Diabetes Mellitus
Background
Definition
Insulin physiology
- Produced in β-cells of pancreatic islets.
- Synthesis: proinsulin has its C peptide chain cleaved to become insulin (A and B chains), which is packed into granules along with free C peptides.
- Mechanism of secretion: glucose from GI tract → activates GLUT2 receptors of β-cells → ↑ATP closes ATP-gated K+ channels to stop it flowing out → depolarisation → Ca2+ entry and insulin granule exocytosis.
- Once secreted, acts on receptors to trigger glucose uptake from blood.
Presentation
- Polydipsia and polyuria.
- Weight loss due to reduced calorie uptake. Commoner in type 1.
- Visual blurring from lens swelling.
- Genital thrush.
- Muscle cramps.
- Lethargy. In some cases of type 2, this may be the only symptom initially.
Most signs are rare at presentation, except for neuropathy:
- Neuro: peripheral neuropathy (found in 50% of type 2 at diagnosis), postural ↓BP from dysautonomia, Romberg's +ve from dorsal column disease.
- Eyes: xanthelasma, retinopathy, ophthalmoplegia from mononeuritis multiplex.
- Mouth: candida.
- Legs: ulcers, necrobiosis lipoidica.
- Lipoatrophy from insulin use.
It may also present with complications, such as DKA (type 1) or MI (type 2).
Diagnosis
- Fasting glucose ≥7 mmol/L (8 hrs fast, typically overnight).
- Random glucose ≥11.1 mmol/L.
- Oral glucose tolerance test (OGTT) ≥11.1 mmol/L: fast overnight, then measure glucose before and 2 hours after a glucose drink in the morning.
- HbA1c ≥48 mmol/mol (6.5%).
In the absence of classical symptoms, confirm diagnosis by repeating the same test (except random glucose, which requires a different test) on another day.
Management
- Upon diagnosis of type 1 diabetes, same day referral to hospital diabetes team to initiate insulin.
- Oral hypoglycaemic agents or insulin for type 2.
- Flu vaccine.
- ACEi/ARB to keep BP <130/80 if type 1 with albuminuria or metabolic syndrome, <135/85 if type 1 without those added features, or 140/90 if type 2.
- Statin if >40 years old (type 1) or >10% 10 year CVD risk (type 2).
HbA1c monitoring:
- Aim for 48 mmol/mol (6.5%).
- Check every 6 months if controlled, and every 3 months if not.
Annual review:
- CV: BP, lipids.
- Renal: U+E, urine albumin. Microalbuminuria is an early sign of diabetic nephropathy.
- Eyes: retinal photography.
- Neuropathy testing by clinical examination.
- Feet checks.
- Most of these tests don't need to start until 12 years old in type 1.
- Ask about erectile dysfunction.
Complications and prognosis
- Neuropathy: glove + stocking, tingle, numb, pain, parasthesia.
- Retinopathy (50%): diplopia, blurring.
- Nephropathy (25%).
Macrovascular (and relative risks):
- MI (RR 4), cerebrovascular events (RR 2), PVD (RR 50).
Others:
- Diabetic foot, a combination of vasculopathy and neuropathy.
- Commoner in type 1: DKA, hypoglycaemia.
- Commoner in type 2: hyperosmolar hyperglycaemic state.
Long-term prognosis for type 1 diabetes:
- Life expectancy is reduced by around 10 years, with most early death due to CVD.
Diabetic foot
Clinical features
- Neuropathy: may be sensory (painless or painful), motor, and/or autonomic.
- Peripheral vascular disease: usually presents with intermittent claudication, but may be painless due to the neuropathy.
- Ulcers: neuropathic ulceration, often in combination with arterial ulceration (neuroischaemic ulceration). Results from impaired pain perception, poor vascular supply, and increased falls and trauma due to impaired proprioception.
- Deformities: Charcot foot, toe clawing, high arched foot.
- Infection: cellulitis and osteomyelitis. Hyperglycaemia impairs WBC function, and neuropathy and ischaemia impair normal inflammatory and immune response. XR may show bone destruction and cortical thinning.
- May ultimately lead to amputation of toes or whole foot.
Neuropathic ulcer
- Punched out.
- Callus base/border.
- On plantar surface. Arterial ulcers may be on toes or malleoli.
- Signs of infected ulcer: cellulitis of margin, increased pain, smell (suggests anaerobes), fever.
Skin changes
- ↓Sensitivity but may also have painful sensations, especially if neuroischaemic.
- Dry, no sweat, warm, bounding pulses. Mainly due to autonomic neuropathy.
