test 7 insulin and insulin analogues

Question 1

Basic facts on insulin

Answer 1

• Insulin is a polypeptide, consisting of 2 chains and connecting peptide (c-peptide). Referred to proinsulin.
• Proteases cleave the c-peptide from the A and B chains, producing insulin and c-peptide, and both are contained in secretory granules prior to release.
• Insulin undergoes significant hepatic degradation during its “first pass”. Hence, the half life of insulin is short and under 6 minutes. The half live of c-peptide is ~ 30 minutes.
• Thus, plasma insulin levels do not accurately reflect insulin production. C-peptide is a better index.

Question 2

Insulin preparations are categorized by their

Answer 2

• onset and duration of activity.

Question 3

how is insulin administered

Answer 3

• Insulin is generally administered by subcutaneous injections. Insulin may be given by an intravenous infusion in case of hyperglycemic conditions.
• Continuous subcutaneous infusion infusions (insulin pump) is another method of delivery.

Question 4

Rapid onset and short-acting insulin

Answer 4

• Modification of regular insulin produces fast-acting analogues with rapid absorption, quicker action, and shorter duration.
• Administered to mimic mealtime insulin levels and control for postprandial blood glucose.

Question 5

Intermediate-acting insulin

Answer 5

• Neutral protamine Hagedorn (NPH) is intermediate acting by the addition of zinc and protamine to regular insulin. (Humulin N, Novolin N)
• This complex is less soluble, delaying the absorption, resulting in a longer duration of action. Only given by SC.

Question 6

Long-acting insulin

Answer 6

• Long-acting insulin contain a fatty acid chain that binds to albumin. Slow dissociation from albumin results in long-lasting effects.
• Should only be given SC and not mixed with other types of insulin.

Question 7

Insulin combinations

Answer 7

• Premixed combinations such as NPH and regular insulin can be used. This cocktail decreases the number of daily injections.

Question 8

Importance of tight blood glucose regulation

Answer 8

• Risk of cardiovascular disease and neuropathies is enhanced in the diabetic patient and the incidence of diabetics undergoing CABG is increased.
• Severity (and complications) of cardiovascular complications is also increased by the diabetic state.
• Mortality rates after CAGB is also higher in diabetes.
• Aggressive treatment, although associated with increased frequency of hypoglycemia, this reduces the incidence of long-term complications

Question 9

The ADA recommends blood glucose levels

Answer 9

• below 150 mg/dl or glycated hemoglobin (HBA1c, a form of Hb) under 7% (normal is below 5.7%).
• HBA1c identifies 3 month average blood glucose control. As the average amount of plasma glucose in the blood increases, the fraction of glycated hemoglobin increases.
• With diabetes, as expected, both glucose levels and fluctuation of, increase thus resulting in higher HBA1c percentages.