Download Strategies for Identifying and Avoiding Hypoglycemia in Your Type 2

Learning Objectives
•
•
Recognize particular patient characteristics associated with susceptibility
to hypoglycemia and take these characteristics into consideration when
evaluating the most appropriate individualized treatment options
As part of diabetes self-management education, teach patients that
awareness of hypoglycemia can become impaired and provide instruction
on how to recognize hypoglycemia under such circumstances
Strategies for Identifying and Avoiding Hypoglycemia in Your Type 2
Diabetes Mellitus Patients
Introduction
It is well-accepted that maintaining glycemic control over time prevents or delays
microvascular, and possibly macrovascular, complications of diabetes.1 Glycemic
control strategies depend on interventions that regulate insulin replacement or
secretion in a way that consistently achieves and maintains euglycemia safely.
However, hypoglycemia remains a significant limiting factor in glycemic
management of diabetes, otherwise blood glucose could be kept low in people
with diabetes and they could have normal A1C levels over a lifetime of diabetes.
Hypoglycemic incidents that occur in diabetes patients can often result in
recurrent physical morbidity, recurrent or persistent psychosocial morbidity, or
both, and sometimes cause death. The prevention of hypoglycemia is a central
aspect of any diabetes treatment and is achieved through a balance between
glycemic control and minimizing the risk of hypoglycemia. Effective glycemic
control strategies are implemented through: 1) patient education and
empowerment, 2) frequent self-monitoring of blood glucose (SMBG), 3) flexible
insulin and other drug regimens, 4) individualized glycemic goals, and 5) ongoing
professional guidance and support.
Defining Hypoglycemia
Hypoglycemia is described as a condition characterized by low plasma glucose
levels with neuroglycopenic symptoms of the sympathetic autonomic nervous
system that can be relieved by the administration of carbohydrates in patients,
especially those using glucose-lowering medications such as sulfonylureas,
glinides, or insulin injection. Hypoglycemia is found whenever plasma glucose
levels fall to abnormally low levels, to the extent that the patient is potentially
exposed to harm. Patients with diabetes being treated with an insulin injection or
glucose-independent insulin secretagogues should be aware that a blood
glucose level of ≤ 70 mg/dL represents the alert threshold for onset of a
hypoglycemic episode, as illustrated in Figure 1.2,3
1
Figure 1. The Alert Threshold for Hypoglycemia Is ≤ 70 mg/dL.3
Plasma
Glucose
(mg/dL)
110 —
Upper limit
100 —
90 —
Mean
Decreased insulin secretion
80 —
70 —
60 —
50 —
Lower limit
Increased glucagon secretion
Increased epinephrine secretion
Symptoms
Decreased cognition
Aberrant behavior, seizure, coma
40 —
30 —
20 —
Neuronal death
10 —
0—
Etiology of Hypoglycemia
People who do not have diabetes have physiologic feedback mechanisms that
are able to prevent or rapidly correct hypoglycemia by adjusting key glucoseregulatory factors, including a decrease in pancreatic β-cell insulin secretion, an
increase in pancreatic α-cell glucagon secretion, and, if necessary, an increase in
adrenomedullary epinephrine secretion.1 Hypoglycemia that occurs in type 1
diabetes patients and type 2 diabetes patients who are actively treating their
disease follows an imbalance between absolute or relative insulin levels and the
glucose counterregulation mechanisms that normally raise blood glucose levels.
In such patients, insulin levels fail to decrease as blood glucose levels fall and
the combination of deficient glucagon and epinephrine responses precludes a
compensatory increase in glucose secretion.
Hypoglycemia Unawareness
Many of the symptoms that serve as warning signs of hypoglycemia, such as
tremor, palpitations, and anxiety, are due to release of epinephrine by the
autonomic nervous system, triggered by low glucose levels.1 Symptoms of
hypoglycemia include tremor; palpitations; anxiety; feeling weak, shaky, or
lightheaded; sweaty or clammy skin; feeling or acting crabby or confused; numb
or tingling lips; or undue hunger. A phenomenon called “hypoglycemia
unawareness” is the result of an attenuation of the autonomic response, leading
to a loss of the typical warning signs. Thus, after experiencing recurrent episodes
of hypoglycemia, some patients may no longer perceive hypoglycemic
2
symptoms. However, patients can be taught to look for subtle symptoms in this
regard; they may wake up with a headache they didn’t go to sleep with,
remember nightmares/vivid dreams, awaken with bedsheets or pajamas soaked
with sweat, or experience a “hangover-like” sensation.4 People around patients
with diabetes should be taught to look for neuroglycopenic symptoms in these
patients, such as acute loss of memory or inability to perform simple tasks.
