6.1.4 Management of T1D and Insulins

Management of Type 1 Diabetes and Insulins

You will recall that in T1DM there is a total (or nearly total) insulin deficiency.  As such, administration of exogenous insulin is the cornerstone of BGL management (and ketosis prevention) in T1DM.  T1DM is also referred to as insulin-dependent diabetes mellitus (IDDM).   The onset of T1D peaks in adolescence and early adulthood but can occur at any stage. The symptoms of T1D are common to those of hyperglycaemia, including polyuria, polydipsia and weight loss.

Patients with T1DM require lifelong exogenous insulin.  It is the most potent therapy available for the reduction of BGL.Insulin is a peptide hormone and susceptible to degradation in the gastrointestinal tract.  Insulin is administered parenterally by subcutaneous (usually) or intravenous (infrequently) administration to avoid degradation in the gastrointestinal tract.  If insulin intended for subcutaneous administration is inadvertently administered intramuscularly it typically leads to much faster onset of action and a higher risk of hypoglycaemia.

Insulin binding to insulin receptors results in increased expression of glucose transporters (GLUT4) on the cell wall which allows glucose to move across the cell membrane into muscle and adipose cells.  This intracellular shift leads to significant BGL reduction.  In the liver, insulin leads to a reduction in glycogenolysis, reduction in gluconeogenesis and increases glycogenesis resulting in a net reduction of BGL by reducing hepatic glucose release and increasing glucose conversion to stored glycogen.

T1D is managed using human or analogue insulin therapy. Insulin therapy can be:

  • Multiple daily injections (usually 4 injections a day);
  • Continuous subcutaneous insulin infusion (CSII) by portable pump; or
  • Premixed insulin (usually 2 injections a day).

Targets for insulin therapy are:

  • Blood Glucose concentration of 4-8 mmol/L and
  • Glycated haemoglobin (HbA1c) Less than 7% (53mmol/L)

Hypoglycaemia and Adverse Effects

Insulin’s potency also results in the highest risk of hypoglycaemia.  The risk of hypoglycaemia is impacted by a variety of factors including insufficient food intake, exercise, alcohol consumption, illness, type of insulin, administration site and technique amongst numerous other factors.  Read the following patient handout and refer back to chapter 6.1.2 on the acute complications of diabetes for more information about hypoglycaemia.

Patients using insulin require frequent BGL monitoring and adjustment of their insulin dose based on these results and carbohydrate intake.  Equipping patients and carers with the skills required to self-manage their insulin dose is very important.

Insulin use is also associated with weight gain (remember insulin facilitates lipogenesis and resists catabolism) and injection site reactions.

Types of insulin and insulin devices

Insulin and glucose homeostasis in healthy individuals. Source: Owens D, et al. Insulins today and beyond. Lancet. 2001;358(9283):739-746.

 

As you can see above, insulin release consists of two portions, a background ‘basal’ release and a prandial ‘bolus’ release in response to eating and subsequent increase in BGL, amino acids and incretins (we will discuss incretins next week!)

Much effort has been made to alter the peptide chains of exogenous insulin to produce pharmacokinetics that better replicate the pancreatic insulin release characteristics in health individuals.  Substitutions of amino acids within the A and B chain tails have been utilised to adjust the onset and duration of action of various insulin analogues.

 

Substitutions of amino acids within the peptide chains can alter the pharmacokinetics of exogenous insulin. Source: Donnor and Sarkar. Insulin- Pharmacology, Therapeutic Regimens and Principles of Intensive Insulin Therapy. In: Endotext

These modifications have resulted in a variety of different insulin formulations.  They are typically classified according to their duration of action (rapid, intermediate, or long-acting).  Some insulin products contain a mixture of both rapid and intermediate or long-acting insulin (pre-mixed).

 

Source: Wong J, et al. The introduction of insulin in type 2 diabetes mellitus. Aust Fam Physician. 2015;44(5):278-283. Originally source J Am Osteopath Assoc 2009;109:26–36.

 

Considering insulin release in the healthy individual, you can see how a combination of a long-acting insulin such as insulin glargine once daily and rapid acting insulin such as insulin aspart prior to meals begins to emulate normal insulin release.  This results in 4 injections per day.  In addition to insulin injections, patients will be doing a finger prick BGL test prior to insulin administration (in most circumstances).  Premixed insulins can reduce the number of injections per day as they are often administered only twice daily but don’t replicate normal insulin release as well.

 

Source: Magaji. Inpatient Management of Hyperglycemia and Diabetes. Clin Diabetes 2011;29(1):3–9.

Explore the different types of insulins available in Australia using the link below.  You will not be expected to remember all the different types of insulin available, but we will cover some common examples in the GLS that are important to remember.

