Type 2 Diabetes Mellitus, Prediabetic State
Conditions
Keywords
type 2 diabetes mellitus, prediabetic state, mass screening, glucose tolerance test
Brief summary
People who might have prediabetes or unrecognized diabetes will be screened for these problems at an outpatient visit. For screening, they will take a sugary drink containing 50 grams of glucose, and have a blood sample one hour later. The blood sample will be tested for glucose and A1c (a measure of blood glucose over the previous two months). They will also fill out questionnaires that ask about their health history and how they would feel about exercising and trying to lose weight if they are found to have prediabetes or diabetes. At a subsequent visit, they will have an oral glucose tolerance test (OGTT) - a blood sample, then a sugary drink containing 75 grams of glucose, and a repeat blood sample 2 hours later. We will evaluate the costs of finding out if people have prediabetes or diabetes. For people who are found to have these problems, we will also evaluate how well their doctors treat these problems.
Detailed description
RELEVANCE TO VETERANS' HEALTH: Lack of a good strategy to identify prediabetes - probably \ 10 years prior to the development of diabetes that is recognized clinically - may be the greatest present impediment to diabetes care. We are developing a new way to screen for prediabetes, and it should constitute a major opportunity to improve the health of \ 4 million veterans; early recognition of glucose intolerance would permit institution of preventive strategies which are efficacious, convenient, and cost-effective - improving the health of individual veterans, reducing diabetes-related health care resource use and costs for the VA, and helping to spare VA funds for management of other disorders. BACKGROUND: Prediabetes is a major public health problem which confers risk of diabetes and cardiovascular disease (CVD), but veterans with prediabetes are not detected, and cannot receive interventions to reduce their risks; CVD events, health resource use, and cost all rise before diabetes is diagnosed. Diabetes can be prevented or delayed by lifestyle change or medication, but since we do not identify prediabetes, glucose intolerance progresses for 5-10 years, and many patients have early diabetes complications and increased CVD risk when they are finally recognized. We are developing a new screening test for prediabetes, a glucose challenge test (GCT): patients have a 50g oral glucose challenge at any time of day, regardless of meal status, with a single 1 hr sample. If the GCT exceeds a cutoff, they have a 75g oral glucose tolerance test after an overnight fast, with 0 and 2 hr samples (OGTT). Our GCRC-based Preliminary Data show ROC AUC 0.83 (70% specificity, 82% sensitivity) and $51 per case identified; the GCT should constitute an effective, convenient, inexpensive, cost-effective screen for prediabetes - a critical indicator of individual, VA health care system, and societal risk. OBJECTIVES: To translate our findings into improved health for VA patients, the GCT will need to be implemented in VA primary care settings - where practitioners often do not screen for prediabetes, or manage diabetes optimally. Such barriers must be overcome in order to conduct definitive studies aimed to show that use of the GCT to detect prediabetes (and previously unrecognized diabetes) in primary care leads to improved outcomes. Thus, VA policies for system-wide implementation of GCT screening must be preceded by logical next steps: validation and demonstration of likely cost-effectiveness. METHODS: AIM #1. Validation: (A) To establish feasibility, we will interact with VA primary care providers to solve logistical problems, and determine optimal screening strategies. (B) To assess test performance, we will (a) perform GCTs and measure A1c in \ 1,800 patients, (b) evaluate OGTTs in all subjects, and (c) compare sensitivity, specificity, and ROC curves from GCT vs. A1c or predictive model screening in primary care to those in our GCRC studies. Availability of this dataset will also permit (d) subsequent management of diabetes/prediabetes to be evaluated relative to standardized guidelines. AIM #2. Costs: To evaluate impact, we will (a) capture the costs of diagnostic tests, staff effort, and patient time; (b) express cost per case identified from both VA health system and societal perspectives; and (c) compare GCT vs. alternative strategies with a wide range of assumptions about false-(+)/false-(-) costs to reflect downstream cost implications of test imperfections. Engagement with this process will also provide (d) for those study patients with prediabetes who go on to develop diabetes, an opportunity to explore VA resource use and costs before and after the diagnosis of diabetes. This will provide preliminary data for subsequent proposals to compare resource use and costs vs. those of other VA patients who are newly diagnosed with diabetes in settings where there is no screening for prediabetes.
Interventions
OTHERGlucose challenge test
At a first outpatient visit, at different times of the day and without a prior fast, subjects will have a 50 gram glucose drink followed by measurement of plasma and capillary glucose along with A1c one hour later. They will also fill out questionnaires. At a second outpatient visit, in the morning after fasting overnight, they will have a 75 gram oral glucose tolerance test.
Subjects found to have diabetes or prediabetes on the initial glucose tolerance test may be requested to have a repeat glucose tolerance test and A1c.
