Diabetes Flashcards
Pathophysiology of T1DM
Type 1 diabetes is caused by the autoimmune destruction of the insulin- producing b-cells of the islets of Langerhans. Genetic and environmental factors are thought to play a part in the onset of the disease, which usually occurs in childhood and young adulthood.
Pathophysiology of T2DM
type 2 diabetes mellitus is characterized by peripheral insulin resistance, impaired regulation of hepatic glucose production, and declining β-cell function, eventually leading toβ -cell failure
Clinical presentation of T1DM
- Feeling more thirsty than usual
- Urinating a lot
- Losing weight without trying
- Blurry vision
- Ketosis
- Polyuria
- Polydipsia
Clinical presentation of T2DM
- Feeling more thirsty than usual
- Urinating a lot
- Losing weight without trying
- Fatigue
- Slow healing of wounds
- Frequent infections
Tests used for diagnosis of diabetes
BGLs
Oral glucose tolerance test (OGTT)
Glycosylated haemoglobin (HbA1c)
Long term complications of diabetes
- Glaucoma
- Cataracts
- gastroparesis
- Peripheral neuropathy
- Coronary artery disease
- Sexual dysfunction
Risk factors for T2DM
- Have prediabetes.
- Are overweight.
- Are 45 years or older.
- Have a parent, brother, or sister with type 2 diabetes.
- Are physically active less than 3 times a week.
- Have ever had gestational diabetes (diabetes during pregnancy) or given birth to a baby who weighed over 9 pounds.
Rationale for drug use Diabetes
Symptom relief (eg polyuria, polydipsia).
Control of blood glucose concentration.
Prevention or delay of long-term microvascular complications (eg nephropathy, neuropathy, retinopathy) and macrovascular events.
Management of T1DM
Basal bolus
Split mix
Pros and cons of basal bolus VS split mix
Split-Mixed Regime: 2 daily injections of a premixed insulin eg NovoMix 30 (30% short acting, 70% intermediate acting). Simple, convenient, lower risk of hypos, less flexible, can’t skip meals.
Basal-bolus Regime: 3 short acting (before meals), 1 long acting (eg Lantus) injections daily. Flexible, better BSL control, regular BSL monitoring needed, doesn’t cover snacks, risk of hypos.
Short acting VS long acting insulin
Short/rapid Acting: better control, more flexible but also more injections & more risk of hypos.
Long acting: fewer injections, less risk of hypos but also less flexible & looser control
Goals of T2DM management
- Relieve symptoms of hyperglycaemia (eg polyuria, polydipsia, as well as more subtle changes related to general wellbeing)
- Avoid acute complications of hyperglycaemia, such as diabetic ketoacidosis
- Avoid hypoglycaemia
- Reduce chronic complications.
Management strategies for T2DM
- Individualised treatment targets
- A healthy eating plan
- An exercise plan
- Ways to reduce cardiovascular risk, in particular smoking cessation, blood pressure control and dyslipidaemia management
- SNAP: quit Smoking, improve Nutrition (lose weight if needed), moderate Alcohol, increase Physical activity.
- Using noninsulin anti-hyperglycaemic drugs, if required
- Using insulin, if required
- Education in self-monitoring, adjusting treatment and how to cope with illness that affects the patient’s blood glucose concentration
- Screening for, and treating, complications of diabetes (see Diabetes: complications)
Steps for T2DM if exercise and diet alone don’t work
- Add Metformin
- Add an additional drug: either DPP-4 inhibitor or GLP-1 agonist
- Add a sulfonylurea. If this fails add a DPP-4 inhibitor OR GLP-1 agonist OR acarbose OR thiazolidinediones
- Add insulin
Alt: continue metformin and add a basal bolus
Drugs for Diabetes management
Both T1DM and T2DM
Insulin
Biguanides
T2DM only
Alpha-glucosidase inhibitors
Meglitinides
SGLT2 Inhibitors
DPP-4 Inhibitors
GLP-1 Agonists
Sulfonylureas
Thiazolidinediones
Indication
GLP-1 agonists
T2DM
MOA
GLP-1 agonists
Incretin therapies are utilised to help balance insulin levels in hormones in the GI tract.
