Diabetes Flashcards
1
Q
Define Diabetes Mellitus
A
Diabetes Mellitus = a reduction in insulin action sufficient to cause a level of hyperglycaemia that, over time, will result in diabetes specific microvascular pathology; retinopathy, nephropathy and neuropathy (eyes, kidneys and nerves) and macrovascular pathologies; stroke, MI, renovascular disease and limb ischaemia
2
Q
What are the 3 mechanisms by which ↓ insulin action occurs in Diabetes Mellitus?
A
- ↓ insulin production
- ↓ insulin sensitivity of target organs
- Overwhelming ↑ in catabolic hormones (the anabolic effect of insulin is balanced against 4 main ‘catabolic hormones’ e.g. catecholamines, cortisol, glucagon and growth hormone)
3
Q
Describe Non-diabetic hyperglycaemia (NDH) also called pre-diabetes (for patients) and impaired glucose regulation (healthcare staff).
A
NDH = insulin action ↓ is sufficient to cause hyperglycaemia but not sufficient enough to cause microvascular damage
There are 2 main types of impaired glucose regulation:
-
Impaired fasting glucose (IFG) - due to hepatic insulin resistance
- Fasting glucose 6.1 - 6.9 mmol/L
- Pts with IFG should have an OGTT to rule out diabetes - if ≥ 7.8 but < 11.1 then pt has IGT
-
Impaired glucose tolerance (IGT) - due to muslce insulin resistance
- Fasting glucose < 7.0 mmol/L + OGTT 2-hour ≥ 7.8 but < 11.1
4
Q
What is HbA1c?
A
HbA1c = glycated haemoglobin
- It is an indication of the previous 3-month average plasma [glucose]
- Test is limited to 3-month average as lifespan of RBCs is 120 days i.e. 4 months
5
Q
What are the presenting symptoms of type 2 DM?
A
T2DM patients often present asymptomatically and only present when hyperglycaemia is overt
Symptoms:
- Polyuria
- Polydipsia
- Tiredness
- Polyphagia
- Blurred vision
- Candidal infections e.g. genitals or skin folds
- Unexplained weight loss (this if for T1DM)
6
Q
What are the diagnostic criteria for T2DM for each of the following investigations, with symptoms and then without symptoms:
- Random plasma glucose
- Fasting glucose
- Oral glucose tolerance test (OGTT)
- HbA1c
A
If patient is SYMPTOMATIC + ONE of:
- Fasting glucose ≥ 7.0 mmol/L
- Random plasma gucose ≥ 11.1 mmol/L
- Oral glucose tolerance test (OGTT) - ≥ 11.1 mmol/L (2h after 75g glucose given orally)
If patient is ASYMPTOMATIC the above criteria apply BUT must be demonstrated on two seperate occasions!
HbA1c:
- Diabetes = HbA1c ≥ 48 mmol/mol (6.5%)
- Pre-diabetes = HbA1c 42-47 mmol/mol
- Not diabetic = HbA1c ≤ 41 mmol/mol (5.9%)
- If asymptomatic the test must be repeated to confirm
- Conditions that affects RBC turnover can produced misleading HbA1c - thus the it can’t be used in the following conditions:
- Children
- Pts with symptoms < 2 months
- Haemoglobinopathies
- Haemolytic anaemia
- Untreated iron deficiency anaemia
- Suspected gestational diabetes
- HIV
- CKD
- Medication that may cause hyperglycaemia (e.g. corticosteroids)
7
Q
What is the risk that gestational diabetes poses?
How can it be diagnosed via fasting glucose or OGTT?
A
↑ foetal morbidity/mortality
- Fasting glucose ≥ 5.6 mmol/L
- OGTT ≥ 7.8 mmol/L
8
Q
Are men or women more likely to have Diabetes?
A
MEN
9
Q
What Kidney condition is Diabetes the commonest cause of?
A
End Stage Renal Disease (ESRD)
10
Q
What is the proportion of adults with Type 1 vs Type 2 diabets?
A
10% of adults diagnosed have type 1
90% of adults diagnosed have type 2
11
Q
What % of patients with Non-diabetic Hyperglycaemia progress to T2DM per year?
A
5-10%
12
Q
For Type 1 Diabetes describe the following:
- Cause?
- Onset?
- Degree of Genetic influence?
- Do obesity, sendentary lifestyle or social deprivation impact development of T1DM?
- What acute condition are T1DM patients at risk of?
