Diabetes

• Diabetes is a lack of or diminished effectiveness of endogenous insulin
• May cause serious microvascular (retinopathy, nephropathy, neuropathy) or macrovascular complications (CAD, stroke, peripheral vascular disease)

Type I

• Usually juvenile onset but not always
• Patients always need insulin and are prone to weight loss and ketoacidosis
• >90% carry HLA DR3 or DR4 and it is associated with other autoimmune conditions
• Latent autoimmune diabetes of adults (LADA) is a form of Type I with slower progression to insulin dependence in later life

Type II

• Increased prevalence due to lifestyle changes, increased life expectancy and better diagnosis
• High occurrence in Asian men
• Caused by decreased insulin secretion and increased insulin resistance
• Associated with obesity, lack of exercise and high calorie diet
• Obesity may cause insulin resistance by increasing the rate of release of non-esterified fatty acids causing post-receptor defects in the action of insulin
• Stronger genetic influence than Type I
• Maturity onset diabetes of the young (MODY) is a rare autosomal dominant form of Type II affecting young people with a positive family history

Diagnosis (WHO criteria)

• Symptoms of hyperglycaemia (polyuria, polydipsia, weight loss, visual blurring, genital thrush, lethargy AND raised venous glucose detected once – Fasting plasma glucose greater or equal to 7.0 mmol/L or random plasma glucose greater or equal to 11.1 mmol/L OR
• Raised venous glucose on 2 separate occasions – fasting greater or equal to 7mmol/L, random greater or equal to 11.1mmol/L or OGTT 2hr value > or equal to 11.1 mmol/L

Indications for an OGTT (75g glucose load in 300ml)

• Fasting plasma glucose of 6.1 to 7.0 mmol/L
• Random plasma glucose of 7.8 to 11 mmol/L

Plasma glucose levels are always higher than whole blood

• When a diagnosis of diabetes is confirmed do;
  • U&Es
  • LFTs
  • TFTs
  • Lipids
  • Urine microalbuminaemia

• The recommended HbA1c is 7% or less (measures glucose level over the past 8 weeks)
• Fructosamine levels reflect control over 2-3weeks – useful in pregnancy to assess shorter term control or in haemoglobinopathies which can interfere with HbA1c tests
• Sometimes it can be difficult to differentiate between type I and type II. Features that suggest type I are;
  • Weight loss
  • Persistent hyperglycaemia despite diet and medications
  • Presence of autoantibodies – islet cell antibodies and anti-glutamic acid decarboxylase (GAD)
  • Ketonuria on dipstick

Other causes of diabetes mellitus;

• Drug induced – steroids, thiazides
• Pancreatic – pancreatitis, surgery, trauma, pancreatic destruction (haemachromatosis, CF), pancreatic cancer
• Endocrine – Cushing’s disease, acromegaly, phaeochromocytoma, hyperthyroidism

Acute presentation;

• Ketoacidosis – unwell, hyperventilation, ketones on breath, weight loss, polyuria, polydipsia, fatigue

Management

• Maintain renal function – give ACEi if there is microalbuminaemia
• Control BP
• Regular retinal screening
• Pre-conception advice
• Insulin
  • Strength is 100u/ml
  • Start with around 1 insulin unit for every unit of BMI
  • Insulin:carbohydrate ratio – 0.5 to 2.5:10g carbs
  • Use a variety of short acting, intermediate and long acting insulin
  • Tell the patient to vary their site of injection – fat hypertrophy and scaring
  • If they want to do exercise they need to eat some glucose or take less insulin
  • Remember when they are ill there insulin requirements will go up (cortisol – gluconeogenesis) but they might eat less so will need to monitor the BM more regularly and use short acting insulin to regulate

Diabetic patients on surgical wards

• Try and put the patient first on the list
• Stop any long acting insulin the night before, if surgery is in the morning stop all SC morning insulin. If surgery is in the afternoon have the usual short acting insulin in the morning but no intermediate or long acting insulin
• Aim for a BM of 7-11mmol/L during surgery and monitor BM every hour
• Check U&Es pre-op
• Start a sliding scale – Put up a 500ml bag of 5% dextrose +/- KCl over 6hr.
• Have an infusion pump with 50U of short acting insulin (Actrapid) in 50ml of 0.9% NaCl, give as required according to the BM

Glucose-Potassium-Insulin (GKI) infusion

• Post-op continue IV insulin and dextrose until the patient is tolerating food. Finger prick every 2hr

Type 2 Diabetes

Cause

• Decreased insulin secretion and insulin resistance associated with obesity, lack of exercise and calorie excess

Natural history

• Preliminary phase – impaired glucose tolerance (OGTT more than 7.8 but less than 11.1) or impaired fasting glucose (>6.1 but less than 7) – opportunity for lifestyle intervention
• Symptomatic phase – thirst, polyuria and weight loss
• Complications – infections, neuropathy, retinopathy, arterial disease
• There may be a lower risk of diabetes in IFG than IGT
• Those with heart failure and IFG and ACEi to prevent progression to DM

Gestational diabetes

• A term used for both gestational IGT and gestational DM
•  Around 6wk repeat OGTT
• 50% lifetime risk of developing DM

