Epidemiology

• Diabetes affects 2% of the British population, i.e. over 1 million people, and takes up 5-10% of the health budget.
• The prevalence is increasing rapidly in Western World
• More than 90% of diabetic patients have type 2 diabetes; less than 10% have type 1.

Rare Causes

Clinical presentation

• Polyuria
• Thirst
• Weight loss
• Ketonuria which may progress to ketoacidosis

• Lack of energy
• Blurred vision

Such cases may also present with complications such as…

• Staphylococcal skin infections
• Retinopathy
• Polyneuropathy
• Erectile dysfunction
• Arterial disease
• Inflammation of genitals  – due to Candida infection

Diagnosis

• HbA1c >6.5% (48 mmol/mol)
• OR Fasting glucose > 7 mmol/L and a glucose tolerance test
• OR random glucose > 11mmol/L (usually on 2 separate occasions)

Management

• Insulin and dietary modification

• Lifestyle modification (>>+ metformin >>+ further drugs>> + insulin)

Basic principles of monitoring

• Weight – can have significant impact on insulin sensitivity
• Blood glucose – self-monitoring for those taking insulin
• Urine glucose –is an alternative for those who do not want blood glucose methods, but it is imprecise
• Haemoglobin A1c (HbA1c) – for long term management/risk assessment; should keep the value <7% to minimise complications
• Maintaining other parameters within ideal range in order to minimise risk of complications, including blood pressure (<130/80 mmHg), total cholesterol (<4.5 mmol/L), LDL (<2.6), HDL (>1.1) and triglycerides (<1.7)

Type 1 Diabetes

Epidemiology

• Usually becomes apparent in childhood, with a peak incidence around puberty.
• Incidence of type 1 diabetes is on the increase, particularly in children < 5.

Aetiology

• NOT genetically determined; monozygous twins show concordance rate of 30-50%.
• Often associated with other autoimmune diseases, e.g. autoimmune thyroid disease

Pathology

• A T-cell mediated autoimmune disease resulting in the destruction of pancreatic beta cells.
• The first islet antibodies appear in the blood during the first few years of life; therefore disease is very slow to progress.

1. ↓anabolism → hyperglycaemia (fatigue) → glycosuria → osmotic diuresis (polyuria, polydypsia)→ salt and water depletion (↑HR, ↓BP) → death
2. ↑catabolism → ↑glycogenolysis, ↑gluconeogenesis (wasting), ↑lipolysis (↓ weight)  → hyperketonaemia → acidosis (↑RR, ↓BP, ↓T) → diabetic ketoacidosis → death
3. ↑secretion of glucagon, cortisol, GH and catecholamines

Acute Presentations

• Diabetic ketoacidosis (DKA) characterised by hyperglycaemia, hyperketonaemia and metabolic acidosis
• Thromoembolic episodes
• Non-ketoic hyperosmolar diabetic coma

• Polyuria, thirst
• Weight loss and weakness
• Nausea/vomiting
• Leg cramps
• Blurred vision
• Abdominal pain
• Kussmaul breathing
• Dehydration
• Hypotension
• Cold extremities / peripheral cyanosis
• Tachycardia
• Hypothermia
• Smell of acetone on breath
• Confusion / drowsiness / coma

Management of DKA

Based on Joint British Diabetes Societies Inpatient Care Group guidelines, September 2013 

DKA is a serious and potentially life-threatening presentation. It is a combination of acidosis, hyperglycaemia, and ketonuria. It may be the first presentation of type I diabetes in a child or young adult, but is also a common presentation in type I diabetics with poor insulin compliance. Treatment should be initiated promptly, and needs regular monitoring with (hourly) blood ketone (and glucose) levels, or, if not available, bicarbonate levels on venous blood gas.

You should involve a specialist as soon as possible (ideally within 24 hours), as this has been shown to reduce morbidity and mortality.

