Diabetes Flashcards
1
Q
D I A B E T E S M E L L I T U S
A
- A group of diseases
- Characterised by high blood glucose
- Defects in insulin action or production, or both
2
Q
T Y P E 1 D I A B E T E S
A
- Cells that produce insulin are destroyed
- Immune system destroys β cells of the pancreas
- Lymph nodes produce autoreactive T cells that attack islets
- Results in insulin dependence via IM injection
- Commonly detected before 30 years
- Referred to as insulin dependence diabetes (IDDM)
3
Q
T Y P E 2 D I A B E T E S
A
- Lack of insulin production
- Insufficient insulin action which makes the person insulin resistant
- Commonly detected after the age of 40 years
- Eventually leads to β cell failure resulting in insulin dependence
- Referred as non-inulin-dependent diabetes (NIDDM
4
Q
G E S T A T I O N A L D I A B E T E S
A
- Occurs during pregnancy
- Placental hormones induce insulin resistance in mother
- Increased risk of developing type II diabetes later in life
5
Q
T E S T I N G F O R D I A B E T E S
A
• Fasting Plasma Glucose Test (FPG) - Normal FPG is 4.0-5.5mM (72-99mg/dL) - Type I/II FPG is 4.0-7.0mM (72-126mg/dL) - > 5.9mM indicates diabetes • Oral Glucose Tolerance Test (OGTT) - Tested for 2hrs after glucose-rich test - 7.8-11.1mM indicates pre-diabetes - >11.1mM indicates diabetes
6
Q
D I A G N O S I S O F D I A B E T E S
A
• Blood glucose level above 11.1mM on two separate occasions OR
• Above 7mM in fasting state
• A level exceeding 11.1mM 2 hours after an oral glucose load
• Looking at glycosylation of proteins i.e. haemoglobin – adds sugar moieties to haemoglobin (HbA1c) excessively
- Normal HbA1c = 6.0%
- Prediabetes = 6.0-6.4%
- Diabetes = 6.5% or >
7
Q
T Y P E I C H A R A C T E R I S T I C S
A
- Partial or complete failure of β cells due to development of antibodies against them
- Carbohydrate stores in the liver become exhausted
- Proteins and amino acids are converted to glucose
- Triglycerides are mobilised from fat tissues and converted to ketone bodies in the liver resulting in ketoacidosis
- Fatty acids ketone bodies are utilised instead of glucose by many tissues including the brain
- Glucose gets lost in large amounts in the urine (glycosuria) carrying with it large amounts of water (polyuria)
- Patients begin to drink a lot of water to compensate for the water loss (polydipsia)
- Insulin replacement injections are mandatory for survival
8
Q
T Y P E I I C H A R A C T E R I S T I C S
A
- Insufficient insulin secreted by β cells
- Tissues are insensitive to insulin
- Low birth weight/malnutrition in early life with over nutrition in later life
- Overstimulation of β cells
- May be due to secretion of pro-insulin which is a less active precursor of insulin
- Small blood vessel abnormalities lead to damage in the kidneys, retina and peripheral nerves – leading to impaired sensation
- Damage to larger blood vessels leads to atherosclerosis causing heart attacks, strokes and peripheral vascular disease
- Leads to ulceration, necrosis, gangrene and loss of extremities
9
Q
S U L F O N Y L U R E A S
A
- Stimulate β cells to produce more insulin
- They interact with ATP-sensitive potassium channels blocking and closing them causing an accumulation of K+ and membrane depolarisation
- This in turn leads to the opening of calcium channels
- Leads to exocytotic release of insulin
- First generation: tolbutamide/tolazamide/chlorpropamide
- Second generation: glipizide/glyburide
- Third generation: glimepiride
- Across the generations the potency increases
10
Q
B I G U A N I D E S
A
- Improves insulin’s ability for glucose uptake especially in muscle cells
- Metformin improves insulin sensitivity by increasing uptake and utilisation of glucose in peripheral tissues
- Metformin enters the cell through organic cation transporter (OTC1)
- Increases AMP which activates AMPK (adenosine monophosphate kinase)
- AMPK increases glucose uptake by phosphorylating insulin receptor substrate
- This activates Akt activity which allows GLUT-4 translocation up to the membrane
- Glucose is either metabolised or stored as glycogen
- AMPK also decreases gluconeogenesis
- Widely used monotherapy
- May be used in combination with sulfonylureas
11
Q
E X E R C I S E
A
- Effective primary treatment of diabetes
- Increases muscle contraction producing ATP
- This generates AMP which activates AMPK
- AMPK promotes GLUT-4 translocation to sarcolemma which promotes glucose uptake
12
Q
T H I A Z O L I D I N E D I O N E S
A
- Increase insulin sensitivity especially in adipocytes
- This relies on the peroxisome proliferator-activated receptor (PPAR) α, δ and γ
- They belong to a steroid hormone nuclear receptor superfamily found in adipose tissue, cardiac muscle, skeletal muscle, liver and placenta
- Thiazolidinediones activate PPAR in particular γ
- Binds to a specific region of DNA to regulate transcription of genes involved in glucose and fatty acid metabolism
- Pioglitazone, Muraglitazar, Tesaglitazar
13
Q
A L P H A – G L Y C O S I D A S E I N H I B I T O R S ( A G I s )
A
- Block enzymes that digest starches
- Slow down the absorption of glucose
- Can also be found in natural products i.e. fungi
- Acarbose, miglitol
14
Q
M E G L I T I N I D E S
A
- Block ATP sensitive potassium channels and stimulate more insulin production
- Bind to a different site on the receptor to sulfonylureas
- Repaglinide, nateglinide
15
Q
I N C R E T I N S
A
- Insulin secretagogues – agents that promote insulin secretion
- Stimulate release of insulin by pancreas after eating even before glucose levels rise
- Inhibit glucagon release by the pancreas
- Slow down glucose absorption in to the bloodstream by reducing gastric emptying speed after eating – Makes you more satisfied after a meal
- Incretin mimetics are glucagon like peptide (GLP1) and DDP4 inhibitors
- GLP1 is metabolised by DDP4
- DDP4 inhibitors prevent the breakdown of GLP1 for example sitagliptin, saxagliptin and linagliptin
- DDP4 inhibitors increase cAMP in heart cells potentiating sympathetic β adrenoceptors – may promote apoptosis and heart failure
- GLP1 analogue is exenatide and GLP1 agonist is liraglutide
