Diabetes

Question 1

Insulin synthesis

Answer 1

Pre-proinsulin –> proinsulin –> insulin + cleaved C peptide

Question 2

C peptide

Answer 2

Good indicator of Beta islets cell function. Lasts longer than insulin

Question 3

Insulin

Answer 3

Glycogenesis

Question 4

Glucagon

Answer 4

Glycogenolysis

Question 5

T1DM

Answer 5

Autoimmune Beta cell destruction causing an absolute insulin deficiency - little/no insulin being produced. Therefore, increased glucose in the blood and less glucose bing stored and/or used in the organs

Question 6

T1DM is associated with HLA-DR3 T/F

Answer 6

T1DM is associated with Human leukocyte antigen DR3 or 4. (HLA-DR3/4)

Question 7

T1DM definition

Answer 7

A metabolic disorder characterised by high glucose levels due to absolute insulin deficiency.

• 10-20% of all diabetes
  most common under age of 20yrs
  peak incidence at 10-14yrs

Personal/family history of autoimmune disease e.g. Hashimoto’s - increases risk

Accute manifestation = DKA.

Question 8

T1DM Symptoms

Answer 8

polyuria 
polydipsia 
polyphagia 
weight loss 
fatigue 
poor wound healing

Question 9

T1DM Management

Answer 9

Insulin

Question 10

What would you expect to see with T1DM on investigation?

Answer 10

Low C-peptide (tested in patients with atypical features)

High blood sugar

Question 11

Investigations

Answer 11

• Random blood glucose: >11mmol/l with clinical features –> same day referral
• Fasting blood glucose ≥ 7.0mmol/L is typical
• OGTT >11 mmol/l two hours after a 75g oral glucose load
• HbA1c: >48 mmol/l suggests hyperglycaemia over 3 months. use for monitoring

NB: HBa1C is inaccurate in children, haemolytic anaemia and pregnancy

Question 12

What investigations could you consider in T1DM

Answer 12

• C-peptide: if atypical features are present e.g. age > 50, BMI >25kg/m2
• Autoantibodies: if atypical features are present, e.g. anti-glutamic acid decarboxylase
• VBG: If concerned about DKA

Question 13

First line management of T1DM

Answer 13

Basal bolus regime

Question 14

Management

Answer 14

Urgent referral to daibetes specialist

Lifestyle

• diet high in fibre and low in fat, sugar and sal
• educate regarding carb counting, allows insulin dose to be matched to intake

Insulin therapy

• Basal bolus: 1st line, long acting regularly (basal) with rapid acting insulin before meals (bolus)
• basal - Levemir (detemir) given twice daily. Lantus (glargine) one daiy is an alternative
• bolus insulin lispro (humalog), insulin aspart (novorapid)

Mixed insulin regime - mixed insulin comprises a short acting and long acting insulin, BD.
- used when unable to tolerate basal-bolus regime

Continuous insulin infusion: Disabling hypoglycaemia or persistent hyperglycaemia (HbA1c >69mmol/mol)

Question 15

Monitoring

Answer 15

Glucose
- HbA1c: measured every 3-6 months with a target of ≤48 mol/mol
- Selft monitoring: check blood at least 4 times a day with the following targets
on waking: 5-7mmol/L
before meals and other times 4-7mmol/L

Retinopathy
- Immediate ophthalmoogy referral upon diagnosis and annually thereafter
arrange urgent review thereafter if:
- acute reduction in acuity
- pre proliferative or proliferative retinopathy
- diabetic maculopathy

Diabetic foot
- Should be assess at least annually; refer urgently to foot protection service if at risk (e.g. ulceration)

Diabetic nephropathy
- Annual measurement of eGFR and urinary albumin:creatinine ratio

Question 16

Complications

Answer 16

Macrovascular
- IHD, PVD, Stroke

microvascular
- Diabetic nephropathy
neuropathy and retinopathy

Question 17

DKA

Answer 17

• Metabolic state as a complication of T1DM (predominantly)
• Medical emergency: dehydration and electrolyte imbalance
• Triad: hyperglycaemia, acidosis and ketonaemia
• Mortality rate <1% in UK
• May be a first presentation of T1DM
• Often a precipitating factor: infection, trauma, surgery, corticosteroid use

Question 18

Increased lipolysis is a feature of DKA - T/f

Answer 18

Increased lipolysis is a feature of DKA. as Fats used as the alternative fuel, fats are broken down and transported to the liver. The liver then converts this into ketone bodies and these are used by cells for energy. However this increases the acidity of your blood and acetone which give the sweet smelling breath.

Question 19

How does DKA lead to acidosis?

Answer 19

net reduction of insulin -reduced glucose entry into cells –> metabolism of lipids as an alternative energy sours
–> increase FFA to liver increased ketogenesis –> acidosis

Question 20

Kussmal breathing

Answer 20

Deep breathing due to metabolic acidosis

Question 21

Kussmal breathing

Answer 21

Deep breathing due to metabolic acidosis

Increased acidity of blood–> Reduced CO2 –> reduced acidity

Question 22

Why replace potassium in patients with DKA?