Stimulating glucose-dependent insulin release from the pancreatic islets
Adverse effects
GLP-1 agonists
- Nausea
- Injection site reactions
- Headache
- Nasopharyngitis
Drug interactions
GLP-1 agonists
Other drugs that could lead to hypoglycaemia:
* insulins
* Sulfonylureas
Advantages
GLP-1 agonists
- No hypos
- Reduced CVD
- Improved NAFLD
- Once a week therapy possible
Disadvantages
GLP-1 agonists
- Requires injection
- Pancreatitis
- Thyroid cancer
- Gall bladder disease
Suffix
GLP-1 agonists
“glutide”
Drug class that ends in
“glutide”
GLP-1 agonists
Indication
Sulfonylureas
T2DM
MOA
Sulfonylureas
Increase pancreatic insulin secretion; may decrease insulin resistance.
Contraindications
Sulfonylureas
Ketoacidosis
T1DM
Adverse effects
Sulonylureas
Hypoglycaemia
Weight gain
Practice points
Sulfonylureas
- With food to decreased risk of hypoglycaemia
- Controlled release tablet – DO NOT CRUSH
- Avoid binge drinking, eat when drinking alcohol
Advantages
Sulfonylureas
- Relatively inexpensive
- Multiple formulations
- Minimal side effects
Disadvantages
Sulfonylureas
Progression of T2DM and increased insulin resistance
(secondary failure)
Indication
DPP-4 inhibitors
T2DM
MOA
DPP-4 inhibitors
Inhibit DPP‑4 thereby increasing the concentration of the incretin hormones GLP-1; glucose-dependent insulin secretion is increased and glucagon production reduced.
= reduction in BGLs
Contraindications
DPP-4 inhibitors
- Type 1 Diabetes
- Diabetic Ketoacidosis
What is Diabetic Ketoacidosis
Diabetic ketoacidosis aka DKA involves rapid progression (24hrs) prolonged hyperglycaemia, lathargy, polyuria, polydipsia, and weight progress to neurologic symptoms, including lethargy, focal signs
eventually coma
Adverse effects
DPP-4 inhibitors
- Upper respiratory tract infection
- Nasopharyngitis
- Urinary tract infection
- Headache
Practice points
DPP-4 inhibitors
Can be taken with/without food
Advantages
DPP-4 inhibitors
- No hypos
- Weight neutral
- Decrease postprandial glucose
Disadvantages
DPP-4 inhibitors
- Heart failure
- Pancreatic disease
- Arthritis
Suffix
DPP-4 inhibitors
“gliptin”
Drug class ending in
“gliptin”
DPP-4 inhibitors
Suffix
SGLT2 inhibitors
“flozin”
Drug class that ends in
“flozin”
SGLT2 inhibitors
Indication
SGLT2 inhibitors
T2DM
Think SGLT2 inhibitors
MOA
SGLT2 inhibitors
SGLT2 inhibitors function through a novel mechanism of reducing renal tubular glucose reabsorption, producing a reduction in blood glucose without stimulating insulin release.
Contraindications
SGLT2 inhibitors
Renal impairment
Adverse effects
SGLT2 inhibitors
- Genital infections
- Flu like symptoms
- Urge to urinate
Drug interactions
SGLT2 inhibitors
Diuretics
Both are acting on the kidneys reabsorption or excretion of substances combination may result in increased diuretic effect = hypotension and electrolyte imbalance
Practice points
SGLT2 inhibitors
- Patients on SGL2 inhibitors should be educated to check for ketones if they feel unwell even BSL if not elevated
- Ensure adequate water intake to avoid dehydration
Advantages
SGLT2 inhibitors
- No hypos
- Decrease heart failure
- Decrease renal function
- Once a day dose
Disadvantages
SGLT2 inhibitors
- Genetic myotic infections
- Increased LDL
- Increased risk of DKA
- Postural hypotension
Metformin aka…
Biguanide
Indication
Metformin
T2DM
MOA
Metformin
Reduces hepatic glucose production; increases peripheral utilisation of glucose
Contraindications
Metformin
- Patients with metabolic acidosis
- Renal dysfunction (eGFR <30mL/min)
- Impaired hepatic function
Adverse reactions
Metformin
- Gastrointestinal distress
- Vomiting
- Nausea
- Cramps
- Diarrhoea
- Anorexia
Practice points
Metformin
- Take with/after food to decrease stomach upset
- Controlled release table – DO NOT CRUSH
- Monitor renal function – every 4-6 months
- Watch for lactic acidosis
Advantages
Metformin
- Lower blood glucose levels
- Make patient feel better
- Improve long term health
- Inexpensive
- No hypos
- Once daily
Disadvantages
Metformin
- GI side effects
- B12 deficiency
- Need to monitor renal function
Indication
Insulin
Type 1 diabetes
Type 2 diabetes where: Inadqautely controlled with diet, exercise, and oral anti-diabetic drugs
MOA
Insulin
Insulin promotes glucose and amino acid uptake into muscle and adipose tissues, and other tissues except brain and liver. It also has an anabolic role in stimulating glycogen, fatty acid, and protein synthesis. Insulin inhibits gluconeogenesis in the liver. Insulin binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor.
