- Chronically elevated glucose
- Fasting glucose:
- Normal <6mmol/L
- Impaired glucose tolerance 6-7mmol/L
- Diabetes >7mmol/L
- 2-hours post 75g glucose challenge:
- Normal <7.8mmol/L
- Impaired glucose tolerance 7.8-11.1mmol/L
- Diabetes >11.1mmol/L
DM T1 (insulin dependent):
- Rare disease of white northern Europeans 25:100,000
- p/c: <30yo (average age of presentation = 13yo), FH of other autoimmune conditions (pernicious anaemia, thyroid disease, addison’s disease, coeliac disease), polyuria, polydipsia, thin, weight loss, fatigue, infections (abscesses, candidiasis). Acutely = ketoacidosis = N&V, drowsiness, tachypnoea.
- Cause: Autoimmune beta-bell destruction in pancreas
- Average age of death = 49 years with macrovascular/microvascualr complications
DM T2 (non-insulin dependent):
- Common. Prevalence of 2% in UK. Increasing in prevalence due to lifestyle/dietary factors.
- p/c: middle aged or elderly, overweight, 20% will have IHD/CVA/renal failure/visual impairment/PVD at diagnosis, polyuria, polydipsia.
- Can also present with symptoms of hyperglycaemia, hyperosmolar non-ketosis (HONK), asymptomatic screening
- Cause: peripheral resistance to actions of insulin. Reduced insulin secretion may exist late on, but absolute insulin production is rarely found.
- Genetic factors exist
- Mx: most can be managed with dietary/lifestyle advice and hypoglycaemic drugs. Some may require insulin.
Other types of diabetes:
- Exocrine pancreas failure: pancreatitis, pancreatectomy, destruction of pancreas (=CF, carcinoma, haemochromatosis)
- Endocrine disease: Cushing’s syndrome, acromegaly, glucagonoma, phaechromocytoma
- GDM: in 3rd trimester – similar pathophysiology to DM T2. 30-50% go on develop DM T2 within 10 years
- Genetic syndromes
- o Maturity onset diabetes in the young (MODY): relates to defects in beta-bell function
- o MODY type 1: abnormal hepatocyte nuclear factor HNF-1alpha
- o MODY type 2: glucokinase defect
- o MODY type 3: abnormal HNF-1alpha
Mx of diabetes:
- Patient education
- Tx of acute metabolic complications
- Long-term hypoglycaemic therapy
- Assessment of end organ damage every 6-12months: eyes (retinopathy and cataracts), CV system (peripheral pulses, HF, HTN), nervous system (peripheral sensory, autonomic neuropathy), feet (ulcers, gangrene, infections), renal function (creatinine, albuminuria).
- Best prognosis in those with excellent blood glucose control, stopping smoking, BP <130/80, and good lipid profile (statins advised to keep cholesterol <5mmol/L).
Specific Tx options:
- Dietary advice: healthy BMI (as obesity increases insulin resistance), reduce sat fats, reduce alcohol etc.
- Oral hypoglycaemics: give in DM T2 if diet and lifestyle not sufficient.
- o Sulphonylureas: gliclazide, glibenclamide, tolbutamide. Increase insulin release from b-cells (closes K channels). May cause weight gain or hypoglycaemia.
- o Biguanides: metformin. Mech of action unknown. Mild anorectic action – therefore indicated in obese individuals. Reduces insulin resistance and hepatic gluconeogenesis (stop sugar being made in liver). s/e: GI upset and lactic acidosis.
- o Alpha-glucosidase inhibitors: Acarbose. Inhibits carbohydrate digestion. s/e: diarrhoea and bloating.
- o Post-prandial glucose regulators (PPGR’s): Repaglinide. Stimulates insulin release from b-cells. Shorter action than Sulphonylureas, so less chance of hypoglycaemic episodes. s/e: hepatic dysfunction.
- o Thiazolidinediones: Rosiglitazone, pioglitazone. Insulin sensitizing agents which activate the peroxisome proliferator-activated receptor (PPAR-y), stimulating transcription of the glucose transporter molecule (Glut-1) = increased glucose uptake into tissues. S/e: hepatoxicty.
- o Insulin: subcut used in all T1 and some T2. There are several types:
- Recombinant human insulin: most common, can be short/medium/long acting. Some preps have a combination of short +med/long acting components.
- Insulin analogues: chemically modified forms of insulin (=lispro – which rapid onset and short duration) – ideal to be taken before meal.
- Hypoglycaemic agents can be added in in DM T2 to improve insulin sensitivity.
- S/e of insulin: hypoglycaemia, weight gain, lipohypertrophy at injection sites.
Assessing for diabetic complications:
- Eyes: visual acuity (maculopathy), fundal exam (retinopathy)
- BP: sittingstanding = postural/orthostatic change (for autonomic neuropathy)
- ECG: silent MI
- Renal: creatinine, GFR, proteinuria (dipstick, 12hour)
- Bruits over femoral artery
- Injection sites: lipohypertrophy, infections, abscesses, pain.
- Feet: pulses (PVD), ulceration
- Vibration senses: neuropathy
- Also check BMs, CVD RFs, weight.
