Editor’s Note: Corrections to this article were published

in the July 2013 issue of The Journal of the American

Osteopathic Association (2013;113[7]:507). The corrections
have been incorporated in this online version of the article,

Identifying and Addressing Barriers is available at http://www.jaoa.org/content/113/7/507.1.full.

which was posted July 2013. An explanation of these changes

to Insulin Acceptance and Adherence

in Patients With Type 2 Diabetes Mellitus
Allison M. Petznick, DO

From Firelands Regional Medical

Center and Northern Ohio Medical
Specialists, both in Sandusky, Ohio.

This article is based on a continuing

medical education symposium held on
October 10, 2012, during the American
Osteopathic Association’s 2012 annual
Osteopathic Medical Conference &
Exposition in San Diego, California.
This article was developed
with assistance from Global
Directions in Medicine.
The author has approved the
article and all of its content.

Financial Disclosures:
Dr Petznick is on the speakers’
bureaus for Boehringer
Ingelheim Pharmaceuticals Inc,
Eli Lilly and Company,
Merck & Co Inc,
and sanofi-aventis US.
Address correspondence to
Allison M. Petznick, DO,
2500 W Strub Rd, Suite 230,
Sandusky, OH 44870-5390.
E-mail: apetznick@gmail.com
Progressive hyperglycemia is a characteristic of type 2 diabetes
mellitus (T2DM) that poses a challenge to maintaining optimal
glycemic control. Achieving glycemic control early in the course
of disease can minimize or prevent serious complications. Most
patients with T2DM eventually require insulin replacement
therapy to attain and preserve satisfactory glucose control.
For decades, the use of insulin to address the primary defect
of T2DM has been a cornerstone of diabetes therapy. Insulin
is indicated for patients with T2DM presenting with clinically
significant hyperglycemia, and it is mandatory for patients
exhibiting signs of catabolism. Insulin should be considered for
patients in whom hyperglycemia persists despite attempts to
control the condition through diet and exercise modifications
and the use of noninsulin therapies. Many physicians delay
initiation of insulin until absolutely necessary, sometimes
overestimating patient concerns about its use. Modern insulin
analogs, treatment regimens, and delivery devices make insulin
more user friendly, and physicians can promote patient accep-
tance of insulin by reviewing the benefits of controlled glycated
hemoglobin levels and addressing patient concerns.
J Am Osteopath Assoc. 2013;113(4 suppl 2):S6-S16 [Published correction appears
in J Am Osteopath Assoc. 2013;113(7):507.]

S6 A Supplement to The Journal of the American Osteopathic Association April 2013 | Vol 113 | No. 4 | Supplement 2

Downloaded from https://jaoa.org by guest on 09/16/2019

 A
pproximately 26 million Ameri-
cans were living with diabetes
in 2010.1 Data from a 2012
report indicated a substantial increase
2 Type 2 diabetes mellitus is a disease
in the prevalence of diagnosed diabe-
tes mellitus throughout the 50 states,
Washington, DC, and Puerto Rico dur-
ing a 16-year period (1995-2010), with
the age-adjusted prevalence increasing
by more than 50% in most states and by
100% or greater in 18 states. Figure 1
shows the areas of the United States
that had the highest concentrations of
diagnosed diabetes in 2009, whereas
Figure 2 presents the lifetime risks of
developing diabetes. 4 In the United
States, approximately one-third of pa-
tients who have diabetes (7 million) are
unaware of their disease.1
Like many chronic conditions, type
2 diabetes mellitus (T2DM) has a pro-
longed asymptomatic phase. Even after
T2DM has been diagnosed, symptoms
(eg, fatigue, weight loss, increased thirst,
frequent urination, blurred vision) are
nonspecific rather than acute. These
characteristics of T2DM contribute to
the challenges of achieving early diag-
nosis, intervention, and active follow-up.
Unlike patients with acute diseases, pa-
tients with diabetes mellitus who have
few or no symptoms may not visit a phy-
sician. They may be reluctant to initiate
or follow through with therapy. Such pa-
tients benefit both from receiving educa-
tion from a caring physician about the
toll of T2DM and from attaining good
glycemic control.
A Supplement to The Journal of the American Osteopathic Association
Downloaded from https://jaoa.org by guest on 09/16/2019
Pathophysiologic Profile:
Increasing Insulin
Deficiency
of dysfunctional glucose metabolism
that is characterized by worsening hy-
perglycemia and a loss of response to
therapy over time. Insulin resistance is
an early factor in the pathophysiologic
profile of T2DM, which may be associat-
3 ed with unhealthy lifestyle choices and
weight gain. However, weight loss will
not ameliorate all problems associated
with T2DM. Insulin release declines
progressively in patients with T2DM
and begins well before diagnosis. In
fact, studies suggest that 50% to 80%
of β-cell function is lost by the time of
diagnosis.5-7 The decline continues as
the disease progresses, from impaired
fasting glucose levels and impaired glu-
cose tolerance to full-blown T2DM, and
it continues to progress until the patient
becomes increasingly insulin deficient.
Figure 3 depicts the changes in insulin
resistance and insulin secretion that oc-
cur over time in patients with T2DM.8 A
decline in β-cell function leads to persis-
tent hyperglycemia.
In many patients, the metabolic ab-
normalities associated with persistent
hyperglycemia lead to complications
such as vision loss, renal failure, and
neuropathy. Moreover, T2DM is the
leading cause of kidney failure, non-
traumatic lower-limb amputations, and
new cases of blindness among adults
in the United States, and it is a major
April 2013 | Vol 113 | No. 4 | Supplement 2
Key Points
◾ Individualize glucose targets.
◾ Most patients with type 2 diabetes
mellitus require insulin therapy
because of a progressive decline
in β-cell function.
◾ Any insulin will lower glucose
and glycated hemoglobin levels.
◾ All insulins are associated
with some weight gain and
some risk of hypoglycemia.
◾ Analog insulins, pens, pumps,
and finer needles allow for more
flexible use of insulin with less
hypoglycemia and weight gain.
◾ Allow patients to share in making
decisions and setting goals, but
keep them accountable and
provide positive reinforcement.
◾ Understand the physiologic
profile of each type of insulin
therapy to better tailor treatment
for your patients.
◾ Involve other health care
professionals to facilitate integrated
care for patients with type 2
diabetes mellitus.
cause of heart disease and stroke.1 It
is imperative that increased measures
are taken to improve rates of glycemic
control in patients with T2DM. In addi-
tion, appropriate intervention can often
forestall the development of microvas-
cular complications in many patients.9
The earlier that patients can establish
glycemic control, the better.10
S7
7