- In neuroischaemic ulceration, the surrounding foot may be pale, painful, pulseless, cool, and hairless.
Charcot foot (aka neuropathic joint)
- Acute swelling – red and hot – and deformity, which may include joint subluxation. May follow minor trauma, but skin is intact.
- Though painful, will often be less than expected given its appearance.
- Commonly affects the tarsals and metatarsals, including the tarsometatarsal joint and the cuneonavicular, talonavicular, and calcaneocuboid articulations.
- Reflects bone damage due to neuropathic (insensate) fractures, inflammation, and/or ↑osteoclast activity. Osteopenia may also contribute.
- Distinguished from osteomyelitis by presence of deformity, and bloods, XR, and microbiology. However, they may co-exist.
Other deformities, which result from motor neuropathy:
- Toe clawing: MPJ hyperextension and interphalangeal flexion.
- High arched foot (pes cavus).
Management
- Inspect and wash feet daily, with careful drying.
- Keep feet away from fires, hot water bottles, and very hot baths.
- Don't go barefoot indoors.
- Toenail care: important to prevent ingrown toenails, but may need to be done by podiatrist for those with poor vision or problems bending.
- Wear comfortable, spacious shoes.
Monitoring:
- Check feet at annual review, which should include neurovascular examination to determine ulcer risk.
- Stratify risk of foot problems based on presence of deformity, neuropathy, ischemia, and history of ulceration, amputation, or renal replacement therapy. If increased risk, should get 1-6 monthly checks and foot care, depending on severity.
Treatments:
- Refer to podiatry and/or diabetic foot MDT if there are new diabetic foot problems, urgently if life/limb-threatening (ulceration with sepsis or ischemia, suspected deep infection, gangrene). MDT should include diabetologist, surgeon, specialist nurse, podiatrist, and tissue viability nurse.
- Infection: antibiotics (e.g. flucloxacillin), swabbing first.
- Ulcer: debridement, wound dressings, and/or offloading (e.g. with cast).
- Painful neuropathy: TCAs are 1st line. Gabapentin or carbamazepine are 2nd line.
- Charcot foot: offloading and immobilisation with a cast for 3-6 months.
- May need prescription shoes.
See limb sensory examination for how to examine diabetic feet.
Diabetic retinopathy
Definition and epidemiology
- Retinal disease due to diabetic microvascular damage.
- Affects 30% of diabetes patients.
- Diabetes also causes ↑risk of cataracts and glaucoma.
- Visual symptoms – blurred vision, floaters, visual loss – usually absent until advanced stages.
Signs
- Microaneurysms: earliest sign. Small red dots.
- Dot and blot haemorrhages from aneurysm rupture.
- Hard exudates: lipid and protein leak from vessels.
- Cotton wool spots: retinal nerve fibre ischaemia.
- Venous beading (dilation) and loops: retinal ischaemia.
- Intraretinal microvascular abnormalities (IRMA): remodelled capillary beds.
Classification
- 'Mild' if there are only microaneurysms; 'severe' if there is 4-quadrant haemorrhage/aneurysms, ≥2-quadrant venous beading, or ≥1-quadrant IRMA; 'intermediate' for anything in between.
- Previously divided into 'background retinopathy' – microaneurysms and hard exudates only – and 'pre-proliferative retinopathy' – everything else.
Proliferative retinopathy (PDR):
- Defined by presence of neovascularisation.
- Vitreous haemorrhage. May cause symptoms such as floaters, flashes, and sudden painless loss of vision.
- Tractional retinal detachment: appears as 'tented' retina.
Macular oedema:
- Appear as blurring of retinal layers.
- Presents with gradual blurring of vision.
- Can occur in NPDR and PDR.
- Commonest cause of vision loss in diabetes.
Investigations
- Screening and diagnosis: annual retinal photography with pupillary dilation in all diabetics.
- Optical coherence tomography to assess severity in macular oedema.
- Fluorescein angiography to assess leak from fragile new vessels in PDR.
Management
- Glucose and BP control to prevent development or progression of DR.
PDR with vitreous haemorrhage or extensive neovascularisation:
- Panretinal laser photocoagulation. May also be indicated in severe NPDR.
- Vitrectomy if there is vitreous haemorrhage persisting >6 months or tractional retinal detachment.
Macular oedema:
- Intravitreal anti-VEGF drugs: aflibercept, ranibizumab, bevacizumab.
- Focal laser photocoagulation.
Perioperative diabetes management
Pre-op
- Optimise glycaemic control. Refer to diabetes specialist team if HbA1c is >69 mmol/mol (8.5%).