Severe DKA is characterised by:

• Blood ketones >6 mmol/L
• Bicarb <5 mmol/L
• pH <7.0
• Hypokalaemia (k+ <3.5)
• GCS <12
• O2 <92% on room air
• Systolic BP <90
• HR >100 or <60
• Raised anion gap

• Insulin dose should be based on weight. Sliding scales should not be used, as they can be inaccurate in overweight and pregnant patients
• The type of insulin regimen is often referred to as a Fixed rate Intravenous Insulin Infusion, or FRIII
• Check the effectivesness of the FRIII using blood ketones and revise the dose if it is not effective
• If bedside blood ketone testing is not available, venous blood gasses can be used to asses bicarbonate level, but only for the first 6 hours, as this becomes inaccurate after infusion of large amount of normal saline.

• Use IV 0.9% sodium chloride (normal saline)
• If hypotensive (systolic BP <90mmHg) give a bolus of 500mls normal saline. If still hypotensive, seek senior help. Consider discussion with ICU, and think about other possible causes of hypotension.
• Once hypotension is resolved, or if it is not present at presentation, patient will still require large amounts of IV fluid. A typical regimen might be 1L normal saline in the first hour, then 1L over 2 hours, then 1L over 4 hours etc, but be wary of a ‘one size fits all’ regimen
• Monitor electrolytes, particularly potassium  closely. You will likely need to replace potassium, which can be done by adding KCl to the bags of normal saline. Be careful not to infuse potassium too quickly.

Potassium
DKA patients are at risk of both hypokalaemia, and hyperkalaemia. Initially they are often hyperkalaemic, but their total body potassium is low. This is because potassium is taken up into cells with insulin, so with a lack of insulin, extra cellular potassium rises, and the intracellular level falls.
Titrate potassium replacement to the potassium level, as measured on hourly venous blood gasses.

• K+ >5.5mmol/L – dont replace
• K+ 3.5 – 5.5 mmol/L – replace by using 40mmol/L in infused solution
• K+ <3.5 – seek senior help – additional potassium replacement may be required

Approach
DKA patients are often very sick. As with any sick patient, it is useful to have a systematic approach. Do the basics first:

• A – Airway
  • ​Are they maintaining their own airway?
  • Do you need urgent airway assistance? Consider ICU / anaesthetic input
• B – Breathing
  • ​What are the O2 saturations?
  • What is the respiratory rate?
  • Do they need oxygen?
• C – Circulation
  • ​Get IV access
  • Send regular bloods (FBC, U+Es, CRP, formal glucose level, blood cultures)
  • Blood ketone and glucose (bedside testing)
  • Venous blood gas
• D – Disability (/conscious level)
  • Assess GCS – helps to assess severity of DKA
  • Consider causes for DKA (e.g. infection – send off cultures, check temperature)
• Start IV fluids – as described above
• Replace Potassium – as described above
• Start Fixed Rate Intravenous Insulin Infusion – as described above

Monitoring

• Re-assess hourly, including bedside ketones and glucose, venous blood gas (VBG) and clinical assessment and examination.
• The aim is to reduce the ketone level, and stop ketogenesis.
• Aim for reduction of ketone level of >0.5mmol/L/hr
  • If unable to measure blood ketones, use VBG instead, and aim for bicarbonate rise of >3.0mmol/L/hr, and blood glucose fall of 3.0mmol/L/hr
• Maintain serum potassium of 3.5 – 5 mmol/L (see above for potassium management)
• Avoid hypoglycaemia. It may be necessary to use 10% dextrose IV
• Consider urinary catheter if anuric
• Consider NG tube if persistent vomiting or obtunded

Resolution of DKA

• Defined as blood ketones <0.6 mmol/L and venous pH >7.3
• After 6 hours, bicarbonate level should not be used as a measure of progress, as hyperchloraemia may exist secondary to saline infusion. Hyperchloaraemic acidosis can lower bicarb.
• Continue to treat precipitating factors
• If patient is eating and drinking, start subcutaneous insulin. If not, can start a sliding sclae (VRIII – variable rate intravenous insulin infusion)
• Most cases resolve within 24 hours. If not resolving, seek specialist / senior support urgently.