Figure 1.
Age-adjusted estimates of the percentage of adults with diagnosed diabetes in 2009.3
Treatment Goals
The goal of T2DM therapy is to reestab-
lish normoglycemia and avoid both the
excesses of hyperglycemia and the
dangers associated with hypoglycemia.
For patients with T2DM, the goals for a
patient-centered approach to glycemic
treatment are evidence based and are
predicated on data from landmark trials
showing reductions in the microvascu-
lar complications of diabetes mellitus
associated with glycated hemoglobin
(HbA1c) levels of less than 7%; these
levels generally correspond to premeal
or fasting glucose levels of 70 mg/dL
to 130 mg/dL and postprandial glucose
levels of less than 180 mg/dL.11,12 In the
past 2 years, however, most major or-
ganizations have recognized the need
for an individualized approach to both
treatment goals and treatment options,
weighing both the risks and the benefits
to the patient. In 2012, the American
Diabetes Association (ADA), in con-
junction with the European Association
for the Study of Diabetes (EASD), is-
sued a position statement for the man-
S8 A Supplement to The Journal of the American Osteopathic Association
Downloaded from https://jaoa.org by guest on 09/16/2019
Age-adjusted
estimate, %
0-6.3
6.4-7.5
7.6-8.8
8.9-10.5
⩾10.6
agement of hyperglycemia that em-
phasizes a patient-centered approach,
with the avoidance of hypoglycemia
considered a primary tenet, particularly
in at-risk patients.12 The ADA and the
EASD suggest less stringent goals for
HbA1c levels (7.5% to 8.0%) for patients
with a history of severe hypoglycemia,
a limited life expectancy, advanced
complications, or extensive comorbid
conditions, or for those who have dif-
ficulty attaining glycemic control,11,12
drawing on lessons from studies by the
Action to Control Cardiovascular Risk
in Diabetes (ACCORD) trial,13 the Vet-
erans Affairs Diabetes Trial (VADT),14
and the Action in Diabetes and Vascular
Disease: Preterax and Diamicron Mod-
ified-Release Controlled Evaluation
(ADVANCE) trial.15 However, for young-
er patients or for patients with disease
of short duration, a long life expectancy,
and no significant cardiovascular dis-
ease, HbA1c goals closer to normal (eg,
6.0% to 6.5%) are recommended.11,12
The American Association of Clinical
Endocrinologists concurs with the in-
dividualization of treatment goals and
has led the way to the development of
a comprehensive care plan for patients
with T2DM.16 Paying attention to car-
diovascular risk factors (eg, high blood
pressure, high cholesterol levels) is im-
portant for all patients with T2DM, as is
focusing on glucose control.
Current Treatment
Recommendations
The position statement of the ADA
and the EASD quotes the Committee
on Quality of Health Care in America
of the Institute of Medicine in defining
patient-centered care as an approach
“to providing care that is respectful of
and responsive to individual patient
preferences, needs, and values and
ensuring that patient values guide all
clinical decisions.”17 This position state-
ment acknowledges that glycemic man-
agement in patients with T2DM has
become increasingly complex and, to
some extent, controversial, consider-
ing the increasing number and type of
pharmacologic agents now available.
I truly believe in a patient-centered ap-
proach. The patient has to be part of the
decision-making process. I talk to all of
my new patients, and I explain every
different medication that is available.
I tell them about the risks and benefits of
the medications, and I let them decide
which medication to take.
Management of T2DM consists of in-
terventions designed to affect the physi-
cal activity levels and food intake of an
individual. However, current treatment
April 2013 | Vol 113 | No. 4 | Supplement 2
 recommendations now also include ini-
70 Men, 1980-1989 Men, 2000-2004
tiation of pharmacotherapy at the time
Women, 1980-1989 Women, 2000-2004
of diagnosis, in part as a result of our 60