‘Traditional’ insulin devices

Traditionally, insulin is administered as a subcutaneous injection into the abdomen.  This is typically via an ‘insulin pen’ but there are other devices available for those with vision impairment or needle phobia.  Insulin can also be administered into other sites of adipose tissue including the thighs, buttocks and arms.

📺 Watch the following video showing the use of a Flexpen device.

To maximise shelf life, insulin is stored under refrigeration 2-8oC.  Insulin can be stored at <30oC for up to 28 days, this is called the ‘in-use’ stability.  Injecting cold insulin typically stings more than room temp.  Patients must be instructed to not freeze insulin and if frozen, the insulin should be discarded.  Freezing may alter the peptide structure resulting in unpredictable effects or lack of efficacy.

Each injection of insulin requires a new needle (something a lot of patients don’t do).  Leaving the needle on an insulin pen and reusing it increases the likelihood of scarring and lipohypertrophy which can alter the absorption of insulin from subcutaneous tissue and it is also more painful to use a blunt needle.  Good injection technique and rotation of the injection site are very important to help avoid lipohypertrophy and inadvertent intramuscular injection.

Insulin-Induced Lipohypertrophy Source: Roy et al. N Engl J Med 2024;390: e60.

 

Source: Koreneff C. 5 Expert Tips on Injecting Insulin. https://www.diabetesqualified.com.au/5-expert-tips-to-injecting-insulin/

Fortunately, insulin needles and other consumables are subsidised via the National Diabetes Services Scheme.

Insulin Pumps and Continuous/Flash Glucose Monitors

The burden of multiple times per day injections and BGL monitoring can be significant.  Insulin pumps and continuous blood glucose monitors can help to overcome this and their uptake amongst T1DM patients is increasing.

Example of a subcutaneous insulin pump that is typically worn on a belt or placed in a pocket or ‘bum bag’ with the subcutaneous cannula placed on the abdomen. Source: Paldus B, et al. Insulin pumps in general practice. Aust Prescr 2018;41:186–90

The insulin pump delivers a continuous background infusion of a rapid acting insulin and then deliver a bolus dose when eating. Both are delivered via the same subcutaneous cannula.  The cannula and tubing are typically replaced every 3 days.

Example of a continuous or flash glucose monitor. Source: Paldus B, et al. Insulin pumps in general practice. Aust Prescr 2018;41:186–90

Insulin pumps, continuous/flash glucose monitors and smartphones continue to improve.  Over the last few years significant advances have been made making them easier to manage and ‘smart’ functions have become available that assist with insulin dosing calculations.

Despite the apparent advantages, these devices are not suitable for all patients and they require an individualised assessment to determine their utility in a specific patient.

Non-BGL Insulin Indications

Before we move onto non-insulin therapies used in T2DM next week we will quickly look at some uses of insulin that are not related to BGL control.

Absence of insulin leading to diabetic ketoacidosis. Source: https://www.nipro-group.com/en/inspire/diabetic-ketoacidosis-dka-why-should-it-matter-me

 

As we have discussed earlier, insulin not only reduces BGLs but it also reduces ketone body formation.  This is important to remember as it forms the basis of diabetic ketoacidosis management alongside fluid and electrolyte replacement.

Insulin is infused intravenously to prevent further ketone formation and correct hyperglycaemia.  The hyperglycaemia is generally corrected quite quickly but ketone bodies persist.  A glucose infusion is commenced alongside the insulin infusion to prevent life threatening hypoglycaemia while the insulin infusion is continued until ketone bodies have dropped sufficiently via renal and other forms of clearance.

Another common use of insulin in acute care is the management of hyperkalaemia.  Insulin binding to insulin receptors leads to activation of the Na+/K+ ATPase in skeletal muscle resulting in an intracellular shift of potassium and subsequent reduction in serum levels.  It is important to give glucose alongside the insulin to prevent hypoglycaemia.  Beta-2 agonists (from week 1) also trigger the Na+/K+ ATPase and salbutamol is often used alongside insulin to reduce serum potassium levels.  In severe hyperkalaemia we also give intravenous calcium to help stabilise the myocardium and prevent arrythmia formation.

 

Insulin binding to the insulin receptor triggers intracellular pathways including the activation of the Na+/K+ ATPase. The Na+/K+ ATPase results in increased intracellular potassium shift ultimately lowering serum potassium levels. Source: Depret F, et al. Management of hyperkalemia in the acutely ill patient. Ann Intensive Care 2019;28;9(1):32.

Check Your Understanding:

📺 Watch this video on insulin therapy (19:23 mins)

Download lecture notes here:

PC3300 Type 1 and Insulin Notes JS

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