Type 2 Diabetes

Epidemiology

• Four main determining factors are age, obesity, family history and ethnicity.
• Overall prevalence of this disease in the UK is about 2%, rising to 10% by age 70.
• Relatively common in all populations enjoying an affluent lifestyle.
• Onset can be accelerated by stress, pregnancy, illness or certain drugs.
• Insulin resistant state often presents with other risk factors that put someone at greater risk of cardiovascular disease, including hypertension, obesity, hypertriglyceridaemia, decreased HDL cholesterol and acanthosis nigricans.

Aetiology

• Under activity, over-eating and obesity are all factors in the formation of this disease.
• Presence of excess triglyceride within the cell has some effect in causing the insulin resistance.
• The genetic link is type 2 diabetes is stronger than that in type 1 – monozygotic twins have a greater than 50% chance of developing the disease.
• Low birth weight and low weight at 12 years of age predisposes to type 2 diabetes.
• Inflammatory markers, i.e. CRP, and cytokines are raised in obesity, and may play a role in the development of diabetes.

Pathology

• Insulin resistance and relative secretory failure of insulin occur for unknown reasons resulting in hyperglycaemia.
• Hyperglycaemia has a secondary effect on the liver, promoting glycogenolysis, raising blood glucose levels even further.
• Patients will have up to 50% of their beta cell mass at diagnosis, however, this destruction of beta cells is nowhere near as extensive as in type 1 diabetes.

Management

Complications of diabetes

• Cardiovascular disease (70%)
• Renal failure (10%)
• Infection (6%)
• Other causes (14%)

• Non-enzymatic glycosylation (glycation) – this leads to accumulation of AGE’s, leading to direct cellular damage and inflammation.
• Polyol pathway – when intracellular levels of glucose are elevated, glucose that can’t be metabolised via the TCA cycle, will enter this pathway, where aldose reductase reduces glucose to sorbitol, which is further reduced to fructose.
• This mechanism causes diabetic complications as cells of the retina, kidney and nerves DO NOT REQUIRE INSULIN for intracellular glucose uptake. Therefore these cells receive a high intra-cellular concentration of glucose when glucose levels are raised in the blood.
• Sorbitol cannot cross the cell membrane,thus water is drawn into the cell via osmosis. Fructose has a similar effect, modifying cell permeability to various ions and compounds, therefore altering normal cell functioning.
• The sorbitol pathway also produces reactive oxygen species which directly causes cell damage.
• Abndormal microvascular blood flow – this impairs the supply of nutrients and oxygen.
• Other factors – excess growth factors, particularly VEGF (vascular endothelial growth factor), are produced by ischaemic tissues in diabetics which cause endothelial cells to proliferate, exaggerating and accelerating microvascular damage.
• Activation of protein kinase C

• Stroke – 2x as likely
• MI – 3-5x as likely – women also lose their pre-menopausal protection
• Amputation of a foot due to gangrene is 50x as likely.

• Hypertension – treatment by at least 2 drugs concomitantly.
• Smoking
• Lipid abnormalities – virtually all diabetics are on statins.
• Low dose aspirin
• ACE inhibitors – also greatly reduce the risk of nephropathy.

• Non-proliferative/background retinopathy
• Diabetic maculopathy
• Pre-proliferative retinopathy
• Proliferative retinopathy
• Cataracts

• Glomerular damage
• Ischemia caused by damage to efferent and afferent arterioles.
• Ascending infection – remember that the immune system of diabetic patients is often compromised, thus resulting in a greater risk of UTI.

• Renal hypertrophy – indicated by a raised GFR often presenting soon after diagnosis.
• Albuminurea – this is the first detectable marker of diabetic nephropathy.
• Transient nephrotic syndrome – may exist, inducing oedema and hypoalbuminurea.

• Symmetrical mainly sensory neuropathy – “stocking and glove” distribution.
• Acute painful neuropathy – often felt in shins and feet, worse at night.
• Mononeuropathy and mononeuritis multiplex – most commonly in CN III and VI, and carpal tunnel syndrome.
• Diabetic amyotrophy – this is progressive wasting of muscle tissues.
• Autonomic neuropathy = CV and bladder problems; silent MI; erectile dysfunction

References

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