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Hypoglycemia in Patients With Type 2 Diabetes Mellitus
Christopher D. Miller, MD;
Lawrence S. Phillips, MD;
David C. Ziemer, MD;
Daniel L. Gallina, MD;
Curtiss B. Cook, MD;
Imad M. El-Kebbi, MD
Arch Intern Med. 2001;161:1653-1659.
ABSTRACT
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Background Although hypoglycemia is the most common complication of intensive diabetes
therapy, there is little information about risk factors for hypoglycemia in
patients with type 2 diabetes mellitus.
Objective To determine the prevalence and predisposing factors for hypoglycemia
in patients with type 2 diabetes.
Methods Retrospective, cross-sectional analysis set in an outpatient specialty
diabetes clinic. We included those patients who had baseline and follow-up
visits from April 1 through October 31, 1999. Hypoglycemia was defined as
typical symptoms relieved by eating, and/or blood glucose level of less than
60 mg/dL (<3.3 mmol/L). Univariate and multivariate logistic regression
were used to determine the contributions to hypoglycemia of age, sex, diabetes
duration, body mass index (calculated as weight in kilograms divided by the
square of height in meters), fasting plasma glucose level, glycosylated hemoglobin
(HbA1c) level, type of therapy, and previous episodes at the follow-up
visit.
Results We studied 1055 patients. Prevalence of hypoglycemic symptoms was 12%
(9/76) for patients treated with diet alone, 16% (56/346) for those using
oral agents alone, and 30% (193/633) for those using any insulin (P<.001). Severe hypoglycemia occurred in only 5 patients (0.5%),
all using insulin. Multiple logistic regression analysis demonstrated that
insulin therapy, lower HbA1c level at follow-up, younger age, and
report of hypoglycemia at the baseline visit were independently associated
with increased prevalence of hypoglycemia. There were no significant predictors
of severe hypoglycemia.
Conclusions Mild hypoglycemia is common in patients with type 2 diabetes undergoing
aggressive diabetes management, but severe hypoglycemia is rare. Concerns
about hypoglycemia should not deter efforts to achieve tight glycemic control
in most patients with type 2 diabetes.
INTRODUCTION
HYPOGLYCEMIA is a significant complication of diabetes therapy. Although
mild hypoglycemia causes unpleasant symptoms and disrupts patients' daily
activities, severe hypoglycemia can result in coma, seizures, and death. Moreover,
recurrent episodes of mild hypoglycemia can alter the counterregulatory response
to decreased blood glucose levels and lead to hypoglycemia unawareness, placing
patients at increased risk for development of severe hypoglycemia.1 Recurrent hypoglycemia has also been found to decrease
quality of life in patients with diabetes.2-4
Although hypoglycemia is well recognized as a problem in management
of type 1 diabetes mellitus,5-7
less is known about hypoglycemia in patients with type 2 diabetes mellitus.
The Diabetes Control and Complications Trial (DCCT) found a 3-fold greater
incidence of severe hypoglycemia in a group of patients with type 1 diabetes
undergoing intensive treatment compared with those treated less aggressively.8 In contrast, the feasibility trial of the Veterans
Affairs Cooperative Study on Glycemic Control and Complications in Type II
Diabetes (VA CSDM) showed an increase in mild and moderate, but not severe,
hypoglycemia in patients undergoing intensive treatment,9
whereas the Kumamoto study showed no increase in mild or severe episodes in
patients with type 2 diabetes undergoing intensive treatment compared with
those undergoing less intensive treatment.10
Although the United Kingdom Prospective Diabetes Study (UKPDS) showed an increase
in hypoglycemia in patients with type 2 diabetes assigned to the intensive
protocol arm, it was largely a study of monotherapy, and many patients had
elevated glucose levels.11
While these studies have assessed hypoglycemia in controlled research
settings, there is little information on the frequency of hypoglycemia in
typical clinical practice settings. Despite the adverse events associated
with hypoglycemia and the potential of fear of these events to limit the use
of intensive diabetes therapy, few studies have examined the risk factors
for hypoglycemia in patients with type 2 diabetes. Moreover, even less is
known about hypoglycemia in minority populations with low literacy levels
and high rates of poverty, where tight glycemic control might be more difficult
to attain. Therefore, we conducted a cross-sectional study to assess the prevalence
of hypoglycemia and its associated risk factors in urban, predominantly African
American patients with type 2 diabetes who were treated in a specialized diabetes
clinic.
