Diabetes Flashcards by Devini de Alwis

What is glucose?

Ubiquitous energy source stored as glycogen in the body

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What are the types of glycaemia and what are the defined levels?

Hypoglycaemia <2.5mmol/L
Fasting normoglycaemia 3-5mmol/L
Post-prandial normoglycaemia 7-8mmol/L
Hyperglycaemia >10mmol/L (sustained)

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Describe the homeostasis of hyperglycaemia

Blood glucose rises after food intake or glycogenolysis in the liver
Pancreatic beta cells release insulin
Insulin acts on liver, muscle cells, adipocytes and CNS to increase glucose uptake
Blood glucose returns to normal

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Describe the homeostasis of hypoglycaemia

Blood glucose falls following fasting or overnight fast
Pancreatic alpha cells release glucagon
Glucagon acts on liver, muscle cells and adipocytes to stimulate conversion of glycogen to glucose
Blood glucose returns to normal

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How is proinsulin converted to insulin?

23 amino acids removed (C-peptide subunit) - leaves A and B chains

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Where is insulin produced and stored?

Beta cells of islets of Langerhans

Stored in secretory granules as a crystal structure (complex with zinc)

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What is the half life of insulin?

3-5 minutes

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Where is insulin metabolised?

The liver

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Describe the physiology of the islets of Langerhans

Clusters of alpha, beta, delta, epsilon and pancreatic polypeptide cells

Innervated and vascularised

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What hormones are released from the pancreas? What are their functions?

Insulin and glucagon - blood glucose control

Somatostatin and ghrelin - control of growth hormone production, increase appetite and fat storage

Pancreatic polypeptide - Regulation of pancreatic secretions

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How is insulin released?

Glucose taken up by beta cells

K-channels close causing depolarisation

Ca2+ channels open

Influx of Ca2+ causes release of insulin from granules

Gut hormones (e.g. GLP-1) released into blood, activation of receptors of beta cells results in insulin release

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How does insulin reduce blood glucose?

Increased GLUT-4 presence and activity to increase glucose uptake

Decreased breakdown of glycogen

Increased fat storage and protein production (to make more insulin)

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What are the homeostatic mechanisms for blood glucose control in the CNS?

Increase/decrease appetite

Increase/decrease energy use

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What are the homeostatic mechanisms for blood glucose control in the GI tract?

Increase/decrease glucose uptake from food

Incretins secreted from GI tract in response to nutrient ingestion, stimulates insulin production in beta cells

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What are the homeostatic mechanisms for blood glucose control in the liver?

Increase/decrease endogenous glucose production

Increase/decrease glycogen storage

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What are the homeostatic mechanisms for blood glucose control in the Islet cells?

Release of insulin and glucagon

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What are the homeostatic mechanisms for blood glucose control in the kidney?

Increase/decrease loss of glucose through reabsorption

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What are the homeostatic mechanisms for blood glucose control in the skeletal muscle?

Increase/decrease glucose uptake and utilisation

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What are the homeostatic mechanisms for blood glucose control in the adipocytes?

Increase/decrease lipolysis and glucose uptake

Increase decrease leptin

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What is the function of leptin?

Signals to hypothalamus when enough fat is stored so appetite is reduced - calorie regulation

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What is diabetes?

Hyperglycaemia as a result of little/no insulin production or decreased insulin sensitivity

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What are the therapeutic targets for diabetes treatment?

Promoting excretion of glucose through kidneys
Delay glucose absorption from GI tract
Promote insulin release from islet cells
Sensitise targets to endogenous insulin
Replace islet cells

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What are the non-medical causes of hypoglycaemia?

Irregular/insufficient food intake
Insulin overdose
Sulfonylurea overdose

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What are the medical causes of hypoglycaemia?

Insulinoma
Hyperinsulinism
Nocturnal type 1 diabetes
Post gastric bypass hypoglycaemia
Transient neonatal hypoglycaemia

