Diabetes management: optimizing roles for nurses in insulin initiation

Figures & data

Figure 1 Relationship of hemoglobin A_1C (HbA_1C) and incidence of diabetes complications.⁴ In the United Kingdom Prospective Diabetes Study (UKPDS), each percentage point reduction in HbA_1C was linked with substantial risk reductions in diabetes-related morbidity and mortality.

Table 1 Selected major evidence and rationale for intensive diabetes management

Study The UKPDS (United Kingdom Prospective Diabetes Study) found that poor glycemic control in patients with type 2 diabetes is associated with an increased risk of cardiovascular complications, including coronary heart disease, myocardial infarction, and peripheral vascular disease, as well as microvascular complications and death.^Citation3 Figure 1 shows the relationship of hemoglobin A1C (HbA1C) to diabetes-related complications.^Citation4 The DCCT (Diabetes Control and Complications Trial) reported that maintaining fasting plasma glucose (FPG) between 70 and 120 mg/dL (3.89–6.67 mmol/L) and postprandial glucose (PPG) <180 mg/dL (10 mmol/L) helps sustain endogenous insulin secretion.^Citation5 Residual beta-cell function, in turn, is associated with better metabolic control and a lower risk of hypoglycemia and chronic complications, such as retinopathy and microalbuminuria.^Citation6 The EDIC (Epidemiology of Diabetes Interventions and Complications) study found that early glycemic control reduces the risk of cardiovascular events.^Citation7 The ARIC (Atherosclerosis Risk in Communities) study reported that elevated HbA1C leads to atherosclerosis and cardiovascular disease.^Citation8,Citation9 The Steno-2 study found that intensive, multifactorial intervention reduced diabetes-related mortality and cardiovascular events.^Citation10 The ADVANCE (Action in Diabetes and Vascular Disease) study found that intensive glucose control reduced major macrovascular and microvascular events, primarily due to a 21% reduction in nephropathy.^Citation11 Li et al^Citation4,Citation12 reported that short-term intensive insulin therapy titrated to maintain FPG <110 mg/dL (6.11 mmol/L) and PPG <160 mg/dL (8.89 mmol/L) prevented progression of beta-cell dysfunction and insulin resistance in newly diagnosed type 2 diabetic patients with severe hyperglycemia. Weng et al^Citation3,Citation13^–^Citation17 found that hyperglycemia is brought under control more quickly, and the effects of insulin on beta-cell function are superior to those of oral hypoglycemic agents.

Table 2 Therapeutic goals for FPG, PPG, and HbA_1C

	FPG	2-h PPG	HbA1C
ADA^Citation19	90–130 mg/dL (5–7.22 mmol/L)	<180 mg/dL (10 mmol/L)	<7%
IDF^Citation17	<110 mg/dL (6.11 mmol/L)	<145 mg/dL (8.06 mmol/)	<6.5%
ADA/EASD Consensus^Citation14	70–130 mg/dL (3.89–7.22 mmol/L)	<180 mg/dL (10 mmol/L)	<7%
AACE^Citation15	<100 mg/dL (5.56 mmol/L)	<140 mg/dL (7.78 mmol/L)	≤6.5%

Abbreviations: FPG, fasting plasma glucose; PPG, postprandial glucose; HbA_1C, hemoglobin A_1C; ADA, American Diabetes Association; IDF, International Diabetes Federation, EASD, European Association for the Study of Diabetes; AACE, American Association of Clinical Endocrinologists.