Proportion of 18-Year-Olds, %
improved understanding of the patho-
50
physiologic profile of T2DM.12,18
Metformin, which has been used for 40

decades in the management of T2DM,

30
continues to be considered a corner-
stone of therapy, and it remains the 20

most widely used first-line therapy for

10
this disease.19 Its mechanism of action
predominantly involves reducing hepat- 0
All BMI Normal/ Overweight Obese
ic glucose production. Metformin is gen- Levels Underweight
erally considered weight neutral, and it
Figure 2.
is not associated with hypoglycemia.
Proportion of 18-year-olds in the United States who will
Metformin therapy has been shown develop diabetes, by sex, body mass index (BMI), and
to reduce the risk of microvascular period, as determined by the American Diabetes Association.
Reprinted with permission from the American Diabetes
complications associated with T2DM. Association, from Cunningham SA, et al. Decreases in
The United Kingdom Prospective Dia- diabetes-free life expectancy in the U.S. and the role of
obesity. Diabetes Care. 2011;34(10):2225-22304; permission
betes Study9 demonstrated a reduction
conveyed through Copyright Clearance Center, Inc.
in the rate of mortality from all causes
in a subgroup of obese patients with
T2DM treated with metformin; this find-
ing was also confirmed in a 10-year
postinterventional follow-up study. 10 250 At risk for diabetes Years of diabetes
Decision making is based on the
Relative Function, %

200
Insulin resistance
needs and characteristics of individual
150
patients, including their comorbidities,
their hyperglycemia levels, and numer- 100

ous other factors.18 Ultimately, patients 50 Insulin level

β-cell failure
make the final decisions regarding
0
their lifestyle choices and, to some
-10 -5 0 5 10 15 20 25 30
extent, the pharmaceutical interven- Disease Onset Diagnosis
tions that they use. Certainly, adoption
of and adherence to therapy occur in Figure 3.
the context of the real lives of the pa- Progression of type 2 diabetes mellitus. This figure was
published in DeGroot LJ, Jameson JL, eds. Endocrinology.
tients. Patient involvement in medical 4th ed. Philadelphia, PA: WB Saunders; 2001:821-835.8
decision making constitutes one of the Copyright WB Saunders, 2001. Reprinted with permission.
core principles of an osteopathic phy-
sician’s clinical practice.

A Supplement to The Journal of the American Osteopathic Association April 2013 | Vol 113 | No. 4 | Supplement 2 S9
Downloaded from https://jaoa.org by guest on 09/16/2019
 Insulin Therapy
Insulin, like metformin, is a cornerstone
of T2DM therapy. By activating the in-
sulin receptor, exogenous insulin ther-
apy increases peripheral glucose up-
take and suppresses hepatic glucose
production. Outcome studies have also
provided evidence that insulin therapy
reduces the risk of microvascular com-
plications associated with T2DM. 20
More than 90 years of clinical experi-
ence with insulin support its use. Insulin
is universally effective in lowering glu-
cose and HbA1c levels. Any insulin dose
will lower these levels in a dose-related
manner, and the upper threshold of the
dose is limited only by the associated
risk of hypoglycemia. Although many
physicians delay using insulin therapy
until the development of later stages
of disease or extremely high levels of
hyperglycemia, insulin therapy can be
initiated at any HbA1c level in patients
with T2DM. Insulin therapy is simply
one of the many effective therapeutic
options for which assessment of the
risk-benefit ratio of a patient’s particular
medical history is warranted. Specific
indications for insulin therapy are dis-
cussed in the following paragraphs and
are summarized in Table 1.
Initiation of insulin therapy is indicated
for patients with T2DM who present with
clinically significant hyperglycemia and
is mandatory for those with signs of ca-
tabolism (eg, weight loss and ketosis).
It is strongly recommended for patients
with extreme hyperglycemia (ie, a blood
glucose level ⩾300-350 mg/dL or an
HbA1c level ⩾10%-12%). Oral noninsulin
therapies decrease HbA1c levels by ap-
proximately 0.5% to 1.5%.12 Therefore, if
patients have HbA1c levels of more than
9%, insulin may be the most appropri-
ate treatment option, as suggested by
the American Association of Clinical En-
docrinologists. However, as discussed
18
in reviews by Garber21 and Freeman,22
emerging data also indicate that some of
the long-acting glucagon-like peptide-1
receptor agonists result in robust lower-
ing of the glycemic level. Insulin therapy
should also be considered for patients
who have hyperglycemia despite making
lifestyle modifications (diet and exercise)
and taking maximal doses of noninsulin
therapies during a 3- to 6-month period.
This is called the “step-up” approach.
Waiting a long time before adjusting ther-
apies should be avoided.
The Fenofibrate Intervention and
Event Lowering in Diabetes (FIELD)
trial provided an opportunity to observe
glycemic control in a real-world setting.
For 4900 patients who were allocated to
receive placebo in the nonintervention
arm of the study, diabetes control was
measured at baseline and then yearly
for a median of 5 years. The median
HbA1c level was 6.9% at baseline, and
it increased by an average of 0.22%
over the course of 5 years (P<.001).23
Only 2% of patients at baseline and
4% of patients after 5 years were tak-
ing oral agents other than metformin or
sulfonylureas. During a 5-year period,
the percentage of patients using insulin
increased to 32% (21% were also tak-
ing oral agents).23 Use of oral agents by
patients remained similar (56% of pa-
tients during the same period). In 855
patients, initiation of insulin therapy
produced a sustained reduction in the
HbA1c level from a median of 8.2% to
a median of 7.7%, with a weight gain
of 4.6 kg occurring over the course of
5 years.23 In this trial, the need for insu-
lin therapy doubled over 5 years.23
Another philosophy involves start-
12
ing intensive insulin therapy at the time
of either initial patient presentation or
diagnosis of T2DM. Evidence indicates
that short-term use of intensive insulin
therapy allows either more preserva-
tion or partial reversal of β-cell function
in these patients, which allows them
to have a normal glycemic profile and
to continue with normal glycemia with-
out diabetes medications for multiple

