Diabetes and Endocrine

Question 1

Type II Diabetes

What is the basic medical pathway following trial of diet, exercise and weight reduction to lower HbA1c for patients with type II diabetes melitus?

Answer 1

Question 2

Type II Diabetes

What is the mechanism, indication and adverse effects metformin?

Answer 2

1. Mechanism: biguanide; decreases gluconeogenesis, increases peripheral utilisation of glucose . Requires residual pancreatic islet cells
2. Indication:
   
   1. 1st line if dietary control fails. May combine with sulphonylurea and insulin.
   2. Benefits; less hypoglycaemia, less weight gain, lower plasma insulin concentration, reduced CV mortality
3. Adverse effects:
   
   1. anorexia, nausea, vomiting, diarrhoea, abdominal pain all common - slowly increase dose.
   2. Lactic acidosis is a rare but serious consequence if renal impairment

Question 3

**Type II Diabetes **

In which situations is metformin contraindicated, and what are possible risks?

Answer 3

Concern that lactic acidosis may be induced in renal impairment:

1. Avoid if eGFR < 30mls/min or creatinine > 150 micromol/L
2. Temporarily contraindicated in acute situations where lactic acidosis may occur:
   
   1. Tissue hypoxia likely (sepsis, respiratory failure, hepatic impairment, recent MI)
   2. Use of iodine containing contrast media (restart when GFR returns to normal)
   3. General anaesthetic (stop on morning of surgery, restart when RF normal)
   4. Pregnancy

Question 4

Type II Diabetes

What is the mechanism, indication and adverse effects of sulphonylureas (e.g. gliclazide)?

Answer 4

1. Mechanism: increase insulin secretion (require residual pancreatic beta activity) by binding to K_ATP channel in beta cells, inducing membrane depolarization and opening Ca²⁺channels causing insulin secretion. Extra-pancreatic activity if used long term.
2. Indications: usually if metformin contra-indicated / not tolerated. More likely to cause **hypoglycaemia and weight-gain **(but ess common in short acting sulphonylureas eg. gliclazide)
3. Adverse effects:
   
   1. ​Occasional: GI disturbance (nausea, vomiting, diarrhoea, constipation). Hypoglycaemia
   2. Rare: abnormal LFT causing cholestatic jaundice, hepatitis, hepatic failure. Hypersensitivity (skin reaction) can occur in first 6 - 8 weeks.

Question 5

Type II Diabetes

What are the contra-indications and cautions of sulphonylureas?

Answer 5

1. Contraindications:
   
   1. ​Insulin therapy instituted temporarily during intercurrent illness (MI, coma, infection, trauma)
   2. Ommitted on the morning of surgery - insulin required for ensuing hyperglycaemia
   3. Severe renal / hepatic impairment
2. Cautions:
   
   1. ​Hypoglycaemia: risk in elderly, those with mild / moderate renal and hepatic impairment.
   2. Tolbutamine (short acting) and gliclazide (hepatic metabolism) safe in renal impairment, but monitor BM cautiously.

Question 6

Type II Diabetes

What is the mechanism of acarbose and when is it considered for use? What is the main adverse effect?

Answer 6

1. Mechanism: inhibitor of intestinal alpha-glucosidase (breaks down starch / disaccharides to glucose) .
2. Indication: small but significant effect to lower BM, can be used as adjunct to glucose metformin / sulphonylurea
3. **Adverse effects: **flatunence, decreases with time

Question 7

Type II Diabetes

What is the mechanism of GLP-1 analogues (e.g. exenatide), indication and adverse effects

Note: administered as an injection

Answer 7

1. Mechanism: GLP-1 (glucagon like peptide) is produced in the small intestine in response to nutrients and exerts downstream effects to stimulate insulin release from pancreatic islets, slow gastric emptying and inhibit glucagon secretion.
2. **Indication: **third line, useful if BMI > 35 as promotes weight loss.
3. **Adverse effects: **GI: nausea, reduced with dose titration

Note: administered by Injection

Question 8

Type II Diabetes

What is the mechanism of DDP-4 inhibitors (gliptins), and when are they indicated?

