Endocrinology and metabolic Flashcards
Type 1 diabetes
Autoimmune disease where the pancreas stops producing adequate insulin, cells in the body cannot absorb glucose from the blood = hyperglycaemia.
Associated with autoimmune thyroid disease, coeliac disease, Addison’s disease, vitiligo, and pernicious anaemia
ideal blood glucose is 4.4 to 6.1mmol/L
Clinical features of type 1 diabetes
- Diabetic ketoacidosis
- Classic triad of polyuria, polydipsia and weight loss (dehydration)
- Clinical diagnosis in adults if presenting with type 1 diabetes (random blood glucos for children in presence of symptoms - more details in paeds)
Diabetic Ketoacidosis
Consquence of inadequate insulin.
Key features:
- Hyperglycaemia
- Ketoacidosis (metabolic acidosis with high ketones and low bicarbonate - the kidneys producing bicarbonate are no longer able to compensate for the high ketone levels)
- Dehydration
- Potassium imbalance (insulin drives potassium into cells)
Presents as polydispia, polyuria, N+V, dehydration, weight loss, hypotension, altered consciousness
Diagnosis of DKA
ALL three
- Hyperglycaemia (e.g., blood glucose above 11 mmol/L)
- Ketosis (e.g., blood ketones above 3 mmol/L)
- Acidosis (e.g., pH below 7.3)
Management of DKA
Medical emergency! Seniors and HDU
FIG-PICK
- F – Fluids – IV fluid resuscitation with normal saline (e.g., 1 litre in the first hour, followed by 1 litre every 2 hours)
- I – Insulin – fixed rate insulin infusion
- G – Glucose – closely monitor blood glucose and add glucose infusion if < 14 mmol/L
- P – Potassium – monitor hourly initially
- I – Infection – tx underlying infection
- C – Chart fluid balance
- K – Ketones – monitor blood ketones, pH and bicarbonate
Normally, K+ infusion rate =< 10mmol/hr (arrhythmia risk). DKA up to 20mmol/L (expert supervision + central line)
Long-term management of type 1 diabetes
- Patient education
- Basal -bolus insulin regime - long-acting once a day, short-acting before each meal
- Moniotr dietary carb intake
- Monitor blood glucose (e.g. flash glucose monitors e.g. FreeStyle Libre 2)
- Insulin pumps
Long-term complications of type 1and type 2 diabetes
Macrovascular
- Coronary artery disease+
- Peripheral ischaemia > diabetic foot ulcers
- Stroke
- Hypertension
Microvascular:
- Peripheral neuropathy
- Retinopathy
- Kidney disease, particularly glomerulosclerosis
Infections:
- UTI
- Pneumonia
- Cellulitis especially feet
- Fungal e.g. oral and vaginal candidiasis
+ significant cause of death in diabetics
Type 2 diabetes
Combination of insulin resistance and recued insulin production causes persistent hyperglycaemia.
Pathophysiology
- Repeated exposure to glucose and insulin increases resistance of the body’s cells to the effects of insulin.
- More insulin needed to stimulate cells to take up and use glucose.
- Eventually, pancreas becomes fatigued and damaged from increased inslun production, unable to produce as much insulin.
Risk factors for type 2 diabetes
Non-modifiable risk factors:
- Older age
- Ethnicity (Black African or Caribbean and South Asian)
- Family history
Modifiable risk factors:
- Obesity
- Sedentary lifestyle
- High carbohydrate (particularly sugar) diet
Presentation of type 2 diabetes
- Tiredness
- Polyuria + polydipsia
- Unintentional weight loss
- Opportunistic infections e.g. oral thrush
- Slow wound healing
- Glycosuria on dipstick
- Acanthosis nigricans+
Consider TDM2 in pts with RFs, screen with HbA1c
+Thickening, darkening, velvety texture of neck/axilla/groin skin = insulin resistance
Define pre-diabetes
Indicates that patient is heading towards diabetes
HbA1c between 42 - 47mmol/mol
Diagnosis of type 2 diabetes
- HbA1c of 48mmol/mol or more
- Repeated after 1m to confirm dx unless symptoms/complications present
General management of type 2 diabetes
NICE recommends:
- A structured education program
- Low-glycaemic-index, high-fibre diet
- Exercise
- Weight loss (if overweight)
- Antidiabetic drugs
- Monitoring and managing complications
Tx targets for HbA1c (every 3 - 6m until under control):
- 48mmol/mol
- 53 mmol/mol if > 1 antidiabetic med
Medical management of type 2 diabetes
- 1st line: metformin + add SGLT-2 inhibitor (e.g. dapagliflozin) if CVD or HF or QRISK > 10%.