Sponsors
Emory University
US Department of Veterans Affairs
Study design
Observational model
COHORT
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* veteran status, * ambulatory outpatient at Atlanta VA Medical Center, * visit to primary care clinic, AND * meet criteria for screening (age \>= 45 years or other risk factors \[body mass index \>=25 or hypertension or systolic blood pressure \>=140 or HDL cholesterol \<35 in men or \<45 in women or fasting triglycerides \>250 or first-degree relative with diabetes or minority race or minority ethnicity or history of diabetes during pregnancy or history of having a baby weighing \>9 pounds or history of polycystic ovary syndrome\])
Exclusion criteria
* known to have diabetes, OR * taking steroids OR pregnant, OR * not well enough to have worked during the previous week (actual employment not necessary)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ability of Different Screening Tests Which Can be Performed Opportunistically (During Outpatient Visits -- at Any Time of Day, Regardless of Meal Status) to Predict Findings With the Oral Glucose Tolerance Test (in the Morning, After an Overnight Fast) | 3 years | Area under ROC curve (AROC) for prediction of diabetes (based on OGTT) and high-risk dysglycemia (based on OGTT, IGT with 2 hour OGTT glucose 140-199 mg/dl, and/or IFG with fasting glucose 110-125 mg/dl). ROC curves are plots of (1-sensitivity) vs. (1-specificity) for all possible screening cutoffs, so a higher AROC indicates higher predictive accuracy. A perfect test would have an AROC of 1.00, while a test equivalent to tossing a coin (random) would have an AROC of 0.50; if confidence limits include 0.50, predictive accuracy is no better than chance. It is important to appreciate that while AROC analysis can show the relative accuracy of different screening tests, and aid the selection of which test to use in clinical practice, such an analysis does not define what the optimal screening test cutoff is. Selection of the optimal cutoff generally requires consideration of other factors, such as costs and/or the clinical importance of having higher or lower sensitivity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cost to Identify a Single Case of High-risk Dysglycemia or Previously Unrecognized Diabetes | 3 years | Cost was expressed as cost (dollars) to identify a single case, with cases defined as (i) diabetes or (ii) high-risk dysglycemia. Cost projections for screening were conducted from both Medicare and VA perspectives. All screening projections assumed follow-up testing with an OGTT if the screening test exceeded a 70% specificity cut-off. |
Countries
United States
Participant flow
Recruitment details
Atlanta VA patients without known diabetes, who were at high risk of having unrecognized dysglycemia based on age \>=45 years, BMI \>=25 kg/m2, or other risk factors, were eligible for the study. Patients presenting for primary care visits were approached if they appeared to have age \>=45 years and BMI \>=25 kg/m2.
Participants by arm
| Arm | Count |
|---|---|
| Group 1 Atlanta VA Medical Center patients who meet criteria for screening for prediabetes and early diabetes based on standard guidelines of the VA, American Diabetes Association, and NIH. This primarily included outpatient Veterans. Subjects were primarily included if they had age at least 45 years and BMI of 25 or greater, but some younger subjects were also included if they had risk factors for diabetes. | 1,535 |
| Total | 1,535 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Failure to have the OGTT was most common | 404 |
Baseline characteristics
| Characteristic | Group 1 |
|---|---|
| Age, Continuous | 56.1 years STANDARD_DEVIATION 9.93 |
| BMI | 30.3 kg/m2 STANDARD_DEVIATION 5.2 |
| Region of Enrollment United States | 1535 participants |
| Sex: Female, Male Female | 94 Participants |
| Sex: Female, Male Male | 1441 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 11 / 1,939 |
| serious Total, serious adverse events | 0 / 1,939 |
Outcome results
Primary
Ability of Different Screening Tests Which Can be Performed Opportunistically (During Outpatient Visits -- at Any Time of Day, Regardless of Meal Status) to Predict Findings With the Oral Glucose Tolerance Test (in the Morning, After an Overnight Fast)
Area under ROC curve (AROC) for prediction of diabetes (based on OGTT) and high-risk dysglycemia (based on OGTT, IGT with 2 hour OGTT glucose 140-199 mg/dl, and/or IFG with fasting glucose 110-125 mg/dl). ROC curves are plots of (1-sensitivity) vs. (1-specificity) for all possible screening cutoffs, so a higher AROC indicates higher predictive accuracy. A perfect test would have an AROC of 1.00, while a test equivalent to tossing a coin (random) would have an AROC of 0.50; if confidence limits include 0.50, predictive accuracy is no better than chance. It is important to appreciate that while AROC analysis can show the relative accuracy of different screening tests, and aid the selection of which test to use in clinical practice, such an analysis does not define what the optimal screening test cutoff is. Selection of the optimal cutoff generally requires consideration of other factors, such as costs and/or the clinical importance of having higher or lower sensitivity.