Table 3 Differentiating available diabetes therapies^{14,15,23–28}

Antidiabetic agent	Advantages	Disadvantages
Metformin	Weight neutral, inexpensive, oral	GI side effects, rare lactic acidosis
Thiazolidinediones	Improved lipid profile, oral	Fluid retention, weight gain, CHF, may not see reduction in glucose for several weeks, expensive, increased cardiovascular risk
Alpha-glucosidase inhibitors	Weight neutral, oral	Frequent GI side effects, 3 times/day dosing, expensive
Sulfonylureas	Inexpensive, oral	Weight gain, hypoglycemia
Glinides	Short duration	Hypoglycemia, 3 times/day dosing, expensive
DPP-4 inhibitors Saxagliptin Sitagliptin	Weight neutral, less hypoglycemia, oral	Lack of long-term data regarding safety and efficacy
GLP-1 agonists Exenatide Liraglutide	Less hypoglycemia, weight loss	Injections, lack of long-term data on safety and efficacy
Insulin	Inexpensive, no dose limit, improved lipid profile	Injections, monitoring, hypoglycemia, weight gain
Human insulin Regular or short acting Intermediate acting (NPH)	Many physicians still most comfortable with standard insulin therapy	Limited pharmacokinetic/pharmacodynamic features, hypoglycemia, injections, monitoring, weight gain, variability in time-action profile
Insulin analogs Rapid-acting analogs ○ Aspart ○ Lispro ○ Glulisine Long-acting basal analogs ○ Glargine ○ Detemir Premixed analogs ○ Biphasic insulin aspart 70/30 ○ Insulin lispro 75/25 ○ Insulin lispro 50/50	Less hypoglycemia than human insulin, absorption more consistent, less weight gain; rapid- and long-acting formulations, predictable time–action profiles, simplified dosing with premixes	Injections, monitoring
Devices for insulin delivery
• Traditional vial and syringe	Some physicians most comfortable with standard vial and syringe insulin therapy	Can be complicated to administer, not discreet, time consuming, and potential for dosing errors; patients may have needle aversion
• Pen-injection devices	Convenient, discreet, simple, may improve confidence/adherence and reduce insulin-related adverse events, good for patients who have vision or dexterity problems, decreased dosing errors and more accurate dosing	Some patients are averse to injections in any form

Abbreviations: GI, gastrointestinal; CHF, congestive heart failure; DPP-4, dipeptidyl peptidase-4; GLP-1, glucagon-like peptide 1; NPH, neutral protamine Hagedorn.

Table 4 Insulin initiation strategies

The AACE notes that insulin can be initiated by addition to any and all oral antidiabetic drug (OAD) therapies, as long as appropriate blood glucose monitoring is performed. Several different approaches are possible: 1) add a basal insulin,^Citation29,Citation30 2) add a premixed insulin,^Citation31 or 3) add rapid-acting insulin boluses at mealtimes.^Citation9,Citation32,Citation33 The specific approach and insulin doses will depend on individual patients’ needs, preferences, HbA1C levels, and fasting plasma glucose (FPG) levels.

Initiation with basal insulin Basal initiation therapy aims to normalize fasting blood glucose and HbA1C Metformin is the preferred first-line OAD for patients with type 2 diabetes but can be expected to reduce HbA1C values by only ∼1.5%.^Citation14,Citation34,Citation35 To achieve target HbA1C goals, basal insulin is added to metformin, typically at a dose of 10 units/day. Adjustment of the daily dose will depend on the FPG and on the basal insulin selected.^Citation36,Citation37 Two long-acting basal insulin analogs, insulin detemir and glargine, have pharmacodynamic profiles that provide up to 24-hour basal insulin levels, generally with a once-daily injection at bedtime. Because type 2 diabetes is a progressive disease, most patients will ultimately require the addition of rapid-acting bolus insulin injections at mealtimes to control postprandial glucose (PPG) (see below). A basal-bolus regimen is ideal for many patients, as it mimics the body’s constant release of insulin throughout the day and supplements the body’s need for insulin after a meal.

Premixed insulins Premixed insulins are formulated to combine both basal and rapid-acting components in 1 injection and thus provide a simple way to achieve near-normal insulin profiles at mealtime and between meals. Premixed insulins are easy to use, ensure that the correct amount of insulin is injected every time, and may improve adherence to therapy. They are especially helpful for patients who are older, averse to multiple injections, or prefer a simple insulin regimen. Premixed insulins are given in once-, twice-, or 3-times daily schedules, depending on the patient’s needs. When initiating a premixed insulin, metformin should be continued, but if the patient is currently taking a secretagogue, it should be discontinued. Individuals who eat regular meals on a schedule are ideally suited for premixed insulins; however, premixes are not a preferred option for patients with varied daily schedules or those who require flexibility around mealtimes. Specific dosing and titration information depend on the formulation chosen.