Managing Type II DM

• Tight BP control most important for preventing macrovascular disease and mortality
• Involve MDT
• Do regular follow ups and regular exercise
• Diet – ¯saturated fat, ¯ sugar
• If microalbuminaemia restrict protein and give and ACEi or AT-2 blocker
• Give a statin if LDL is >3mmol/l
• If diet and exercise don’t work then give a tablet

Oral hypoglycaemics

• Metformin (Biguanide)
  • Start with this if patient BMI is >25 (if <25 can either start on metformin or sulphonylurea)
  • Can help maintain weight loss and increase insulin sensitivity
  • SE – anorexia, D&V, decreased Vit B12 absorption, NOT hypoglycaemia
  • Avoid is creatine is >150?mol/L due to risk of lactate acidosis
  • Stop if there is tissue hypoxia (e.g. sepsis or MI) and 48hr before a GA and for 3d after contrast medium containing iodine
• Sulphonynlureas
  • Induce insulin secretion
  • Ineffective in patients without a functioning beta-cell mass
  • They encourage weight gain
  • Can cause hypoglycaemia
  • Interact with warfarin and can bind to albumin so displace other drugs
  • Examples;
    • Tolbutamide – short acting, hypoglycaemia is rare
    • Gliclazide – medium acting
• Glitazones
  • Reduce insulin resistance by interacting with PPAR-? (nuclear receptor which regulates genes involved in lipid metabolism and insulin action)
  • May preserve beta-cells and control glycaemia for longer than secretagues or biguinides
  • Examples – Rosiglitazone (monitor LFTs)
  • Use if metformin plus sulfonylurea combination is problematic, the glitazone replaces whichever is CI or not tolerated

• Insulin
  • Subcutaneous insulin comes in 100u/ml strength. There are many types following into 6 groups;
  • Ultra-fast acting e.g. Humalog to Novorapid  - inject at start of meal or immediately afterwards
  • Soluable insulin e.g. Humulin S or Actrapid – inject 15-30 mins before meal
  • Immediate e.g. Humulin I or Insulatard
  • Long acting e.g. Ultratard
  • Long acting analogue  e.g. Lantus – given once at bedtime
  • Pre-mixed insulins e.g with ultra-fast component

Commonly used regimes

• BD regime – twice daily premixed insulins, useful in type I and type II with regular lifestyles
• QDS regime – before meals ultra-fast or soluable insulin with bedtime intermediate or long acting analogue
• Once daily intermediate or long acting insulin – good in type II when switching from tablets to insulin
• Begin with at least of total daily dose of 1 unit of insulin for each BMI in adults

Subcutaneous dosing during intercurrent illness

• Illness often increases insulin requirements despite reduced food intake
• Maintain calorie intake with milk or juice
• Check BM >4 times per day – increase insulin if BM is rising. Seek advice if concerned
• Admit if vomiting, dehydrated or ketotic
• Admit if pregnant or a child

• Starting insulin in those with Type II
• The patient must be glucose self-testing
• Continue metformin to limit weight gain

Causes of insulin resistance

• Syndrome X – central obesity, dyslipidaemia, hyperglycaemia, hyperinsulinaemia, hypertension
• Renal failure
• Polycystic ovary syndrome
• Asians
• Pregnancy
• TB
• CF

Complications

• Vascular disease
  • Cerebrovascular, cardiovascular and peripheral vascular disease
  • MI 5 times more likely, 3 times more likely to have a stroke
  • Give ACEi, statin, consider fibrinates for high triglycerides and low HDL, asprin
• Kidneys
  • Microalbuminaemia is when the urine dipstick is negative but the urine albumin:creatine ration is raised
  • Give and ACEI or ARB regardless of BP
• Diabetic retinopathy;
  • Background – microaneurysms, microhaemorrhages and hard exudates
  • Pre-proliferative changes – cotton wool spots and microhaemorrhages
  • Proliferative retinopathy – new vessels form, urgent referral
  • Maculopathy – more common in DM type II. Consider if reduced acuity
  • Cataracts
  • Rubeosis iridis – occur late and may lead to glaucoma
• Diabetic neuropathy
  • Motor and sensory neuropathy
    • Signs – reduced sensation is stocking distribution, absent ankle jerks, neuropathic deformity, pes cavus, claw toes, loss of transverse arch, rocker bottom sole
    • Foot ulceration – usually painless, punched out lesion in area of thick callous. May lead to cellulitis, abscess formation and osteomyelitis
    • Drugs;
      • Asprin/paracetamol – tricylics (amitriptyline) – gabapentin (alternatives, carbamazepine, lamotrigine, capsaicin cream)
  • Mononeuritis multiplex
    • Especially III and VI CN
    • If sudden give corticosteroids, IVIg and cyclosporine
  • Amyotrophy
    • Painful wasting of quadriceps and other pelvifemoral muscles
  • Autonomic neuropathy
    • Excessive postural BP drop, urine retention, erectile dysfunction, diarrhoea, gastroparesis
    • Gastroparesis is diagnosed by scintigraphy using Tc99 labelled meal. It may respond to antiemetics
    • Postural drop may respond to fludrocortisone (SE oedema and hypertension)

