T2dm Flashcards
definition of T2dm
increased peripheral resistance to insulin action, impaired insulin secretion and increased HGO
what is metabolic syndrome
central obesity (BMI >30, or increased waist circ, ethnic-specific values),
plus two of:
- BP ≥130/85,
- triglycerides ≥1.7mmol/L,
- HDL ≤ 1.03 male/1.29 female mmol/L,
- fasting glucose ≥5.6mmol/L
- type 2 DM.
~20% are affected;
weight, genetics, and insulin resistance important in aetiology.
Vascular events—but probably not beyond the combined effect of individual risk factors
Mx of metabolic syndrome
exercise
reduced weight
treat components
aetiology of T2dm
reduced insulin secretion and increased resistance
genetic and environmental components
genetic
- monozygotic twins - 90% concordance rate
- life time risk for 1st degree relative - 5-10x higher than those w/o FH of dm
- monogenic causes are a very small fraction
- Several inherited polymorphisms (e.g. in the gene for the transcription factor 7-like 2) may contribut
obesity
- high plasma free fatty acid levels and adipocytokines secreted by adipocytes (leptin, adiponectin, TNF-a, resistin) contribute to peripheral insulin resistance
- chronic hyperglycaemia have toxic effect on B cells - glucotoxicity
- high FFA levels worsen pancreatic B cell function - lipotoxicity
impaired glucose tolerance
Fasting plasma glucose <7mmol/L
and OGTT (oral glucose tolerance) 2h glucose ≥7.8mmol/L but <11.1mmol/L.
impaired fasting glucose
Fasting plasma glucose ≥6.1mmol/L but <7mmol/L (WHO criteria).
Do an OGTT to exclude DM.
impaired glucose tolerance and impaired fasting glucose relation to T2dm
Typically progresses from a preliminary phase of IGT or IFG - unique window for lifestyle intervention
denote different abnormalities of glucose regulation (post-prandial and fasting).
There may be lower risk of progression to DM in IFG than IGT.
Manage both with lifestyle advice + annual review.
Incidence of DM if IFG and HbA1C at high end of normal (37–46mmol/mol) is ~25%.
epidemiology of T2dm
Prevalence in the UK: 5–10%.
People of Asian, African and Hispanic descent
male
The incidence has increased over the last 20 years - increasing prevalence of obesity worldwide, better diagnosis and improved longevity
most >40yrs - teenagers now getting it
sx of T2dm
may be incidental finding
polyuria, polydipsia, tiredness
hyperosmolar hyperglycaemic state(also known as hyperosmolar non-ketotic state)
infections - foot ulcers, candidiasis, balanitis or priritis valvae
assess for other CVS risk factors - HTN, hyperlipidaemia, smoking
signs of t2dm
BMI - measure weight and height (kg/m squared)
waist circumference
BP
signs of complications
dm foot
skin changes
dm foot
ischemic and neuropathic signs
dry skin
reduced subcut tissue
corns
calluses
ulceration
gangrene
Charcot’s arthropathy and signs of peripheral neuropathy, foot pulses are reduced in ischaemic foot
t2dm skin changes
Necrobiosis lipoidica diabeticorum (well-demarcated plaques on the shins or arms with shiny atrophic surface and red–brown edges)
granuloma annulare (flesh-coloured papules coalescing in rings on the back of hands and fingers)
diabetic dermopathy (depressed pigmented scars on shins).
Necrobiosis lipoidica diabeticorum
granuloma annulare
diabetic dermopathy
monitoring for T2dm
HbA1c
UE
lipid profile
estimated GFR using MDRD calculator
spot urine albumin:creatinine ratio to detect microalbuminuria
dx of T2dm
dm is diagnosed if 1/more of follwoing are present:
- Symptoms of diabetes and a random plasma glucose >=11.1mmol/L.
- Fasting plasma glucose >=7.0 mmol/L (after an overnight fast of at least 8 h).
