Diabetes 🍬

Question 1

Define type 2 diabetes

Answer 1

Insulin resistance and a relative insulin deficiency resulting in persisting hyperglycaemia

Question 2

Risk factors for type 2 diabetes

Answer 2

Obesity
Physical inactivity
Family history
Ethnicity
Polycystic ovary syndrome
Diet
Statins / corticosteroids

Question 3

Diagnosing type 2 diabetes

Answer 3

Persistent hyperglycaemia and / or blurred vision / unexplained weight loss / recurrent infections / dark pigmentation appearing in folds of skin / risk factors

Question 4

Values of persistent hyperglycaemia

Answer 4

HbA1C 48 + mmol / L
Fasting plasma glucose 7+ mmol / L
Random plasma glucose 11 + mmol / L

Question 5

Metformin action

Answer 5

Decreases gluconeogensis
Decreases intestinal absorption of glucose
Increases insulin sensitivity by increasing peripheral glucose uptake and utilisation (kidneys)

Question 6

Metformin benefits

Answer 6

Weight neutral
Beneficial effect on ischaemic cardiovascular disease risk
Little risk of hypoglycaemia

Question 7

Metformin cautions

Answer 7

NOT FOR EGFR OF LESS THAN 30 / creatinine 150+/ CKD stage 4
GI side effects (change to MR)
Can cause B12 deficiency (test if fatigue)
Stop if unwell / vomiting (renal failure)
Stop for 48 hours following radiological investigation involving IV contrast media (renal failure)

Question 8

SGLT 2 inhibitor action (sodium-glucose co-transporter 2) (flozins)

Answer 8

Reversibly inhibits sodium-glucose co-transporter 2 in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose secretion (can cause UTIs)

Empagliflozin

Cardioprotective: use in Q risk 10+ / established CVD

Question 9

SGLT 2 inhibitor benefits

Answer 9

Decreases HbA1C levels
Increased WEIGHT LOSS
decreased blood pressure

Question 10

SGLT 2 inhibitor cautions

Answer 10

Genitourinary infections
Increased risk of diabetic ketoacidosis
Increased risk of acute kidney injury
Increased risk of amputation (Cana…flozin)
Increased risk of hypotension

Question 11

Sulphonylureas (gliclazide) action

Answer 11

Augments insulin secretion. Only effective when some residual pancreatic beta-cell activity is present.

Question 12

Sulphonylureas (gliclazide) benefits

Answer 12

Well established
Good if underweight
Rapid decreased blood glucose

Question 13

Sulphonylureas (gliclazide) cautions

Answer 13

Risk of hypoglycaemia: higher risk for older people. Dangerous due to falls risk.
Weight gain

Question 14

Dipeptidyl peptidase inhibitors (DPP - 4 inhibitors) action

Answer 14

Inhibits DPP-4 to increase insulin secretion and lower glucagon secretion.
Linagliptin
Mono / dual / triple therapy
DPP4i + Metformin or SU or Pio
DPP4i + Metformin + SU

Question 15

DPP-4 inhibitor benefits

Answer 15

Lower risk of hypo
Generally weight neutral
HbA1C reduction

Question 16

DPP-4 inhibitor cautions

Answer 16

Joint pain: discontinue
Acute pancreatitis
Increased risk of HF
Except for linagliptin, check eGFR as dose changes needed with reduced renal function

Question 17

Diet & lifestyle advice

Answer 17

Encourage fibre, low glycemic-index source of carbs (fruit + veg), low fat dairy , oily fish
Control intake of saturated fats, high-sugar drinks, high salt foods
Discourage foods marketed for diabetics, limit substitution of sucrose and excessive energy intake
Individualise alcohol + regular meal pattern

Question 18

How is insulin secreted?

Answer 18

STEPS:
1. Potassium ions flow out of the cell under normal conditions.
2. Glucose diffuses into the cell via facilitated diffusion when there is a concentration gradient.
3. Glucose is respired and ATP is produced.
4. ATP binds to potassium channels to close them.
5. Potassium ions remain in the cell because the channels are closed.
6. Accumulation of potassium ions increases the potential difference of the membrane.
7. Change in potential difference causes voltage-gated calcium ion channels to open, allowing calcium ions (Ca²⁺) to enter.
8. Calcium ions bind to vesicles containing insulin, causing them to fuse with the membrane and release insulin.