Patients should understand that, over time, excessive weight gain after starting
hypoglycemic agents is a not-so-subtle sign of hypoglycemia unawareness;
patients get increased appetite with early hypoglycemia, forcing them to eat extra
calories to avoid overt hypoglycemia.5,6 Individuals with hypoglycemia
unawareness or 1 or more episodes of severe hypoglycemia are advised to raise
their glycemic targets and strictly avoid further hypoglycemia for at least several
weeks to partially reverse hypoglycemia unawareness and reduce the risk of
future episodes.2
Hypoglycemia Is Found in Both Type 1 and Type 2 Diabetes
It is estimated that severe hypoglycemia in type 1 diabetes patients ranges from
62 to 170 episodes per 100 patient-years during intense insulin therapy. In
contrast, the range in type 2 diabetes patients runs from 3 to 73 episodes per
100 patient-years.1 Episodes of hypoglycemia experienced by patients with type
2 diabetes who use intense insulin therapy represent 10% of the rate found in
type 1 diabetes. While this rate is lower in patients using oral glucose-lowering
agents, it is very important to note that, since type 2 diabetes accounts for 90%95% of all adult diabetes, the absolute number of hypoglycemic episodes is
actually greater in type 2 than in type 1 diabetes.7
Hypoglycemia Increases as the Duration of Diabetes Increases
Data from the UK Hypoglycemia Study Group, shown in Figure 2, demonstrate
that, in patients with either type 1 or type 2 diabetes, there is an increase in the
risk of hypoglycemia associated with increasing duration of diabetes and
increasing duration of insulin therapy.8 The figure displays the proportion of
patients with either type of diabetes who reported 1 or more episodes of
hypoglycemia during a follow-up period of 9-12 months. In patients with type 2
diabetes who were using insulin for longer than 5 years, the prevalence of mild or
severe hypoglycemia was similar to that found in patients with type 1 diabetes of
short duration.
3
Figure 2. Frequency of Hypoglycemia in Both Type 1 and Type 2 Diabetes Is Related to
Disease Duration8
Proportion reporting at least 1
severe hypoglycemic episode
0.8
0.6
Sulfonylurea treatment
Insulin < 2 years
Insulin > 5 years
Insulin < 5 years
Insulin > 15 years
0.4
0.2
(n = 75)
(n = 54)
(n = 46)
(n = 103) (n = 85)
0
Type 2
Type 1
Hypoglycemia Is Associated With Type 2 Diabetes Treatment Using Either
Insulin or Oral Agents
As shown in Figure 3, a comparison between type 2 diabetes patients using
insulin and those using oral agents found that the frequency of hypoglycemic
symptoms during a 1-month period was lower in those using only oral agents
than in those using insulin.9 However, it is noteworthy that, even in this
population, over 20% of patients using oral agents reported experiencing a
hypoglycemic event. Symptoms were reported by 115 of 309 patients during the
study period and this represented a 37% incidence of hypoglycemia. It was
further revealed that 24% of patients experienced symptoms every month, 11%
every week, and 2% every day.
4
Figure 3. Frequency of Hypoglycemic Symptoms Among Patients With Type 2 Diabetes 9
60
Patients self-reporting
hypoglycemic events (%)
50
40
30
20
10
0
Any insulin
(n = 133)
Oral agents
only
(n = 176)
All patients
(n = 309)
Factors Associated With Increased Risk of Hypoglycemia
Hypoglycemia may be a concern for all patients with type 2 diabetes; however,
certain patient populations are at an increased risk of hypoglycemia. Higher risk
populations include older patients, those with a longer duration of diabetes, those
who regularly miss meals, those who exercise, and those who take a greater
than prescribed dose of their medication.10,11 The underlying cause of the
increased risk in elderly patients is most often related to a diminished
counterregulatory hormone response, which is more attributable to diabetes than
to old age itself. A lack of self-monitoring or insufficient patient/caregiver
awareness concerning symptoms of hypoglycemia is of particular importance
with elderly patients.12 Factors that increase the risk of hypoglycemia in type 2
diabetes include:
 Renal impairment
 Psychiatric disorders, particularly depression
 Hospitalization; a 5-fold increase for 1 month following hospitalization
 Adherence to dietary recommendations and schedules; 53% of
hypoglycemic episodes are related to missing a meal
 Physical exercise
 Dosing errors with glucose-lowering agents
 Alcohol intake (infrequent)
While the characteristics listed above may increase the risk that diabetes patients
will experience a hypoglycemic incident, patients should also be aware of factors
that may increase their risk of being harmed by the incident, as discussed below.