Answer 8

1. Mechanism: DDP-4 is an enzyme expressed ubiquitously on most cell types that deactivates bioactive peptides, including GLP-1. Share downstream effects as GLP-1 agalogues of increased insulin and reduced glucagon secretion
2. **Indication: **
   
   1. second line instead of sulphonylurea in patients at **significant risk of hypoglycaemia or its consequences **(e.g. elderly, operating heavy machinery)
   2. third line in combination with metformin and sulphonylurea

Question 9

Type II Diabetes:

What is the mechanism of thiazolidinedione (e.g. pioglitazone), indication and contra-indications?

Answer 9

1. Mechanism: bind to and activate PPARs (peroxisome proliferator-activated receptors) and regulate gene expression to increase insulin sensitivity of adipose, muscle and liver.
2. Indication: second line in combination with metformin if contraindications. Risk of hypo- if combined with sulphonylurea or insulin
3. **Contra-indication: **heart failure (exacerbates fluid retention). Can cause bone-fracture.

Question 10

Type II Diabetes

When is insulin therapy considered in type II diabetes, and what are typically regimens:

1. When added to oral therapy
2. When replacing oral therapy

Answer 10

Considered if inadequate control from diet and oral hypoglycaemics. May be complicated by weight gain and hypoglycaemia, but risk reduced if combined with metformin

1. Adding: as long acting insulin / isophane, given at bed time
2. Replacing: twice daily injections of biphasic insulin, or multiple insulin regimen.

Question 11

Type II Diabetes

What types of insulin are available for the treatment of type I and II diabetes, how long do they take for action, duration of action, and give an example of each?

Answer 11

1. Rapid: e.g. NovoRapid, Onset 5-10 minutes, duration 2-4 hours
2. **Short: **e.g. Humulin S, Actrapid, Onset 30 minutes, duration 4-6 hours
3. Intermediate: e.g. e.g. Humulin I, Onset 2 hours, duration 18-24 hours
4. Long: e.g. Lantus / levemir (note: different from intermediate as no peak action, provide flat basal level). Onset 1-3h, duration 12-24h.

Question 12

Diabetes

What are typical insulin regiments that may be trialled?

Answer 12

1. Multiple injection: short or rapid acting insulin analogue before meals, with intermediate or long acting insulin once or twice daily.
2. Short or rapid acting insulin analogue mixed with intermediate or long acting insulin, once / twice daily before meals
3. Intermediate or long acting insulin once or twice daily (basal), +- short /rapid insulin before meals (basal bolus)

Question 13

Diabetes

Which factors determine insulin regimen suitability?

Answer 13

1. Compliance / resistance to injections
2. Risk of hypoglycaemia
3. Lifestyle
4. Age
5. Complications

Question 14

Diabetes

What factors are important to remember with insulin injection technique?

Answer 14

1. Depth of penetration affects absorption
   
   1. Shallow insertion into dermis causes pain and poor absorption
   2. Deep injection into muscle causes pain and more rapid absorption
   3. 5-8mm needles usually appropriate; avoid long needles in short patients
   4. Insert perpendicularly to pinched skin, inject over 5-6 seconds
2. Rotate injection sites to reduce skin or fat atrophy and hypertrophy. Lack of rotation causes daily variation in control
3. Absorption is quickest from the abdomen, slowest from legs and buttocks
4. Skin temperature changes absorption (> if warmer)

Question 15

Diabetes

What “sick day” rules should be followed by patients taking insulin who become unwell

Answer 15

1. Don’t stop taking insulin, even if not eating. Dose may need to be increased
2. Test BM more frequently (> 4 times per day)
3. Drink lots of fluids to prevent dehydration
4. Replace normal meals with carbohydrate drinks if necessary
5. Test urine for ketones
6. Seek medical advice if developing vomiting, or unsure what to do

Question 16

Diabetes

What regimen is suitable when a patient with Type I Diabetes requires IV infusion of insulin for 12h or longer (e.g. usually for major surgery)

Answer 16

1. Reduce usual insulin by 1/2 to 1/3rd on the nigh before, omit morning insulin. Ideally patient is first on list
2. Early on day of operation:
   
   1. IVI dextrose 5% with KCl 20mmol/L (providing patient not hyperkalaemic) and influse at 100mL/hr
   2. Use pre-mixed solution of soluble insulin 1U/mL in NaCl 0.9% (prescribe as Human soluble insulin 50U in 50mL IV), and infuse I.V with syringe pump piggy-backed to IVI.
   3. Note: dextrose essential to avoid intraoprative hypo; aim for 4-10mmol glucose intraoperatively
3. Post op:
   
   1. Check capillary BM post-op, then 2hrly (or hrly if uncontrolled)
   2. Check U&E and lab blood gluocse daily while on infusion
   3. Continue infusion until next meal, with S/C short acting insulin 20mins before meal
   4. Stop IV Insulin and Dextrose 30-60mins after S/C injection

Question 17

Diabetes: Diabetic Ketoacidosis

What are the recommendations for insulin influsion for a patient presenting in Diabetic Ketoacidosis?

