2. Treatment of diabetes mellitus Flashcards
How is blood glucose normally controlled?
- Pancreas monitors blood glucose
- The liver is central to controlling glucose levels
If blood glucose is low…..
Glucagon is released from α cells + upper GI to stimulate glycogen breakdown + gluconeogenesis in the liver
if blood glucose is high….
• Insulin is released from β cells to stimulates the liver, adipose and muscle to take up glucose
Diabetes occurs when regulation of blood glucose is ______
Diabetes occurs when regulation of blood glucose is disrupted
Diabetes symptoms?
Fatigue Poor wound healing Blurred vision Thirst Numb/tingling hands and feet Sex porblems Weight loss suddenly Vaginal infections Hunger Frequent urination
Genetic influence on Type 2 diabetes?
- Gene set that causes greater insulin resistance
- Gene set that causes hunger
- Gene set that makes islets cells in the pancreas wear out early, so cannot make enough insulin
Type 1 diabetes:
- onset?
- Weight gain?
- Ketone level association?
- Treatment?
- Duration of treatment?
Often diagnosed in childhood
Not associated with excess body weight
Often associated with higher than normal ketone levels at diagnosis
Treated with insulin injections or insulin pump
Cannot be controlled without taking insulin
Type 2 diabetes:
- onset?
- Weight gain?
- Ketone level association?
- Treatment?
- Duration of treatment?
Usually diagnosed in over 30 year olds
Usually diagnosed in over 30 year olds
Often associated with high blood pressure and/or cholesterol levels at diagnosis
Is usually treated initially without
Sometimes possible to come off diabetes medication
Progression from pre-diabetes to type 2 DM?
- T2D - there is a natural progression from prediabetes to diabetes.
- This is due to a disruption of an individual’s ability to metabolise glucose.
- Might not yet appear to have diabetes but may have hyperinsulinemia due to lower insulin sensitivity
- Full diabetes progresses when beta-cell failure surpasses a critical threshold usually ~90%
Aim in type 1 DM treatment?
Aim in treating Type I diabetics - replacement therapy to normalize glucose levels 4-7 mM (pre- prandial/fasting).
Blood glucose levels >10 mM will overload the renal capacity and be detected in the urine.
Normal glucose level?
In normal individuals glucose level can rise higher but should be <7.8 mM two hours after a meal.
Why is insulin given parenterally?
- 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.
Name 4 different insulin formulations?
Insulin Lispro or Insulin Aspart
Neutral Protamine Hagedorn/Isophane Insulin
Insulin Glargine
Insulin Detemir
Insulin Lispro or Insulin Aspart, what is it?
Rapid-acting soluble insulin: Insulin Lispro or Insulin Aspart, designer insulins that prevent dimer formation allowing more active monomers to be bioavailable and used rapidly.
Neutral Protamine Hagedorn/Isophane Insulin, what is it?
Neutral Protamine Hagedorn/Isophane Insulin is an intermediate-acting insulin that precipitates insulin into suspensions which slowly dissolve.
Insulin Glargine, what is it?
Insulin Glargine is a longer acting designer Insulin which has decreased solubility at neutral pH - forms aggregates that slowly dissolve.
Insulin Detemir, what is it?
Insulin Detemir is a long-acting designer insulin with a fatty acid – this confers albumin binding, which slowly dissociates prolonging circulation.
Use of insulin formulations in T1 and T2 DM’s?
Insulin is used type 1 diabetic patients
T1Ds require insulin replacement so an intermediate-acting preparation or a more long-acting analogue is often combined with a short-acting analogue taken before meals.
1/3rd of T2D and for some women with gestational diabetes.
What is the difference and benefits of fixed and flexible insulin regimens?
- On a fixed dose insulin therapy, the amount of insulin taken at each meal will not vary from day to day.
- A FIXED dose therapy 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
- FLEXIBLE insulin therapy is used for patients that really understand glucose metabolism and gives patients more control of what they eat and how they balance their blood glucose levels but will take time and commitment to learn how best to adjust insulin doses.
- On a flexible insulin therapy patients choose how much insulin to inject at each meal and also allows doses to be varied in response to different carbohydrate quantities in meals.
Oral hypoglycemic tablets are used to…
Oral hypoglycemic tablets are used to alter glucose metabolism in T2Ds.
Principal oral hypoglycemia agent used in T2Ds?
Metformin
Action of metformin on insulin
Potentiates residual insulin sensitivity by increasing insulin sensitivity
Metformin actions of gluconeogenesis?
Acts to reduce gluconeogenesis in the liver, which is markedly increased in type 2 diabetes and opposes the action of glucagon.