Hypoglycemia Diminishes Quality of Life for Diabetes Patients
Hypoglycemia can significantly diminish quality of life (QOL) for people with
diabetes through effects on their relationships, employment, driving, recreational
5
activities involving exercise, and travel.4 Patients tend to associate hypoglycemic
episodes with loss of personal control and potential embarrassment, as well as
unpleasant symptoms, mood changes, and disruption of many everyday
activities. Hypoglycemia while driving is recognized to cause road traffic
accidents, although the frequency is difficult to ascertain. Patients sometimes try
to compensate by avoiding hypoglycemia at all costs and deliberately maintain a
degree of hyperglycemia, having an adverse effect on their glycemic control.
Hypoglycemia Can Have Serious Consequences for Patients’ Health
Normal brain function requires an adequate, continuous supply of glucose in the
blood since it cannot synthesize its own glucose. When arterial glucose levels
fall, there is a corresponding slow-down in the blood-to-brain transport of
glucose, limiting brain metabolism and, in turn, survival.1 Severe and prolonged
hypoglycemia significantly increases morbidity and mortality in patients with
diabetes. In fact, hypoglycemia underlies at least 6% of deaths in patients with
type 1 diabetes.13 Furthermore, fatal hypoglycemia is not limited to type 1
diabetes; there have been reports of fatal hypoglycemia in type 2 diabetes
patients treated with sulfonylureas.14
Severe Hypoglycemia Raises the Risk of Dementia
Cognitive dysfunction often follows repetitive hypoglycemia; this is commonly
reported in type 1 diabetes studies and almost all studies of type 2 diabetes have
shown similar results.15,16 For example, a longitudinal study examining all
hospitalization and emergency department diagnoses of hypoglycemia in a
cohort of 16,667 patients with type 2 diabetes found that 11.0% of patients had a
diagnosis of dementia during a mean follow-up of 3.8 years, and that 8.8% had
reported at least 1 episode of hypoglycemia. As shown in Figure 4, patients with
no prior dementia reporting at least 1 hypoglycemic event were more likely to be
diagnosed with dementia, with an attributable risk of 2.39% per year compared
with those with no episodes.17 The excess risk in Figure 4 increases from 1.64%
per year for 1 hypoglycemic episode to 4.28% per year for 3 or more episodes.
Recurrent hypoglycemia can also lead to other noncognitive, psychological
abnormalities.18
6
Figure 4. Patients With a History of Severe Hypoglycemia Are More Likely to Be Diagnosed
With Dementia17
Excess attributable
risk per year, %
5
(n = 258)
(n = 205)
2 episodes
3 or more
episodes
4
3
2
(n = 1002)
1
0
1 episode
Severe hypoglycemia
Hypoglycemia May Have Cardiovascular Consequences
Another important consequence of hypoglycemia, which can be even more
serious in the elderly, is increased risk of myocardial infarction, ventricular rhythm
disorders, and stroke. In the study represented in Table 1, continuous glucose
monitoring was conducted over a 72-hour period in patients with type 2 diabetes
and coronary artery disease, and hypoglycemia was found to more likely be
associated with cardiac ischemia than hyperglycemia or normoglycemia.19 Out of
54 recorded episodes of hypoglycemia, 10 were associated with symptoms of
chest pain. A more recent study has found an association between nocturnal
hypoglycemia and abnormalities in cardiac repolarization parameters that may
conceivably contribute to sudden cardiac death in diabetes patients. 20
Interestingly, the effects observed in this study were not associated with the
increase in epinephrine that typically accompanies hypoglycemia.
