Clinical trial NCT00787839: Opportunistic Screening for Prediabetes and Early Diabetes in Primary Care
Official title: Screening for Prediabetes and Early Diabetes in Primary Care
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Type 2 Diabetes Mellitus
Prediabetic State
Keywords: type 2 diabetes mellitus
prediabetic state
mass screening
glucose tolerance test
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
Collaborators: name: Emory University
First posted: 2008-11-10
Enrollment: 1939
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: initial primary study population will be drawn primarily from veterans receiving primary care at the Decatur Clinic CBOC in metropolitan Atlanta, GA

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.

Eligibility criteria: 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)

Primary outcomes:
measure: 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)
timeFrame: 3 years
Secondary outcomes:
measure: Cost to Identify a Single Case of High-risk Dysglycemia or Previously Unrecognized Diabetes
timeFrame: 3 years
Other outcomes:
Locations:
city: Decatur
country: United States
facility: Atlanta VA Medical and Rehab Center, Decatur, GA
state: Georgia
Study officials:
affiliation: Atlanta VA Medical and Rehab Center, Decatur, GA
name: Lawrence S Phillips, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Twombly JG, Long Q, Zhu M, Wilson PW, Narayan KM, Fraser LA, Webber BC, Phillips LS. Diabetes care in black and white veterans in the southeastern U.S. Diabetes Care. 2010 May;33(5):958-63. doi: 10.2337/dc09-1556. Epub 2010 Jan 26.
citation: Ziemer DC, Kolm P, Weintraub WS, Vaccarino V, Rhee MK, Twombly JG, Narayan KM, Koch DD, Phillips LS. Glucose-independent, black-white differences in hemoglobin A1c levels: a cross-sectional analysis of 2 studies. Ann Intern Med. 2010 Jun 15;152(12):770-7. doi: 10.7326/0003-4819-152-12-201006150-00004.
citation: Rhee MK, Herrick K, Ziemer DC, Vaccarino V, Weintraub WS, Narayan KM, Kolm P, Twombly JG, Phillips LS. Many Americans have pre-diabetes and should be considered for metformin therapy. Diabetes Care. 2010 Jan;33(1):49-54. doi: 10.2337/dc09-0341. Epub 2009 Oct 6.
citation: Olson DE, Rhee MK, Herrick K, Ziemer DC, Twombly JG, Phillips LS. Screening for diabetes and pre-diabetes with proposed A1C-based diagnostic criteria. Diabetes Care. 2010 Oct;33(10):2184-9. doi: 10.2337/dc10-0433. Epub 2010 Jul 16.
citation: Fraser LA, Twombly J, Zhu M, Long Q, Hanfelt JJ, Narayan KM, Wilson PW, Phillips LS. Delay in diagnosis of diabetes is not the patient's fault. Diabetes Care. 2010 Jan;33(1):e10. doi: 10.2337/dc09-1129. No abstract available.
citation: Lin E, Liang Z, Frediani J, Davis SS Jr, Sweeney JF, Ziegler TR, Phillips LS, Gletsu-Miller N. Improvement in ss-cell function in patients with normal and hyperglycemia following Roux-en-Y gastric bypass surgery. Am J Physiol Endocrinol Metab. 2010 Nov;299(5):E706-12. doi: 10.1152/ajpendo.00405.2010. Epub 2010 Aug 17.
citation: Chatterjee R, Narayan KM, Lipscomb J, Phillips LS. Screening adults for pre-diabetes and diabetes may be cost-saving. Diabetes Care. 2010 Jul;33(7):1484-90. doi: 10.2337/dc10-0054.