Table 1.
Indications for Insulin Therapy in Patients With Type 2 Diabetes Mellitus

Mandatory Indicated Consider Supportive Data Exist

Patients with catabolic features Patients with significant Other patients with First-line therapy in patients
(weight loss, ketosis) hyperglycemia hyperglycemia despite diet, presenting with newly diagnosed
exercise, and maximal doses type 2 diabetes mellitus
of noninsulin therapies

S10 A Supplement to The Journal of the American Osteopathic Association April 2013 | Vol 113 | No. 4 | Supplement 2

Downloaded from https://jaoa.org by guest on 09/16/2019

 60

50
years.24 (See also the article by Joseph
Tibaldi, MD,25 in this supplement to The 40

Patients, %
Journal of the American Osteopathic
30
Association for further discussion of this
topic.) The ADA supports this approach 20

in their recommendations, stating the 10

following: “In newly diagnosed type 2
0
diabetic patients with markedly symp- Unwilling to Ambivalent Willing to
tomatic and/or elevated blood glucose Start Insulin Take Insulin
levels or HbA1c, consider insulin ther- Figure 4.
apy, with or without additional agents, Patient willingness to start insulin therapy. Data are from a survey
of 1400 insulin-naive patients with type 2 diabetes mellitus.29
from the outset.”11

and it progressively declines; therefore, preferred.34,36 Patients may also omit

Attitudes and
Initiation Concerns
About Insulin Therapy
Many physicians prefer to delay initiation
of insulin therapy until absolutely neces-
sary. 26,27
The reasons for this delay are
partly attributed to the perceived con-
cerns of patients, including the develop-
ment of hypoglycemia and the pain as-
sociated with both injections and blood
tests28; however, data show that less
than 20% of patients are truly unwill-
ing to start insulin therapy (Figure 4).29
One of the most important messages to
convey to patients is that they have not
“failed” themselves or their physicians
by needing insulin therapy. Patients
need to understand that T2DM is a pro-
gressive illness. In the DAWN (Diabetes
Awareness Wishes and Needs) survey,
almost half of the patients believed that
they were given insulin therapy because
they had somehow “failed,”27 and they
believed that the insulin therapy was
their punishment. In patients with T2DM,
a large percentage of β-cell function is
already lost by the time of diagnosis,
most patients with T2DM eventually will
need insulin at some point in their lives.
The need for insulin therapy does not
mean that failure has occurred. Instead,
the need for insulin is due to the pro-
gression of T2DM.
Delivery of the message regarding
the value of insulin therapy, in addition
to providing encouragement and edu-
cation, can usually overcome any reti-
cence on the part of patients.12 It is im-
portant to address the issues that may
affect patient adherence, because the
data do support a link between poor ad-
herence and poor outcomes, including
hospitalization and death.
initiation of and adherence to medica-
tion is influenced by many interrelated
factors (Figure 5).32 Convenience and
flexibility (ie, having therapy fit into the
lifestyle of patients) are very important
because they play into the ability of
patients to adhere to therapy. Patients
may skip insulin injections because the
injections interfere with their lifestyle33;
therefore, fewer injections
use of insulin pen delivery devices are
injections because they worry about hy-
poglycemia,33 which can be addressed
in part by the use of insulin analogs and
by patient education.37,38 Because insu-
lin pen delivery devices allow patients
the convenience of carrying their ther-
apy with them, dosing accuracy is im-
proved and administration is simplified.
Insulin pump therapy might be an option
for some patients who have erratic or
spontaneous lifestyles and for patients
for whom diet and exercise modifica-
tions are less predictable. Fewer injec-
tions are involved with the use of in-
sulin pump therapy as well. Therapy
30,31
Patient can be adjusted to accommodate the
vagaries of modern life. In summary,
it is less likely that patients choose to
be nonadherent and more likely that
they struggle with the constraints that
T2DM places on their lifestyle. By pro-
viding options that enhance the flex-
ibility of therapy, we may be able to
improve patient adherence and, ulti-
mately, patient outcomes.
34,35
and the Patient education needs to take into
account, among other things, patients’

A Supplement to The Journal of the American Osteopathic Association April 2013 | Vol 113 | No. 4 | Supplement 2 S11
Downloaded from https://jaoa.org by guest on 09/16/2019
 ◾ Medication beliefs
◾ Symptom severity Condition Patient Oriented
◾ Regimen comprehension

◾ Benefits
◾ Side effects ◾ Communication
Therapy Related Provider Related
◾ Regimen complexity ◾ Treatment beliefs
◾ Costs

