Medicine chapters
Complications of diabetes (screening, referral, management) and diabetes in pregnancy
The eye, kidney, nerve, foot and vascular complications of diabetes with how to screen for them and when to refer, followed by pre-existing and gestational diabetes in pregnancy.
- Screen every year: retinal photographs, urine albumin:creatinine ratio and eGFR, foot check with a 10 g monofilament, BP and lipids; refer proliferative retinopathy urgently.
- ACE inhibitors or ARBs (plus SGLT2 inhibitors) slow diabetic nephropathy; tight glucose and BP control prevent most microvascular damage.
- In pregnancy aim for HbA1c below 48 mmol/mol before conception, give folic acid 5 mg, keep fasting glucose below 5.3 mmol/L; screen at-risk women for gestational diabetes with a 75 g OGTT at 24–28 weeks.
On this page
Overview
Long-standing high glucose damages small vessels (eyes, kidneys, nerves) and speeds up atherosclerosis in large vessels. Most of this damage is silent until late, so diabetes care is built around regular screening, early referral and control of glucose, blood pressure, lipids and smoking. Pregnancy turns diabetes into a high-risk state for mother and baby and needs tight control from before conception.
Why complications happen (brief)
- Basement membrane thickening of capillaries and arterioles is the hallmark; vessels narrow and close, causing ischaemia.
- Excess glucose forms advanced glycation end-products (HbA1c is one example), drives the sorbitol (polyol) pathway, activates protein kinase C and growth factors such as VEGF.
- Risk rises with duration and degree of hyperglycaemia, high BP, smoking and genetic factors.
- Microvascular disease is rare in the first years of type 1 diabetes, but is often already present at diagnosis of type 2 because of years of hidden hyperglycaemia.
Screening schedule (at diagnosis of type 2, and at least yearly)
| Check | How | Looks for |
|---|---|---|
| Eyes | Retinal photography through dilated pupils | Retinopathy, maculopathy, cataract |
| Kidneys | Urine albumin:creatinine ratio (ACR) on an early-morning sample; eGFR | Nephropathy |
| Feet | 10 g monofilament, vibration, pulses, skin, deformity | Neuropathy, ischaemia, ulcer risk |
| Heart and vessels | BP, lipids, smoking, weight | Cardiovascular risk |
| Control | HbA1c (every 3–6 months) | Glycaemic control |
For early nephropathy, the routine annual test is the urine albumin:creatinine ratio, not a dipstick or 24-hour protein. Dipsticks miss small amounts of albumin.
Diabetic retinopathy
The commonest complication and a leading cause of blindness in working-age adults. Almost all type 1 patients have some changes after 20 years.
Grading and action
| Grade | Findings | Action |
|---|---|---|
| Background (non-proliferative, R1) | Microaneurysms (dots, the earliest sign), blot haemorrhages, hard exudates (yellow, glossy, sharp edges), occasional cotton wool spots (soft, grey, fluffy micro-infarcts) | Annual screening; improve control |
| Pre-proliferative (R2) | Venous beading and loops, IRMA (intraretinal microvascular abnormalities), multiple deep haemorrhages | Non-urgent referral to ophthalmologist |
| Proliferative (R3) | New vessels on the disc or elsewhere; pre-retinal or vitreous haemorrhage | Urgent referral |
| Advanced | Fibrosis, traction retinal detachment, rubeotic glaucoma | Urgent referral; vision often already lost |
| Maculopathy (M1) | Exudates or haemorrhages close to the macula (within a disc-width), or macular oedema | Prompt referral |
- Ischaemia → VEGF → new vessels. Fragile new vessels bleed into the vitreous, causing sudden painless loss of vision with a dull red reflex.
- Macular oedema is invisible to the ophthalmoscope; it is shown by optical coherence tomography (OCT). Maculopathy is the commonest cause of visual loss in type 2 diabetes.
- New vessels on the iris (rubeosis) cause rapidly rising eye pressure.
Management
- Prevention: tight glucose and BP control; stop smoking; fenofibrate slows progression.
- Intravitreal anti-VEGF injections (e.g. ranibizumab, aflibercept, bevacizumab) for maculopathy and proliferative disease.
- Panretinal laser photocoagulation for proliferative retinopathy: burning the ischaemic peripheral retina removes the stimulus for new vessels. Cost: reduced peripheral field and night vision.
- Vitrectomy for non-clearing vitreous haemorrhage or traction detachment.