citation: Twombly JG, Long Q, Zhu M, Fraser LA, Olson DE, Wilson PW, Narayan KM, Phillips LS. Validity of the primary care diagnosis of diabetes in veterans in the southeastern United States. Diabetes Res Clin Pract. 2011 Mar;91(3):395-400. doi: 10.1016/j.diabres.2010.11.001. Epub 2010 Nov 26.
citation: Phillips LS, Ziemer DC, Kolm P, Weintraub WS, Vaccarino V, Rhee MK, Chatterjee R, Narayan KM, Koch DD. Glucose challenge test screening for prediabetes and undiagnosed diabetes. Diabetologia. 2009 Sep;52(9):1798-807. doi: 10.1007/s00125-009-1407-7. Epub 2009 Jun 26.
citation: Shikany JM, Tinker LF, Neuhouser ML, Ma Y, Patterson RE, Phillips LS, Liu S, Redden DT. Association of glycemic load with cardiovascular disease risk factors: the Women's Health Initiative Observational Study. Nutrition. 2010 Jun;26(6):641-7. doi: 10.1016/j.nut.2009.08.014. Epub 2010 Jan 6.
citation: Buse JB. Screening for diabetes and prediabetes with proposed A1C-based diagnostic criteria: comment on Olson et al. Diabetes Care. 2010 Dec;33(12):e174; author reply e175. doi: 10.2337/dc10-1720. No abstract available.
citation: Margolis KL, Wei F, de Boer IH, Howard BV, Liu S, Manson JE, Mossavar-Rahmani Y, Phillips LS, Shikany JM, Tinker LF; Women's Health Initiative Investigators. A diet high in low-fat dairy products lowers diabetes risk in postmenopausal women. J Nutr. 2011 Nov;141(11):1969-74. doi: 10.3945/jn.111.143339. Epub 2011 Sep 21.
citation: Tinker LF, Sarto GE, Howard BV, Huang Y, Neuhouser ML, Mossavar-Rahmani Y, Beasley JM, Margolis KL, Eaton CB, Phillips LS, Prentice RL. Biomarker-calibrated dietary energy and protein intake associations with diabetes risk among postmenopausal women from the Women's Health Initiative. Am J Clin Nutr. 2011 Dec;94(6):1600-6. doi: 10.3945/ajcn.111.018648. Epub 2011 Nov 9.
citation: Chlebowski RT, McTiernan A, Wactawski-Wende J, Manson JE, Aragaki AK, Rohan T, Ipp E, Kaklamani VG, Vitolins M, Wallace R, Gunter M, Phillips LS, Strickler H, Margolis K, Euhus DM. Diabetes, metformin, and breast cancer in postmenopausal women. J Clin Oncol. 2012 Aug 10;30(23):2844-52. doi: 10.1200/JCO.2011.39.7505. Epub 2012 Jun 11.
citation: Ma Y, Hebert JR, Manson JE, Balasubramanian R, Liu S, Lamonte MJ, Bird CE, Ockene JK, Qiao Y, Olendzki B, Schneider KL, Rosal MC, Sepavich DM, Wactawski-Wende J, Stefanick ML, Phillips LS, Ockene IS, Kaplan RC, Sarto GE, Garcia L, Howard BV. Determinants of racial/ethnic disparities in incidence of diabetes in postmenopausal women in the U.S.: The Women's Health Initiative 1993-2009. Diabetes Care. 2012 Nov;35(11):2226-34. doi: 10.2337/dc12-0412. Epub 2012 Jul 25.
citation: You NC, Chen BH, Song Y, Lu X, Chen Y, Manson JE, Kang M, Howard BV, Margolis KL, Curb JD, Phillips LS, Stefanick ML, Tinker LF, Liu S. A prospective study of leukocyte telomere length and risk of type 2 diabetes in postmenopausal women. Diabetes. 2012 Nov;61(11):2998-3004. doi: 10.2337/db12-0241. Epub 2012 Jul 24.
citation: Gletsu-Miller N, Kahn HS, Gasevic D, Liang Z, Frediani JK, Torres WE, Ziegler TR, Phillips LS, Lin E. Sagittal abdominal diameter and visceral adiposity: correlates of beta-cell function and dysglycemia in severely obese women. Obes Surg. 2013 Jul;23(7):874-81. doi: 10.1007/s11695-013-0874-6.
citation: Phillips LS, Olson DE. Diabetes: normal glucose levels should be the goal. Nat Rev Endocrinol. 2012 Sep;8(9):510-2. doi: 10.1038/nrendo.2012.139. Epub 2012 Jul 31. No abstract available.