Figure 5.
Factors influencing medication initiation, adherence, and persistence.32

knowledge regarding insulin therapy,
patients’ main concerns and perceived
problem areas, collaborative goal set-
ting and problem solving, and contin-
ued support. Some patients believe
that insulin may cause harm. This belief
dates back to times when insulin ther-
apy was started so late in the disease
process that its introduction coincided
with the development of some of the
very serious sequelae of T2DM, such
as amputations resulting from diabetic
neuropathy or blindness resulting from
diabetic retinopathy. We need to be able
Physiologic
Insulin Replacement
and Approaches
to Starting Insulin
Ideally, the principle of insulin use is to
create as normal a glycemic profile as
possible without causing unacceptable
weight gain or hypoglycemia. There are
2 specific insulin patterns: basal and
prandial. The prandial pattern is further
subdivided into first and second phases.
Breakfast Lunch Dinner
The light gray portions of Figure 6 39
show normal insulin release, which
is what occurs in a healthy person.
Figure 6 also shows how insulin ana-
logs mimic that process fairly closely,
with rapid-acting analogs providing
prandial insulin coverage and with long-
acting insulin analogs providing basal
insulin needs. Figure 740 illustrates both
human insulin profiles (regular and neu-
tral protamine Hagedorn [NPH]) and in-

to communicate to patients that insulin

Relative Plasma Insulin Levels

can help prevent the risks of these com-

plications. Physicians can help patients
accept insulin therapy by reviewing the
benefits of HbA 1c control and by ad- Prandial (rapid acting)

dressing the myths and concerns about

insulin therapy. We need to be sure that Basal (long acting)
we are sending patients the right mes-
sage about insulin therapy. Modern in-
sulin analogs and treatment regimens
make insulin a user-friendly therapy, as
does the use of insulin pen delivery de- Breakfast Lunch Dinner

vices and even insulin pumps. Figure 6.

Table 2 provides some suggestions Mimicking a normal physiologic profile with basal and prandial insulin
analogs. Reprinted from Current Paediatrics, Vol 16, Thompson R, Christie D,
of how to respond to patient concerns
Hindmarsh PC, The role for insulin analogs in diabetes care, pages 117-122.
about insulin therapy.27 Copyright 2009, with permission from Churchill Livingstone.

S12 A Supplement to The Journal of the American Osteopathic Association April 2013 | Vol 113 | No. 4 | Supplement 2

Downloaded from https://jaoa.org by guest on 09/16/2019

 Table 2.
Strategies to Address Patients’ Concerns Regarding the Use of Insulin

Barrier Strategies to Address Concerns

Sense of loss of control Counsel patients that they can take control of their diabetes by following an insulin regimen.
Belief that disease has worsened Explain that most patients will require insulin because the body is not able to make enough
insulin itself.
Show how insulin can be used to improve glycemic control at any point in therapy.

Sense of personal failure Explain that insulin is required because of the natural course of diabetes, not patient behavior—
it is inevitable and the patient could not have done anything to prevent it.
Introduce the possibility of insulin use at diagnosis.
Do not use insulin as a threat for not dieting, exercising, or taking oral agents.
Injection-related anxiety Show that needles are small and very fine.
Assure patient that injections are less painful than finger sticks for blood glucose self-monitoring.
Introduce prefilled insulin pens, which make injection very straightforward.
Perception that insulin is not effective Explain that insulin improves glycemic control when used properly.
Assure patient that insulin will improve symptoms and make him or her feel better and have
more energy.
Fear of weight gain Explain that some modern insulins have been shown to result in less weight gain than others.
Daily exercise can minimize weight gain and improve glycemic control.
Fear of hypoglycemia Incidence of serious hypoglycemia is rare.
Modern insulin analogs are associated with less hypoglycemia,
especially nocturnal hypoglycemia.
Teach about prevention, symptoms, and treatment of hypoglycemia.
Lack of confidence in ability to Long-acting insulins are easily administered with the evening meal or at bedtime (detemir)
manage insulin therapy or once daily at any time of day, but preferably at the same time of day (glargine).
Insulin pens make administration easier.
Diabetes educators are available.
Concerns of family, work, and friends Explain that although taking insulin should not affect ability to work as long as treatment
guidelines are observed, employers should be informed.
In general, patients should ensure that those close to them know everything they need to know.

Source: Reprinted from Peyrot M, Rubin RR, Khunti K. Addressing barriers to initiation of insulin in patients with type 2 diabetes. Prim Care Diabetes.
2010;4(suppl 1):S11-S18.28 Copyright 2010, with permission from Elsevier BV.

sulin analog profiles. Rapid-acting insu-
lins (insulin aspart, insulin glulisine, and
insulin lispro) work fairly quickly, have
a high peak, and return to baseline
fairly quickly, a pattern that is similar
to that of how food enters our system
and leaves. This pattern is in contrast to
how regular human insulin works. Reg-
ular human insulin takes longer to start
working, so patients should administer
it at least 30 minutes before eating to
have the onset of action peak at the
time that they need the insulin action.
Human insulin also tends to last a little
longer than needed, which may place
the patient at a small risk of hypogly-
cemia. For these reasons, rapid-acting
insulin analogs are considered to have
a more physiologic profile than regu-
lar human insulin. These differences
are more profound when NPH insulin
(which is really not a basal insulin but,
rather, is an intermediate-acting insulin)
is compared with the long-acting insu-
lin analogs (currently, insulin detemir
and insulin glargine). Neutral protamine
Hagedorn insulin has a peak, lasts on
the order of 12 to 20 hours (rather than
24 hours), and often requires adminis-
tration twice per day if it is used for bas-
al coverage. The NPH insulin peak also
increases the risk for hypoglycemia. A
meta-analysis 41 confirmed that basal