- 2hr plasma glucose >=11.1mmol/L after a 75g oral glucose tolerance test
- HbA1c ≥48mmol/mol. Avoid in pregnancy, children, type 1DM, and haemoglobinopathies
In the absence of unequivocal hyperglycaemia and acute metabolic decompensation, these criteria should be confirmed by repeat testing on another day.
glycaemic control in t2dm
- at diagnosis - lifestyle and metformin
- if HbA1c >=7% after 3mo: lifestyle and metformin and sulphonylurea
- if >=7% after 3mo: lifestyle, metformin and basal insulin
- if >=7% after 3mo and fasting glucose <7mmol/l: add premeal rapid acting insulin
sulphonylurea may bemonotherapy if cant tolerate metformin
If sulphonylureas are CI pioglitazone may be given instead (with metformin).
Pioglitazone can be given with metformin and sulphonylurea.
monitor control of sx, capillary blood glucose, HbA1c every 3mo
less validated therapies for t2dm
When hypoglycaemia is particularly undesirable (hazardous jobs): Add pioglitazone or exenatide to metformin instead of sulphonylureas.
If weight loss is a major consideration & HbA1C<8% use SC exenatide
sulphonylureas
eg gliclazide
block ATP sensitive K+ channels in B cells = insulin release
SE - hypoglycaemia, weight gain
metformoin
biguanide
increases insulin sensitivity
helps weight
inhibits hepatic glucneogenesis
SE - GI disturbance (nausea, diarrhoea), abdo pain, rarely lactic acidosis so stop in unwell/septic/eGFR <36mL/min
SGLT2 inhibitors
Selective sodium–glucose co-transporter-2 inhibitor.
Blocks the reabsorption of glucose in the kidneys and promotes excretion of excess glucose in the urine
eg empagliflozin, shown to reduce mortality from cardiovascular disease in patients with type 2DM
thiazolidinediones
eg pioglitazone
activates PPAR y and reduces peripheral insulin resistence
SE: hypoglycaemia, fractures, fluid retention, high LFT (do LFT every 8wks for 1yr, stop if ALT up >3-fold).
CI: past or present CCF; osteoporosis; monitor weight, and stop if increases or oedema.
(Note: rosiglitazone, another thiazolidinedione, is not recommended as associated with increased risk of myocardial infarction and incidence of fractures.)
glucagon-like peptide-1 agonist
eg exenatide
given subcut
GLP produced by L cells in gut
it increases glucose stimulated insulin secretion
reduces glucagon release, gastric emptying, appetite
dipeptidyl peptidase IV inhibitor/gliptins
eg sitagliptin
dipeptidyl peptidase 4 is the enzyme that degrades GLP-1
used in pts who have CI or intolerance for metformin, sulfonylureas or pioglitazone eg with CKD
acarbose
inhibits intestinal glucosidases and reduces carbohydrate digestion
less used because of side effects (bloating, flatulence).
screening for and mx of retinopathy
regular digital retinal photography
ophthalmology referral and laser photo-coagulation if necessary.
screening for and mx of nephropathy
monitor UEs and estimated GFR using MDRD calculator
spot urine analysis (albumin:creatinine ratio)
mx
- BP control
- ACEi/ARB - protects the kidneys
- monitor K+
- Spironolactone may also help.
screening for and mx of neuropathy
regular examination and inspection of the feet for ulcers
10g monofilament testing
join vibration
mx
- foot hygiene
- amitriptyline
- duloxetine
- gabapentin or capsaicin cream for painful neuropathy
screening for vascular disease in t2dm
regular examination of foot pulses
mx of dm foot
educate to examine foot properly
amputation common but avoidable
diabetic footwear
podietry assessment
Distinguish between ischaemia (critical toes ± absent foot pulses and worse outcome) and peripheral neuropathy (injury or infection over pressure points, eg the metatarsal heads).
regular chiropody
bed rest
degree of peripheral vascular disease, general health, and patient request will determine degree of vascular reconstruction/surgery.
absolute indications for surgery:
- Abscess or deep infection; spreading anaerobic infection; gangrene/rest pain; suppurative arthritis.
IV insulin might help recovery
Mx of infected foot - dm
cellulitis common organisms - staphs, streps, anaerobes
clean and dress regularly
swab for culture and sensitivity
IV AB eg flucloxacillin, co-amoxiclav, cephalosporin and metronidazole
look for osteomyelitis on XR
surgical debridement or amputation if necessary
Mx of charcot’s foot
bed rest/crutches/total contact cast until oedema and local warmth reduce and bony repair is complete (>8wks).
Bisphosphonates may help.
Charcot joints are also seen in tabes dorsalis, spina bifida, syringomyelia, and leprosy.
