Endo Flashcards
T1DM is an autoimmune disease caused by
- Destruction of pancreatic beta cells (Islets of Langerhans) by autoantibodies
- Complete insulin deficiency
- Reduced glucose uptake by cells (raised blood sugars)
4 key sx of T1DM
- Polyuria / glycosuria
- Polydipsia
- Weight loss
- Fatigue
Complications of T1DM:
* Microvascular (3)
* Macrovascular (4)
* Infective/immunosuppressed (3)
* Emergencies (3)
* Ischemic/poor wound healing (2)
- Retinopathy, Peripheral neuropathy, Nephropathy
- Stroke, PVD, CAD
- Pneumonia, UTIs, oral/vaginal candidiasis
- Hypo, DKA, HHS
- Ulceration, diabetic foot
Diagnosis for T1DM (5)
- note difference for sx and asx patients
- OGTT
- Fasting glucose test
- Autoantibody screen
- Urine dip (increased ketones & glucose)
- Serum C-peptide (reduced)
For symptomatic = OGT or GFT.
For asx = Evidence of raised OGT or FGT on 2 occasions
Cut offs for OGTT and FGT
> =7 mmol/l
=11.1mmol/l
What autoantibodies could be present in T1DM?
1. in 80%
2. In 70%
3. In younger kids
4. Rare
- Anti-GAD (glutamic acid carboxylase)
- Anti-islet cell (ICA)
- Anti-insulin (IAA)
- Insulinoma-associated 2 (IA-2A)
Normal physiology: GAD (in beta cells) produces GABA which produces insulin. In diabetes: anti-GAD –> reduced GABA, reduced insulin release.
Two main insulin regimes for T1DM are basal-bolus and pre-mixed. Explain the difference.
Basal-bolus = 4 inj/day
* One long acting in AM
* + 3 short/rapid acting, 30 mins prior to meals
Pre-mixed/biphasic = 2 inj/day, e.g. 70/30
* 70% intermediate acting
* 30% short/rapid acting
* Each given before breakfast & dinner
Insulin therapy
Rapid acting
Short-acting (soluble)
Intermediate
Long
- Aspart, lispro
- Actrapid, Humulin.S
- Isophane
- determir, glargine
Duration of action: 3-5, 5-8, 12-18, up to 24
How does the insulin pump work?
- Continuous S/C Insulin Infusion - rapid acting
- Delivered at an adjustable constant basal rate
- boosts at meal times
What sx do these cause in DKA?
* Increased blood glucose
* Increased ketones
* Electrolyte imbalance
* Hypovolaemia/dehydration
- Polyuria and polydipsia
- Nause and vomiting
- Abdominal pain and muscle cramps
- Shock –> seizure/coma
DKA - diagnosis
Considerations to investigate (2)
Blood glucose >11mmol/l
Ketonaemia >3 or >2 ketonuria
Acidosis pH <7.3
Bicarb <15mmol
- Consider ECG/CXR for arrythmias/pneumonia as underlying cause
most dangerous aspects of DKA that require correcting by fluid resus are (3)
- K+ imbalance
- Dehydration
- Acidosis
Insulin normally drives potassium into cells - in DKA (lack of insulin) K+ can start off high
Management of DKA (4 key points)
FIGP –> ICK
* IV fluids - 0.9% normal saline - most impotant to do first
* IV insulin infusion- e.g. Actarapiad 0.1unit/kg/hr
* Add Glucose infusion to insulin infusion- once glucose levels have e.g. <14mmol/l
* Potassium? - correct low K+ as a result of insulin treatment to prevent arrythmia, normal =3.5-5.5
* Infection? Manage underlying cause
* Chart - fluid chart
* Ketones - monitoring, 1hr then 2hrly
Insulin - long acting; stop short acting temporarily
What if the ketonaemia and acidosis haven’t returned to normal within 24hr?
Reqs senior review from endocrinologist
normally should have resolved by then –> pt back to subcut
Pre-diabetes Hba1c mmol/mol
42-47
Targets for HbA1c in T2DM:
* Lifestyle, or Lifestyle + Metformin
* On an antidiabetic causing hypo / already on drug but HbA1c has risen to 58
- <48
- <53
1st line treatment T1DM:
Exception to rule: If cardiovascular risk factors (Q-risk >10, risk of CVD or existing chronic heart failure):
Metformin 500mg OD –> titrate
Metformin + SGLT2 inhibitors
Stepwise treatment T2DM
1. If target 48
2. If target 53
3. “
4. “
- Lifestyle only
1. Metformin
2. + AD
3. +1AD or + Insulin
4. Swap 1AD for GLP-1 mimetic
1st line treatment if Metformin contra-indicated
SGLT2 inhib
Metformin
Class
MOA
Side effects
Note - metformin is what % renally excreted?
- Biguanide
- Insulin sensitiser (increases cell sensitivity to insulin)
- Reduced glucose outpout from liver (reduced gluconeogenesis, glycogenolysis)
- GI upset & lactic acidosis
- 100% renal excretion - CI in AKI/alcohol abuse
Sulfonylureas (Gliclazide/Glimepiride)
- Stimulates insulin release form the pancreas (blocks ATP dependent K+ channels on beta cells)
- Risk of Hypo and weight gain
Click, GIMME
Similar drug to Sulphonylurea useful for patients with renal insufficiency
Repaglinide
DPP4 Inhibitors (Sita/Lina-gliptins)
- Increase levels of GLP-1 (inhibiting DPP4 prevents its breakdown)
- incretin effect - enhanced effect of insulin in response to food
* hypoglycaemia
pancreatitis
Thiazolidinedione (Pioglitazone)
- PPAR-y agonist (on adipose tissue)
- Promotes genetic transcription –> insulin senitisation (& glucose metabolism)
- SEs; weight gain, fluid retention- heart failure, #s, bladder cancer
- CI liver disease
- Low risk of hypo
PARTY –> Fatty food (adipose tissue), wearing jeans (alters gene transcription) and taking drugs (steroid type SEs; weight gain, fluid retention), long term partying –> #s, bladder cancer. People with liver disease shouldn;t be drinking at parties. Low risk of hypo —>hyper at parties.
SGLT2 inhb (Empagiflozin)
- Increased urinary excretion of glucose
- Blocks SGLT2 on proximal tubule
- UTI, candidiasis. DKA & gangrene
- Must check renal function before initiating, avoid if eGFR <60
GLP-1 Analogues (Sub-cut) (Liraglutide)
Mimics GLP-1 (incretin)
INhibits glucagon release,
Reduced appetite (reduces greediness)
Gastric SE: Pancreatitis
**
HHS (emergency for T2 diabetics) - describe the diagnostic features
- Hyperglycaemia >30mmol
- Hyperosmolarity >320mOsm/kg
- Absence of ketones/ no significant ketonaemia (<3)
- Absence of acidosis
Causes osmotic diuresis and severe Gdehydration