Opportunistic Screening for Prediabetes and Early Diabetes in Primary Care

• Sponsor: US Department of Veterans Affairs (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT00787839
• Collaborator: Emory University (Other)
• Enrollment: 1,939
• Location: 1
• Duration (Months): 42
• Patients Per Site Per Month: 46.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus; Prediabetic State	Other: Glucose challenge test; Other: Glucose tolerance test

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.

Study Design

• Study Type: Observational
• Actual Enrollment: 1939 participants
• Observational Model: Cohort
• Time Perspective: Cross-Sectional
• Official Title: Screening for Prediabetes and Early Diabetes in Primary Care
• Study Start Date: Jun 1, 2009
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

Arm

Intervention/Treatment

Group 1 Atlanta VA Medical Center patients who meet criteria for screening for prediabetes and early diabetes based on standard guidelines of the VA, the American Diabetes Association, and the National Institutes of Health

Other: Glucose 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.; Other: 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.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Atlanta VA Medical and Rehab Center, Decatur, GA	Decatur	Georgia	United States	30033

Sponsors and Collaborators

• US Department of Veterans Affairs
• Emory University

Investigators

• Principal Investigator: Lawrence S Phillips, MD, Atlanta VA Medical and Rehab Center, Decatur, GA

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: US Department of Veterans Affairs
• ClinicalTrials.gov Identifier: NCT00787839
• Other Study ID Numbers: IIR 07-138
• First Posted: Nov 10, 2008
• Last Update Posted: Apr 27, 2015
• Last Verified: Oct 1, 2014

• Keywords provided by US Department of Veterans Affairs: type 2 diabetes mellitus; prediabetic state; mass screening; glucose tolerance test
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Prediabetic State

Study Results

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.

Arm/Group Title	Group 1
Arm/Group Description	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. Glucose 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. 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.
Period Title: Overall Study
STARTED	1939
Consented	1939
Completed GCT Screening	1876
Complete GCT, OGTT, A1c, Demographics	1535
COMPLETED	1535
NOT COMPLETED	404

Baseline Characteristics

Arm/Group Title	Group 1
Arm/Group Description	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.
Overall Participants	1535
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.1 (9.93)
Sex: Female, Male (Count of Participants)
Female	94 6.1%
Male	1441 93.9%
Region of Enrollment (participants) [Number]
United States	1535 100%
BMI (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	30.3 (5.20)

Outcome Measures

1. Primary Outcome

Title	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)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	GCTpl - Diabetes	GCTcap - Diabetes	RPG - Diabetes	RCG - Diabetes	A1c - Diabetes	GCTpl - Dysglycemia	GCTcap - Dysglycemia	RPG - Dysglycemia	RCG - Dysglycemia	A1c - Dysglycemia
Arm/Group Description	plasma glucose measured 1 hour after a 50g oral glucose challenge, performed at any time during the day, without requiring a prior overnight fast	capillary glucose measured 1 hour after a 50g oral glucose challenge, performed at any time during the day, without requiring a prior overnight fast	random plasma glucose measured prior to administration of the 50g oral glucose challenge, at any time during the day, without requiring a prior overnight fast	random capillary glucose measured prior to administration of the 50g oral glucose challenge, at any time during the day, without requiring a prior overnight fast	hemoglobin A1c, measured at the time of the OGTT	plasma glucose measured 1 hour after a 50g oral glucose challenge, performed at any time during the day, without requiring a prior overnight fast	capillary glucose measured 1 hour after a 50g oral glucose challenge, performed at any time during the day, without requiring a prior overnight fast	random plasma glucose measured prior to the 50g oral glucose challenge, performed at any time during the day, without requiring a prior overnight fast	random capillary glucose measured prior to the 50g oral glucose challenge, performed at any time during the day, without requiring a prior overnight fast	hemoglobin A1c, measured at the time of the OGTT
Measure Participants	1535	1535	1535	1535	1535	1535	1535	1535	1535	1535
Number (95% Confidence Interval) [area under ROC curve]	.85	.82	.76	.72	.67	.76	.73	.66	.64	.63

2. Secondary Outcome

Title	Cost to Identify a Single Case of High-risk Dysglycemia or Previously Unrecognized Diabetes
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	GCTpl - Diabetes - VA	GCTcap - Diabetes - VA	GCTpl - Dysglycemia - VA	GCTcap - Dysglycemia - VA	GCTpl - Diabetes - Medicare	GCTcap - Diabetes - Medicare	GCTpl - Dysglycemia - Medicare	GCTcap - Dysglycemia - Medicare
Arm/Group Description	VA costs per case of diabetes identified, using the GCTpl screening test	VA costs per case of diabetes identified, using the GCTcap screening test	VA costs per case of dysglycemia identified, using the GCTpl screening test	VA costs per case of dysglycemia identified, using the GCTcap screening test	Medicare costs per case of diabetes identified, using the GCTpl screening test	Medicare costs per case of diabetes identified, using the GCTcap screening test	Medicare costs per case of dysglycemia identified, using the GCTpl screening test	Medicare costs per case of dysglycemia identified, using the GCTcap screening test
Measure Participants	1535	1535	1535	1535	1535	1535	1535	1535
Number [Dollars]	100	93	42	37	133	125	55	50

Adverse Events

Arm/Group Title	Group 1
Arm/Group Description	Atlanta VA Medical Center patients who meet criteria for screening for prediabetes and early diabetes based on standard guidelines of the VA, the American Diabetes Association, and the National Institutes of Health
All Cause Mortality
	Group 1
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Group 1
	Affected / at Risk (%)	# Events
Total	0/1939 (0%)
Other (Not Including Serious) Adverse Events
	Group 1
	Affected / at Risk (%)	# Events
Total	11/1939 (0.6%)
Metabolism and nutrition disorders
hypoglycemia during OGTT	7/1939 (0.4%)	7
hyperglycemia before 50g glucose challenge	2/1939 (0.1%)	2
hyperglycemia after 50g glucose challenge	2/1939 (0.1%)	2

Limitations/Caveats

Study in a single healthcare system, in a convenience sample of patients receiving care in a VA primary care clinic, in a population that was largely older, heavier, and predominantly male, and a single OGTT was used as the "gold standard".

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.