A
- Cause: insulin deficiency due autoimmune destruction of pancreatic B-cells
- Onset: Childhood (<30yrs)
- Genetics: concordance in identical twins is ~30% (indicating environmental influence)
- Obesity, sedentary lifestyle, social deprivation = no impact on developing T1DM
- Risk of DKA - because lack of insulin results in abnormally high ‘burning’/metabolism of fat to produce ketone bodies for energy (as opposed to glucose)
13
Q
For Type 2 Diabetes describe the following:
- Cause?
- Onset?
- Degree of Genetic influence?
- Do obesity, sendentary lifestyle or social deprivation impact development of T1DM?
A
- Cause: combination of insulin resistance + B-cell dysfunction (no autoimmune associations)
- Onset: Most adult onset (>30yrs)
- Genetics: concordance in identical twins is ~80% (implying a STRONG genetic element)
- Obesity, sedentary lifestyle, social deprivation = strong impact
14
Q
What are the risk factors for T2DM?
A
- Gender - type 1 and type 2 more prevalent in men
- Age - prevalence of T2DM ↑ from 25yrs - 80yrs
-
Weight - as BMI ↑ so does risk of T2DM
- Insulin resistance has been closely linked with abdominal obesity (i.e. visceral fat)
- BMI is more impactful than age on development of T2DM
-
Black African / Caribbean (3 times risk) and South Asian (6 times risk)
- T2DM affects these ethnicities 10yrs earlier than Europeans
- Lower BMI thresholds are used for South Asians compared to Caucasians
- Sedentary lifestyle
- FHx of T2DM
- HTN / CVD
- Pre-diabetic state
- Gestational diabetes - 60% of women with gestational diabetes will develop T2DM
15
Q
- What are the blood pressure targets for T2DM for risk factor modification?
- What is the 1st line treatment for BP management in these patients?
- What drugs are used to ↓ CVD risk in T2DM?
- What drug is 1st line for ↓ CVD risk?
A
- BP target = < 140/80 mmHg (or < 130/80 mmHg if end-organ damage is present)
-
ACE inhibitors are first line for BP
- ACE-I are renoprotective in diabetes - hence they are 1st line
- African or Caribbean pts whould be offered ACE-I + either thiazide diuretic or Ca2+ channel blocker
- Statins - only patients with 10-year cardiovascular risk > 10% (using QRISK2) should be offered a statin
- Atorvastatin 20mg once daily
16
Q
What are the side-effects of Statins?
A
- Muscle aches/pain
- Rhabdomyolysis - if muscle pain becomes severe or worsens contact GP immediately
- GI disturbances (constipation, diorrhoea, flatulence)
- Thrombocytopenia (prolonged bleeding / bruising)
- Headaches
17
Q
What Lifestyle Interventions are suggested for managing T2DM and it’s risks?
A
- Weight loss - initial target of 5-10% weight loss
- Exercise - ↑ insulin sensitivity with or without weight loss
-
Diet
- High fibre, low glycaemix index (charts online indicate what is high and low)
- Include low-fat dairy, oily fish
- Minimise saturated fats and fatty acids
- Replace saturated fat intake with olive oil or rapeseed oil
- Smoking cessation
18
Q
What medications can be used to manage T2DM?