Retinopathy can worsen temporarily after a rapid improvement in glucose control and during pregnancy. This is not a reason to avoid good control, but such patients need closer eye checks.
Other eye problems
- Cataract occurs earlier; a rapid "snowflake" cataract can appear with very poor control.
- Fluctuating glucose changes the lens and blurs vision temporarily.
- Cranial nerve palsies (third, sixth): see neuropathy.
Diabetic nephropathy (diabetic kidney disease)
Course
- Glomerular hyperfiltration.
- Microalbuminuria (moderately increased albuminuria): detectable only by ACR.
- Persistent proteinuria (dipstick-positive), sometimes nephrotic in range.
- Falling eGFR → end-stage kidney disease, often over 5–10 years once proteinuria is established.
- Histology: basement membrane thickening, mesangial expansion, diffuse and nodular glomerulosclerosis (Kimmelstiel–Wilson nodules), hyaline arteriolosclerosis.
- Kidneys are normal or large on ultrasound even when eGFR is low.
- Up to half of type 2 patients lose eGFR without much albuminuria.
- Associated: hypertension, anaemia (low erythropoietin), type 4 renal tubular acidosis (hyperkalaemia with normal anion gap acidosis), papillary necrosis, urinary infection.
Screening
- ACR on a first-morning sample every year. Upper normal: about 2.5 mg/mmol in men and 3.5 mg/mmol in women.
- A raised ACR must be confirmed on repeat samples because false positives are common (exercise, infection, menstruation, fever, heart failure).
Management
- ACE inhibitor or ARB, even if BP is normal, once albuminuria is confirmed.
- BP target below 130/80 mmHg.
- SGLT2 inhibitor to slow decline; good glucose control; statin; stop smoking.
- Adjust renally cleared drugs: stop or reduce metformin and avoid long-acting glibenclamide.
- Refer to a nephrologist when eGFR is falling quickly, ACR is very high, there is haematuria or a non-diabetic cause is suspected, or for planning dialysis or transplant.
Think of another kidney disease if proteinuria appears without retinopathy, early in type 1 diabetes, with active urine sediment (red cell casts), or with a very rapid fall in eGFR.
Diabetic neuropathy
| Type | Features | Key points |
|---|---|---|
| Symmetrical distal sensory polyneuropathy | Commonest. Glove and stocking loss; vibration lost early; absent ankle jerks; "walking on cotton wool"; unsteady in the dark | Main cause of foot ulcers and Charcot joints |
| Acute painful neuropathy | Burning feet and shins, worse at night, contact pain from bedclothes; often after rapid glucose change or weight loss | Treat with duloxetine, amitriptyline, gabapentin or pregabalin; capsaicin cream; improves over months |
| Mononeuropathy / mononeuritis multiplex | Sudden, often painful. Third nerve palsy with pupil spared, sixth nerve palsy; carpal tunnel and other pressure palsies | Usually recover in 3–6 months |
| Diabetic amyotrophy (lumbosacral radiculoplexus) | Older men; painful asymmetrical wasting of the quadriceps, lost knee jerk, weight loss | Recovers slowly with good control |
| Autonomic neuropathy | Postural hypotension, resting tachycardia with fixed heart rate, painless MI, gastroparesis, nocturnal diarrhoea, bladder retention, erectile dysfunction, retrograde ejaculation, gustatory sweating, loss of hypoglycaemia awareness | Bedside tests: postural BP drop, loss of heart rate variation with deep breathing and Valsalva |
In diabetic third nerve palsy, the pupil is usually spared because the central nerve fibres are infarcted while the outer pupillary fibres survive. A dilated pupil suggests compression (e.g. posterior communicating artery aneurysm): image urgently.
- Gastroparesis: small frequent meals, metoclopramide or erythromycin; pyloric botulinum toxin or gastric stimulator in severe cases.
- Erectile dysfunction: check testosterone, prolactin and thyroid; first-line PDE-5 inhibitors (e.g. sildenafil) unless the patient takes nitrates; then alprostadil.
The diabetic foot
Neuropathy, ischaemia and infection combine to cause ulcers, and diabetes is the leading cause of non-traumatic lower limb amputation.
| Feature | Neuropathic foot | Ischaemic foot |
|---|---|---|
| Temperature | Warm | Cold |
| Pulses | Present, often bounding | Absent or weak |
| Skin | Dry, cracked, callus | Thin, shiny, hairless |
| Ulcer site | Pressure points: sole, metatarsal heads | Toe tips, heel, foot edges |
| Pain | Painless | Painful (rest pain) unless neuropathy too |
Risk assessment and prevention
- Annual check: 10 g monofilament, vibration (128 Hz tuning fork), pulses, deformity, callus, footwear, previous ulcer.