7
Table 1. Association Between Hypoglycemia and Cardiac Symptoms 19
Glucose Monitoring
Abnormalities
Hypoglycemia
Total
Episodes
Chest
Pain or
Abnormal
Angina Electrocardiogram
54
10
6
Symptomatic
26
10
4
Asymptomatic
28
–
2
–
0
0
59
1
0
50
9
2
Normoglycemia
(No Rapid
Changes)
Hyperglycemia
Rapid Changes
(> 100 mg/dL/h)
Hypoglycemia Can Have a Serious Impact on Health Care Delivery
During a period spanning from 1993 to 2005, there were 380,000 emergency
department visits per year in the United States that were attributed to
hypoglycemia.21 Of those visits, 25% resulted in hospital admission, 72% were
for patients who had hypoglycemia as their primary diagnosis, and about 44%
involved adults aged 65 years or older. Notably, however, elderly patients are
actually less likely to recognize symptoms of hypoglycemia, most often due to a
decreased counterregulatory hormone response, a less adapted behavioral
response, and less awareness about symptoms and self-monitoring on the part
of the patient and caregiver.12
Glycemic Control Should Be Balanced Against Avoidance of Hypoglycemia
At its most basic level, hypoglycemia is the result of an absolute or relative
excess of insulin.1 Excess insulin can come from either injected or secreted
insulin and occurs when the wrong type of medication is used, when medication
doses are too high or poorly timed, or when renal clearance of insulin is
attenuated. A relative excess of insulin can be the result of increased sensitivity
to insulin following exercise, weight loss, improvements in fitness or glycemic
control, or when using an insulin-sensitizing medication. A relative insulin excess
can also be the result of decreased blood glucose due to missed meals or
overnight fasting, decreased glucose production following alcohol consumption,
or increased glucose expenditure.
Hypoglycemia Can Often Limit Effective Glycemic Control
Hypoglycemia can often become a limiting factor in effective glycemic control
when patients become frustrated with attempts to intensify treatment.22 For
8
instance, fear of nocturnal hypoglycemia was noted as a major cause of regimen
nonadherence in the Treat-to-Target study.
Fear of Hypoglycemia Can Worsen Blood Glucose Control
Since the fear of hypoglycemia can often become a barrier to consistent glycemic
control, education in such cases should be aimed at improving self-management
by emphasizing the tools that can best combat the fear of hypoglycemia.
Knowledge is a very important tool. Well-informed patients who are willing and
able to effectively manage their diabetes are most likely to successfully avoid
hypoglycemia.12,22 Patients who fear hypoglycemia should be encouraged to ask
questions of their health care team and gain a more accurate understanding of
the causes and effects of hypoglycemia. Enrollment in a diabetes education
program provides the added benefit of the social support that may be found in
peer groups. Subscribing to a popular diabetes magazine can also reinforce the
learning process. Well-prepared patients can learn to avoid overreactions that
may lead to chronically high blood sugars and achieve a balance between their
lifestyles and the timing of their medications, meals, and physical activity.
The Role of SMBG in Glycemic Control
In patients treated with insulin, SMBG is an important tool in preventing both
hyperglycemia and asymptomatic hypoglycemia.2 SMBG allows patients to
evaluate their individual response to therapy and assess whether glycemic
targets are being achieved and whether glucose may be approaching
hypoglycemic levels. Clinical trials of insulin-treated patients that have
demonstrated the benefits of intensive glycemic control have included education
of patients and physicians on how to use the data of SMBG as a part of the
intervention, suggesting that SMBG should be included in an effective diabetes
regimen.
The usefulness of regular SMBG in type 2 diabetes patients who are not using
insulin therapy is debated within the medical community.23 The potential benefits
of SMBG include providing motivation and feedback for patients about
medication changes, dietary programs, or exercise regimens, including resultant
improvements in self-efficacy, as well as the ability to detect and treat
hypoglycemia or hyperglycemia. Disadvantages include the possibility of
increasing negative emotions, the discomfort of getting blood samples, and the
time and effort spent by the patient.