METHODS AND RESEARCH DESIGN
SETTING
The study was conducted at the Diabetes Clinic of the Grady Health System,
Inc, Atlanta, Ga. The clinic serves a predominantly African American population
and provides care for approximately 900 new and 5000 returning patients each
year. Plasma glucose level is measured at each visit, and glycosylated hemoglobin
(HbA1c) level is determined onsite every 2 to 3 months.12 Patients are initially examined by a nurse provider
who provides diabetes education and makes recommendations for changes in therapy.
Patients then undergo reevaluation by an endocrinologist who makes final treatment
decisions. The clinic management protocol emphasizes lifestyle modification
and an attempt to reduce the use of pharmacologic agents during the first
2 months after initial presentation. If adequate glycemic control is not attained
after 2 months, pharmacologic therapy is instituted (or increased), and the
goal of near normoglycemia is pursued aggressively. Pharmacologic therapy
is advanced using a stepped-care approach, beginning with a single oral agent
(long-acting glipizide, glyburide, or metformin), and then progressing to
combination oral agents, oral agents plus bedtime insulin, and finally multiple-dose
insulin regimens. The goal for glycemic control is HbA1c level
of less than 7.0%.
DESIGN
We examined patient visits from April 1 through October 31, 1999. Patients
were included in the analysis if they had received a diagnosis of type 2 diabetes
mellitus (by clinical criteria described previously13),
had been followed up in the Diabetes Clinic for at least 2 months (to avoid
the period of deintensification of therapy), and had had at least 2 visits
during the study period (baseline and study follow-up visits). Data from the
baseline visit were collected to allow hypoglycemia at baseline to be assessed
as a contributing factor to hypoglycemia at follow-up. The prevalence of hypoglycemia
and other information presented in the results are based on data collected
at the follow-up visit.
Data from every patient visit at the Grady Diabetes Clinic are entered
into a computerized registry. These data include information on demographics,
laboratory test values, current diabetes therapy, and any changes in therapy
made at the visit. Answers to the following questions about hypoglycemia are
also entered into the database: (1) How many times was your blood glucose
level low since the last visit? (2) What was the lowest home glucose monitoring
value obtained during these episodes? (3) Were there symptoms associated with
these episodes? and (4) How many times did you need help from someone else
to treat your low blood glucose level? Hypoglycemia was thus assessed at baseline
and follow-up visits.
DEFINITION OF HYPOGLYCEMIA
For purposes of the analysis, mild hypoglycemia
was defined as patient report of typical symptoms of hypoglycemia (eg, sweating,
tremulousness, hunger, and/or dizziness) that were relieved by eating, or
patient report of home glucose monitoring values of less than 60 mg/dL (<3.3
mmol/L). The cutoff blood glucose level of 60 mg/dL (3.3 mmol/L) was selected
to define biochemical hypoglycemia because it is the approximate level at
which counterregulatory systems are normally activated and nondiabetic individuals
may begin to experience neuroglycopenic and adrenergic symptoms characteristic
of hypoglycemia.14-17
To estimate the prevalence of biochemical hypoglycemia that would have been
obtained if all patients had monitored their capillary blood glucose level
during reported symptoms, the number of patients reporting blood glucose levels
of less than 60 mg/dL (<3.3 mmol/L) during symptoms was divided by the
number of patients reporting any glucose measurement during symptoms. This
proportion was then multiplied by the total prevalence of reported hypoglycemic
symptoms to yield an estimated prevalence of biochemical hypoglycemia. Severe hypoglycemia was defined as loss of consciousness
or other major alteration of mental status caused by hypoglycemia that required
the assistance of another person to treat the condition.
At clinic visits, plasma glucose levels were measured using the glucose
oxidase method. We measured HbA1c level using a turbidimetric immunoinhibition
assay (reference range, 3.5%-6.0%) (Roche, Basel, Switzerland).
ANALYSIS
Statistical analysis was conducted using commercially available software
(Statview 5.0; SAS Institute Inc, Cary, NC). We used analysis of variance
and unpaired 2-tailed t tests to compare means between
subgroups of patients and  2 analysis to compare frequency
of events between groups. We performed univariate and multivariate logistic
regression to determine clinical predictors of hypoglycemia. P<.05 was considered significant.