Answer 17

1. Give as an IVI of **fixed rate **insulin (0.1unit/kg until pH > 7.3). Do not use variable rate in this setting.
2. Start at 50units in 50ml via pump (available in ready mixed syringe)
3. Rate of infusion based upon weight: 70-79.9kg = 8ml/h, 80 - 89.9kg = 9ml/h etc.
4. Monitoring includes:
   
   1. Glucose → if not falling by 3mmol/h and capillary ketones by 0.5mmol/hr increase infusion rate by 1ml / h
   2. Continue fixed rate until:
      
      1. Ketones < 0.3mmol
      2. venous pH > 7.3
      3. Bicarbonate > 18mmol/L

Question 18

Diabetes: Hypoglycaemia

How are hypoglycaemic episodes treated in:

1. Conscious patients
2. Unconscious patients

Answer 18

1. Conscious: oral treatment → aim for 10-20g PO as liquid or granulated sugar:
   
   1. 10g in 2 teaspoons of sugar, 5 jelly babies, 90mL coca-cola
   2. Hypostop → thick glucose gel; given bucally, useful if patients vomiting
   3. **Sustained carbohydrate **e.g. sandwhich, milk, biscuits to prevent another ↓
2. Unconscious:
   
   1. 50mL glucose 20% by IVI → into **large vein **through large-gauge needle
   2. Glucagon injection, with carbohydrates ASAP to restore liver glycogen. Inappropriate in chronic hypoglycaemia. If no effect in 10 minutes give intravenous glucose

Question 19

Anti-Thyroid Drugs: Carbimazole

Carbimazole is first line for treatment of Grave’s disease, followed by PTU. What is the mechanism, doseage, monitoring and adverse effects of carbimazole?

Answer 19

1. Mechanism: Carbimazole and PTU both interfere with synthesis of thyroid hormones
2. **Dose: **15-40mg daily → continued until patient becomes euthyroid (4 - 8 weeks), then reduced to maintenance (5 - 15mg)
3. **Monitoring: **TSH, free T3 and T4 every 4-6 weeks
4. Adverse effects:
   
   1. ​Common: rashes and pruritis → give antihistamines or switch to PTU
   2. **Rare: **
      
      1. ​agranulocyosis (all patients should report if sore throat / fever so FBC can be done)
      2. hypothyroidism: from overtreatment. If pregnant → foetal goitre

Question 20

Anti-thyroid Drugs

What treatments other than carbimazole alone may be used in the treatment of hyperthyroidism? What is the treatment of a thyroid storm?

Answer 20

1. Carbimazole and Levothyroxine → blocking-replacement regimen; higher dose (40-60mg) carbimazole, with levothyroxine to replace. Treatment for 18 months
2. Propranolol: rapid relief of thyrotoxic symptoms, used in combination with antithyroids, or as an adjunct to radioactive iodine
3. Thyrotoxic crisis:
   
   1. IV fluids
   2. Propranolol (5mg)
   3. Hydrocortisone (100mg every 6hrs, as sodium succinate)
   4. Oral iodine, carbimazole or PTU → may require NG tube

Question 21

Hypothyroidism

What is the treatment of hypothyroidism, how is treatment monitored and adjusted. Which situations is sub-clinical hypothyroidism present?

Answer 21

1. **Treatment: **thyroxine → start with 100mcg in young, 25 - 50mcg in elderly or those with ischaemic heart disease due to risk of angina
2. **Monitoring: **TSH lags 6 weeks behind dose changes; allow adequate intervals for measurement and changes
3. Dose **adjustment: **increase by 25mcg at a time, with aim for TSH in the lower part of normal
4. Sub clinical hypothyroidism