A
-
Metformin
- ↓ liver glucose production (gluconeogenesis), ↓ weight, ↑ insulin sensitivity
-
Sulphonylureas
- e.g. gliclazide, glipizide, glimepiride and glibenclamide
- ↑ insulin secretion via stimualting pancreatic ß-cells
-
Thiazolidinediones (glitazones)
- e.g. Pioglitazone or rosiglitazone
- Stim nuclear receptor PPAR-gamma (perioxisome proliferator-activated receptor gamma) –> this causes gene modulation resulting in; ↑ storage of fatty acids in adipocytes (adipogenesis) - thus ↓ fatty acids in circulation, making the body depend on carbohydrates more (e.g. glucose)
- ↓ insulin resistance, ↓ liver gluconeogenesis, ↑ adipogenesis
-
Gliptins
- e.g. sitagliptin, vildagliptin, linagliptin and alogliptin
- Are DPP4-inhibitors
- DPP4 breaks down GLP-1 (glucagon like peptide-1) - which is an incretin (↓ plasma glucose via ↑ insulin section and ↓ glucagon secretion)
-
SGLT-2 inhibitors (-gliflozins)
- e.g. dapagliflozin, canagliflozin, empagliflozin
- Inhibit glucose reabsorption in kidney
-
GLP-1 receptors agonists (-tides)
- e.g. exanatide or liraglutide
- Mimic GLP-1 –> ↓ plasma glucose via ↑ insulin section and ↓ glucagon secretion
19
Q
What are the side-effects of the following drugs:
- Insulin
- Metformin
- Sulfonylureas
- Thiazolidinediones (pioglitazone)
- Gliptins
- SGLT-2 inhibitors
- GLP-1 agonists
A
-
Insulin
- Hypoglycaemia
- Weight gain
- Lipohypertrophy - small lump under skin due to fat accumulation at injection sites (insulin causes fat hypertrophy)
-
Metformin
- GI disturbances (diorrhorea, cramps, flatulence, nausea)
- Lactic acidosis
-
Sulfonylureas
- Hypoglycaemia
- Weight gain / ↑ appetite
- Jaundice (is hepatically cleared so jaundice can occur in hepatic impairment)
- Chlorpropamide - can ↑ ADH –> hyponatraemia
-
Thiazolidinediones (pioglitazone)
- Weight gain
- Fluid retention
- Fractures (2 x risk in women, but not men)
-
Gliptins
- ↑ risk of pancreatitis
-
SGLT-2 inhibitors
- UTIs
-
GLP-1 agonists
- Nausea / vomiting
- Pancreatitis
20
Q
In what order are the pharmacological treatments for T2DM escalated?
- Metformin
- Sulphonylureas
- Gliptins
- Pioglitazone
- SGLT-2 inhibitors
- GLP-1 agonists
A
21
Q
By what two mechanisms does diabetic retinopathy occur?
A
-
Capillary Leakage
- Intra-retinal haemorrhages cause retinal oedema and leakage of lipid deposits which form ‘hard’ exudates
- Hard exudates matter most if they occur in the macular region (maculopathy) –> causing loss of central vision
-
Capillary Occlusion
- If retinal ischaemia occurs in vessels supplying macula –> maculopathy
- Retinal ischaemia can induce new retinal BV formation and potential vitreal haemorrhage (as newly formed vessels aren’t as structurally mature) –> this can eventually cause retinal detatchment or neovascular glaucoma (BV formation in anterior chamber over iris)
22
Q
What is DKA (Diabetic Ketoacidosis)?
A
DKA = acute metabolic complication of diabetes (most common acute hyperglycaemic complication of T1DM) – it is characterised by the triad of;
- Hyperglycaemia
- Ketonaemia
- Acidaemia
23
Q
What are the 3 most common events precipitating DKA?
(Besides new presentation of Diabetes as DKA)
A
- Inadequate insulin therapy (e.g. missed insulin dose)
-
Infection (causes ↑ in bodies metabolic demands, for which there is insufficient insulin to accommodate for i.e. not enough to move enough glucose into cells)
- Pneumonia and UTI are most common
- MI - cardiovascular events can stim release of counter-regulatory hormones that precipitate DKA (catecholamines, cortisol, glucagon, growth hormone)
The following are other known risk factors for precipitating DKA:
- Pancreatitis
- Acromegaly (↑ GH production due to benign pituitary adenoma)
- Hyperthyroidism
- Cushing’s Syndrome
- Drugs affecting carbohydrate metabolism e.g. corticosteroids, thiazides, anitipsychotics
24
Q
What is the mechanism underpinning the development of DKA?
A
- Foundation is a combination of:
- ↓ net effective insulin
- ↑ counter-regulatory hormones (e.g. glucagon, catecholamines, cortisol and growth hormone)
- ↓ net effective insulin –> hyperglycaemia (as body is unable to move glucose into cells)
- The ↑ plasma [glucose] results in ↑ glucose in kidney nephrons –> this increases osmotic pressure (lowers H2O potential) causing solutes and H2O to move into the nephrons –> this is called osmotic diuresis
-
Osmotic diuresis causes:
- Polyuria
- Dehydration
- Polydipsia
- Electrolyte loss/disturbances
- ↓ glucose moving into cells also causes ↑ lipolysis –> releasing fatty acids, which are converted by beta-oxidation (in the liver) into ketone bodies; acetoacetate and β-hydroxybutyrate
- Ketone bodies are used as an energy source in starvation (i.e. absence of carbohydrate energy sources fat stores are used) –> however they turn blood acidic
- The body initially buffers the ketoacidosis with bicarbonate (HCO3-), but is overwhelmed
- The body hyperventilates (respiratory compensation) to lower blood CO2 (reduce acidity)
- Kussmaul Breathing – is a form of hyperventilation involving deep + laboured breathing and associated with metabolic acidosis
25
What are the signs / symptoms of DKA?