What are the symptoms of hypoglycaemia?

``` Hunger Sweating Shaking Increased HR Headache Nausea Confusion and drowsiness Odd behaviour Incoherent speech Poor coordination ```

How is hypoglycaemia treated if glucose is unavailable?

Glucagon as IM, IV or SC injection

How do diazoxide treatments work? What are the side effects?

Reverse action of glucose on beta cells (reduce insulin production) Anorexia, N&V hypotension, oedema, tachycardia, arrythmias, hypertrichosis

How does type 1 diabetes present? (4 Ts)

Polyuria: Increased need to go to the TOILET Polydipsia: Increased THIRST Fatigue/Lethargy: TIRED Weight Loss: THINNER

Why are most type 1 diabetics diagnosed?

Present with DKA

Describe the physiology of DKA

Increased glycongeolysis and gluconeogenesis plus reduced glucose uptake - hyperglycaemia Increased urine output containing glucose - dehydration Suppressed lipolysis - Excess fatty acids metabolised to ketones Result in acidosis

What are the symptoms of DKA?

Tachypnoea Altered mental state (drowsiness to coma) N&V, abdo pain

What should be done in the first 4 hours of DKA? (Adults)

Fluid resus in first hour Variable insulin infusion 1-2 hours after fluid, hourly cBG Max. 2L maintenance fluid (glucose + NaCl) with KCl daily once cBG <15mmol/L Reduce insulin when ketones <3mmol/L Once able, give food, SC insulin and then stop maintenance infusion 30mins later

How does DKA treatment differ in children?

50% of normal maintenance fluid - 2ml/kg/hr (<10kg), 1ml/kg/hr (10-40kg), 40ml/hr (>40kg) Replace fluids over 48 hours Give SC insulin when cBG <14mmol/L, ketones <3mmol/L, acidosis is treated and oral fluids tolerated

How many fatalities in children from DKA and why?

0.15-0.31% due to cerebral oedema

What are the symptoms of cerebral oedema?

Bradycardia Altered mental state Dilated pupils

How is DKA avoided?

``` Good glucose control Early T1DM diagnosis Education Appropriate monitoring Symptom recognition ```

What causes increase and decrease in blood glucose?

Increase: Food intake, stress Decrease: Exercise, insulin

What is basal bolus insulin?

First line T1DM Long acting given at night (and morning) Rapid acting with meals TDS (dose depends on carbs)

What is biphasic insulin?

Short/rapid acting insulin in protamine suspension BD depending on when biggest meals are (e.g. morning and dinner time) Duration up to 12 hours, onset 30mins T2DM

What are the advantages and disadvantages of biphasic insulin?

Ad.: Less injections, no carb counting Disad.: Not great for control

Give 4 examples of biphasic insulins

Humulin M3 Insuman Comb 15/25/50 Humalog mix 25/50 Novomix 30

What is one downside of exogenous insulin?

Difficult to mimic rapid response due to time for onset of action

Describe rapid acting insulin and give 3 examples

5-15min onset, peak 30-90mins, 4-6hr duration Humalog (Lispro), Novorapid (Aspart), Apidra (Glulisine)

Describe short acting insulin and give 3 examples

30-60mins onset, peak 2-3hrs, 8-10hr duration, soluble Human Actrapid, Humulin S, Insuman Rapid

Describe intermediate acting insulin and give 3 examples

2-4hr onset, peak 4-10hrs, 12-18hr duration Isophane insulin Human Insulatard, Humulin I, Insuman Basal

Describe long acting insulin and give 3 examples

2-4hr onset, 20-24hr duration, no peak as flat profile Basal insulin output profile of non diabetics Low risk of nocturnal hypo Lantus, Abasaglar (Glargine), Levemir (Detemir)

Describe super long acting insulin and give 2 examples

OD, flat insulin profile, up to 42hr duration For nocturnal hypo/forget to inject 3rd line Tresiba (Degludec), Toujeo (Glargine 300units/ml)

When is non human insulin used?

When human insulin is not tolerated

When should blood glucose be checked?

Before meals, bed and driving

How can blood glucose be checked?

Finger prick machine May tell insulin dose if time set before so predicted cBG can be accurate

What is DAFNE?

Dose Adjustment For Normal Eating - Short acting insulin dose altered depending on carb content and portion size to reflect natural insulin response

What is defined as hypoglycaemia in diabetics on medication?

cBG <4mmol/L

How is hypoglycaemia treated?

Replace glucose with short, then long acting carbs Home: Lucozade/sweets, then meal Hospital: Dextrose tabs/glucogel, then meal or snack

How is hypoglycaemia treated if unconscious?

IM Glucagon then 10% glucose 100ml/hr

What is SICK monitoring?

Sugar Insulin Carbs Ketones

What should be done if ketones are present?

Rapid acting insulin and fluids

How is insulin injected?

Stomach, thighs or hips at 90 degree angle Half an hour before meals Lispro, Aspart and Glulisin 5 mins before meals

What types of insulin pens and needles are there?

Refillable, prefilled or single use Needles come in different lengths and thicknesses

What is an alternative if patient has frequent hypos/HbA1c not controlled?

Continuous SC insulin infusion