Introduction to Diabetes
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Diabetes mellitus (to be differentiated from diabetes insipidus, although mellitus is much more prevalent and thus referred to as commonly “diabetes”) is a chronic state of hyperglycaemia caused by a lack of or diminished effectiveness of endogenous insulin. Over time it can cause specific tissue damage, particularly to the retina, kidney, nerves and arteries.
The term diabetes mellitus literally means ‘passage of a large amount of sweet urine’
In the past the definitions IDDDM and NIDDDM were used for type 1 and type 2 diabetes respectively. However, this is not necessarily true in descriptive terms, as not all type 1 sufferers require insulin, and not all type 2 sufferers do not require insulin (many in the later stages of the disease do).
More than 90% of diabetic patients have type 2 diabetes. Less than 10% have type 1.


  • 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

  • Pancreatectomy – in cases where greater than 90% of the pancreas has been removed
  • Drug induced – steroids and thiazides
  • Others – e.g. congential condition that may cause insulin receptor antibodies, glycogen storage diseases
  • Endocrine – such as Cushing’s, hyperthyroidism


Clinical presentation

Acute presentation – typically in those with type 1 diabetes, but not always
  • Polyuria
  • Thirst
  • Weight loss
  • Ketonuria which may progress to ketoacidosis
Subacute presentation – in type 2 diabetes, same as above but also with the following:
  • 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


  • 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)
Blood sugar being tested with a glucometer
Blood sugar being tested with a glucometer. Note that this photo is from the USA and uses the units mg/dL, whereas in the UK and Australia the unit are mmol/L


Type 1 diabetes:
  • Insulin and dietary modification
Type 2 diabetes:
  • 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)


Comparison of type I and type II diabetes

Type IType II
Age at onsetMostly <30Mostly >30 – however due to the rise in obesity this age is becoming lower and lower – sometimes people in their teens!
Autoimmune / HLA related+++——————————————-
Prone to ketosis
It is normal physiology that when fasting you gradually move from glucose metabolism to fat metabolism. However, in total lack of insulin, you will be more prone to ketosis.
In type II diabetes you will usually still have a bit o insulin floating around and thus this prevent ketosis.
Family history+/- if you have an identical twin with this condition, you have a 1/3 chance of getting it yourself.++ if you have an identical twin with type II, you have a 100% risk. Therefore the genetic component in type II diabetes is much greater than in type I
Insulin treatment++++

Type 1 Diabetes


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


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


  • 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.
Metabolic disturbances
The body perceives a lack of glucose because glucose in unable to enter cells due to lack of insulin. Thus, the lack of insulin leads to…
  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
Clinical features of DKA (signs in black and symptoms in green)
  • 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

If any of these features are present, the patient should be considered for HDU admission


  • 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.

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

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


  • 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


  • 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.


  • 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.


  • 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.


It is important that dietary and lifestyle modifications are attempted before tablet treatment. If these are adhered to, the patient will experience improvement to, and perhaps complete control of, the condition.

Complications of diabetes

The duration and degree of hyperglycaemia is directly related to the severity of the complications.   Good control can directly reduce the risk of complications; when the HbA1c is kept below 7%, the risk of developing complications is reduced by 60% over 9 years.
Treated patients still have a lower life-expectancy than normal,i.e. 86% of insulin treated patients die as a result of their diabetes, where death is usually due to:
  • Cardiovascular disease (70%)
  • Renal failure (10%)
  • Infection (6%)
  • Other causes (14%)
The following mechanisms may be involved as a consequence of hyperglycaemia:
  • 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
Macrovascular complications
Diabetes is a risk factor for atherosclerosis, and the following cardiovascular events are more likely to occur:
  • 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.
Therefore, the following factors need to be aggressively dealt with:
  • 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.
Microvascular complications
These are specific to diabetes, and are in contrast to macrovascular disease.
Diabetic eye complications
Diabetes is the most common cause of blindness under the age of 65. Diabetes can affect the eyes in many ways, but diabetic retinopathy is the most common mechanism.
The most common forms of eye damage include:
  • Non-proliferative/background retinopathy
  • Diabetic maculopathy
  • Pre-proliferative retinopathy
  • Proliferative retinopathy
  • Cataracts
Pathology of retinopathy
Diabetes causes thickening of the basement membrane and increased permeability of retinal arteries. This can result in two types of damage:  occlusion, or aneurysm formation. The increased permeability of cells results in the formation of exudates. Flourescin angiography is the best way of detecting these changes early.
Treatment is most effective when given early – usually when the patient is symptomless. This means constant monitoring of patients for any signs of eye problems and initiating treatment immediately as soon as any are recognized.
Diabetic nephropathy
The kidney can by damaged by three mechanisms in diabetes:
  • 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.
There are several different effects that diabetes can exert on the kidney:
  • 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.
Kidney damage in diabetes is a very important cause of morbidity and mortality. It is also one of the most common causes of end-stage renal failure (ESRF) in developed countries.
As with a lot of things to do with diabetes, management is difficult, and thus prevention is very beneficial.
Diabetic neuropathy
This is directly related to the duration and degree of abnormal metabolic control. It tends to occur relatively early on in the progression of the disease, although many patients will be symptomless. The mechanism is not entirely clear; however it is thought to be due to metabolic disturbances. One of the most common theories is that accumulation of fructose and sorbitol in Schwann cells leads to their degradation.
There are several types of neuropathy in diabetes:
  • 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
The first sign in diabetic neuropathy is delayed nerve signal transit time. This is a direct result of demyelination, as a result of damage to Schwann cells. At this stage, the axon itself is still intact, and thus the potential for repair is still present. In later stages, the axons become damaged, indicating that irreversible damage has occurred.
Most diabetic problems are avoidable, but patients must be educated about the principles of foot care, as foot problems are the major cause of admission for diabetic patients. Older patients should visit a chiropodist regularly and may need assistance with basic self care, such as clipping toe nails, to avoid injury.


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Dr Tom Leach

Dr Tom Leach MBChB DCH EMCert(ACEM) FRACGP currently works as a GP and an Emergency Department CMO in Australia. He is also a Clinical Associate Lecturer at the Australian National University, and is studying for a Masters of Sports Medicine at the University of Queensland. After graduating from his medical degree at the University of Manchester in 2011, Tom completed his Foundation Training at Bolton Royal Hospital, before moving to Australia in 2013. He started almostadoctor whilst a third year medical student in 2009. Read full bio

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