* **Polyuria**
* **Polydipsia**
* **Dehydration** - dry mucous membranes, poor skin turgor, sunken eyes, ↑ HR, ↓ BP,
* **Abdominal pain** - correlates with degree of acidosis
* **↑ RR** (**Kussmaul** breathing - deep hyperventilation)
* **Acetone breath** ('pear drops' smell) - due to ketosis
* **Nausea/vomiting** - correlates with degree of acidosis
* **Altered mental status**
26
How is DKA diagnosed from tests (excluding examination)?
* **Hyperglycaemia** - blood glucose **\> 11.0** mmol/L or **known diabetes mellitus**
* **Ketonaemia** - **\> 3.0** mmol/L or **significant ketonuria** (more than ++ on urine dipstick)
* **Acidaemia**:
* Bicarbonate (HCO3-) **\< 15.0** mmol/L and/or
* Venous **pH** **\< 7.3**
27
What are some signs that might indicate SEVERE DKA and require consultant review?
* Blood ketones \> 6 mmol/L
* Bicarbonate \< 5 mmol/L
* Venous/arterial pH \< 7.0
* Hypokalaemia \< 3.5 mmol/L on admission
* GCS \< 12 or abnormal AVPU (alert, voice, pain, unresponseive)
* O2 sats \< 92% on air (assuming no respiratory disease)
* Systolic BP \< 90 mmHg
* Pulse \> 100 or \< 60 bpm
* Anion gap \> 16 (elevated suggests acidosis) - normal = 6-16
28
What tests/investigations might be useful in a patient suspected of DKA?
* Blood ketones
* Lactate - taken to exclude lactic acidosis (result should be normal in DKA)
* Capillary and venous blood glucose
* 5-10% of DKA patients present as being euglycaemic
* VBG / ABG:
* Generally VBG is easier, lower risk, and can be used to diagnose and determine response to treatment
* VBGs can also provide glucose + potassium
* ABG (gold standard for metabolic disturbances) is more accurate for determining hypercapnia and hypoxia
* U+Es:
* Serum K+ often ↑ but total body K+ ↓
* Na+, Cl-, Mg2+ and Ca2+ are normally ↓
* Urine Dipstick:
* +ve for leucocytes in UTI (can precipitate DKA)
* +ve nitrites (infection)
* +ve for glucose
* +ve for ketones
* FBC:
* Leucocytosis (↑ WBC) occurs during hyperglycaemic state and in infection
* Blood culture - looking for infective pathogen
* ECG - to identify MI as precipitant or examine cardiac effects of electrolytes disturbances (Hyperkalaemia = tall-tented T-waves and widened QRS, hypokalaemia = U-waves)
* CXR - if pneumonia thought to be precipitant of DKA
29
What 3 things are done to mange DKA?
1. **Fluid replacement:**
* Typical fluid deficit in DKA ~100ml/Kg e.g. 70kg = 7 litres
* Always consider age, gender and concomitant medication and co-morbidites when replacing fluid
* Cation when replacing fluid in following; Young aged 18-25yrs, Elderly, Pregnant, HF or kidney failure, Concomitant BP affecting medication
2. **Fixed rate Insulin infusion:**
* IV fixed rate infusion pump - made of up of **50 units** insulin made up to **50ml** with 0.9% saline --\> infuse at rate of **0.1 unit/kg/hr**
* When **blood glucose \< 15** mmol/l an **infusion of 5% dextrose** should be started
* Continue pts long-acting insulin at usual dose + times in diabetic patients
* Only give bolus (stat) dose of IM insulin (0.1 unit/kg) if there is delay in setting up infusion
3. **K+ replacement** - correction of hypokalaemia (caused by insulin)
I
30
What is the fluid replacement regime for DKA?
**Fluid replacement**
1. Insert 2 large-bore cannula (one in each arm ideally)
2. If **systolic BP \< 90 mmHg** (and no concomitant HF or sepsis):
* **500ml** 0.9% sodium chloride (Saline) over **10-15 mins**
* If BP doesn’t improve then another 500ml over 10-15 mins + contact senior
* If BP remains low --\> contact ICU
3. If/once **systolic BP \> 90 mmHg**:
* See image
31
What are the potassium cut-offs which dictate potassium replacement during DKA?