RESULTS
A total of 2279 patients had visits during the study period. Of these,
1022 patients (44.8%) had only a baseline visit and therefore were not included
in the study. Patients who had only a baseline visit were not significantly
different from those with baseline and follow-up visits, except that they
were slightly younger (59.4 vs 61.0 years; P = .002)
and had slightly lower fasting plasma glucose values (154 vs 168 mg/dL [8.6
vs 9.3 mmol/L]; P = .01). There was no difference
in the prevalence of hypoglycemia between the groups at the baseline visit.
Of the 1257 patients with a baseline and a follow-up visit, 202 (16.1%) had
incomplete hypoglycemia data and were excluded. Compared with those who were
included in the study, these patients had shorter duration of diabetes (9.4
vs 10.8 years; P = .03) and higher fasting plasma
glucose values (168 vs 154 mg/dL [9.3 vs. 8.6 mmol/L]; P = .01).
A total of 1055 patients were included in the study. Data on patient
demographics, glycemic control, and distribution of type of diabetes therapy
are shown in Table 1 and Table 2. Patients were predominantly female
and nearly all were African American. Patients had an average age of 61 years,
average body mass index (BMI; calculated as weight in kilograms divided by
the square of height in meters) of 33, average fasting plasma glucose level
of 152 mg/dL (8.4 mmol/L), and average HbA1c level of 7.6%. Average
HbA1c level was significantly lower in patients whose diabetes
was managed by means of diet alone (6.0%) compared with those managed by means
of oral agents alone (7.0%) or insulin (8.1%) (P<.001).
Most patients (92.7%) were treated with some form of pharmacologic therapy,
and 60.0% were treated with insulin (alone or in combination with oral hypoglycemic
agents). Long-acting glipizide accounted for 85.6% (326/381) of sulfonylurea
use, glyburide for 14.2% (54/381), and glimepiride for 0.3% (1/381). Patients
had been observed in the diabetes clinic for an average of 6.5 years, and
mean (± SEM) length of time between study visits was 89 ± 1
days.
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Table 1. Characteristics of Patients Studied*
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Table 2. Type of Diabetes Therapy by HbA1c Level*
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At the follow-up visit, 258 patients (24.5%) reported at least 1 episode
of hypoglycemic symptoms or blood glucose level of less than 60 mg/dL (3.3
mmol/L). Prevalence of any hypoglycemic episode varied with type of therapy
(Figure 1). Patients reporting hypoglycemia
included 9 (11.8%) of 76 patients treated with diet therapy alone; 56 (16.2%)
of 346 patients treated with oral agents alone (sulfonylurea, metformin, or
sulfonylurea plus metformin); and 193 (30.5%) of 633 patients treated with
any insulin (P<.001 for trend).
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Figure 1. Prevalence of hypoglycemia by
type of diabetes therapy. Asterisk indicates P<.05 vs diet
alone; dagger, P<.001 vs diet alone; double dagger, P<.05 vs insulin alone; and section sign, P<.01
vs insulin alone.
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There was no significant difference in prevalence of hypoglycemia between
patients treated with sulfonylureas or metformin (15.7% vs 8.6%; P = .28) or between those treated with insulin alone or in combination
with a single oral agent (31.0% [153/493] vs 25.2% [32/127]; P = .20). However, patients in the insulin-treated groups had a higher
prevalence of hypoglycemia than patients in the diet-only group (30.5% [193/633]
vs 11.8% [9/76]; P<.001), and patients treated
with a combination of insulin, metformin, and sulfonylurea (triple therapy)
had a 2-fold increase in any hypoglycemia compared with other patients treated
with insulin (61.5% [8/13] vs 29.8% [185/620]; P
= .01).
Results of capillary home blood glucose monitoring values at the time
of reported hypoglycemia were obtained in 46.1% of patients. Those who reported
monitoring of capillary blood glucose levels during hypoglycemia were slightly
older (61 vs 58 years; P = .04) and had lower HbA1c levels (7.1% vs 7.7%; P = .01) than those
who did not, but otherwise there were no significant differences between the
2 groups. There was also no significant difference in the proportion of patients
reporting a blood glucose level measurement during hypoglycemic symptoms among
those treated with diet alone (5/9 [55.6%]), oral agents alone (30/56 [53.6%]),
insulin and a single oral agent (79/185 [42.7%]), or triple therapy (5/8 [62.5%])
(P = .35). Blood glucose level readings during the
reported hypoglycemia ranged from 17 to 75 mg/dL (0.9-4.2 mmol/L), with a
median of 55 mg/dL (3.1 mmol/L) (Figure 2); 74 (62.2%) of 119 readings were less than 60 mg/dL (3.3 mmol/L).
