T2dm

Question 1

definition of T2dm

Answer 1

increased peripheral resistance to insulin action, impaired insulin secretion and increased HGO

Question 2

what is metabolic syndrome

Answer 2

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

Question 3

Mx of metabolic syndrome

Answer 3

exercise

reduced weight

treat components

Question 4

aetiology of T2dm

Answer 4

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

Question 5

impaired glucose tolerance

Answer 5

Fasting plasma glucose <7mmol/L

and OGTT (oral glucose tolerance) 2h glucose ≥7.8mmol/L but <11.1mmol/L.

Question 6

impaired fasting glucose

Answer 6

Fasting plasma glucose ≥6.1mmol/L but <7mmol/L (WHO criteria).

Do an OGTT to exclude DM.

Question 7

impaired glucose tolerance and impaired fasting glucose relation to T2dm

Answer 7

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%.

Question 8

epidemiology of T2dm

Answer 8

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

Question 9

sx of T2dm

Answer 9

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

Question 10

signs of t2dm

Answer 10

BMI - measure weight and height (kg/m squared)

waist circumference

BP

signs of complications

dm foot

skin changes

Question 11

dm foot

Answer 11

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

Question 12

t2dm skin changes

Answer 12

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).

Question 13

Answer 13

Necrobiosis lipoidica diabeticorum

Question 14

Answer 14

granuloma annulare

Question 15

Answer 15

diabetic dermopathy

Question 16

monitoring for T2dm

Answer 16

HbA1c

UE

lipid profile

estimated GFR using MDRD calculator

spot urine albumin:creatinine ratio to detect microalbuminuria

Question 17

dx of T2dm

Answer 17

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.

Question 18

glycaemic control in t2dm

Answer 18

• 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

Question 19

less validated therapies for t2dm

Answer 19

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

Question 20

sulphonylureas

Answer 20

eg gliclazide

block ATP sensitive K+ channels in B cells = insulin release

SE - hypoglycaemia, weight gain

Question 21

metformoin

Answer 21

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

Question 22

SGLT2 inhibitors

Answer 22

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

Question 23

thiazolidinediones

Answer 23

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.)​

Question 24

glucagon-like peptide-1 agonist

Answer 24

eg exenatide

given subcut

GLP produced by L cells in gut

it increases glucose stimulated insulin secretion

reduces glucagon release, gastric emptying, appetite

Question 25

dipeptidyl peptidase IV inhibitor/gliptins

Answer 25

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

Question 26

acarbose

Answer 26

inhibits intestinal glucosidases and reduces carbohydrate digestion

less used because of side effects (bloating, flatulence).

Question 27

screening for and mx of retinopathy

Answer 27

regular digital retinal photography

ophthalmology referral and laser photo-coagulation if necessary.

Question 28

screening for and mx of nephropathy

Answer 28

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.

Question 29

screening for and mx of neuropathy

Answer 29

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

Question 30

screening for vascular disease in t2dm

Answer 30

regular examination of foot pulses

Question 31

mx of dm foot

Answer 31

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

Question 32

Mx of infected foot - dm

Answer 32

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

Question 33

Mx of charcot’s foot

Answer 33

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

Question 34

screening for and mx for CVS RF in t2dm

Answer 34

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

Question 35

advice and patient education for t2dm

Answer 35

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.

Question 36

mx of hyperosmolar hyperglycaemic state

Answer 36

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

Question 37

best diet for t2dm

Answer 37

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.

Question 38

measuring glucose control

Answer 38

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.

Question 39

controlling BP in t2dm

Answer 39

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

Question 40

complications of t2dm

Answer 40

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,

Question 41

hyperosmolar hyperglycaemic state

Answer 41

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

Question 42

dm neuropathy

Answer 42

• 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

Question 43

diabetic nephropathy

Answer 43

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

Question 44

dm retinopathy

Answer 44

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)

Question 45

pathogenesis of dm retinopathy

Answer 45

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.

Question 46

cataracts

Answer 46

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).

Question 47

rubeosis iridis in dm

Answer 47

New vessels on iris: occurs late and may lead to glaucoma.

Question 48

macrovascular disease in dm

Answer 48

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.

Question 49

foot neuropathy

Answer 49

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)

Question 50

foot ischemia

Answer 50

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)

Question 51

foot ulceration in dm

Answer 51

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

Question 52

symmetric sensory polyneuropathy

Answer 52

(‘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.

Question 53

mononeuritis multiplex

Answer 53

(eg III &VI cranial nerves).

Treatment: hard! If sudden or severe, immunosuppression may help (corticosteroids, IV immunoglobulin, ciclosporin).

Question 54

amytrophy

Answer 54

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

Question 55

autonomic neuropathy

Answer 55

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.

Question 56

prognosis of t2dm

Answer 56

therapy to reduce glycaemia = reduced microvascular complications, MI and mortality