Treatment of Diabetes Mellitus Flashcards
Identify the main organs, and hormones involved in control of blood glucose. When are they produced, where, and what is their effect ?
1) Pancreas GLUCAGON -When: When blood glucose is low -Where: alpha cells and upper GI -Effect: stimulate glycogen breakdown and gluconeogenesis
INSULIN
- When: is blood glucose is high
- Where: Beta cells
- Effects: stimulates muscle and adipose tissue to uptake glucose redistributing Glut4 to the cell membrane
2) Liver
- Controls glucose levels through gluconeogenesis and glycogen synthesis
Identify risk factors for type I diabetes.
- Genetic prediposition
- Exposure to viral infections
- Diet
- Vitamin D deficiency
What proportion of beta cells need to be destroyed in order for clinical type 1 diabetes to present ?
• Clinical T1DM does not present until >80-90% of beta cells have been destroyed
Describe clinical features and their timeline in type 1 diabetes.
- Clinical course of T1DM is characterised by the rapid onset of osmotic symptoms, including polyuria, polydipsia, nocturia, thirst, weight loss and fatigue along with hyperglycaemia (possibly also osmotic lens change), while being clinically dry, and having increased urinary ketones.
- Two thirds of patients present with life-threatening diabetic ketoacidosis at diagnosis (DKA)
What is the main treatment option for type 1 diabetes ?
Insulin therapy (to replace deficient hormone)
To what extent is genetic predisposition present in type 2 diabetes ?
Genetic predisposition may be present
Identify risk factors for type 2 diabetes.
Metabolic syndrome (starts with energy imbalance, high food consumption, and low energy expenditure) Stress
Describe the pathology underlying type 2 Diabetes.
- Fat deposits in visceral organs leads to altered insulin signalling, insulin resistance and beta cell damage
- Often impaired insulin receptor signalling leads to insufficient transport of glucose into tissues
What proportion of beta cells need to be destroyed in order for clinical type 2 diabetes to progress ?
• T2DM progresses when ~80-90% of beta cells fail
What is the main treatment option for type 2 diabetes ?
• Principle for treatment: try to correct energy imbalance, increase sensitivity to insulin, increase natural insulin secretion, supplement with insulin, or decrease blood glucose
When is each type of diabetes usually diagnosed ?
Type 1- in childhood
Type 2- in over 30 year olds
To what extent are DM types 1 and 2 associated with excess body weight ?
Type 1- NOT associated with excess body weight
Type 2- YES associated with excess body weight
To what extent are DM types 1 and 2 associated with higher than normal ketone levels at diagnosis ?
Type 1- Often associated with higher than normal ketone levels at diagnosis
Type 2- Often associated with high blood pressure and/or cholesterol levels at diagnosis
To what extent can type 1 and 2 diabetes be controlled without medication ?
Type 1- Cannot be controlled without taking insulin
Type 2- Sometimes possible to come off diabetes medication
Describe progression to type 2 diabetes.
- T2DM - there is a natural progression from prediabetes to diabetes, due to disruption of individual’s ability to metabolise glucose
- Individuals with prediabetes have lower insulin sensitivity that results in hyperinsulinemia (i.e. due to insulin resistance, plasma insulin has to increase). At the point where insulin resistance overcomes ability to make insulin, blood glucose begins to increase.
- Diabetes progresses when the beta-cells are failing, resulting in low insulin secretion in combination with low insulin sensitivity
What amount of fasting plasma glucose indicates diabetes ? What amount of random glucose ?
• >7 mM Fasting plasma glucose = diabetes
OR
random glucose measurements about 11.1 mM
How is blood glucose monitored ?
• Effective diabetes management is usually measured by self-monitoring of blood glucose through sampling capillary blood after a finger prick
-NICE recommends monitoring this 4 times a day for individuals with type 1 DM (one before each meal, and at bedtime)
2) HbA(1c) measurement is also used to diagnose diabetes and evaluate glucose levels over a longer time-frame
How is HbA(1c) measurement useful for measuring blood glucose ?
• HbA1c provides an integrated measure of control over the lifespan of red blood cells ~120 days – levels above 7% indicate diabetes
What range of glucose do we aim for in type 1 DM ?
• Aim in treating Type I diabetics - replacement therapy to normalize glucose levels 4-7 mM (pre- prandial/fasting).
To what extent should individual glucose levels rise about 8 mM after a meal ?
• In normal individuals glucose level can rise higher than normal range 4-7 but should be <7.8 mM two hours after a meal
At which blood glucose level will glucose be detected in the urine ?
• Blood glucose levels >10 mM will overload the renal capacity and be detected in the urine
Identify the main kinds of insulin formulations which exist. State the duration of action of each.
- Rapid-acting soluble insulin: Insulin lispro, Insulin aspart, and Insulin glulisine- rapid onset (10-20 minutes) and short duration (2-5 hrs)
- Isophane insulin (Neutral Protamine Hagedorn; NPH) is an intermediate- acting insulin
- Insulin glargine is a longer acting designer Insulin
- Insulin detemir is a long-acting designer insulin
- Insulin degludec is a long-acting designer insulin
What is the duration of action of insulin ?
• Durations of activity can be rapid-acting (within 15 min) to long-duration peakless forms (some active >24 hours)
How is insulin administered ? Why ?
- Insulin is administered parentally because it is a protein that would be destroyed/digested by the gut if taken orally.
- For routine use it is given subcutaneously and by IV infusion in emergencies (only soluble forms)
- Can be given as a continuous subcutaneous infusion (CSII), giving background insulin (but also “allows for adjustable boluses to cover ingested carbohydrates”
Describe the main dissolution properties of the main formulations of insulin.
- Insulin lispro, Insulin aspart, and Insulin glulisine- prevent dimer formation allowing more active monomers to be bioavailable
- Isophane insulin (Neutral Protamine Hagedorn; NPH)- recipitates into suspensions which slowly dissolve
- Insulin glargine- has decreased solubility at neutral pH - forms aggregates that slowly dissolve
- Insulin detemir- had a FA, a fatty acid, which confers albumin binding, which slowly dissociates prolonging circulation
- Insulin degludec- has a fatty acid, which results in multi-hexamer formation at injection site with slow release
What proportion of type 2 DM patients use insulin ?
1/3
Graph glucose infusion rate of the main types of insulin formations, over time.
Refer to slide 12
When are fixed dose insulin therapies used ?
• A fixed dose therapy (i.e. amount of insulin taken at each meal does NOT vary from day to day) can help to simplify the understanding of blood glucose results but does not offer the flexibility of how much carbohydrate patients choose to consume at each meal
