Running head: INSULIN RESISTANCE AND GLUCOSE TOLERANCE TESTS
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A Retrospective Review of Two Hour Glucose Tolerance Tests to Diagnose Insulin Resistance
and Type 2 Diabetes Mellitus
Laura Reed, MSN, FNP-C
DNP Scholarly Project
NSG 739-917
June 3, 2014
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Abstract
The purpose of this study is to review the oral glucose tolerance tests that have been performed
in the clinic based upon the protocol that has been established and statistically analyze the results
to show the effectiveness of the 2 hour glucose tolerance test as a predictor and diagnostic tool to
identify insulin resistance and type 2 diabetes. Another outcome will also show any correlation
of gender and BMI if present.
100 Oral Glucose Tolerance Test (OGTT) results were reviewed. The number of males and
females was equal in the group. One-half of the results revealed insulin resistance, one-fourth
were diabetic, and one-fourth were normal. More females had normal results while more males
had diabetes. There was no difference in the BMI results of each group.
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A Retrospective Review of Two Hour Glucose Tolerance Tests to Diagnose Insulin Resistance
and Type 2 Diabetes Mellitus
Type 2 diabetes is a growing disease in our population. According to Ricci-Cabello (2010)
diabetes is “the fourth most common cause of death in the world”. The USPFT (2013) reports
that diabetes was the sixth leading cause of death in the US in 2010. Robertson (2012) reported
that in 2010, an estimated 25.6 million adult Americans are estimated to be living with diabetes
and an estimated 79 million are living with prediabetes. This number is projected to increase to
one in five Americans within the next 10 years (Robertson, 2012). These statistics only illustrate
the beginning of the problem. Robertson (2012) also reported that diabetes is “more prevalent
among women, ethnic minorities, and people with lower socioeconomic levels”. As the American
population continues to become more overweight and age, diabetes will be an epidemic if changes
are not made by healthcare providers to expedite the prevention and detection of diabetes.. There
is also an association of higher incidence of complications and death within these groups as well
(Ricci-Cabello, 2010).
The direct cost for healthcare for those with diabetes is 2 times higher than for those who do not
have diabetes. The indirect costs approach $58 billion a year for those with diabetes ( Hilaire et al,
2013). At this rate, our already failing medical system will not be able to withstand the care of
those with diabetes and its secondary illnesses such as hypertension, kidney disease, heart disease,
blindness and stroke (Hilaire et al., 2013).
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The onset of diabetes is insidious. Diabetic effect to blood vessels and organs begins 5-10 years
prior to an actual diagnosis of diabetes (Reed et al., 2010).
The American Diabetes Association (ADA) criteria for diagnosing diabetes states that “a fasting
plasma glucose of greater than or equal to 126 mg/dl or an oral glucose tolerance test with a two
hour result of greater than 200 mg/dl or a random plasma glucose of greater than or equal to 200
mg/dl is diagnostic for diabetes” (ADA, 2013). Fasting plasma glucose levels do not detect insulin
resistance/impaired fasting glucose and 2 hour OGTT results do not always detect impaired fasting
glucose. Insulin resistance is defined as “a subnormal response to both endogenous and exogenous
insulin as well as a high normal serum insulin level in association with blood glucose levels that
are normal or elevated” (ADA, 2013). In the practice identified, the clinicians believe the OGTT
is the most accurate test to identify insulin resistance or diabetes when the patient has a normal
fasting glucose. In 2008, the United States Preventive Services Task Force (USPSTF) concluded
in a review of the evidence that there is a lack of research to show direct and indirect evidence to
support mass testing/screening of the general population to detect insulin resistance or diabetes.
There is poor evidentiary support of the effects of lifestyle and medication interventions on insulin
resistance and diabetes (Norris et al, 2008).
OGTT testing should be the gold standard for diagnosing insulin resistance and diabetes. In the
clinical practice identified, HgbA1c levels have been found to be normal and OGTTs were
abnormal when diagnosing diabetes. An advantage for OGTT testing includes the ability to
detect subtle changes in carbohydrate metabolism that cannot be seen when measuring fasting
glucose levels and/or HgbA1c levels. However, the test is a time-consuming process for the
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patient and clinical staff, involving multiple steps that must be followed carefully to ensure
accurate results. If the test is done incorrectly, the results could lead to an erroneous diagnosis or
misdiagnosis of a patient (Bisht et al, 2011). Diabetes is a costly and deadly disease that we need
to aggressively prevent and treat. We need to identify those patients with insulin
resistance/diabetes and initiate treatment early instead of waiting 5-10 years until an actual
diagnosis can be made by today’s approved standards. By using OGTT testing, we can identify
those at risk and begin treatment before the diabetic effects can begin.
