Flashcards in Clinical (Weeks 1 + 2 - Diabetes) Deck (115):
What antibodies might be present in T1DM?
When is a person though to have T2DM?
When they don't have:
- Monogenic DM
- Other condition/Treatment causing secondary DM
What are some risk factors for T2DM?
PMHx of MI/CVA
What are some symptoms of DM?
What pancreatic diseases can cause secondary DM?
What endocrine diseases can cause secondary DM?
What drugs can induce DM?
What genetic disorders can result in DM?
What are the principles of T2DM treatment?
Alleviate hyperglycaemia symptoms
Improve glycaemic control
- Weight gain
What do biguanides do?
Increase insulin sensitivty
What dose of biguanide do we usually start with?
500mg once/twice daily
Give an example of a biguanide
Does metformin cause weight loss/no change/weight gain?
How much can metformin reduce a patient's HbA1c?
Does metformin cause hypoglycaemia?
Not if used as monotherapy
What effect does metformin have on a patient's lipid status?
Decreased triglycerides and LDL
Is metformin safe in pregnancy?
What are some side effects of metformin?
- If in renal failure
- If in cardiac/liver failure
In what patient's should metformin be stopped?
- If eGFR 150 micromol/L
- Advanced cirrhosis
- Liver failure
When might metformin be beneficial?
In what patient's should metformin be used with caution due to the increased risk of lactic acidosis?
How do sulphonylureas work?
Give examples of SUs
What complications can metformin prevent?
What complications can SUs prevent?
How do SUs manage hyperglycaemia?
Decrease HbA1c by 15-20 mmol/mol
Increased insulin secretion
More rapid action than metformin
When are SUs used?
1st line in underweight T2DM
2nd line as add-on to metformin/intolerant to metformin
What are some side effects of SUs?
- Caution in elderly/alcoholics/liver disease
What is the only available thiazolidinedione?
How do TZDs work?
They are PPARγ agonists - Increase insulin sensitivity
What effect do TZDs have on weight?
Increase is common:
- Due to increased S/C fat and fluid retention
Why can TZDs increase the risk of CHF?
What other effects do TZDs have?
Prevent macrovascular complications
Increase hip fracture risk
How dies Dapaglifozin work?
Act on the incretin pathway:
- SGLT2 inhibitor
What are the incretins?
Stimulate intestinal secretion of insulin:
- GIP from K cells
- GLP-1 from L cells
What type of drug is exenatide?
GLP-1 receptor agonist
How does exenatide work?
Increased insulin secretion (no hypos)
Decrease gastric emptying -> Early satiety
What are some side effects of exenatide?
Give some examples of DPP-IV inhibitors
What drugs are less potent; GLP-1 receptor agonist, DPP-IV inhibitors?
- Only work on what's present
- DLP-1 decreased in T2DM
What are some benefits of DPP-IV inhibitors?
Increase insulin secretion (no hypos)
How do SGLT2 inhibitors work?
Decrease sugar uptake by ~25%:
- Glycosuria (~80g/day)
- ~1lb decrease in weight/week
What side effects are common with SGLT2 use?
Sugar in urine:
What type of insulin is used in T2DM?
When is bariatric surgery considered?
What is acanthosis nigricans?
What is acanthosis nigricans a sign of?
Insulin resistance ie T2DM
What are some microvascular complications of T2DM?
- Digestion/Urination problems
What are some macrovascular complications of T2DM?
How can alcohol result in hypoglycaemia?
Increases insulin activity
How long do rapid-acting insulin analogues last and give examples?
How long do short-acting insulin analogues last and give examples?
- Humulin S (human insulin)
- Insuman rapid
How long do intermediate-acting insulin analogues last and give examples?
- Humulin I
- Insuman basal
How long do long-acting insulin analogues last and give examples?
- Lantus (Levels remain high at end of day)
- Levemir (Levels reduced at end of day)
How can we evaluate glucose control?
Home blood glucose monitoring
What does glycated Hb give us an idea of?
Measure of blood glucose over 6-8 weeks
What is the ideal HbA1c target?
What are the downsides to injectable insulin?
It's into the S/C tissue (instead of portal blood)
Peaks too slow -> Can't prevent post-meal hyperglycaemia
What factors affect the absorption of injectable insulin?
When is IV insulin prescribed?
Fasting patients who cannot tolerate PO intake
What monitoring is important during the delivery of IV insulin?
Hourly BG (5-12 mmol/L)
Free of hypos
Ketones if BG > 12 mmol/L
Transition from IV to S/C
What are some indications for a pancreas transplant?
Imminent/ERSD with kidney transplant
What are the four mains steps in islet transplantation?
1. Donation and retrieval
2. Islet isolation
- Pancreas digestion
- Islet purification
3. Islet culture (24 hours)
What are some signs and symptoms of hypoglycaemia?
Weakness + fatigue
What can severe hypoglycaemia lead to?
What is the immediate treatment of hypoglycaemia?