Time frame: 3 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GCTpl - Diabetes | Ability of Different Screening Tests Which Can be Performed Opportunistically (During Outpatient Visits -- at Any Time of Day, Regardless of Meal Status) to Predict Findings With the Oral Glucose Tolerance Test (in the Morning, After an Overnight Fast) | .85 area under ROC curve |
| GCTcap - Diabetes | Ability of Different Screening Tests Which Can be Performed Opportunistically (During Outpatient Visits -- at Any Time of Day, Regardless of Meal Status) to Predict Findings With the Oral Glucose Tolerance Test (in the Morning, After an Overnight Fast) | .82 area under ROC curve |
| RPG - Diabetes | Ability of Different Screening Tests Which Can be Performed Opportunistically (During Outpatient Visits -- at Any Time of Day, Regardless of Meal Status) to Predict Findings With the Oral Glucose Tolerance Test (in the Morning, After an Overnight Fast) | .76 area under ROC curve |
| RCG - Diabetes | Ability of Different Screening Tests Which Can be Performed Opportunistically (During Outpatient Visits -- at Any Time of Day, Regardless of Meal Status) to Predict Findings With the Oral Glucose Tolerance Test (in the Morning, After an Overnight Fast) | .72 area under ROC curve |
| A1c - Diabetes | Ability of Different Screening Tests Which Can be Performed Opportunistically (During Outpatient Visits -- at Any Time of Day, Regardless of Meal Status) to Predict Findings With the Oral Glucose Tolerance Test (in the Morning, After an Overnight Fast) | .67 area under ROC curve |
| GCTpl - Dysglycemia | Ability of Different Screening Tests Which Can be Performed Opportunistically (During Outpatient Visits -- at Any Time of Day, Regardless of Meal Status) to Predict Findings With the Oral Glucose Tolerance Test (in the Morning, After an Overnight Fast) | .76 area under ROC curve |
| GCTcap - Dysglycemia | Ability of Different Screening Tests Which Can be Performed Opportunistically (During Outpatient Visits -- at Any Time of Day, Regardless of Meal Status) to Predict Findings With the Oral Glucose Tolerance Test (in the Morning, After an Overnight Fast) | .73 area under ROC curve |
| RPG - Dysglycemia | Ability of Different Screening Tests Which Can be Performed Opportunistically (During Outpatient Visits -- at Any Time of Day, Regardless of Meal Status) to Predict Findings With the Oral Glucose Tolerance Test (in the Morning, After an Overnight Fast) | .66 area under ROC curve |
| RCG - Dysglycemia | Ability of Different Screening Tests Which Can be Performed Opportunistically (During Outpatient Visits -- at Any Time of Day, Regardless of Meal Status) to Predict Findings With the Oral Glucose Tolerance Test (in the Morning, After an Overnight Fast) | .64 area under ROC curve |
| A1c - Dysglycemia | Ability of Different Screening Tests Which Can be Performed Opportunistically (During Outpatient Visits -- at Any Time of Day, Regardless of Meal Status) to Predict Findings With the Oral Glucose Tolerance Test (in the Morning, After an Overnight Fast) | .63 area under ROC curve |
Secondary
Cost to Identify a Single Case of High-risk Dysglycemia or Previously Unrecognized Diabetes
Cost was expressed as cost (dollars) to identify a single case, with cases defined as (i) diabetes or (ii) high-risk dysglycemia. Cost projections for screening were conducted from both Medicare and VA perspectives. All screening projections assumed follow-up testing with an OGTT if the screening test exceeded a 70% specificity cut-off.
Time frame: 3 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GCTpl - Diabetes | Cost to Identify a Single Case of High-risk Dysglycemia or Previously Unrecognized Diabetes | 100 Dollars |
| GCTcap - Diabetes | Cost to Identify a Single Case of High-risk Dysglycemia or Previously Unrecognized Diabetes | 93 Dollars |
| RPG - Diabetes | Cost to Identify a Single Case of High-risk Dysglycemia or Previously Unrecognized Diabetes | 42 Dollars |
| RCG - Diabetes | Cost to Identify a Single Case of High-risk Dysglycemia or Previously Unrecognized Diabetes | 37 Dollars |
| A1c - Diabetes | Cost to Identify a Single Case of High-risk Dysglycemia or Previously Unrecognized Diabetes | 133 Dollars |
| GCTpl - Dysglycemia | Cost to Identify a Single Case of High-risk Dysglycemia or Previously Unrecognized Diabetes | 125 Dollars |
| GCTcap - Dysglycemia | Cost to Identify a Single Case of High-risk Dysglycemia or Previously Unrecognized Diabetes | 55 Dollars |
| RPG - Dysglycemia | Cost to Identify a Single Case of High-risk Dysglycemia or Previously Unrecognized Diabetes | 50 Dollars |