- 2nd line: add sufonlyurea, pioglitazone, DPP-4 inhibtor or SGLT-2 inhibitor
- 3rd line: Metformin + two 2nd line drugs OR insulin therapy (specialist nurses)
- 4th line: if BMI > 35, switch one drug to GLP-1 e.g. semaglutide
SGLT-2 increasingly being reocmmeded as older pts often ahve QRISK > 10%
Metformin: MOA and side effects
Increases insulin sensitivity and decreases glucose production by the liver. Does not cause weight gain and hypoglycaemia.
Side effects:
- GI symptoms: pain, nausea and diarrhoea - try modified release
- Lactic acidosis (due to AKI)
SGLT-2 inhibitors MOA and side effects
- Blocks action of sodium-glucose co-transporter 2 proteins in kidneys, they usually reabsorb glucose from urine back to blood.
-gliflozin e.g. dapagliflozin
- Side effects: glycosuria, genital and urinary infections (e.g. thrush) and DKA!
Can cause hypoglycaemia in combo with insulin or sulfonylureas
DPP-4 inhibitors and GLP-1 mmetics
Incretins = hormones in GI tract, released after large meals and reduce blood sugar.
GLP-1 (glucagon-like peptide-1) = incretin, inhibited by dipeptidyl peptidase-4 (DPP-4)
GLP-1 mmetics e.g. semaglutide, liraglutide. Side effects: reduced apetite, weight loss, GI symptoms e.g. nausea/diarrhoea
DPP-4 inhibitors increase GLP-1 by blocking DPP-4, do not cause hypoglycaemia, side effects: headaches, acute pancreatitis
Insulin: types and side effects
Diabetic specialist nurses
- Rapid-acting e.g. Novorapid (works in 10 mins, lasts 4 hours)
- Short-acting e.g. Actrapid, within 30 mins, lasts 8hrs
- Long-acting e.g. Lantus, within 1hr, last 24hrs
- Combos = rapid + intermediate-acting e.g. Humalog 25 (25:75)/50 (50:50)
Common exam scenario: discussing starting insulin with HGV driver, pts on insulin = strict criteria for driving = livelihood impact. Motivation for lifestyle changes and taking meds to avoid insulin.
What medication is 1st line for hypertension in patients with type 2 diabetes?
- ACE inhibitors - any age
- In CKD, ensure albumin-to-creatinine ratio (ACR) > 3mg/mmol
What medication is used to treat erectile dysfunction in type 2 diabetes?
Phosphodiesterase‑5 inhibitors (e.g., sildenafil)
What medications are used to treat gastroparesis (slow stomach emptying)?
Prokinetic drugs e.g. metoclopramide
What medications are used to treat neuropathic pain in diabetic neuropathy?
Amitriptyline – a tricyclic antidepressant
Duloxetine – an SNRI antidepressant
Gabapentin – an anticonvulsant
Pregabalin – an anticonvulsant
Type 2 diabetes: hyperosmolar hyperglycaemic state (HHS)
Rare, potentially life-threatening complication:
- Hyperosmolality (water loss = very concentrated blood)
- Hyperglycaemia
- Absence of ketones (different from DKA)
Clinical features: polyuria, polydipsia, weight loss, dehydration, dehydration, tachycardia and confusion
Mx: expereinced seniors, IV fluids (0.9% NaCl) and monitoring