Several studies have looked at the use of OGTT testing and fasting glucose levels to diagnose
insulin resistance/diabetes and then to evaluate treatment regimens. Lifestyle changes that
include diet, exercise, and weight loss have been successful with the management as well as the
use of cinnamon supplements over the counter and prescription medications.
Dr. Ralph DeFronzo suggested in a 2009 lecture titled “From the Triumvirate to the Ominous
Octet: A New Paradigm for the Treatment of Type 2 Diabetes Mellitus,” that” it is time for a
new algorithm for the diagnosis and treatment of Type 2 Diabetes”. He suggests the earlier we
begin treatment for insulin resistance or impaired fasting glucose, the more we can minimize or
even prevent long term effects such as neuropathy, retinopathy, vascular damage, end organ
damage. He feels that lifestyle changes are the first step followed by the initiation of metformin
therapy as the first drug choice (DeFronzo, 2009).
Abdul-Ghani et al performed 2- hour glucose tolerance tests on 3,450 patients. The study
revealed that” the normal 2- hour reading of less than 140 mg/dl is associated with a significant
increase incidence of diabetes and a 1- hour reading of greater than 150 mg/dl is also associated
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with an increase prevalence of diabetes”. They suggested that the 1- hour reading is” a better
measure for type 2 diabetes risk”. They also suggested that the ADA guidelines need to adjusted
to include definitions of glucose intolerance or update the readings for normal glucose tolerance
tests (Abdul-Ghani et al, 2010).
In a landmark Finnish study performed by Lakka et al in 2002, 1,209 men, 42-60 years of age
without cardiovascular disease, diabetes mellitus, or cancer were identified and followed for 12
years. At that endpoint, the men had a 3.55 relative risk for cardiovascular death if they had
developed metabolic syndrome.
In 1999, The European Diabetes Epidemiology Group Collaborative Analysis of Diagnostic
Criteria in Europe (DECODE ) study group was a landmark study that followed patients with the
diagnoses of normal glucose tolerance, impaired glucose tolerance, and diabetes mellitus. At the
10- year data point, risk of cardiovascular disease had increased two-fold for those participants
with impaired glucose tolerance versus normal glucose tolerance and a four-fold increased risk
with diabetes mellitus versus normal glucose tolerance.
The Finnish Diabetes Prevention Study Group ( FINDRISC) concluded that the use of fasting
serum glucose levels or hgba1c levels missed a large number of abnormal glucose tests. The
results showed that a single hgbA1C level identified a lower prevalence of diabetes (3.6%)
compared with 2 hour plasma glucose (9.2%). Fasting serum glucose levels were 3.1%. This
study supports the principle that the 2 hour glucose test is a more accurate way to diagnose
diabetes (Costa et al, 2013).
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Gavi et al (2009) established a guideline to identify and treat prediabetes and type 2 diabetes
mellitus. Prediabetes was defined as “a fasting glucose of 100-125mg/dl or a glucose level on an
oral glucose tolerance test from 140-199mg/dl”. Type 2 diabetes was defined as “ a fasting
glucose greater than or equal to 126mg/dl on 2 occasions, symptoms of diabetes or a random
glucose of greater than or equal to 200mg/dl or plasma glucose result greater than or equal to
200mg/dl on a 2 hour glucose tolerance tests”. The guidelines suggested not using HgbA1c for
diagnosing diabetes. The prediabetes patients were treated with lifestyle and dietary changes, as
well as a physical activity plan. The patients with type 2 diabetes required pharmacologic
treatment as well as lifestyle change and physical activity. This guideline is to be updated every
3 years and is meant to address the health concerns of the elderly.
Studies have also associated increased BMI >25 and female gender with increased incidence of
diabetes and/or insulin resistance (Cosson et al, 2011). The association of an elevated body mass
index with insulin resistance/diabetes in adults is strong. An elevated BMI is also strongly
associated with cardiovascular disease (Tirosh et al, 2011). Kerr et al (2011) stated that the
average BMI has increased from 28-31kg/m2 over the last 10 years in the United States.
Berrington de Gonzalez et al studied 1.46 million adults ages 19-84 years old (median, 58) over
a 10- year period. They found that the optimal BMI range was 22.5-25.0 in all participants and
20.0 to 25.0 in the participants who never smoked. There were “5 times as many deaths among
participants in the highest obesity range (BMI 35.0-49.9)” than in the other BMI ranges
(Berrinton de Gonzalez et al, 2011).
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Methodology
Setting
The setting of this study is an internal medicine practice in a large metropolitan area of West
Tennessee. The practice consists of 1 Internal Medicine physician, 1 full time nurse practitioner
and 1 part time nurse practitioner.