The Diabetes Glycaemic Education and Monitoring trial recently associated
SMBG with higher costs and lower QOL in patients with noninsulin-treated type 2
diabetes, whether or not it was coupled with additional training on how to
incorporate the results into self-care decisions.24 Further analysis showed an
initial negative impact of self-monitoring on QOL. Other findings, showing little or
no benefit with SMBG and coupled with possible reductions in well-being,
9
suggest that routine use of SMBG is not beneficial for noninsulin users within the
context of a well-organized program of diabetes care that includes frequent
assessments of A1C followed by algorithm-based medication adjustment.23
A synthesis of these data suggests that SMBG use should be recommended in
those using hypoglycemic oral agents, especially if they fall into 1 of the high risk
categories mentioned above.
The Glycemic Treatment Strategy Should Accommodate Hypoglycemia
Avoidance
When developing an overall treatment strategy, the recommended, general goal
for glycemic therapy is A1C < 7.0%, but health care providers should work with
individual patients to agree upon the most appropriate goal for each individual.
For relatively healthy patients, the recommended goal is as close to normal (<
6.0%) as possible without causing significant hypoglycemia.25 On the other hand,
less stringent A1C goals than < 7.0% should be considered for those with a
history of severe hypoglycemia, limited life expectancy, advanced microvascular
or macrovascular complications, extensive comorbid conditions, or patients with
longstanding diabetes in whom the general goal is difficult to attain.2 As shown in
Figure 5, the second step of the American Diabetes Association/European
Association for the Study of Diabetes (ADA/EASD) algorithm diverges into 2
recommended strategies for achieving glycemic control in patients who are no
longer achieving their treatment goal using the first treatment step (ie, metformin
plus lifestyle interventions).26
Figure 5. Step 2 of the ADA/EASD Algorithm26
Tier 1: Well-validated therapies
Lifestyle + Metformin
+
Basal Insulin
Lifestyle + Metformin
+
Sulfonylurea
Tier 2: Less well-validated therapies
Lifestyle + Metformin
+
Pioglitazone
Lifestyle + Metformin
+
Pioglitazone
+
Sulfonylurea
Lifestyle + Metformin
+
GlucagonGlucagon-like
peptidepeptide-1 agonist
Lifestyle + Metformin
+
Basal Insulin
10
As outlined in Figure 6, avoidance of hypoglycemia is a determining factor in
selecting either of the 2 treatment strategies.12,26 Active clinicians may recognize
other clinical situations that can make a patient more likely to be harmed by a
specific hypoglycemic event and would argue for use of tier 2 agents over agents
that can cause hypoglycemia. Examples of such patients include those who:
drive a great deal; walk up and down stairs frequently; have increased risk of
falling; have a history of stroke; have a history of arterial disease with angina,
arrhythmia, or myocardial infarction; are on anticoagulation therapy; use electric
tools (including blow dryers or curling irons); or are responsible for little children.
(S. Schwartz, MD, personal communication) To some extent, most diabetes
patients should avoid hypoglycemia and avoid or carefully use agents that can
cause hypoglycemia.
Figure 6. Choosing Treatment Options on the ADA/EASD Algorithm 12,26
Tier 1 Agents
•
When metformin is not tolerated or is contraindicated:
– Glomerular filtration rate < 30 mL/min
•
When a large reduction in A1C is needed:
– A1C reduction ≥ 1.5%
•
When medication cost is a hardship
Tier 2 Agents
•
When avoidance of hypoglycemia is important:
– Certain occupations (eg, drivers, heavy
equipment operators, using power tools, public
safety jobs)
– Certain populations (eg, history of hypoglycemia,
alcohol use, elderly patients, renal insufficiency)
•
When promotion of weight loss is important
The ADA/EASD Algorithm Provides Guidance for Selection of Glycemic
Therapies
Different glucose-lowering agents have different propensities for causing
hypoglycemia, depending on their mechanisms of action. Table 2 summarizes
the association of a number of glycemic agents with episodes of hypoglycemia in
type 2 diabetes patients.2,25-27 In theory, monotherapy treatment of type 2
diabetes with many of the agents listed in Table 2 should not cause
hypoglycemia. Patients who respond to these drugs must be early enough in the
course of their disease that they still have endogenous insulin secretion, which is
still able to decrease appropriately as the plasma glucose concentrations fall.1
11
Table 2. Association of Glycemic Agents With Hypoglycemia*
Class
Metformin
Hypoglycemia
No
Insulin, long acting
Yes
Insulin, rapid acting
Sulfonylureas
Thiazolidinediones
Glucagon-like peptide-1 agonists
Repaglinide
Nateglinide
α-Glucosidase inhibitor
Amylin mimetics
Dipeptidyl peptidase-4 inhibitors
Bile acid sequestrant
Bromocriptine
Yes
Yes
No
No
Yes
Rare
No
No
No
No
No
*
Provided by John B. Buse, MD, PhD.
