Diabetes mellitus describes a group of metabolic disorders characterised by increased blood glucose concentration. People living with diabetes have a higher risk of morbidity and mortality than the general population and the global prevalence of diabetes in adults has been increasing rapidly over recent decades.
In 2015 it was estimated that, worldwide, there were 415 million people with diabetes between the ages of 20 and 79 years. Furthermore, there were five million deaths attributable to diabetes. The total global health expenditure due to diabetes was estimated at $673bn annually (+/- R9.6tn). About 75% of those with diabetes live in low- and middle-income countries. According to data published by the International Diabetes Federation’s most recent Diabetes Atlas, the number of people with diabetes aged 20–79 years is predicted to rise to 642 million by 2040.
As outlined by the South African National Health and Nutrition Examination Survey (SANHANES-1), South Africa is experiencing a transition in its epidemiological profile, from infectious to non-communicable diseases (NCDs), including diabetes. This transition is mostly caused by preventable factors such as an increasing lack of physical activity, higher body mass index (BMI) ratios, and a lack of knowledge concerning proper nutrition in lower-income communities, and increased access to unhealthy food.
In 2000, the estimated prevalence of diabetes among South African adults was 5.5%, but recent data from the International Diabetes Foundation suggests that up to 7% of local adults might be diabetic.
NEED FOR INSULIN
Insulin is secreted continuously by beta cells in a glucose-dependent manner throughout the day. It is also secreted in response to oral carbohydrate loads, including a large first-phase insulin release that suppresses hepatic glucose production followed by a slower second-phase insulin release that covers ingested carbohydrates.
Insulin must be given to all patients with type 1 diabetes (T1DM), which is usually due to autoimmune islet-cell injury that eventually leads to virtually complete insulin deficiency. Ideally, physiologic replacement of insulin, emulating the secretory pattern of the nondiabetic pancreas, but keeping in mind the limitations associated with subcutaneous administration, is desirable.
Type 2 diabetes mellitus (T2DM) is associated with insulin resistance and slowly progressive beta-cell failure. By the time T2DM is diagnosed in patients, up to 50% of their beta cells are not functioning properly. Beta-cell failure continues at a rate of about 4% each year. Therefore, patients with T2DM often benefit from insulin therapy at some point after diagnosis.
Insulin is used in the treatment of patients with diabetes of all types. The need for insulin depends upon the balance between insulin secretion and insulin resistance. All patients with T1DMneed insulin treatment permanently, unless they receive an islet or whole organ pancreas transplant. Many patients with T2DM will require insulin as their beta-cell function declines over time.
Insulin therapy is recommended for patients with T2DM and an initial A1C level greater than 9%, or if diabetes is uncontrolled despite optimal oral glycaemic therapy. Insulin therapy may be initiated as augmentation, starting at 0.3 units per kg, or as replacement, starting at 0.6 to 1.0 units per kg. When using replacement therapy, 50% of the total daily insulin dose is given as basal, and 50% as bolus, divided up before breakfast, lunch and dinner.
INSULIN REPLACEMENT THERAPY
Insulin replacement therapy, also referred to as intensive insulin therapy or basal-bolus therapy, is a comprehensive approach to helping patients achieve optimal blood glucose control by mimicking the physiologic delivery of insulin. This approach uses current understanding of factors affecting glucose homeostasis to empower patients to use flexible insulin dosing to match their lifestyles and preferences.
People without diabetes secrete insulin in two basic patterns: Background and prandial. The background pattern is a continuous secretion of small amounts of insulin at relatively constant levels, which restricts hepatic glucose production and lipolysis in the unfed state. This secretion is closely linked to changes in glycaemia, so that the level falls during fasting states and increased physical activity and rises when blood glucose increases under the influence of counter-regulatory hormone secretion.
Prandial insulin is secreted rapidly in levels proportional to the glucose rise that results from food ingestion. This higher insulin level suppresses lipolysis and glucose production, and it stimulates the uptake of ingested glucose by the tissues. The goal of contemporary diabetes management is to achieve and preserve a glycaemic level as close to normal as possible.
Normoglycaemia can reduce acute complications (hypoglycaemia, hyperglycaemia, and diabetic ketoacidosis), reduce microvascular and macrovascular complications, enhance quality of life and reduce the fiscal burden of the disease.
For patients who require insulin, this goal can be accomplished with insulin regimens in which basal insulin formulation is used to mimic normal physiologic insulin secretion. Short- or rapid-acting insulin formulation can help simulate the prandial insulin response to nutrient intake.
A significant and ever-growing number of diabetic patients require regular large doses of concentrated insulin via insulin replacement therapy multiple times a day. As of 2012, more than 60% of all American patients with T2DM injecting mealtime insulin were taking more than 20 units of their mealtime insulin per day (mealtime defined as rapid-/short-acting insulin, excludes pumpers); in Western Europe, the percentage was even higher (70% of all mealtime insulin-injecting patients with T2DM were taking 20 or more units of mealtime insulin per day).
