflects mean BG over 120 days (RBC turnover)
Limitations:
- not useful in coexisting diseases causing rapid RBC turnover e.g. pregnancy, haemochromatosis, thalassemia major
- measured by ion chromatography which is interfered by haemoglobinopathies
Other methods for monitoring DM
Other glycated proteins
- fructosamine (glycated serum protein nd albumin) –> reflect more recent glucose status (1-3 wks)
- seldom used as no large scale studies
Haemoglucostix as POCT glucometers
- poor precision at low glucose concentration as not designed to detect hypoglycaemia
- only for gross changes (need to see doctor early is 10-20 mmol)
- not for screening/ detection as not reliable
- send FLUORIDE blood to main lab for confirmation (fasting BG and HbA1c)
Monitoring DM: urine albumin excretion
Microalbuminuria to detect early nephropathic changes – requires spot urine as quantity too low to detect by urine dipsticks
Represents widespread vascular damage and predicts CVS events, deterioration in renal function and early death in type I/II DM
Measurement: early morning urine, timed (4 or 24 hrs) or random spot
- marked day-to-day variations
- 2 of 3 collections in 4-6 wks
- no UTI, fever, heavy exercise
First void spot urine ACR accepted as screening test
- recall cutoff values for ACR and AER
Monitoring DM: GFR
CrCl
- 24 hr urine sample –> inconvenient and oliguric patients may have difficulty
==> eGFR
- no need 24hr urine
- well correlated with CrCl
- takes into account [Cr]p, age, sex, ethnicity
- limitations: extreme ages, extreme BMI, amputees, pregnancy, multiple co-morbidities (unstable renal fx)
Common eGFR formulae:
- CKD-EPI or MDRD
- CKD-EPI better than MDRD at higher GFR (MDRD underestimates)
Metabolic syndrome
Pre-diabetic condition leading to
- elevated TG due to increased VLDL
- -> higher LDL
- -> lower HDL
Therapeutic targets
Glycaemic control
- HbA1c <7%
- fasting glucose 5.0-7.2
- post-prandial glucose <10
Blood pressure
- 130/80
Lipids
- LDL <1.8 (CHD equivalent risk)
- TG <1.7
- HDL >1.1 (male), >1.3 (female)
Markers of diabetic complications
Serum osmolality (2Na+urea+glucose)
- DKA
- HOC (hyperosmolar coma)
==> elevated glucose, mild/moderate hypoNa (dilutional), elevated urea due to osmotic diuresis and loss of ECF (pre-renal AKI)
Blood gases/pH
- HAGMA in DKA
- -> lower insulin:glucagon ratio = less cellular uptake of glucose and glycolysis + less inhibition of carnitine acyltransferase –> increase fatty acid oxidation into ketoacids as alternative energy source
- -> ketoacids neutralised by HCO3 which lowers [HCO3] and pH
- -> hyperventilation as resp compensation (low pCO2)
- Urine ketostix detects acetoacetate –> false negative in DKA possible since raised NADH:NAD+ increases conversion to beta-hydroxybutyrate
==> need to measure blood ketones
Vascular complications
- microvascular: retinopathy, neuropathy, nephropathy
- macrovascular: cerebrovascular diseases, PVD, IHD
DKA vs HOC/HHS (type of DM, onset, pathophysiology, symptoms, ABG, urine dipstick; common features - Na, K, treatment)
DKA
- T1DM
- acute onset
- lack of insulin = unopposed lipolysis and ketogenesis
- hyperventilation, abdominal pain, few neurological symptoms
- increased glucose and osm
- HAGMA (very low pCO2)
- urine dipstick: ketones +++
HOC/HHS (hyperosmolar hyperglycaemic state)
- T2DM
- insidious onset
- partial deficiency of insulin = able to suppress ketogenesis but not gluconeogenesis
- neurological symptoms (lethargy, focal signs –> coma)
- high glucose and osm
- normal ABG
- urine dipstick: ketone -, glucose +++
Common features:
- early hypoNa (dilution) and late hyperNa (osmotic diuresis)
- normal/hyperK (as shift from ICF to ECF in insulin deficiency, hyperosm) but actual total body K deficit due to osmotic diuresis
- treatment: underlying cause, NS rehydration, insulin + KCl, monitor glucose and K