A Supplement to The Journal of the American Osteopathic Association April 2013 | Vol 113 | No. 4 | Supplement 2 S13
Downloaded from https://jaoa.org by guest on 09/16/2019
 Insulin aspart, insulin glulisine, insulin lispro
4-6 hours
Regular
6-8 hours

NPH
Plasma Insulin Levels

12-20 hours

Insulin glargine, insulin detemir

Up to 24 hours

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

Hours
Figure 7.
Time-action profiles of insulin products. Abbreviation: NPH, neutral protamine Hagedorn.
From Hirsch IB. Insulin analogues. N Engl J Med. 2005;352(2):174-183.40 Copyright 2013
Massachusetts Medical Society. Reproduced with permission from the Massachusetts
Medical Society.

analogs are associated with less noc- Patient Education tients choose the therapies that best fit
turnal hypoglycemia than NPH insulin. and Self-Management their lifestyles and are cost effective,
Adding basal insulin is a simple It is important to help patients under- because otherwise they are not going
approach to initiating insulin therapy, stand that insulin is not a last resort to take their medications and receive
and it generally requires only 1 injec- but is just another option, like the use their benefits. I often use an approach
tion, which is often combined with oral of metformin, sulfonylureas, thiazoli- referred to as the “5C intervention.”43
therapy. Premixed insulin, which com- dinediones, and other secretagogues, The basic premise of this interven-
bines basal and prandial coverage in as well as incretin therapies. However, tion is to find out what is important to
a single injection, is another option for multiple factors come into play when the patient on the day of their visit.
patients who require prandial cover- we consider using insulin to success- An example is provided in Table 3.
age and who have relatively structured fully treat patients with T2DM. The
schedules for this fixed-dose combi- patient is the key factor in achieving
nation drug. Patients can progress to treatment success. It is so important Conclusion
more complex regimens as their com- for patients to understand why they Physicians need to balance the over-
fort levels build and as their treatment are taking insulin. Many times I have all benefits and risks of therapies, but
requires.12 When initiating basal insulin heard patients say, “The doctor just they also need to recognize that insulin
therapy for a patient, I typically use a gave me this medication, and I was not replacement therapy addresses the pri-
weight-based approach, with 0.2 U per really told why I should take it, so I just mary defect. The overwhelming majority
kilogram of body weight as a starting stopped taking it.” Patients need to un- of patients with T2DM eventually require
dose. It is important to have patients derstand why they are taking insulin, insulin therapy to achieve or preserve
check their blood glucose levels and and they need to understand how to satisfactory glucose control and to
to titrate therapy against those blood take it appropriately to decrease their achieve an HbA1c level of less than 7%.
glucose levels, not the HbA 1c levels. risks for adverse effects and complica- In general, the sooner insulin therapy is
Figure 842 provides some guidance on tions. Our job as physicians is to teach started, the better off patients will be in
adjusting insulin doses. our patients. We need to help our pa- terms of avoiding complications.

S14 A Supplement to The Journal of the American Osteopathic Association April 2013 | Vol 113 | No. 4 | Supplement 2

Downloaded from https://jaoa.org by guest on 09/16/2019

 Start once-a-day long-acting insulin analog or NPH,
bedtime or morning,
starting dose 10 U or 0.2 U/kg

Titrate against FPG until in target range (70-130 mg/dL).

Increase dose typically by 2 U every 3 days.
Can increase dose by 4 unites every 3 days if blood glucose level is >180 mg/dL

HbA1c <7% after 2-3 months?

If hypoglycemia occurs
or if FBG level is <70 mg/dL,
reduce dose by ⩾4 U,
No
or by 10% if dose >60 U Yes

Premixed Intensify basal-

Continue regimen, recheck HbA1c level every 3 months bolus regimen

Figure 8.
Initiation and adjustment of insulin regimens. Republished with permission from American Diabetes Association, from
Nathan DM, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and
adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the
Study of Diabetes. Diabetes Care. 2009;32(1):193-203; permission conveyed through Copyright Clearance Center, Inc.