Patients treated with pharmacologic therapy tended to have lower reported
blood glucose values during hypoglycemia than did those treated with diet
alone (P = .06, Kruskal-Wallis test), whereas patients
treated with diet alone reported significantly fewer values of less than 60
mg/dL (<3.3 mmol/L) than did those treated with pharmacologic agents (20.0%
[1/5] vs 64.0% [73/114]; P = .047). Only 1 blood
glucose value in the diet-only group was less than 60 mg/dL (3.3 mmol/L),
indicating that most patients treated with diet alone did not have biochemical
hypoglycemia.
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Figure 2. Distribution of blood glucose
values reported during symptoms of hypoglycemia in patients treated with diet
alone (median level, 65 mg/dL [3.6 mmol/L]), oral hypoglycemic agents alone
(median level, 59 mg/dL [3.3 mmol/L]), and insulin (median level, 54 mg/dL
[3.0 mmol/L]). Darker bars show glucose values of less than 60 mg/dL (<3.3
mmol/L). To convert glucose values to millimoles per liter, multiply by 0.0555.
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Since the report of hypoglycemia in each group of patients includes
subjects with measured blood glucose levels of at least 60 mg/dL ( 3.3
mmol/L), we estimated the prevalence of biochemical hypoglycemia that would
have been obtained if all patients had monitored their glucose values during
symptoms. The estimated prevalence of biochemical hypoglycemia was 2.4% for
patients treated with diet alone (among the 11.8% of diet-treated patients
reporting hypoglycemia, 1 of the 5 patients undergoing glucose level measurement
during symptoms reported glucose levels of <60 mg/dL [<3.3 mmol/L]).
The estimated prevalence of biochemical hypoglycemia was 9.4% for patients
treated with oral agents alone (among the 16.2% of patients reporting hypoglycemia,
18 of the 31 patients undergoing glucose level measurement during symptoms
reported glucose levels of <60 mg/dL [3.3 mmol/L]), and 19.9% for patients
treated with insulin (among the 30.5% of patients reporting hypoglycemia,
58 of the 89 patients undergoing glucose level measurement during symptoms
reported glucose levels <60 mg/dL [3.3 mmol/L]).
An associated cause was reported by 147 (57.0%) of 258 patients who
reported hypoglycemia. The most common event associated with hypoglycemia
was a missed meal (119 patients [80.9%]), followed by use of medications in
doses greater than those prescribed (8 patients [5.4%]), exercise (5 patients
[3.4%]), and other (12 patients [8.2%]). There were no differences between
groups as to the events associated with hypoglycemia.
Univariate logistic regression demonstrated that patients treated with
insulin were more likely to report hypoglycemia than patients in other treatment
groups (P = .001). Similarly, patients who reported
any hypoglycemia at the baseline visit were more likely to report hypoglycemia
at the follow-up visit (P<.001). In addition,
fasting plasma glucose level at the time of the follow-up visit and being
in the highest age quartile (age >70 years) were negatively correlated with
any hypoglycemia (P<.001 and P = .03, respectively). Race, sex, duration of diabetes, BMI, and follow-up
HbA1c level were not predictors of hypoglycemia by univariate analysis.
We also performed multiple logistic regression analysis, which showed that
lower follow-up HbA1c level (P = .006),
use of any insulin therapy (P = .005), younger age
(P = .04), and report of hypoglycemia at the baseline
visit (P<.001) were all independent predictors
of any hypoglycemia at the follow-up visit (Table 3). Race, sex, duration of diabetes, BMI, and whether diabetes
medication therapy was increased at the baseline visit did not predispose
to hypoglycemia. Figure 3 shows
the relationship between follow-up HbA1c values and the prevalence
of hypoglycemia in patients receiving different types of diabetes therapy,
illustrating the trend toward increasing prevalence of both reported and estimated
biochemical hypoglycemia with decreasing HbA1c level.
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Table 3. Results of Multiple Logistic Regression Analysis for Predicting
the Occurrence of Any Hypoglycemia*
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Figure 3. Relationship between prevalence
of hypoglycemia and glycosylated hemoglobin (HbA1c) level in different
treatment groups. A, Prevalence of reported hypoglycemia (percentage of patients
within each therapy group reporting any hypoglycemia). B, Estimated prevalence
of biochemical hypoglycemia (prevalence of reported hypoglycemia adjusted
for the proportion of patients measuring glucose levels during hypoglycemic
symptoms and obtaining values of <60 mg/dL [<3.3 mmol/L] within each
therapy group).