Basically Beta Cells respond both to the absolute glucose concentration and to the rate of change of blood glucose

Normally potassium ions flow out of cell, when there is a conc gradient glucoses moves into cell – it is respires and ATP produced

ATP binds to potassium channels to close them which means potassium ions stay in the cell as the channels have been closed

Because of the accumulation of potassium in the cell, the potential diff of the membrane changes which then causes calcium channels to open

Calcium enters the cell, binds to vesicles containing insulin and causes them to fuse with membrane

Question 19

Type 2 diabetes sick day rules

Answer 19

Unwell: (infection and high temperature) body less responsive to the insulin produced naturally or may be injecting
Being unwell therefore usually makes blood glucose levels rise, even if eating less than usual

• Continue to take tablets even if not eating
• If taking metformin or an SGLT2 inhibitor and you are vomiting or have diarrhea, you should stop this medication immediately as you may be at risk of dehydration. You will need a check for ketones if you take an SGLT2 inhibitor
• If you take a tablet which helps your body to produce more insulin, such as gliclazide, you may need to increase the dose or even need insulin injections for a short time while you are ill. You will need meal replacements if you are unable to eat normally
• Contact your GP if you feel like your symptoms are prolonged or getting worse
• If you are injecting a non-insulin glucose-lowering medication and develop acute abdominal pain, nausea and vomiting, stop the injections immediately and seek urgent medical attention
For insulin:

Never stop or omit insulin
• Check blood glucose more frequently, for example every 1-2 hours including through the night
• Consider checking blood or urine ketone levels regularly, for example every 3-4 hours including through the night, and sometimes every 1-2 hours depending on results.
•If the urine ketone level is greater than 2+ or blood ketone levels are greater than 3 mmol/L, the person should contact the GP or diabetes care team immediately.
• Maintain their normal meal pattern (where possible) if appetite is reduced
• Aim to drink at least 3 L of fluid (5 pints) a day to prevent dehydration
• Seek urgent medical advice if they are violently sick, drowsy, or unable to keep fluids down
• When feeling better, continue to monitor their blood glucose carefully until it returns to normal

Rest: avoid strenuous exercise
Prevent dehydration by drinking plenty of sugarfree fluids
Treat symptoms such as a high temperature or a cough with basic over-the-counter medicines such as painkillers and cough syrups (sugar free)
If able to monitor blood glucose, check at least 4 times daily while unwell

Question 20

Key points that people living with diabetes should consider when fasting during Ramadan

Answer 20

Break the fast immediately if blood glucose drops below 4 mmol/ L (hypo) or rises above 16.7 mmol/L (hyper)
Avoid strenuous exercise
Drinking plenty of water during non-fasting hours is crucial to prevent dehydration. Aim to drink at suhoor and iftar, and avoid sugary drinks that can lead to blood sugar spikes. Including fruits like watermelon, cucumber, and oranges can help you stay hydrated throughout the day. Dehydration can cause serious problems, so prioritise water intake and watch for signs of dehydration such as dry mouth, dark urine, or dizziness.

Eat balanced meals: When breaking your fast try to avoid sweets and foods high in carbs Instead, opt for foods high in protein and slow-releasing carbs and also try to incorporate healthy fats into your diet
Consult GP prior
Check blood glucose more often

Avoid heavy, fried foods and sugar-laden drinks

Question 21

How the body responds to food

Answer 21

• Before eating, glucose levels low
• Eat food - make glucose
• Spike in glucose level (post prandial spike)
• Insulin released
• Levels of glucose decreases (glucose uptake into cells or stored)

Blood glucose levels must be maintained within a narrow range: 4-6 mol/I, because the brain has an absolute dependency on glucose as its source of fuel

Question 22

How does insulin decrease blood glucose?

Answer 22

increasing glucose uptake into muscle and fat via Glut-4 (insulin regulated glucose transporter)

increasing glycogen synthesis

decreasing gluconeogenesis

decreasing glycogen breakdown.

Question 23

Glucagon

Answer 23

Glucagon is a fuel-mobilising hormone, stimulating gluconeogenesis and glycogenolysis, also lipolysis and proteolysis. It increases blood sugar and also increases the force of contraction of the heart (positive inotrope)

When glucagon is released, it binds to the receptors on its target cells:
activates the adenyl cyclase, stimulating the production of cAMP, which will be the eventual trigger for the reactions.

Question 24

Effects of glucagon

Answer 24

• the polymer glycogen is broken down into the monomer glucose, this is called glycogenolysis
• more fatty acids are used in respiration
• amino acids and lipids are converted into glucose by a process known as gluconeogenesis

Question 25

Effects of insulin

Answer 25

more glucose channels are inserted into the cell surface membrane, so that more glucose can enter the cell

glucose inside the cell is polymerised into glycogen by a process known as glycogenesis (happens in the liver)

more glucose is converted into fats, and more glucose is respired

Question 26

Type 1 diabetes

Answer 26

Caused by an absolute insulin deficiency, usually resulting from autoimmune destruction of the insulin-producing beta cells in the pancreas

Genetic factors

Environmental factors: can trigger the development of autoimmunity to the pancreatic beta cells

diet, vitamin D exposure, obesity, early-life exposure to viruses associated with islet inflammation (such as enteroviruses), and decreased gut-microbiome diversity.