In practice, there have been reports of major hypoglycemia with metformin. In
patients using a sulfonylurea, hypoglycemia is more often reported in association
with long-acting agents, such as chlorpropamide or glyburide (glibenclamide)
than with metformin.28 Original US Food and Drug Administration submission
data for repaglinide suggest 50% less hypoglycemia with repaglinide than with
sulfonylureas (Table 3). A direct comparison of repaglinide and nateglinide
suggested less hypoglycemia with nateglinide, but the difference failed to reach
statistical significance (P = 0.3).29 Both agents stimulate insulin secretion by the
same glucose-independent mechanism, but act through different molecular
binding sites.
Table 3. Low Risk of Severe Hypoglycemia*
Hypoglycemia
Parameter
Repaglinide*
Sulfonylureas
P Value
Hypoglycemic symptoms
with < 50 mg/dL
9.7%
20.2%
0.001
Discontinuation due to
hypoglycemia
1.4%
2.8%
Not
significant
Nocturnal hypoglycemia
1.7%
3.9%
0.04
*No
serious hypoglycemic episodes with repaglinide in long-term clinical trials
(serious defined as resulting in coma or requiring hospitalization)
*
Provided by Stanley Schwartz, MD.
Systematic Review of Glycemic Agents
12
Hypoglycemia in randomized clinical trials has recently been reviewed in more
detail for some of the more commonly used glycemic agents; the results are
summarized in Figure 7.28 Minor and major hypoglycemic episodes were more
frequent in patients using second-generation sulfonylureas (especially glyburide)
than in those using metformin or thiazolidinediones. Absolute risk differences
between groups ranged from 4% to 9% when sulfonylureas were compared with
metformin or thiazolidinediones in short-term randomized trials, although
reported levels of hypoglycemic risk ranged widely across studies. Glyburide and
glibenclamide conferred a slightly higher risk for hypoglycemia compared with
other second-generation sulfonylureas (absolute risk difference: about 2% in
trials of short duration). Repaglinide and second-generation sulfonylureas
conferred similar risks for hypoglycemia. Comparative data on acarbose and
nateglinide were sparse. The incidence of minor and major hypoglycemia was
higher with combinations that included sulfonylureas compared with metformin or
sulfonylurea monotherapy. Overall, these results agree with the more general
description shown in Table 2.
Figure 7. Pooled Hypoglycemia Results for Randomized Trials by Drug Comparison 28
Drug 1 Less Harmful Drug 1 More Harmful
Met vs Met + TZD
SU vs repaglinide
Glyburide vs
other SU
SU vs Met
SU + TZD vs SU
SU vs TZD
SU + Met vs SU
SU + Met vs Met
0.0
0.5
0.1
0.15
0.2
Weighted absolute risk difference
(± 95% CI)
Met: metformin; SU: sulfonylurea; TZD: thiazolidinedione
Other Glycemic Agents
A recent review of dipeptidyl peptidase (DPP)-4 inhibitors in 25 studies
investigating sitagliptin and vildagliptin found that severe hypoglycemia was not
reported in patients taking either of the medications.30 There were no statistically
significant differences in hypoglycemic episodes between sitagliptin or vildagliptin
and comparator groups. Although DPP-4 inhibitors are not yet recommended on
the ADA/EASD algorithm, they may be appropriate in patients with a particular
13
need to avoid hypoglycemia. Additional data have recently demonstrated the
safety of the DPP-4 inhibitor saxagliptin.31 These agents have a low association
with hypoglycemic episodes and would be an appropriate choice for selected
diabetes patients who have a special need to avoid hypoglycemia.