Hypokalaemia and hyperkalaemia can occur in DKA:
* K+ is normally ↑ on admission (even though the total body K+ is ↓)
* But will ↓ post insulin treatment
32
What are some causes of Polyuria?
Can you comment on how common each cause is?
Common (\>1 in 10 cases):
* Diuretics, caffeine & alcohol
* **Diabetes mellitus**
* Lithium
* Heart failure
Infrequent (1 in 100)
* Hypercalcaemia
* Hyperthyroidism
Rare (1 in 1000)
* Chronic renal failure
* Primary polydipsia
* Hypokalaemia
Very rare (\<1 in 10 000)
* Diabetes insipidus
33
What types of Insulin classifications are there based on their profile of action/duration?
1. **Rapid-acting insulin analogues**
* Onset = 5 mins
* Peak = 1 hour
* Duration = 3-5 hours
2. **Short-acting insulin** (also called soluable insulin)
* Onset = 30 mins
* Peak = 3 hours
* Duration = 6-8 hours
3. **Intermediate-acting insulin**
1. Onset = 2 hours
2. Peak = 5-8 hours
3. Duration = 12-18 hours
4. **Long-acting insulin analogues**
1. Onset = 1-2 hours
2. Peak = flat profile
3. Duration = 24 hours
34
What is a basal-bolus regime for Insulin?
It is the combination of:
1. Rapid/short-acting '**bolus**' insulin **before** meals
2. Intermediate/long-acting '**basal**' insulin **once** or **twice** daily
35
Name some examples of the following Insulin types:
1. Rapid-acting insulin analogues
2. Short-acting insulins
3. Intermidate-acting insulins
4. Long-acting insulin analogues
1. **Rapid**-acting insulin analogues:
* Insulin Aspart (**Novorapid**)
* Insulin Lispro (**Humalog**)
2. **Short**-acting insulins:
* Actrapid
* Humulin S
3. **Intermidate**-acting insulins:
* Isophane insulin
4. **Long**-acting insulin analogues:
* Insulin determir (**Levemir**) - once or twice daily
* Insulin glargine (**Lantus**) - once daily
36
What are 'Premixed' preparations of Insulin composed of?
Combinations of **intermediate** acting insulin + either a **rapid**-acting insulin analogue or **short**-acting insulin e.g.
* Novomix 30:
* 30% insulin aspart (rapid-acting)
* 70% insulin aspart protamine (intermediate-acting)
* Humalog Mix 25:
* 25% insulin lispro (rapid-acting)
* 75% insulin lispro protamine (intermediate-acting)
* Humalog Mix 50:
* 50% insulin lispro
* 50% insulin lispro protamine
37
Is Insulin typically administered; subcutaneously, intramuscularly, IV or oral?
**Subcutaneously**
38
How often should HbA1c be check for type 1 and type 2 diabetes?
Every 3-6 months
(Then every 6 months when stable for Type 2)
39
What are the DVLA regulations regarding 1) Cars 2) HGVs for diabetes mellitus patients?
Cars:
* If on Insulin, pt can drive a car if:
1. They have hypoglycaemic awareness
2. No more than 1 episode of hypoglycaemia requires assistance of another person in the last 12 months
3. No relevant visual impairement
4. Drivers are normally contacted by DVLA
* If on drugs than can cause hypos (e.g. sulphonylureas):
* No more than 1 episode of hypoglycaemia requires assistance of another person in the last 12 months
* If diet controlled:
* No need to inform DVLA
HGV:
If on Insulin or other hypo causing medication (e.g. sulphonylureas);
* Must not have had any severe hypoglycaemic event in the previous 12 months
* The driver has full hypoglycaemic awareness
* The driver must show adequate glucose control via regular blood glucose monitoring (at least twice daily and at times relevant to driving)
* The driver must demonstrate an understanding of the risks of hypoglycaemia
* There are no other debarring complications of diabetes
40
What is MODY (Maturity-onset diabetes of the young)?
* MODY = development of T2DM in patients **\< 25** years old
* Genetic condition - typically **autosomal dominant**
* ****Over 6 different mutations are known e.g. MODY 1, MODY 2 etc.