Sample
Medical records of 300 patients that are over the age of 18 years and have had a
minimum of 1 oral Glucose tolerance tests will be reviewed. The majority of the patients are of
Caucasian descent with African Americans making up the sizable minority.
Intervention
This is a retrospective analysis of data that has already been collected in our clinic over the last
3-4 years. There was no intervention.
Procedures
The participants included in this study underwent a 2 hour glucose tolerance test using 75
grams of oral glucose dissolved in 250-300 ml of water and consumed in no more than 5
minutes, followed by another 100 mls of water. Serum blood glucose levels were taken prior to
ingestion of glucose, 60 minutes after ingestion and 120 minutes after ingestion. The patients
remained in the office and were sedentary. No tobacco use, no oral intake of anything other than
water was allowed for the two hours. A normal glucose tolerance test was defined as a fasting
glucose of less than 100 mg/dl and a 2 hour glucose reading of less that 140mg/dl. A one hour
glucose above 155mg/dl increases the risk of diabetes by 13.1. 25-40% of subjects who develop
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diabetes have initial 2 hour glucose of greater that 140mg/dl. 20% of normal glucose tolerance
participants are insulin resistant (fasting glucose less than 100mg/dl, 2-hour glucose less that
140mg/dl) 2 -hour glucose readings are interpreted as follows: 100-119 mg/dl, beta cell function
begins to decline; 120-139 mg/dl beta cell function has decreased by 40-50%. 140-200 mg/dl,
beta cell function has decreased more than 50%.
The extant OGTT database was examined through the following procedure. All patients were
assigned a number 1-300. Once the patients were assigned a number, the primary investigator
(PI) selected every third patient until the 300 patients had been randomized. 100 patient results
were randomly selected to be analyzed. Once the patients were selected, the PI reviewed the
blinded data and interpreted the results by comparing OGTT results and fasting glucose levels to
determine those that are insulin resistant, Type 2 Diabetes, or norm glycemic. The PI also
collected gender and BMI to determine if there was a correlation between these variables and the
diagnosis of Type 2 DM/Insulin Resistance. The PI reviewed the results of the study with the
clinical healthcare providers and staff to educate them on the accuracy and importance of OGTT
testing to identify those patients with insulin resistance/Type 2 DM.
Results
100 OGTT results were analyzed. 48 were male (48%) and 52 were female (52%). 22% were
normal results (n=22), 54 % revealed insulin resistance (n=54), and 24% were positive for
diabetes mellitus (n= 24) 32% of the subjects in the normal group were male (n= 7) and 68%
were female (n=15). For the insulin resistance group, 46 % were male (n= 25) versus 54%
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female (n=29). The diabetic group was 62% male (n= 15) and 38% female (n=38%). The
average BMI results for the group was 28.387 (range 18-44). The male BMI average was 28.1
(range 22-44) and the female average was 26.4 (range 18-34.4). For the normal OGTT results,
the average BMI was 29.5 (range 18.6-36.1). The average BMI for the insulin resistant group
was 28.8 (range 20.2 -43.4), and the average BMI for the diabetic group was 27.6 (range 18-44).
Discussion
The oral glucose tolerance tests done on patients with normal fasting glucose levels revealed
that one-half of the patients (54 %, n=54) had insulin resistance, one-fourth were normal (22%,
n=22) and one-fourth were found to have diabetes (24 %, n=24). These statistics show that use of
OGTTs as diagnostic tools for diagnosing diabetes is a viable tool for identifying abnormal
glucose metabolism in patients with normal fasting glucose levels. The males and females were
equal in both groups. More females were found to have normal glucose tolerance tests than
males. Interestingly, there were more males found to have diabetes than females. Both genders
were equally represented in the insulin resistance group. The males had a higher average BMI
(28.05) than the females (26.4) but both groups average BMIs were interpreted as overweight.
There were no BMI differences between the three test results groups (29.5, 28.8, and 27.6).
Clinical Implications
Two hour oral glucose tolerance tests are a viable option as a diagnostic tool for insulin
resistance and diabetes. It should be used for any patient in which the provider suspects insulin
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resistance or type 2 diabetes. The benefits of using oral glucose tolerance tests include a more
accurate evaluation of a patient’s glucose metabolism and an early stage predictor of insulin
resistance and/or diabetes. The limitations are that performing the test is tedious and time
consuming and must be performed accurately to obtain correct results. More studies need to be
completed to further support or refute the efficacy of the OGTT testing. A larger study
population would also give a better idea of the clinical relevance of this testing. The earlier
insulin resistance and diabetes are detected and treatment initiated, the less end organ damage
will ultimately occur and fewer healthcare costs to our already stressed system will be incurred.
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