Prevention of Hypoglycemia Through Diabetes Self-Management Education
Results of the Real-Life Effectiveness and Care Patterns of Diabetes
Management (RECAP) study indicate a significant decrease in self-reported
adherence among patients experiencing hypoglycemia compared with patients
with no hypoglycemia.32 Type 2 diabetes patients in RECAP answered
questionnaires in which they self-reported on whether they had experienced
hypoglycemic symptoms, severity of the symptoms, treatment satisfaction, and
treatment adherence. Overall, 38.4% of patients reported hypoglycemia
compared with 61.6% with no hypoglycemia. Patients with hypoglycemia were
significantly less likely to report never having problems getting their prescriptions
filled, never being bothered by side effects, never being unable to follow
treatment plans, or never being unsure about regimen instructions. While poor
regimen adherence is attributable to many different causes, effective diabetes
self-management education can bring significant improvements in most cases
and potentially reduce the chances of experiencing hypoglycemia.
Learning to Recognize Hypoglycemic Symptoms
Education should enable patients to readily recognize various symptoms of a
hypoglycemic episode and take appropriate action to correct the low glucose
level, as outlined in Table 4.2 Patients can be encouraged to fight their fear of
hypoglycemia with knowledge and to be mindful of the fact that it is poorly
controlled diabetes that typically causes serious problems, not diabetes itself.
Encourage patients to ask questions about hypoglycemia. Other educational
resources include enrolling in a diabetes education program or subscribing to a
popular diabetes magazine.
14
Table 4. Recognition and Treatment of Hypoglycemia1,2
Symptoms
Feeling weak, shaky, or
lightheaded
Sweaty or clammy skin
Self-Care
If symptoms occur, do a self-test
If blood glucose is too low, eat or drink 15 g of
carbohydrates
Low reading on glucose selfWait 15 minutes and test again
test
Feeling or acting crabby or If blood glucose is still too low, eat or drink
confused
another 15 g of carbohydrates
Fast heartbeat
Wait 15 minutes and test again; if necessary,
eat or drink another 15 g of carbohydrates
–
Numb or tingling lips
Undue hunger
Test blood sugar
Patients should also be instructed that hypoglycemia can sometimes go
unnoticed. For example, a study using continuous glucose monitoring in 31
patients with type 2 diabetes revealed a total of 83 hypoglycemic events in the
study population over a 3-day period, with 45 nighttime events going completely
unnoticed by the study participants.33 Nocturnal hypoglycemia is often
accompanied by a “rebound” or overcompensation reaction called a “Somogyi
effect”, characterized by high blood levels in the morning.34 Physicians and
patients alike should be trained to monitor patterns of fasting blood glucose
patterns (normal, high, or low) over a week, despite following a diet and taking
the same doses of hypoglycemic medications that would suggest this rebound
effect on some nights.
Patients may not recognize nocturnal hypoglycemia without specific instruction
on its characteristics, as described above. This is especially true of those
patients who wake up with high glucose levels on some days and normal levels
on other days. Patients who note high blood sugar levels in the morning should
be instructed to test their blood glucose levels in the middle of the night (eg, 3:00
am). If falling or low blood sugar levels are found at that time, the risk of
nocturnal hypoglycemia may be reduced by delaying the evening isophane
insulin until bedtime, using a fast-acting insulin analogue before a late evening
meal, or using a long-acting insulin analogue as the basal insulin in the morning.4
Weight gain resulting from bedtime snacks that are intended to prevent nocturnal
hypoglycemia can become a significant problem for people with type 1 or type 2
diabetes who use intensive insulin therapy.35
15
Conclusion
Hypoglycemia is experienced through both catechol and/or neuroglycopenic
symptoms, although certain populations may have a reduced awareness and
response to hypoglycemia. Avoidance of hypoglycemia should be considered an
important aspect of most glycemic treatment plans, because severe and
prolonged hypoglycemia may be associated with severe consequences, such as
seizure, coma, dementia, electrocardiogram abnormalities, and arrhythmia.
Furthermore, fear of hypoglycemia may become a barrier to consistent glycemic
control and is recognized as the leading limiting factor in glycemic management.
Patient concerns about hypoglycemia and the risk of hypoglycemia associated
with individual glucose-lowering agents are important factors to consider in the
development of a medication regimen for diabetes. However, with proper
instruction and support, well-informed and motivated physicians and patients can
achieve good glycemic control while minimizing the risk of hypoglycemia.
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