- Patients on twice daily insulin regimen may need to switch to MDI for 2 days to tighten control.
Surgery day
- Omit oral hypoglycaemic agents on day of surgery, except metformin and pioglitazone.
- Continue usual long acting insulins, but no short-acting.
Planning and monitoring:
- Try and schedule patients to be first on list, to minimize fasting time.
- Check capillary blood glucose (CBG) hourly, aiming for 6-10 mmol/L (but 4-12 mmol/L is acceptable). Treat as hypoglycaemia if glucose <4 mmol/L.
Variable rate insulin infusion (VRII):
- Start in the morning, and then don't stop even for bath trips, X-ray etc., since IV short-acting insulin half life is only 5 minutes.
- Make up rapid/short-acting insulin in syringe with 50 ml normal saline.
- Initial infusion rate is based on pre-op CBG e.g. 0.5 u/hr if <4 mmol/L, 1 u/hr if 4-7 mmol/L, 2 u/hr if 7-9 mmol/L etc.
- Unlike a GKI, in a VRII the insulin isn't pre-mixed in the fluid bag, thus allowing continuous control over dose. Fluid is given separately; ideally use 0.45% NaCl with 5% glucose and 0.15% or 0.3% KCl. Set to provide the usual hourly requirements i.e. around 100 ml/hr.
Surgery without VRII:
- This is acceptable in well-controlled type 2 diabetes for shorter procedures (missing only 1 meal).
- Hartmann's is the IV fluid of choice in these patients.
Post-op
- Try and start eating and usual meds as soon as possible.
- Switch to SC insulin once eating normally, overlapping 60 minutes with infusion.
- Re-start oral hypoglycaemic agents once eating normally. Only re-start metformin if eGFR >50.
Diabetes management in pregnancy
MDT approach
- Obstetrician
- Endocrinologist
- Diabetes specialist nurse or midwife.
- Dietician
Counselling
- Avoid unplanned pregnancy.
- Monthly HbA1c when trying to conceive and aim for <48 mmol/mol (6.5%). Definitely avoid pregnancy if >86 mmol/mol (10%).
- Stop any statins and ACEi/A2RB.
- If on oral hypoglycaemic agents (OHA), metformin and glibenclamide can be continued, though switching to or adding insulin is often needed, especially once pregnant. All other OHA should be stopped and replaced with insulin.
- High dose (5 mg) folic acid due to higher risk of neural tube defects.
Maternal risks:
- Increased risk of hypoglycaemia (especially) or DKA as they may be harder to identify.
- Acceleration of retinopathy and nephropathy.
- Obstetric: pre-eclampsia, VTE, miscarriage, stillbirth, preterm, C-section.
Fetal risks:
- Antenatal: macrosomia, IUGR, malformation, polyhydramnios.
- Perinatal: shoulder dystocia.
- Neonatal: hypoglycaemia, jaundice, polycythaemia, perinatal mortality. May require SCBU admission.
Management
- See diabetic team every 2 weeks.
- Monitor glucose pre-meal (aim <5.3), 1 hr post-meal (aim <7.8), and 2 hrs post-meal (aim <6.4), ideally using continuous glucose monitoring device.
- Check HbA1c at booking, which should be <48 mmol/mol (6.5%). Can also be checked in 2nd and 3rd trimester, but less reliable.
- Retinopathy checks: dilated eye exam at first antenatal visit (if not done in last 12 months) and 28 weeks.
- Renal function tests at first visit (if not done in last 12 months). eGFR not useful during pregnancy. Avoid pregnancy if creatinine > 120 μmol/L.
- Give ketone test strips to allow patient to check for blood and urine ketones if they feel unwell.
Insulin:
- Insulin requirements initially rise, drop at 8-16 weeks, then rise again
- MDI regime or insulin pump is best.
- Rapid acting insulin is safe, and NPH is preferable to glargine.
- Add metformin if can't control.
- Give partner IM glucagon.
Fetal monitoring:
- Fetal echocardiography at 20 weeks.
- Fetal growth and amniotic fluid volume at 28, 32, and 36 weeks.
Delivery:
- Offer delivery at 37 weeks, either induced vaginal or caesarean if indicated.
- Variable rate insulin infusion to maintain glucose 4-7 intra-partum; monitor hourly.
- It not delivered by 38 weeks, check CTG every 2 weeks.
Post-partum:
- Check baby for glucose <2 mmol/L within 30 minutes, then every 3 hours.
- Reduce mum's insulin infusion 50% then return to normal regime.
- Breastfeeding may lower insulin requirements by 25%.
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