Contraindications
Insulin
- Diarrhoea
- Fever
- Hepatic disease
- Hypoglycaemia
Adverse effects
Insulin
- Weight gain
- Lipohypertrophy
- Hypoglycaemia
Drug interactions
Insulin
- Oral contraceptives
- Antibiotics
- Nicotinic acids
Advantages
Insulin
- Lower blood glucose levels
- Make patient feel better
- Improve long term health
Disadvantages
Insulin
- Can lead to hypos
- Weight gain
Clinical signs of Hypoglycaemia
Signs and symptoms
Hypoglycaemia
- cool & clammy skin
- Sweating (diaphoresis)
- palpitations
- Fatigue and weakness
- Confusion
- Headache
- Shakiness
- unrousable
- Coma
Treatment
Hypoglycaemia
Conscious
* 15g carbs: juice, soda
* recheck BGL 15 mins later
* Give another 15g carbs
Unconscious
Administer IV 50% glucose injection
Signs and symptoms
Hyperglycaemia
- polyuria (peeing alot)
- Polydipsia (thirst)
- Polyphagia (hunger)
- Hot and dry skin
- Dry mouth
- Fruity breath
- Deep rapid breaths
- Numbness and tingling
- slow wound healing
- Vision changes
Treatment
Hyperglycaemia
Administer insulin
Test for ketones
Types of insulins
Rapid acting insulin
Short acting
Intermediate acting
Long acting
Mixed
Brain dump
Rapid acting insulin
onset: 5–15 minutes
peak: 0.5–1.5 hours
duration: 3–5 hours
give at start of meal
compared to standard insulin aspart:
marginally faster time to effect
may increase infusion site reactions and need for non-routine change of infusion pump
**Increased risk of hypos **
Drug names: Aspart (NovoRapid), lispro, glulisine
Brain dump
Short acting insulin
onset: 30 minutes
peak: 2–3 hours
duration: 6–8 hours
give within 30 minutes before meal
soluble insulin
clear solution
Drug names human / neutral insulin (Actrapid)
Brain dump
Intermediate insulin
onset: 1–2.5 hours
peak: 4–12 hours
duration: 16–24 hours
also known as intermediate-acting insulins
give once or twice daily
cloudy solution
Drug names Isophane insulin (Humilin NPH)
Brain dump
Long acting insulin
insulin detemir (Levemir)
onset: 1–2 hours
peak: 6–8 hours
duration: 12–24 hours
give once or, more commonly, twice daily (effect often wears off before 24 hours)
clear solution
do not mix with other insulins; inject separately
Insulin glargine 100 units/mL (Optisulin)
onset: 1–2 hours
no peak
duration: 24 hours
give once daily
provides a constant basal insulin level
do not mix with other insulins; inject separately
clear solution
the 2 strengths are not directly interchangeable
Brain dump
Mixed insulin
insulin aspart with aspart protamine (NovoMix 30)
onset: 10–15 minutes
peak: 1 hour
duration: 16–18 hours
also known as biphasic insulins
give once or twice daily
give immediately before meal(s)
cloudy solution
Indication
Glucagon
Hypoglycaemia
Taken orally