1. 15-20g of glucose/simple carbohydrates
2. Recheck BG after 15 minutes
3. If still hypo -> Repeat
4. Once BG normal -> Small snack if next meal >1hr away
Treatment of severe hypoglycaemia?
1mg glucagon injection:
What is the definition of impaired hypoglycaemia awareness?
During DKA what hormones increase in levels?
What does the activation of certain hormones in DKA cause?
Decreased glucose utilization:
What does hyperglycaemia result in?
-> Electrolyte loss
-> Dehydration and Hyperosmolar state
What is the biochemical diagnosis of DKA?
1. Ketonaemia > 3mmol/L OR Ketonuria > ++
2. BG > 11.0mmol/L OR Known DM
3. Bicarbonate <15mmol/L OR venous pH <7.3
What can commonly precipitate DKA?
Non-adherence to therapy
Newly diagnosed DM
What signs and symptoms are caused by the following in DKA:
- Osmotic changes
- Ketone body related
- Polyuria -> Dehydration
- Abdominal pain
- Kussmaul's respiration
- +/- Ketone breath
What other biochemical changes can be seen in DKA?
Potassim is often raise (> 5.5mmol/L)
Creatinine is often raised
Sodium is often decreased
- β-hydroxybutarate in blood
- Acetoacetate in urine
What causes death in DKA?
- Aspiration pneumonia
- Cerebral oedema
How is DKA managed?
- Fluid -> 0.9% NaCl
-> Dextrose when glucose
What HbA1c levels indicate the following:
What fasting glucose levels indicate the following:
What 2hr OGTT levels indicate the following:
What is the normal blood ketone level?
What is the typical biochemistry in Hyperglycaemia Hyperosmolar Syndrome?
Higher glucose than DKA
Significant renal impairment
Increased osmolarity (~400)
Where does lactate originate from?
How is lactate cleared?
Aerobic conversion -> Pyruvate -> Glucose
What is the normal range for lactate?
How do we calculate the anion gap?
[Na+ + K+] - [HCO3- + Cl-]
What is the normal ion gap?
What causes of acidosis present with a normal ion gap?
- Bicarbonate is reduced
- Cl- is raised
What causes of acidosis present with a high ion gap?
- Bicarbonate reduced
- Replaced by sulfate, phosphate
- Cannot be replaced sufficiently
What is Type A lactic acidosis?
Associated with tissue hypoxia:
- Cardiogenic shock
- Hypovolaemic shock
What is Type B lactic acidosis?
Associated with DM:
- Metformin in illness/renal failure
What are the targets for each of the following in DM?
- Total cholesterol
BMI -> 25
HbA1c -> 7% (75mmol/mol)
How do we treat T2DM in the following situations:
- BMI >25
- Metformin up to 1g tds
What anti-lipid therapies are recommended in diabetes?
- Increase dose to lower cholesterol
What is peripheral neuropathy?
Pain/Loss of feeling in:
What is autonomic neuropathy?
Changes in bowel habit
What is proximal neuropathy?
Pain in thigh/hips/buttocks:
- Leg weakness (Amyotrophy)
What factors precipitate neuropathy?
Increased length of DM
Poor glycaemic control
T1DM > T2DM
A diabetic patient presents with numbness, tingling and sharp pains in their foot. It is very sensitive to touch and they have lost their balance.
Peripheral nerve damage
What complications can peripheral neuropathy result in?
What is the step up treatment for painful neuropathy?
1. Simple analgesia
2. TCAs (amitryptiline at night)
A patient presents with constipation, nausea, bloating and a loss of appetite. He has difficulty swallowing and has known, poorly controlled DM.
How can gastroparesis be treated?
What is diabetic nepropathy also known as?
What can result in diabetic nepropathy?
Decreased renal function:
- GFR down by 1ml/min/month
Accelerated vascular disease
How is diabetic nephropathy screened for?
Urinary albumin creatinine ratio (ACR)
Confirm with EMU
U+Es -> eGFR
What is a normal ACR?
What is defined as microalbuminuria?
30-300mg/L of urine
What is macroalbuminuria?
> 300mg/L of urine
What can cause a false positive urinary albumin excretion rate? (UAER)
What are cotton wool spots a sign of in diabetic retinopathy?
What are hard exudates a sign of in diabetic retinopathy?
Lipid break down products
Which of the following drugs doesn't cause erectile dysfunction:
- Beta blcoerks
Put the following steps in atheroslcersosis development in order:
- Macrophages ingest LDL to become foam cells
- Fibrous cap forms from smooth muscle migration
- Cap rupture
- Monocytes migrate into epithelium
- Smooth muscle degenerated by activated macrophages
- Cytokines produced result in smooth muscle migration
- Platelets aggregate at site of rupture and thrombus forms
1. Monocytes migrate into epithelium (become macrophages)
2. Macrophages ingest LDL to become foam cells
3. Cytokines produced result in smooth muscle migration
4. Fibrous cap forms from smooth muscle migration
5. Smooth muscle degenerated by activated macrophages
6. Cap rupture
7. Platelets aggregate at site of rupture and thrombus forms