Emergencies in diabetes;

• DKA
• Hypoglycaemia
• HONK

Diabetic ketoacidosis

• Cardinal biochemical features;
  • Hyperglycaemia
  • Hyperketonaemia
  • Metabolic acidosis (pH <7.3)
• Generally associated with Type I DM
• Precipitants – infection, surgery, MI, non-compliance, wrong insulin dose
• Symptoms and signs
  • Polyuria, polydipsia, lethargy, anorexia, hyperventilation, ketotic breath, dehydration, vomiting, abdo pain, coma

Investigations

• Glucose, U&Es, bicarbonate, amylase, osmolality, ABG, FBC, blood cultures
• Urine – ketones, MSU
• CXR
• ECG, cardiac enzymes
• To estimate plasma osmolality – 2[Na] + [Urea] + [Glucose] mmol/L
• Some assays for creatine cross-react with ketones

Pitfalls in DKA

• Plasma glucose is usually high but not always
• A high WCC can be seen in the absence of infection
• There is often no fever with the infection
• Hyponatreamia is common due to osmolar compensation for the hyperglyaemia. It will rise with rehydration
• Ketonuria doesn’t equate to ketoacidosis
• Serum amylase can be 10 times normal

Management

• IV access start fluid replacement 0.9% NaCl immediately
• Check plasma glucose usually it is >20mmol/L if so give 4-8 soluable insulin IV
• Do the above blood and urine tests
• NG tube only if vomiting, nauseated or unconscious
• Start insulin sliding scale
• Continue fluid replacement along with K
• Check glucose, U&Es, bicarbonate regularly (hourly initially).
• Find out what precipitated coma

Fluid replacement

• Give 1L of 0.9% saline stat, the 1l over the next hour, 1L over 2 hr, 1L over 4hr and 1L over 6hr
• Use dextrose saline or 5% dextrose when glucose is <15mmol/L
• Those >65 or with CCF need less saline and give it more cautiously

K replacement

• Don’t add K to the first bag, less will be required if there is renal failure or oligouria. Check U&Es regularly and replace as required;

• Aim for a fall in glucose of 5mmol/hr
• If acidosis is severe give IV bicarbonate (1ml/kg of 8.4% over 1hr) and recheck ABG
• Insert urine catheter if no urine is passed >4hr
• Give heparin 5000U/8hr until mobile

Complications

• Cerebral oedema
• Aspiration pneumonia
• Hypokalaemia
• Hypomagnesaemia
• Hypophosphataemia
• Thromboembolism

Hypoglycaemia

• The commonest endocrine emergency
• Definition – plasma glucose <3mmol/L
• Type types;
  • Fasting
  • Post-prandial hypoglycaemia
• Symptoms
  • Autonomic – sweating, anxiety, hunger, tremor, palpitations
  • Neuroglycopenic – confusion, drowsiness, seizures, coma

Fasting hypoglycaemia

• Most common cause – insulin or sulphonylurea treatment in a diabetic
• In a non-diabetic patient – EXPLAIN
• E – Exogenous drugs, insulin, oral hypoglycaemics, alcohol (with no food)
• P – Pituitary insufficiency
• L – Liver failure
• A – Addison’s disease
• I – Islet cell tumours
• N – Non pancreatic tumours e.g. retroperitoneal fibrosarcomas
• Investigations

·        Finger prick and lab glucose

·        Exclude liver failure and malaria

·        Insulin and C-peptide

Interpreting results;

• Hypoglycaemia with high or normal glucose and no elevated ketones
  • Causes – insulinomas, sulphonyureas, insulin administration (no detectable C peptide)
• Insulin low or undetectable no excess ketones
  • Causes – non pancreatic neoplasm, anti-insulin antibodies e.g. seen in Hodgkins disease
• Insulin low ketones high
  • Causes – alchohol, pituitary insufficiency, addison’s disease

Post-prandial hypoglycaemia

• Most common in gastric surgery (dumping syndrome) and type II diabetes
• Usually odd behaviour, sweating, increased pulse, seizures

Management

• 20-30g dextrose IV (200-300ml 10% dextrose) (preferable to 50-100ml of 50% dextrose as this causes phlebitis)
• Glucagon 1mg IV/IM is nearly as rapid as dextrose but doesn’t work in drunks!
• Once conscious give the patient sugary drinks and a meal

Hyperglycaemic hyperosmolar non-ketotic coma (HONK)

• Only occurs in those with Type II DM
• The history is longer (>1wk) with severe dehydration and glucose >35mmol/L
• Acidosis is absent
• Patient is often old and presenting for the first time
• The osmolality is >340mosmol/kg
• The risk of DVT is high so give full heparin anticoagulation
• Rehydrate over 48hr with 0.9% NaCl (1/2 the rate of DKA)
• Wait an hour before giving any insulin – it may not be required
• If needed give 1U/hr
• Look for cause e.g. bowel infarct or MI

Hyperlactataemia

• Rare but serious complication of DM
• Blood lactate >5mmol/L
• Seek expert help
• Give oxygen
• Treat any sepsis vigorously