References
7. Gastaldelli A, Ferrannini E, Miyazaki Y,
1. Centers for Disease Control and Prevention.
National Diabetes Fact Sheet: National
Estimates and General Information on Diabetes
and Prediabetes in the United States, 2011.
Atlanta, GA: US Dept of Health and Human
Services, Centers for Disease Control and
8. Bergenstal RM, Kendall DM, Franz MJ,
Prevention; 2011. http://www.cdc.gov/diabetes
/pubs/pdf/ndfs_2011.pdf. Accessed
February 13, 2013.
2. Centers for Disease Control and Prevention.
Increasing prevalence of diagnosed diabetes—
United States and Puerto Rico, 1995-2010.
MMWR Morb Mortal Wkly Rep.
9. United Kingdom Prospective Diabetes Study
2012;61(45):918-921.
3. Centers for Disease Control and Prevention.
County level estimates of diagnosed diabetes—
U.S. maps: 2009 age-adjusted estimates of the
percentage of adults with diagnosed diabetes.
10. Holman RR, Paul SK, Bethel MA,
http://apps.nccd.cdc.gov/DDT_STRS2
/NationalDiabetesPrevalenceEstimates.
aspx?mode=DBT. Accessed January 15, 2013.
4. Cunningham SA, Riosmena F, Wang J, Boyle JP,
11. American Diabetes Association. Standards of
Rolka DB, Geiss LS. Decreases in diabetes-
free life expectancy in the U.S. and the role of
obesity. Diabetes Care. 2011;34(10):2225-2230.
12. Inzucchi SE, Bergenstal RM, Buse JB, et
5. U.K. Prospective Diabetes Study 16. Overview
of 6 years’ therapy of type II diabetes: a
progressive disease. U.K. Prospective Diabetes
Study Group. Diabetes. 1995;44(11):1249-1258.
6. Butler AE, Janson J, Bonner-Weir S, Ritzel
R, Rizza RA, Butler PC. Beta-cell deficit and
increased beta-cell apoptosis in humans with
type 2 diabetes. Diabetes. 2003;52(1):102-110.
13. Gerstein HC, Miller ME, Byington RP, et al.
Matsuda M, DeFronzo RA. Beta-cell dysfunction for the Action to Control Cardiovascular
and glucose intolerance: results from the Risk in Diabetes Study Group. Effects of
San Antonio metabolism (SAM) study. intensive glucose lowering in type 2 diabetes.
Diabetologia. 2004(1);47:31-39. N Engl J Med. 2008;358(24):2545-2559.
14. Duckworth W, Abraira C, Moritz T, et al;
for the VADT Investigators. Glucose control and
Rubenstein AH. Management of type 2 diabetes:
vascular complications in veterans with type 2
a systematic approach to meeting the standards
diabetes. N Engl J Med. 2009;360(2):129-139.
of care. II: oral agents, insulin, and management
of complications. In: DeGroot LJ, Jameson JL,
15. Patel A, MacMahon S, Chalmers J, et al; for
eds. Endocrinology. 4th ed. Philadelphia, PA:
the ADVANCE Collaborative Group. Intensive
WB Saunders; 2001:821-835.
blood glucose control and vascular outcomes
in patients with type 2 diabetes. N Engl J Med.
2008;358(24):2560-2572.
(UKPDS) Group. Effect of intensive blood-
glucose control with metformin on complications
16. Handelsman Y, Mechanick JI, Blonde L,
in overweight patients with type 2 diabetes
et al; for the AACE Task Force for Developing
(UKPDS 34). Lancet. 1998;352(9131):854-865.
Diabetes Comprehensive Care Plan. American
Association of Clinical Endocrinologists Medical
Guidelines for Clinical Practice for developing
Matthews DR, Neil HA. 10-year follow-up of
a diabetes mellitus comprehensive care plan.
intensive glucose control in type 2 diabetes.
Endocr Pract. 2011;17(suppl 2):S1-S53.
N Engl J Med. 2008;359(15):1577-1589.
17. Committee on Quality of Health Care in America,
Institute of Medicine. Crossing the Quality
medical care in diabetes—2013. Diabetes Care.
Chasm: A New Health System for the 21st
2013;36(suppl 1):S11-S66.
Century. Washington, DC: National Academy
Press; 2001:40.
al. Management of hyperglycemia in type 2
18. Rodbard HW, Jellinger PS, Davidson JA,
diabetes: a patient-centered approach: position
et al. Statement by an American Association
statement of the American Diabetes Association
of Clinical Endocrinologists/American
(ADA) and the European Association for the
Study of Diabetes (EASD). Diabetes Care. College of Endocrinology consensus panel
2012;35(6):1364-1379. on type 2 diabetes mellitus: an algorithm
for glycemic control. Endocr Pract.
2009;15(6):540-559.

A Supplement to The Journal of the American Osteopathic Association April 2013 | Vol 113 | No. 4 | Supplement 2 S15
Downloaded from https://jaoa.org by guest on 09/16/2019
 Table 3.
Example of Patient Education and Self-Management of Type 2 Diabetes Mellitus

Step Goal Conversation

Constructing a problem definition What is the patient’s Patient: My HbA1c is starting to get high again—it’s 7.5%.
concern or problem area?
Collaborative goal setting Set specific, measurable, action- Physician: I want your blood sugar levels in the morning
oriented, and realistic goals between 70 and 130 mg/dL and I want your blood sugar
levels after meals less than 180 mg/dL.
Collaborative problem solving Identify barriers and formulate Patient: But when I go out and mow my grass, my blood
a strategy for success sugar level drops, so I can’t take my insulin on the days
I mow my grass.
Contracting for change Track outcomes and reward Physician: On the days you mow your grass, take
successes 2-3 units less of your prandial insulin before the meal
around the time you mow the lawn. (If the patient just
takes basal insulin, he or she should have a snack before
mowing the lawn.)
Continuing support Give positive reinforcement Physician: How did that work out? I’d like to review your
blood sugar logs. You are getting good results—well done!