Answer 22

When you are acidityc lots of H+ irons in blood. They move into your cells, and potassium moves out into the blood (via the transporter). This contributes to hyperkalaemia. This can be worsened for your Na+/K+ atpase so this can also worsen your hyperkalaemia. Despite all this there is total body potassium loss as the potassium in your blood is being excreted out into your urine. Therefore serum potassium levels in DKA doesnt reflect your total body potassium. this is why you replace K+ in people with DKA as they are overall losing K+

Question 23

Clinical features of DKA

Answer 23

Abdo pain 
N+V 
Polyuria and polydipsia 
weight loss 
inability to tolerate oral fluids 
lethargy and confusion

Question 24

Signs of DKA

Answer 24

• Fruity pear drop smell
• Dehydration
• mild: only just detectable
• moderate: dry skin and mucus membranes; reduced skin turgor
• shock: tachycardia, hypotension, drowsiness, reduced urine output
• Kussmal breathing

Question 25

investigations of DKA

Answer 25

Bedside: - urine dip: glycosuria and ketonuria - Bedside ketone and capillary glucose Bloods: - ABG/VBG: quickest way to ascertain pH and HCO2 levels - U&E: electrolyte derangement and AKI due to dehydration - FBC and CRP: raised inflammatory markers may suggest underlying infection as a percipitant - Infection screen: if an infection is the suspected trigger

Question 26

Diagnostic criteria of DKA

Answer 26

Triad: Hyperglycaemia, acidosis, ketonaemia * Glucose > 11mmol/L or known DM * HCO3 <15 mmol/L and/or venous pH <7.30 * Ketonaemia (≥3mmonl/l( or 2+ ketonuria NB: can have DKA in children and young people with normal blood glucose. Also low ketone levels does not exclude DKA

Question 27

First line treatment of DKA with a SBP above 90 in adults

Answer 27

1L of normal saline over 1 hour Then 1L Normal saline with KCL over the next 2, 2, 4, 4, the 6 hours. Insulin - fixed rate insulin infusion Give anticoags and closely monitor

Question 28

First line treatment of DKA with a SBP below 90

Answer 28

1L of normal saline over 15mins | - call for senior help

Question 29

Complications of DKA

Answer 29

Hypokalaemia and Hyper - potentially life-threatening Hyperkal - extracellular shift of K+ due to acidosis hypo- due to correction of acidosis Hypoglycaemia - due to rapid correction of ketoacidosis - may get rebound ketosis Cerebral oedema - more common in children (70-80% of diabetes-related deaths) - Likely to be iatrogenic. - DKA = Hypervolaemic Hypoglycaemic state - drop in serum osmolality, if drops too quick you can get cerebral oedema.

Question 30

T1DM and Lorry Drivers

Answer 30

* Need to monitor blood sugars atleast twice daily * need to check 2 hours before starting their drive * Need to monitor every 2 hours.

Question 31

DKA

Answer 31

Triad: - Acidaemia (pH < 7.3) - Hyperglycaemia - Ketones An alternative metabolic pathway which occurs when the body requires energy but the body does not have enough insulin to turn sugar (carbohydrates) into energy Ketones are produced when the liver metabolises fatty acids. They are then released into the blood stream which if excessively released can turn the blood acidotic having global negative impact.

Question 32

DKA presentation

Answer 32

Presentation: - General drowsiness - Vomiting - Dehydration * In severe cases they could feel SOB with a tachypnoea in their bodies attempt to "blow off" CO2 to try and compensate for the metabolic acidosis. Treatment: FLUIDS, actarapid 50U and 50ml 0.9% saline mix infused at 0.1units/kg/hr. Potassium replacement. Glucose infusion once BM <14mmol Continue fixed rate insulin until ketones <0.3mmon/l, venous pH >7.3 and Bicarb >18mmol/L - Always continue the long acting insulins even on a sliding scale/fixed rate infusion.

Question 33

HHS

Answer 33

Typically those with T2DM are at risk of this - It is a complication where high blood sugar (>35) results in high osmolality without significant ketoacidoses - symptoms include marked dehydration, weakness, leg cramps, vision problems, and an altered level of consciousness - Acidosis is ABSENT as no switch to ketone metabolism - Osmolality >340mosmol/kg - Treatment: FLUIDS! Only give insulin if levels are not falling by 5mmol/L/hour, replace potassium, give DVT prophylaxis if no contraindication. * Keep blood glucose at least 10-15mmol for the first 24 hours to avoid cerebral oedema

Question 34

Hyperglycaemia

Answer 34

* High blood sugars * If you ever see high BM don't forget to check ketones and pH also! * Treatment: Fast acting insulin such as actarapid or novorapid

Question 35

Hypoglycaemia

Answer 35

* Blood sugars <4 * Symptoms: Drowsy, confused, coma * Treatment: - oral sugar (gluco-gel/lucozade) - Glucagon (however, if they dont have a good store of sugar within cells or you have maximised the glucagon receptors then this wont necessarily work) - Glucose/Dextrose infusion