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Severe hypoglycemia was rare and was reported by only 5 patients (0.5%)
at the follow-up visits studied (Table 4). Patients 1 and 2 suffered loss of consciousness and required
transport to the emergency department by emergency medical services (EMS).
Patients 3 and 4 were taken to the emergency department by EMS but did not
lose consciousness, and patient 5 was treated at home by EMS without loss
of consciousness. Age, sex, race, diabetes duration, BMI, follow-up fasting
plasma glucose level, follow-up HbA1c level, type of diabetes therapy,
hypoglycemia at the baseline visit, and whether diabetes medication therapy
was increased at the baseline visit were not significant predictors of severe
hypoglycemia by univariate or multivariate logistic regression.
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Table 4. Characteristics of Patients With Severe Hypoglycemia*
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COMMENT
In this cross-sectional study, we found a high prevalence of any form
of reported hypoglycemia in an urban African American population with type
2 diabetes (24.5%), but a low prevalence of severe hypoglycemia (0.5%). As
expected, the prevalence of any hypoglycemia was dependent on type of diabetes
therapy. Patients receiving triple therapy had the highest prevalence, followed
by those receiving insulin therapy alone or with a single oral agent, those
receiving oral hypoglycemic agents alone, and those receiving diet therapy
alone. It is not clear why those patients receiving triple therapy had such
a high prevalence of hypoglycemia. Although mean HbA1c level for
the group was not unusually low (7.4%), it may be that these patients represent
a group whose diabetes is more difficult to manage. In all treatment groups,
the prevalence of any hypoglycemia tended to increase as HbA1c
level decreased. The highest prevalence was seen in patients receiving insulin
therapy who had an HbA1c level of less than 7.0%.
Surprisingly, 9 (11.8%) of the 76 patients treated with diet alone reported
some hypoglycemic symptoms, although only 1 patient reported biochemical hypoglycemia.
Measurement error may explain the apparent biochemical hypoglycemia in the
single patient reporting a blood glucose level of 42 mg/dL (2.3 mmol/L) during
symptoms, as such low glucose levels were not reported by this patient at
subsequent visits. It is possible that the hypoglycemia-like symptoms reported
by some diet-treated patients were unrelated to low blood glucose levels and
were, instead, nonspecific symptoms, perhaps related to hunger or anxiety.
All patients who attend the Grady Diabetes Clinic are instructed about symptoms
of hypoglycemia, including patients treated with diet. In addition, 47 (61.8%)
of the 76 patients treated with diet alone at the time of the study had previously
been treated with pharmacologic agents and might have experienced hypoglycemia
before. Pohl et al18 studied nondiabetic subjects
who underwent insulin-induced hypoglycemia and then were told they were to
receive a second insulin injection but were actually given isotonic sodium
chloride solution; such subjects reported more neuroglycopenic symptoms than
did those who had been told they were to receive a second injection of isotonic
sodium chloride solution. A similar phenomenon of expectant hypoglycemia might
occur in diet-treated patients who are warned about hypoglycemia, particularly
those who had been receiving pharmacologic therapy in the past.
Another interesting finding was that older age did not predispose patients
to hypoglycemia in our population, although previous reports have suggested
that older age is associated with hypoglycemia.19-20
Although older patients in our study were less likely to receive insulin therapy
(potentially making their risk for hypoglycemia lower), they also had lower
average HbA1c levels (potentially making their risk higher). Several
factors may contribute to lower prevalence of hypoglycemia in older patients.
First, activity levels in the elderly are likely to be lower than those in
younger patients, making exercise-associated hypoglycemia less likely. Second,
eating habits may be more regular in the elderly, so that missed meals causing
hypoglycemia are less of a problem. Older patients may also have atypical
symptoms21 or be less symptomatic during mild
hypoglycemia, and therefore not report as many episodes. Nevertheless, as
life expectancy increases, older patients should benefit more from good glycemic
control, and fear of hypoglycemia should not discourage attempts at achieving
American Diabetes Association goals in the elderly.
The small number of patients with severe hypoglycemia made it difficult
to establish significant predictors by means of logistic regression analysis.