19. Qaseem A, Humphrey LL, Sweet DE,
Starkey M, Shekelle P. Oral pharmacologic
treatment of type 2 diabetes mellitus: a clinical
practice guideline from the American College
of Physicians. Ann Intern Med.
2012;156(3):218-231.
20. UK Prospective Diabetes Study (UKPDS)
Group. Intensive blood-glucose control with
sulphonylureas or insulin compared with
conventional treatment and risk of complications
in patients with type 2 diabetes (UKPDS 33).
Lancet. 1998;352(9131):837-853.
21. Garber AJ. Novel incretin-based agents and
practical regimens to meet needs and treatment
goals of patients with type 2 diabetes mellitus.
J Am Osteopath Assoc. 2011;111(7 suppl
5):S20-S30.
22. Freeman JS. Improving glucagon-like
peptide-1 dynamics in patients with type 2
diabetes mellitus. J Am Osteopath Assoc.
2012;112(1 suppl 1):S2-S6.
23. Best JD, Drury PL, Davis TM, et al.
Glycemic control over 5 years in 4,900
people with type 2 diabetes: real-world
diabetes therapy in a clinical trial cohort.
Diabetes Care. 2012;35(5):1165-1170.
24. Rolla AR. What about insulin as an immediate
first step for type 2 diabetes? Diabetes Obes
Metab. 2009;11(suppl 5):S19-S22.
25. Tibaldi JM. The future of insulin therapy
for patients with type 2 diabetes mellitus.
J Am Osteopath Assoc. 2013;113(4 suppl
2):S29-S39.
26. Peyrot M, Rubin RR, Lauritzen T, et al; for the
International DAWN Advisory Panel. Resistance
to insulin therapy among patients and providers:
results of the cross-national Diabetes Attitudes,
Wishes, and Needs (DAWN) study. Diabetes
Care. 2005;28(11):2673-2679.
27. Peyrot M, Rubin RR, Khunti K. Addressing
barriers to initiation of insulin in patients
with type 2 diabetes. Prim Care Diabetes.
2010;4(suppl 1):S11-S18.
28. Nakar S, Yitzhaki G, Rosenberg R, Vinker S.
Transition to insulin in type 2 diabetes: family
physicians’ misconception of patients’ fears
contributes to existing barriers. J Diabetes
Complications. 2007;21(4):220-226.
29. Polonsky WH, Hajos TR, Dain MP, Snoek FJ.
Are patients with type 2 diabetes reluctant to
start insulin therapy? an examination of the
scope and underpinnings of psychological
insulin resistance in a large, international
population. Curr Med Res Opin.
2011;27(6):1169-1174.
30. Currie CJ, Peyrot M, Morgan CL, et al.
The impact of treatment noncompliance
on mortality in people with type 2 diabetes.
Diabetes Care. 2012;35(6):1279-1284.
31. Ho PM, Rumsfeld JS, Masoudi FA, et al.
Effect of medication nonadherence on
hospitalization and mortality among patients
with diabetes mellitus. Arch Intern Med.
2006;166(17):1836-1841.
32. Rubin RR. Adherence to pharmacologic
therapy in patients with type 2 diabetes mellitus.
Am J Med. 2005;118(suppl 5A):S27-S34.
33. Peyrot M, Rubin RR, Kruger DF, Travis LB.
Correlates of insulin injection omission.
Diabetes Care. 2010;33(2):240-245.
34. Rubin RR, Peyrot M, Kruger DF, Travis LB.
Barriers to insulin injection therapy: patient
and health care provider perspectives.
Diabetes Educ. 2009;35(6):1014-1022.
35. Lloyd A, Nafees B, Barnett AH, et al.
Willingness to pay for improvements in chronic
long-acting insulin therapy in individuals with
type 1 or type 2 diabetes mellitus. Clin Ther.
2011;33(9):1258-1267.
36. Karter AJ, Subramanian U, Saha C, et al.
Barriers to insulin initiation: the translating
research into action for diabetes insulin starts
project. Diabetes Care. 2010;33(4):733-735.
37. Unger J. Comparing the efficacy, safety, and
utility of intensive insulin algorithms for a primary
care practice. Diabetes Ther. 2011;2(1):40-50.
38. Meece J. Dispelling myths and removing barriers
about insulin in type 2 diabetes. Diabetes Educ.
2006;32(suppl 1):S9-S18.
39. Freeman JS. Insulin analog therapy: improving
the match with physiologic insulin secretion.
J Am Osteopath Assoc. 2009;109(1):26-36.
40. Hirsch IB. Insulin analogues. N Engl J Med.
2005;352(2):174-183.
41. Monami M, Marchionni N, Mannucci E. Long-
acting insulin analogues versus NPH human
insulin in type 2 diabetes: a meta-analysis.
Diabetes Res Clin Pract. 2008;81(2):184-189.
42. Nathan DM, Buse JB, Davidson MB, et al.
Medical management of hyperglycemia in type 2
diabetes: a consensus algorithm for the initiation
and adjustment of therapy: a consensus
statement of the American Diabetes Association
and the European Association for the Study of
Diabetes. Diabetes Care. 2009;32(1):193-203.
43. Peyrot M, Rubin RR. Behavioral and
psychosocial interventions in diabetes:
a conceptual review. Diabetes Care.
2007;30(10):2433-2440.
© 2013 American Osteopathic Association

S16 A Supplement to The Journal of the American Osteopathic Association April 2013 | Vol 113 | No. 4 | Supplement 2

Downloaded from https://jaoa.org by guest on 09/16/2019