* ~ 90% are misdiagnosed as having T1 or T2 diabetes
* MODY 2 and MODY 3 are most common forms
Features:
* Typically \< 25yrs
* **FHx** of early onset diabetes
* Ketosis is not a feature on presentation
* Responds very well to **sulphonylureas** (insulin not usually necessary)
**MODY 2**:
* 20% of cases
* **Glucokinase** mutation
**MODY 3**:
* 60% of cases
* **HNF-1 alpha** (hepatocyte nuclear factor 1 alpha) mutation
* Associated with ↑ risk of hepatocellular carcinoma
41
What is LADA?
Latent Autoimmune Diabetes of Adults
* Autoimmune type diabetes which present later in life
* Often misdiagnosed as type 2 - even though the pt is more likely to be:
* Low BMI
* Ketotic
* Poor response to non insulin therapies
42
What should be involved in the 'Baseline' care plan for a newly diagnosed diabetic patient?
1. Book eduction programme
2. Lifestyle changes:
* Diet - minimise sugar, ↑ fibre, ↓ fat, ↓ calories
* Exercise - 150 mins/week of moderate intensity or 75 mins/week of vigorous intensity
* Smoking cessation
3. Agree target weight loss e.g. 5% in 6 months and 10% in 1 year
4. Refer to smoking cessation
5. Review in 3 months
43
What messages should be given to diabetic patients regdarding
Sick Days, so called 'Sick Day Rules'?
1. **Increase frequency of blood glucose monitoring** to 4-hourly or more
2. Encourage **fluid intake** - aim for at \> 3L in 24hrs
3. If unable/struggling to eat --\> **keep sugary drinks** to maintain blood glucose
4. Advise pts to keep a box of **'sick day supplies'** for if they become unwell
5. **Continue** to take **oral hypoglycaemic medication** even if not eating - bodies response to stress is ↑ cortisol --\> ↑ glucose
6. If on **insulin** --\> take doses as normal - if blood glucose + ketones are high --\> give corrective insulin dose
* Rule of thumb: total daily insulin / 6 (max 15 units)
7. Advise pt to keep **access to a mobile phone** --\> has been shown to reduce progression of ketosis to diabetic ketoacidosis
44
Which of the following hormones oppose action of Insulin?
* Glucagon
* Thyroxine
* GLP-1
* Noradrenaline
* Cortisol
* Testosterone
Glucagon, Noradrenaline (catecholamine) and cortisol
45
What test can be done to differentiate between Type 1 diabetes / LADA and T2DM?
GAD antibodies test (Glutamic Acid Decarboxylase autoantibodies)
* Often done when pt \> 30yrs + T2DM is in doubt (e.g. low BMI or weight loss)
* In autoimmune style diabetes GAD antibodies often exist in circulation
46
Which of the following are true about Diabetic Eye Disease?
* Can be detected by checking visual acuity
* Is related to HbA1c
* Always lead to total blindness
* May be present at diagnosis of Type 2 diabetes
* Doesn't occur in young people
Diabet eye disease:
* Is related to HbA1c
* May be present at diagnosis of Type 2 diabetes
47
What is HHS (Hyperosmolar Hyperglycaemic State)?
**General:**
* Medical emergency, difficult to manage, significant mortality
* Typically seen in **elderly T2DM**
* DKA present in hours whereas HHS comes on over **several days** - thus dehydration + metabolic disturbances are more extreme
**Pathophysiology:**
* Hyperglycaemia --\> **osmotic diuresis**:
* Polyuria
* Dehydration
* Polydipsia
* Electrolyte loss of Na+ and K+
* Volume depletion causes --\> **↑ serum osmolarity** (typically \> 320 mosmol/kg) --\> causes **hyperviscosity** of blood
* Despite electrolyte losses + total body volume depletion the typical patient with HHS, may not look dehydrated --\> because hypertonicity leads to preservation of intravascular volume
**Presentation:**
* General: fatigue, lethargy, nausea and vomiting
* Neurological: altered level of consciousness, headaches, papilloedema, weakness
* Haematological: hyperviscosity (may result in myocardial infarctions, stroke and peripheral arterial thrombosis)
* Cardiovascular: dehydration, ↓ BP, ↑ HR (tachy)
**Diagnosis:**
1. **Hypovolaemia**
2. Significant **Hyperglycaemia** ( \> 30 mmol/L) **without** significant **ketonaemia** or **acidosis**
3. Significant **↑ serum osmolarity** (\>320 mosmol/kg)
**Mangement:**
* Normalise the Osmolarity (gradually)
1. Replace fluid + electrolyte losses
2. Normalise blood glucose (gradually)