However, examination of the patients' characteristics (Table 4) showed that severe hypoglycemia only occurred in patients
who were treated with insulin and that duration of diabetes was longer than
15 years in 4 of the 5 patients. None of the patients was receiving a particularly
high dose of insulin (all <0.70 U/kg per day). Although all of these patients
were overweight (BMI >25), it is possible that insulin resistance plays a
relatively minor role in their disease and that they may have more beta-cell
dysfunction than do other patients with type 2 diabetes in our population.
Our results indicate that severe hypoglycemia occurs in patients with type
2 diabetes, but it is uncommon and it is difficult to predict which patients
are at risk solely on the basis of clinical criteria. An exaggerated fear
of severe hypoglycemia should not be the limiting factor in achieving good
glycemic control in patients with type 2 diabetes.
Because of population differences and the cross-sectional design of
this study, our results cannot be compared directly with those of the UKPDS
or DCCT. However, some trends were similar. As in the UKPDS, we found that
any hypoglycemia was more common in insulin-treated patients than in those
treated with oral hypoglycemic agents or diet alone.11
We also found a low prevalence of severe hypoglycemia at the visits studied,
but, unlike the UKPDS, all episodes in our study were associated with insulin
therapy. The DCCT found that the prevalence of severe hypoglycemia increased
as HbA1c levels fell and that patients with previous episodes of
hypoglycemia were more likely to experience hypoglycemia in the future.22 In our study, multiple logistic regression also showed
lower HbA1c levels and a report of hypoglycemia at the baseline
visit to be independent predictors of any hypoglycemia. Our results are consistent
with those of Hayward et al,23 who found that
38% of patients treated with insulin reported hypoglycemic symptoms more than
once a month. Jennings et al24 examined the
prevalence of hypoglycemia in patients treated with oral hypoglycemic agents
and found that 20% of patients treated with sulfonylureas had symptoms of
hypoglycemia during the previous 6 months, but none of 16 patients receiving
metformin alone had symptoms. Although 3 (8.6%) of our 32 patients treated
with metformin alone reported hypoglycemic symptoms, this rate was comparable
to the prevalence in diet-treated patients. Accordingly, our results also
support those of Jennings et al,24 although
patients treated with oral agents in our study had an average HbA1c
level of 7.0% vs 11.0% in theirs (reference range, 6%-8%).
Limitations of our study include its cross-sectional design, which prevents
an exact calculation of incidence of hypoglycemia and therefore prohibits
direct comparison of the results of our study with those of the UKPDS,11 VA CSDM,9 or DCCT.8 In addition, the data rely on patients' abilities
to remember and interpret symptoms as a consequence of low blood glucose levels.
Consistent with earlier studies and routine practice, which rely on patient
self-reports to make clinical decisions, our results reflect information that
is clinically relevant and available to most practitioners. Another limitation
may be that most of our patients are urban and African American. Although
we do not know whether our results are generalizable to other populations,
the findings suggest that hypoglycemia is not a major problem in a population
with an average HbA1c level of 7.6%, despite the limitations of
poverty and low literacy levels.13, 25
However, we consider it unlikely that African Americans are more or less prone
to hypoglycemia than are other ethnic groups.
CONCLUSIONS
Hypoglycemia can be an important limiting factor in the treatment of
patients with type 2 diabetes. Our results suggest that aggressive management
aimed at achieving near-normal glucose levels is associated with increased
risk for hypoglycemia as HbA1c level approaches the American Diabetes
Association goal of less than 7.0%. However, fear of severe hypoglycemia should
not deter the attempt to achieve tight glycemic control. Those patients who
are younger or have a lower HbA1c level may be at higher risk for
hypoglycemia and should be encouraged to be more diligent about meal planning,
home monitoring of glucose levels, and symptom awareness. Finally, older patients
may not be particularly prone to hypoglycemia and therefore should not be
disqualified from intensive control of blood glucose level on the basis of
risk for hypoglycemia alone.
AUTHOR INFORMATION
Accepted for publication January 1, 2001.
This work was supported in part by awards DK 48124 (Dr Phillips) and
DK 07298 (Dr Miller) from the National Institutes of Health, Bethesda, Md,
and HS 07922 (Drs Phillips, Ziemer, Gallina, Cook, and El-Kebbi) from the
Agency for Healthcare Research and Quality, Rockville, Md.
Corresponding author: Imad M. El-Kebbi, MD, Emory University School
of Medicine, Diabetes Unit, 69 Butler St SE, Atlanta, GA 30303 (e-mail: ielkebb{at}emory.edu).
From the Division of Endocrinology and Metabolism, Department of Medicine,
Emory University School of Medicine, Atlanta, Ga.
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