- Low, moderate and high-risk groups decide how often a podiatrist sees the patient.
- Education: daily inspection, proper shoes, never walk barefoot, no hot-water bottles.
Management of an active foot problem
- Refer urgently to the multidisciplinary foot team: any ulcer, spreading infection, gangrene or suspected Charcot foot.
- Off-loading (total contact cast or special boot), debridement, dressings.
- Infection: antibiotics guided by deep tissue cultures; X-ray or MRI for osteomyelitis (probe-to-bone).
- Ischaemia: Doppler/ABPI (may be falsely high because of calcified arteries; use toe pressures), angiography, revascularisation.
- Amputation for uncontrolled infection or non-viable tissue.
Charcot neuroarthropathy
- A warm, red, swollen, often painless foot in a patient with dense neuropathy and good pulses; may follow minor trauma.
- Bone and joints of the midfoot fragment and collapse ("rocker-bottom" deformity).
- Easily mistaken for cellulitis, gout or DVT; if unsure, treat as Charcot as well.
- Treatment: immobilise in a non-weight-bearing cast until the warmth settles (often months); bisphosphonates have been used; later special footwear.
Charcot = hot, swollen, painless and pulses present. Cellulitis is usually tender and the patient feels it.
Macrovascular disease
- Coronary disease, stroke and peripheral arterial disease are the main causes of death in diabetes.
- MI may be painless (autonomic neuropathy).
- Manage risk: statin for most adults with diabetes, BP control, aspirin only for established cardiovascular disease, stop smoking, SGLT2 inhibitor or GLP-1 agonist where there is vascular disease.
Other complications
- Infections: candidiasis, UTI, emphysematous pyelonephritis and cholecystitis, malignant otitis externa (Pseudomonas), mucormycosis, TB, Fournier gangrene.
- Skin: necrobiosis lipoidica (yellowish shiny plaques on the shins), diabetic dermopathy (shin spots), acanthosis nigricans (insulin resistance), granuloma annulare.
- Musculoskeletal: frozen shoulder, cheiroarthropathy (limited joint mobility), Dupuytren contracture.
Diabetes in pregnancy
About 85% of diabetes in pregnancy is gestational; the rest is pre-existing type 1 or type 2.
Risks
Mother: miscarriage, pre-eclampsia, preterm labour, infections, worsening retinopathy and nephropathy, hypoglycaemia (early pregnancy), DKA (more dangerous for the fetus).
Fetus and newborn:
- Congenital anomalies (pre-existing diabetes, linked to high glucose around conception): cardiac defects (commonest), neural tube defects, and caudal regression syndrome (most specific to diabetes).
- Macrosomia, shoulder dystocia, birth injury, polyhydramnios (fetal polyuria), stillbirth.
- After birth: neonatal hypoglycaemia (commonest problem), respiratory distress syndrome (insulin delays surfactant), jaundice, polycythaemia, hypocalcaemia, renal vein thrombosis.
- Long-term: obesity and diabetes in the child.
Pedersen idea: glucose passes from mother to fetus, whereas maternal insulin cannot cross. The fetus makes extra insulin → grows big (insulin acts as a growth factor) → after the cord is cut, the high insulin causes neonatal hypoglycaemia.
Pre-existing diabetes: before conception
- Plan pregnancy; use contraception until control is good.
- Aim for HbA1c below 48 mmol/mol (6.5%) if safely possible; advise against pregnancy if HbA1c is above 86 mmol/mol (10%).
- Folic acid 5 mg daily (high dose) from before conception to 12 weeks.
- Stop ACE inhibitors, ARBs and statins; stop oral agents except metformin; stop GLP-1 agonists.
- Check retinae and kidney function; check rubella immunity.
Pre-existing diabetes: during pregnancy
- Targets: fasting below 5.3 mmol/L, 1 hour after meals below 7.8 mmol/L, or 2 hours after meals below 6.4 mmol/L.
- Insulin needs fall in the first trimester (hypoglycaemia risk, with reduced awareness) and rise by 50–100% in later pregnancy because of placental anti-insulin hormones.
- CGM is preferred in type 1 diabetes where available.