Monitoring BMs in DM:
- Tight control = improved outcome
- On oral agents – check fasting BMs
- On insulin – check more frequently (before meals)
- Monotoring should be more frequent if pt is unwell. You can test BMs in urine but this is unreliable.
- HbA1c is a good marker of longer term glycaemic control (~6 weeks). Diabetes diagnosed if HbA1c ≥ 48 mmol/mol (≥6.5%).
Complications of DM:
- Acute: metabolic derangement = hypo/hyperglycaemia
- Later on = micro/macrovascular disease
- Good lifestyle, tight BM control, no smoking, <130/80, low cholesterol – all improve survival.
- Hallmark of DM and takes ~10 years to develop
- 1/3 have retinopathy at 30yo and 5% are blind.
- Due to capillary basement membrane thickening = leaking of vessels (hard exudates and haemorrhage), occluded vessels (retinal ischaemia and unstable neovascularisation), and macular oedema.
- Background retinopathy: blot haemorrhage, dot aneurysms, hard exudates, no change in sight
- Maculopathy: macular oedema, haemorrhages, hard exudates,
- Pre-proliferative retinopathy: CWS (=retinal ischaemia interrupts axoplasmic transport), venous bleeding, intra-retinal microvascular abnormalities due to dilated capillaries.
- Proliferative retinopathy: ischaemia induces new vessels, fragile, bleed easily, retinal detachment from traction scars occur
- Cataracts: occur 10-15 years earlier in DM than in those without DM
- Mx: annual eye check, laser retinal photocoagulation in maculopathy, pre-proliferative and proliferative retinopathy.
- Occurs 15-25 years after diagnosis in 35-45% of patients with DM T1 and <20% with DM T2
- Initial lesion = glomerular hyperfiltration (increased GFR) leads to diffuse thickening of glomerular basement membrane (GBM).
- Manifests as microalbuminuria (urinary albumin 30-300mg/d). An accurate of CVD risk
- Next – Persistent albuminuria (>300mg/d) is usually associated with normal GFR
- Next overt proteinuria (>0.5g protein/d) develops – GFR progressively falls = overt renal failure (end stage renal disease) follows.
- 1. microalbuminuria
- 2. albuminuria
- 3. proteinuria
- 4. ESRD
- Clinical features: asymptomatic early on, then HTN, oedema, and uraemia
- Mx: ACEi for HTN. ACEi also useful if proteinuria – regardless of BP. Chronic renal failure requires renal replacement therapy with dialysis or transplantation.
- Due to damage to small blood vessels nourishing the peripheral nerves. Also due to abnormal sugar metabolism.
- Several manifestations:
- Loss of peripheral vibration senseglove and stocking neuropathy.
- Mononeuropathies: any nerve, but most often oculomotor, with pupillary reactions spared.
- Amyotrophy: painful wasting of thigh muscles
- Automic neuropathy: postural hypotension, absent cardiac vagal tone (no NSR), gustatory sweating, gastroparesis, nocturnal diarrhoea, bladder dysfunction (increased infections, incontinence, ED)
- Mx: supportive.
Macrovascular complications of DM:
- DM is a major RF for the development of atherosclerosis
- DM strongly synergizes with all other CVD RFs!
- CVA risk x 2
- CAD risk x 3-5
- PVD x 40
- Foot disease: as result of PVD (=cold painful foot), peripheral neuropathy (=warm, painless foot), or as increased risk of infections (cellulitis, osteomyelitis) and leading to ulceration, gangrene and Charcot’s foot (=warm/hot foot with destruction to the joint).
- Mx of foot disease: patient education, good footwear, podiatry, Abx for infections, debridement of ulcers, reconstructive arterial wall surgery for PVD. Amputation in gangrene/acute ischaemia.
- Common complication in those treated with insulin and occasionally in those on sulphonylureas.
- Symptoms occur when BM is <2.2mmol/L, although in pts who are used to high BMs, symptoms can start at ~4mmol/L (‘4 to the floor’).
- Causes other than hypoglycaemic agents include:
- o Alcohol
- o Renal or hepatic failure
- o Reactive hypoglycaemia: rebound hypo after a glucose load
- o Insulinoma: pancreatic tumour producing insulin inappropriately
- o Endocrine disease: adrenocortical failure, hypopituitarism
- o Insulin-like growth factor II (IGF-II) producing tumours: pleural fibroma, sarcoma.
- p/c: anxiety, poor concentration, impaired cognition, decreased consciousness, coma, seizures. Sweating, tremor, tachycardia, extensor plantar response.
- o In DM – often due to over-treatment
- o If not DM – glucose, insulin and C-peptide to be measured before giving glucose.
- o Raised insulin and raised C-peptide = insulinoma
- o Raised insulin and low C-peptide = exogenous insulin administration
- o If no obvious cause – rule our Addison’s disease
- o If this is negative, look for IGF-II tumours, with pancreatic MRI and chest CT.
- Tx: glucose PO, otherwise IV 50mL of 50% in a large vein. In emergency IM glucagon can be helpful.