Metatarsal head surgery may be needed
screening for and mx for CVS RF in t2dm
lose weight, healthy eating (low sat fat, sugar, high starch-carb, moderate protein)
exercise (to increase insulin sensitivity)
stop smoking
BP control
assess global vascular risk
all dm patients should be started on statin (CARDS trial)
aspirin in pts with dm and an additional CVS RF
advice and patient education for t2dm
INFORM PT
- I - information - diabetic nurses, leaflets, websites, etc. explaining diabetes control, complications.
- N - nutrition - Optimizing meal plans, diet (complex carbohydrates not simple sugars, reduce fat).
- F - foot care - regular inspection, appropriate footwear, roll of chiropodist
- O - organisations - local and national support groups
- R - recognition and treatment of hypoglycaemia
- M - monitoring CBG and charting it, monitoring ketones during intercurrent illness
- P - pregnancy - strict glycaemic control and planned conception
- T - treatment - action, duration, administration technique for insulin change the site of injection (to avoid lipohypertrophy), explain need to plan exercise.
mx of hyperosmolar hyperglycaemic state
management similar to diabetic ketoacidosis
except use 0.45 % saline if serum Na+>170mmol/L, and a lower rate of insulin infusion (1–3 U/h).
keep blood glucose at 10-15mmol/L for 1st 24hrs to prevent cerebral oedema
replace K when urine starts
DVT prophylaxis with SC heparin
best diet for t2dm
dietary carbohydrate big determinant of postprandial glucose levels,
low-carbohydrate diets improve glycaemic control.
LCKD (low carb ketogenic diets) had greater improvements in HbA1c (-15 vs -5mmol/L), weight (-11kg vs -7kg), and HDL than low glycaemic index reduced calorie diet.
measuring glucose control
Fingerprick glucose if on insulin (type 1/2). NB: before a meal informs about long-acting insulin doses; after meals inform about the dose of short-acting insulin.
Glycated haemoglobin (HbA1c) relates to mean glucose level over previous 8wks (RBC t½).
target depends on pts wish, arterial risk eg past MI/stroke
If at risk from the effects of hypoglycaemia, eg elderly patients prone to falls = less tight control.
Be sure to ask about hypoglycaemic attacks (and whether symptomatic). Hypoglycaemic awareness may diminish if control is too tight, or with time in type 1DM, due to low glucagon secretion. It may return if control is loosened.
controlling BP in t2dm
Target BP<140/80mmHg or <130/80mmHg if kidney, eye, or cerebrovascular damage.
1st-line - ACE-i,
except African or Caribbean origin - ACE-i plus diuretic or a calcium-channel antagonist (CCA)
pregnant - CCA
complications of t2dm
assess vascular risk - BP control crucial for preventing macrovascular disease and reducing mortality - check plasma lipids
hyperosomolar hyperglycaemic state
neuropathy, nephropathy, retinopathy
macrovascular complications
foot neuropathy, ischemia, ulceration,
hyperosmolar hyperglycaemic state
due to insulin deficiency, as diabetic ketoacidosis, but patient is usually old and may be presenting for the first time
history is longer eg 1wk
marked dehydration
high Na
high glucose (>35mmol/L)
high osmolarity (>340 mosmol/Kg)
no acidosis
dm neuropathy
- distal symmetrical sensory neuropathy
- painful neuropathy
- carpel tunnel syndrome
- diabetic amyotrophy (asymmetrical wasting of proximal muscle)
- mononeuritis (eg CN3 palsy with preservation of pupillary response, CN6)
- autonomic neuropathy - eg postural hypotension
- gastroparesis - abdo pain, nausea, vom
- impotence
- urinary retention
diabetic nephropathy
microalbuminuria when urine dipstick is -ve for protein but the urine albumin:creatinine ratio (UA:CR) is >3mg/mmol (units vary, check lab) reflecting early renal disease and increased vascular risk.
proteinuria
eventually renal failure
prone to UTI and renal papillary necrosis
if UA:CR >3 inhibiting RAS with ACEi or sartan protects kidneys
spirinolactone may help
refer if UA:CR >7 +- GFR falling
dm retinopathy
blindness is preventable - annual retinal screening
background - dot and blot haemorrhages, hard exudates (lipid deposits) - Refer if near the macula, eg for intravitreal triamcinolone.