Question 27

Type 1 diabetes diagnosis

Answer 27

Symptoms of diabetes - polyuria, abnormal thirst, unexplained weight loss
PLUS
• Serum glucose level ≥ 11.1 mol/I taken randomly, or
• Serum glucose level > 7 mmol/I for fasting patients, or
• Serum glucose level ≥ 11.1 mol/I two hours after a glucose tolerance test

• When no symptoms present, at least two serum glucose measurements made on different days must be within diabetic range for confirmation of diagnosis

• Random levels of 5.6-11.1 mol/I may indicate pre-diabetic state of reduced glucose tolerance (need glucose tolerance test - fast overnight, ingest 75 glucose drink next day in morning, then take levels)

• Don’t use dipstick test to diagnose - when plasma glucose exceeds renal threshold (around 10 mol/l), glucose appears in urine, glycosuria

Question 28

Microvascular Complications

Answer 28

• Microvascular -damage to small blood cells caused by hyperglycemia

• Nephropathy
  • diabetic kidney disease is caused by damage to small blood vessels in kidney (compromised filtration and then protein in urine), leads to increased risk of CVD, made worse by high blood pressure
• Retinopathy
  diabetic retinopathy caused by small blood vessel damage to retina, leads to progressive loss
  of vision and possible blindness.
• Neuropathy
  • diabetes causes nerve damage through different mechanisms, including direct damage by the hyperglycemia and decreased blood flow to nerves by damaging small blood vessels

• painful neuropathy does not respond to conventional analgesia

• diabetic foot problems can also occur - ulceration and limb amputations autonomic neuropathy (late stage), neurons of autonomic nervous systems damaged due to chronic hyperglycaemia - sweating, postural hypotension, gastroparesis, diarrhoea, also heart, bladder and sexual function affected

Question 29

Macrovascular Complications

Answer 29

• Macrovascular - damage due to large blood vessels caused by hyperglycaemia

• Coronary arteries - development of atheroscelerosis, increased risj CVD (myocardial infarction, heart failure, stroke, peripheral arterial disease)
Normally after eating, insulin induces lipase which breaks down fat particles which are then absorbed into fat cells and recombined into triglycerides and stored
When no insulin is present, fats stay in circulation and are not stored = hyperlipidaemia happens which leads to fat depositing in arterial walls - atherosclerosis

Question 30

Metabolic Complications (Acute)

Answer 30

• Diabetic ketoacidosis, DKA, ‘high BG+ketones+acidosis

• Happens gradually over days
• Insulin deficiency - increase in counter regulatory hormone production (glucagon, cortisol, growth hormone and catecholamines) -enhances hepatic glycogenolysis (glycogen breaks down in liver to make new glucose) and gluconeogenesis (glucose made from other substrates) - hyperglycaemia
  Enhanced lipolysis (as glucose not being used) - larger amounts of serum fatty acids are metabolized as alternative energy source (ketogenesis) -> accumulation of ketones -> metabolic acidosis
• Patient hyperventilates to correct acidosis, acetone breath (pear drops)
• Vomiting - dehydration plus decreased pH - coma, medical emergency

Hyperosmolar non-ketotic hyperglycaemia, HONK, ‘high
BG+dehydrated+no ketones’
• Happens gradually over days
• Blood glucose generally >40 mmol/|

• Hypoglycaemia
- Adverse effect of insulin treatment, blood glucose levels less than 3.5 mmol/l
- Severe hypoglycaemia - convulsions, inability to swallow, loss of consciousness, coma (4-10% deaths due to hypoglycaemia)

Question 31

Non-diabetic insulin profile

Answer 31

Non-diabetic person: insulin continually released to provide background (basal) insulin to meet continuous metabolic demands, after meal/snack, a bolus of insulin released in proportion to the carbohydrate load eaten

Question 32

Type 1 diabetes annual review

Answer 32

• Measure HbA1c and BMI

• Reiterate targets for HbA1c and glucose self monitoring
- 4 x per day (including before meals and before bed), more if doing sport, pregnant, travelling
- Fasting plasma glucose level of 5-7 mol/L on waking
- Plasma glucose level of 4-7 mol/L before meals at other times of the day
- For adults who choose to test after meals, plasma glucose level of
5-9 mmol/L at least 90 minutes after eating

• Check BP, full lipid profile, thyroid profile, renal profile, ACR urine sample

• Check attending screening appts for eye disease and foot problems

• Check smoking status - discuss cessation if applicable

• Assess mood (depression, anxiety, eating disorders)

• Monitor for neuropathy (erectile dysfunction, neuropathic pain, delayed emptying of stomach)

• Check injection sites - check it’s being rotated, no lipohypertophy (lumps under skins)

• Review hypo awareness (see DVLA info) and weight (s/e weight gain - insulin is a growth hormone so you get hungry)

• Check been offered flu vaccination