CONCERNS ABOUT INSULIN THERAPY
Pain, weight gain, and hypoglycaemia may occur with insulin therapy. Pain is associated with injection therapy and glucose monitoring, although thinner and shorter needles are now available to help decrease pain. Weight gain associated with insulin therapy is due to the anabolic effects of insulin, increased appetite, defensive eating from hypoglycaemia, and increased caloric retention related to decreased glycosuria. In the United Kingdom Prospective Diabetes Study, patients with T2DM, who were taking insulin gained an average of 4kg, which was associated with a 0.9% decrease in A1C level compared with patients on conventional therapy.
The American College of Endocrinology and the American Association of Clinical Endocrinologists recommend initiation of insulin therapy in patients with T2DM and an initial A1C level greater than 9%, or if the diabetes is uncontrolled despite optimal oral glycaemic therapy. Initiation of insulin therapy is often unnecessarily delayed, owing to clinician or patient reluctance and other factors, thus exposing patients to the pathologic consequences of prolonged hyperglycaemia.
Patients should be made aware that initiating insulin does not represent a personal ‘failure’ and that many patients with T2DM will eventually require exogenous insulin, due to a decline in endogenous insulin production. The development of concentrated insulin therapies may provide solutions to some of the challenges for patients requiring high doses.
Recently developed concentrated insulins include insulin degludec (200 unit/mL formulation), insulin glargine (300 unit/mL formulation), and insulin lispro (200 unit/mL). The prefilled insulin delivery devices that contain these concentrated insulins ‘dial and dose’ in actual units such that no conversion is needed based on the concentration.
For decades, insulin was delivered only via vials and syringes with large bore needles that caused a lot of pain. However, the use of insulin pens for the self-administration of insulin has become standard over the course of the last decade. These pens contain a cartridge, a dial to measure dosage, and a disposable needle. The pens allow more simple, accurate, and convenient delivery than using a vial and syringe.
There are numerous reasons why using pen devices are increasing in popularity. Adherence to treatment is better because a pen device is easier to carry around, easy to use, provides greater dose accuracy, and is more satisfactory to patients as compared with a syringe. Injecting with devices makes the process discreet, and the overall cost of managing diabetes is also reduced.
Patients across all age spectrums have unique challenges for which pen devices help address. For children, needle fear is minimised significantly. Older patients with diabetes who have comorbidities or disabilities (e.g., visual impairment, impaired motor skills) that may exacerbate the difficulties of self-injection and increase the risk of dosing errors also find solace in using a pen-injecting device that overcomes some of their limitations.
Nowadays, most insurance companies cover the use of pen devices and studies have shown that the overall cost of healthcare delivery is reduced when using pens. But the clinical suitability of a device extends beyond its usability. Insulin pens have been shown to be instrumental in avoiding possible treatment mix-ups caused by injecting the wrong insulin, a situation particularly relevant to patients using a basal-bolus insulin regimen.
Patient preferences in terms of insulin pen choice are significant since satisfaction with the insulin delivery device (a combined measure of ease of use, interference with daily activities, and social acceptability) has been found to be positively linked to patient self-efficacy and adherence in patients with T2DM.
A study was conducted where the preference of insulin pens by patients as well as diabetes caregivers was assessed. The pros and cons of the Humalog KwikPen 200 units/mL (IL 200) versus the Humalog KwikPen 100 units/mL (IL 100) were compared in patients with diabetes requiring >20 units of mealtime insulin. The study also sought to determine which attributes had the greatest influence on pen preference selection.
A total of 106 participants were randomised to one of eight sequences that varied the pen order (IL 100 pen or IL 200 pen) and dosing order (15 units = low dose or 50 units = high dose) for a total of four simulated injections. Participants then completed a self-administered questionnaire to select their overall preference between the two pens and then rated the importance of 11 pen attributes in contributing to their overall preference.
A great majority of patients with diabetes requiring more than 20 units of mealtime insulin as well as their preferred the IL 200 pen over the IL 100 pen. Key pen attributes influencing preference for the IL 200 pen included the total amount of insulin in the pen, the ease of pressing the injection button, and the amount of fluid injected, which are attributes specific to the higher concentration of insulin in the IL 200 pen.
Participants noted anecdotally that they liked the idea of using fewer pens (facilitated by more insulin in each pen), that the pen button was easier to push (due to decreased glide force), and that an injection would be delivered in half the amount of liquid in the IL 200 pen compared to the IL 100 pen (due to the concentration).
Because the IL 200 pen contains an increased strength formulation of insulin lispro where each dose from the IL 200 pen is delivered in half the volume of the IL 100 pen, the pen’s glide force is reduced and there are fewer pen transitions for the user. These benefits may help address the challenges associated with poor treatment adherence.
Insulin is a vital component of the treatment regimen for diabetes mellitus and patient compliance is key to the efficacy of this treatment. Insulin pens have greatly improved treatment compliance among diabetic patients, and among insulin pen users there is a demonstrable preference for pens that deliver higher concentrations of insulin at a decreased glide force, and which require less pen transitions.