- Teach blood ketone testing; DKA carries a high fetal loss rate.
- Low-dose aspirin 150 mg from 12 weeks to reduce pre-eclampsia.
- Retinal screening in each trimester as needed (at least early and late).
- Anomaly scan with fetal heart views at 18–20 weeks; growth scans in the third trimester.
- Birth: usually planned before term (induction or caesarean); VRIII in labour.
- After birth: insulin needs drop immediately to pre-pregnancy levels or lower; early feeding and glucose checks for the baby.
Gestational diabetes (GDM)
- Diabetes first appearing in pregnancy, usually in the second or third trimester, when β cells cannot meet the extra demand of pregnancy insulin resistance (human placental lactogen, progesterone, cortisol).
- Risk factors (screen with a 75 g OGTT at 24–28 weeks): BMI above 30, previous baby ≥4.5 kg, previous GDM (test early as well), first-degree relative with diabetes, high-risk ethnic origin such as South Asian. Many Pakistani centres therefore screen all pregnant women.
| Criteria (75 g OGTT) | Fasting | 1 hour | 2 hours |
|---|---|---|---|
| IADPSG / WHO 2013 | ≥5.1 mmol/L | ≥10.0 mmol/L | ≥8.5 mmol/L |
| NICE | ≥5.6 mmol/L | – | ≥7.8 mmol/L |
One abnormal value is enough with either set.
- Treatment: diet and exercise first; if targets are not met in 1–2 weeks, add metformin and/or insulin (glibenclamide is an alternative in some guidelines).
- After delivery: stop treatment; check glucose before discharge and later. About half develop type 2 diabetes within 10 years: yearly HbA1c and lifestyle advice.
Gestational diabetes does not raise the risk of congenital anomalies (it starts after organogenesis), but it does cause macrosomia and neonatal hypoglycaemia. Major malformations point to pre-existing diabetes.
Expect: the annual screening package and the ACR as the test for early nephropathy; retinopathy grades with the earliest lesion (microaneurysm), the feature needing urgent referral (new vessels) and treatment (laser, anti-VEGF); Kimmelstiel–Wilson nodules and ACE inhibitors/ARBs; pupil-sparing third nerve palsy, amyotrophy and autonomic features; neuropathic versus ischaemic foot, monofilament testing and Charcot foot; pre-conception targets and 5 mg folic acid; drugs to stop before pregnancy; glucose targets in pregnancy; fetal and neonatal complications (cardiac defects, caudal regression, macrosomia, neonatal hypoglycaemia, RDS); GDM risk factors, OGTT timing and cut-offs, and the later risk of type 2 diabetes.
Quick revision
- Yearly: eyes (photo), ACR + eGFR, feet (monofilament), BP, lipids.
- Retinopathy: microaneurysm first; new vessels = proliferative = urgent referral; laser or anti-VEGF.
- Nephropathy: microalbuminuria → proteinuria → ESKD; ACEi/ARB, BP <130/80, SGLT2 inhibitor.
- Neuropathy: glove and stocking; pupil-sparing third nerve palsy; amyotrophy; autonomic.
- Neuropathic foot warm with pulses; ischaemic foot cold, pulseless; Charcot → non-weight-bearing cast.
- Pregnancy: HbA1c <48 before conception; folic acid 5 mg; stop ACEi, ARB, statin.
- Fasting <5.3, 1-h <7.8, 2-h <6.4 in pregnancy; insulin needs rise 50–100% later.
- GDM: OGTT 24–28 weeks; IADPSG 5.1/10.0/8.5; NICE 5.6/7.8; half get type 2 in 10 years.
Written by The House Job from standard references (Kumar and Clark's Clinical Medicine).
FAQ
Why are ACE inhibitors used in diabetics with normal blood pressure?
Once albuminuria is confirmed, blocking the renin–angiotensin system lowers pressure inside the glomerulus and slows the progression of nephropathy, even when systemic BP is normal.
Why does panretinal laser help proliferative retinopathy?
Destroying the ischaemic outer retina removes the source of VEGF that drives new vessel growth, at the cost of some peripheral and night vision.
Why do babies of diabetic mothers become hypoglycaemic?
They have been making extra insulin in response to high maternal glucose; when the cord is cut the glucose supply stops but the high insulin persists.
When should a pregnant woman be tested for gestational diabetes?
Women with risk factors have a 75 g OGTT at 24–28 weeks, and those with previous gestational diabetes are also tested early in pregnancy.