Rapid, short-acting insulin injections at mealtime Tight control over PPG excursions can be exerted using mealtime bolus insulin injections. As beta-cell function declines with disease progression, prandial insulin injections will eventually be required by most patients with type 2 diabetes. Controlling PPG levels so they remain below 140 to 180 mg/dL (7.78–10 mmol/L)^Citation19 is important to delay the onset of vasculardamage,^Citation4,Citation39 and contributes to achievement of overall HbA1C goals.^Citation14,Citation40 Adding a bolus injection of a rapid-acting mealtime insulin analog (lispro, aspart, or glulisine) is ideally suited for patients who require flexibility, since it may be given immediately before or even during a meal, ie, “inject and eat” rather than waiting 15 to 30 minutes with regular insulin. The dose can be varied based on the patient’s glucose levels or the size/type of meal. This approach is supported by AACE medical guidelines.^Citation15

Figure 2 Approximate pharmacokinetic profiles of rapid- and long-acting insulin analogs as compared with an idealized profile of physiological insulin secretion.⁴⁴

Copyright © 2007 [Lippincott, Williams & Wilkins] Reprinted with permission from Boyle PJ, Zrebiec J. Management of diabetes-related hypoglycemia. South Med J. 2007;100(2):183–194.⁴⁴

Table 5 Symptoms and management of hypoglycemia

Hypoglycemia symptoms can vary considerably from patient to patient.^Citation44

Common symptoms Pallor Sweating Increased heart rate Feelings of shakiness Blurred vision Tingling sensation Difficulty concentrating Feeling weak Tiredness or clumsiness Feeling warm or cold Feeling hungry Changes in mood (manifesting as giddiness, anger or irritability, anxiety or frustration, or tearfulness) Seizures or loss of consciousness (if the hypoglycemia is very severe)^Citation44

Management Mild-to-moderate Fast-acting carbohydrates (glucose tablets, fruit juices, drinks high in sugar content, or glucose gels). Five grams of carbohydrate raises plasma glucose by ∼15 mg/dL (0.83 mmol/L). A typical hypoglycemic episode is treated by ingesting 15 g of carbohydrate.^Citation4,Citation67,Citation68 If, after 15 minutes, plasma glucose remains <70 mg/dL (3.89 mmol/L), another carbohydrate-rich snack should be ingested (the 15/15 rule). Glucose gels are absorbed by the buccal mucosa and can be administered by an attendant in the event the patient is not alert. This may be followed by juice or food once the patient is more alert. Severe Very severe hypoglycemia might require intravenous administration of glucose by trained medical personnel. In cases of severe or frequent hypoglycemia or hypoglycemic unawareness, it is prudent to instruct the patient and significant other(s) in the use of glucagon, an injectable treatment for hypoglycemia in the unconscious patient.

Table 6 Reasons for patient referral to insulin therapy evaluation clinics

Initiation of insulin for patients who are poorly controlled on OAD therapies Insulin dose adjustments for patients who are not achieving HbA1C goals with basal-bolus therapy Instruction on self-titration tools for basal insulin Instruction on carbohydrate counting and carbohydrate-to-insulin ratios Evaluation of patients’ ability to self inject (includes pen-vs-syringe demonstrations) General education about the role of insulin in diabetes management Instruction on the use of self-monitoring blood glucose monitors Hypoglycemia prevention and management

Table 7 Self-management and the chronic care model⁷²

Nearly half of all people with chronic illness have multiple conditions. Insurers have an interest in correcting specific issues in chronic disease management, including: Practitioners who, because of high caseload, are too rushed to consult or follow established practice guidelines Lack of care coordination Lack of active follow-up to ensure the best outcomes Patients inadequately trained to manage their illnesses

Notes: To overcome these issues, the Improving Chronic Illness Care organization created the Chronic Care Model, which summarizes basic elements for improving healthcare. The model draws on best practices and research findings and provides a foundation for collaborative programs, tools, and research aimed at improving care for the chronically ill (see http://www.improvingchroniccare.org for additional information and resources).⁷²

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