pre-proliferative - cotton wool spots (ie infarcts), venous bleeding, haemorrhage - signs of retinal ischemia
proliferative - new vessels on the disc and elsewhere
maculopathy - macular oedema, exudates and haemorrhages within 1 disc diameter of the centre of the fovea with reduced visual acuity
prone to glaucoma, cataracts, transient visual loss (sudden osmotic changes)
pathogenesis of dm retinopathy
capillary endothelial change = vascular leak = microaneurysms = capillary occlusion - local hypoxia + ischemia = new vessel formation
High retinal blood flow caused by hyperglycaemia (and high BP and pregnancy) triggers this = capillary pericyte damage.
Microvascular occlusion = cotton-wool spots (± blot haemorrhages at interfaces with perfused retina
New vessels form on the disc or ischaemic areas, proliferate, bleed, fibrose, and can detach the retina.
Aspirin2 (2mg/kg/d) may be recommended by ophthalmologists - no evidence that it increases bleeding.
cataracts
May be juvenile ‘snowflake’ form,
or ‘senile’—which occur earlier in diabetic subjects.
Osmotic changes in the lens induced in acute hyperglycaemia reverse with normoglycaemia (so wait before buying glasses).
rubeosis iridis in dm
New vessels on iris: occurs late and may lead to glaucoma.
macrovascular disease in dm
ischemic heart disease - MI is 4-fold commoner in DM and is more likely to be ‘silent’.
stroke - twice as common in dm
PVD
Women are at high risk— DM removes the vascular advantage conferred by the female sex.
foot neuropathy
in ‘stocking’ distribution:
test sensation with 10g monofilament fibre (sensory loss is patchy so examine all areas),
absent ankle jerks,
neuropathic deformity (Charcot joint): pes cavus, claw toes, loss of transverse arch, rocker-bottom sole.
- loss of pain sensation = increased mechanical stress and repeated joint injury
swelling, instability and deformity
Early recognition is vital (cellulitis or osteomyelitis are often misdiagnosed)
foot ischemia
if cant feel foot pulses - doppler
neuropathy/vascular disease increases risk of ulceration
educate (daily foot inspection—eg with a mirror for the sole; comfortable shoes).
Regular chiropody to remove callus, as haemorrhage and tissue necrosis may occur below, leading to ulceration.
Treat fungal infections
Surgery (including endovascular angioplasty balloons, stents, and subintimal recanalization)
foot ulceration in dm
painless, punched out ulcer
area of thick callus +- superadded infection
causes cellulitus, abscess +- osteomyelitis
assess degree of:
- neuropathy
- ischemia - clinically, doppler +- angiography
- bony deformity eg Charcot - clinically and XR
- infection - swab, blood culture, XR for osteomyelitis, probe ulcer to reveal depth
symmetric sensory polyneuropathy
(‘glove & stocking’ numbness, tingling, and pain, eg worse at night).
paracetamol -> tricyclic (amitriptyline 10–25mg nocte; gradually increase to 150mg) -> duloxetine, gabapentin, or pregabalin -> opiates.
Avoiding weight-bearing helps.
mononeuritis multiplex
(eg III &VI cranial nerves).
Treatment: hard! If sudden or severe, immunosuppression may help (corticosteroids, IV immunoglobulin, ciclosporin).
amytrophy
Painful wasting of quadriceps and other pelvifemoral muscles.
Use electrophysiology to show, eg lumbosacral radiculopathy, plexopathy, or proximal crural neuropathy.
Natural course: variable with gradual but often incomplete improvement.
IV immunoglobulins
autonomic neuropathy
postural BP drop - may respond to fludrocortisone (SE: oedema, high BP)/midodrine (a-agonist; SE: increase BP).
reduced cerebrovascular autoregulation
loss of resp sinus arrhythmia - vagal neuropathy
gastroparesis
urine retention
erectile dysfunction
gustatory sweating
diarrhoea - may respond to codeine phosphate
gastroparesis
- (early satiety, post-prandial bloating, nausea/vomiting) is diagnosed by gastric scintigraphy with a 99technetium-labelled meal;
- anti-emetics, erythromycin, or gastric pacing.
prognosis of t2dm
therapy to reduce glycaemia = reduced microvascular complications, MI and mortality
