Prediabetes confers increased risk of diabetes, and both prediabetes and early diabetes confer increased risk of cardiovascular disease (CVD), but most veterans with prediabetes and early diabetes are not identified - because these disorders are asymptomatic, and we do not screen to find them. As a result, high glucose levels tend to get worse; CVD events, health system resource use, and costs all begin to rise before diabetes is diagnosed; and many patients already have early diabetes complications and increased CVD risk when they are finally recognized. To screen for prediabetes and early diabetes, we developed a new "glucose challenge test" (GCT) - a 50g oral glucose challenge at any time of day, regardless of meal status, followed by glucose measurement 1 hour later. If the GCT exceeds a cutoff, patients undergo "gold standard" oral glucose tolerance tests (OGTTs). In a metabolic ward setting, we found the GCT to be accurate and inexpensive. We hypothesized that the GCT would be a convenient and cost-effective screen for veterans in primary care.
To translate our findings into improved health for VA patients, the GCT needed to be evaluated in VA - to justify trials aimed to assess impact on outcomes, and development of VA policies for system-wide implementation. Accordingly, objectives were (1) validation of the accuracy of GCT screening in VA primary care, and (2) assessment of cost-effectiveness in VA settings.
AIM #1. Validation: We performed plasma and capillary GCTs (GCTpl and GCTcap) during primary care visits in VA patients without known diabetes, who were identified as high-risk based on BMI >25, age >45, or other risk factors. We used receiver-operating-characteristic (ROC) analysis to evaluate the accuracy of identification of previously unrecognized diabetes and prediabetes, based on subsequent OGTTs. The GCT was compared with other screening tests that could be performed opportunistically - during outpatient visits, without restriction by time of day or meal status - A1c, random capillary glucose (RCG) performed immediately prior to the GCT, and random plasma glucose (RPG) obtained within 6 months prior to the GCT.
AIM #2. Costs: We captured the costs of diagnostic tests, staff effort, and patient time. The data are being analyzed to (1) express cost per case identified in both VA and Medicare settings, and (2) compare the GCT vs. alternative strategies for screening of (a) all patients that we evaluated, and (b) subgroups with different risks, using different assumptions about false-positive and false-negative costs to reflect the downstream cost implications of screening - from both VA and Medicare health system and societal perspectives.
1939 subjects were consented, 1876 completed GCT screening, and 1535 had complete data for GCT, OGTT, A1c, and demographic information; mean age was 56 years, BMI was 30.3 kg/m2, 94% were men, and 74% were black. By OGTT criteria, diabetes was present in 10%, and high-risk prediabetes (impaired glucose tolerance, IGT, and/or impaired fasting glucose, IFG, with fasting glucose 110-125 mg/dl) in 22%; high-risk dysglycemia (diabetes or high-risk prediabetes) was present in 32%, and any prediabetes or diabetes in 51%. The GCTpl provided areas under ROC curves of 0.84, 0.76, and 0.71 for detection of diabetes, high-risk dysglycemia, and high-risk prediabetes, respectively. GCTcap performed similarly, with ROCs of 0.82, 0.75, and 0.70 (p=ns vs. GCTpl except for detecting diabetes). The GCTpl was significantly more accurate than A1c, RCG (n=1037), and RPG (n=1025) to detect diabetes, high-risk dysglycemia, or high-risk prediabetes (all p<0.05). GCTcap was also more accurate than A1c, RPG, and RCG to detect diabetes, high-risk dysglycemia, and high-risk prediabetes (all p<0.05, with the exception of GCTcap vs. RPG to detect diabetes, p=ns). Comparisons of the performance of the GCT in this VA population vs. our prior study are underway.
We have begun to examine the cost-effectiveness of GCT screening, projecting 3-year VA and Medicare costs to screen for and treat high-risk dysglycemia, with conservative assumptions generally similar to those in our recent Diabetes Care publications (70% specificity screening cutoffs, screen-positive patients have OGTTs, those with diabetes or high-risk prediabetes are given generic metformin, treatment costs are restricted to those for metformin, and false-negatives miss the opportunity for treatment which reduces costs by 5%). Medicare analyses utilized data from Kaiser Permanente Northwest and the Medical Expenditure Panel Survey (MEPS) to project costs attributable to prediabetes and diabetes. VA analyses reflect cost estimates derived from our VISN 7 data that will be published in an upcoming manuscript.
From a VA perspective, costs in 2012 dollars to identify high-risk dysglycemia would be lowest with GCTcap ($34) and RPG ($31). GCTcap and GCTpl had the lowest projected 3-year health system costs per patient with dysglycemia ($249 and $256, respectively), and the lowest 3-year total health system costs ($82,767 and $84,904) - much lower than 3-year total health system costs with A1c screening ($103,179) or no screening ($152,105), our current practice.
Medicare costs to identify high-risk dysglycemia would be lowest with GCTcap ($50 per case identified) followed by GCTpl and RPG ($55); GCTcap and GCTpl had the lowest projected 3-year health system costs per case ($331 and $333), and the lowest 3-year total health system costs ($110,260 and $110,677). Projected 3-year total health system costs with GCT screening were much lower than costs of $136,224 with A1c screening and $208,032 with no screening.
Our findings in VA primary care show that GCT screening for prediabetes and early diabetes is more accurate and less expensive than alternative opportunistic methods. Since unrecognized diabetes and prediabetes are associated with increases in morbidity, mortality, and costs, and these analyses show that use of the GCT may be cost-saving, a new policy of systematic GCT screening could be a major opportunity to improve the health of veterans, and aid the VA as well. Early identification of prediabetes and previously unrecognized diabetes would permit implementation of preventive strategies which are efficacious, convenient, and cost-effective - improving the health of individual veterans, reducing diabetes-related health care system resource use and costs for the VA, and helping to spare VA funds for other disorders. .
- 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. Obesity surgery. 2013 Jul 1; 23(7):874-81.
- Ma Y, Hébert 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 1; 35(11):2226-34.
- 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 1; 61(11):2998-3004.
- 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. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2012 Aug 10; 30(23):2844-52.
- 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. The American journal of clinical nutrition. 2011 Dec 1; 94(6):1600-6.
- 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. The Journal of Nutrition. 2011 Nov 1; 141(11):1969-74.
- 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 research and clinical practice. 2011 Mar 1; 91(3):395-400.
- Lin E, Liang Z, Frediani J, Davis SS, 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. American Journal of Physiology. Endocrinology and Metabolism. 2010 Nov 1; 299(5):E706-12.
- 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 1; 33(10):2184-9.
- Chatterjee R, Narayan KM, Lipscomb J, Phillips LS. Screening adults for pre-diabetes and diabetes may be cost-saving. Diabetes Care. 2010 Jul 1; 33(7):1484-90.
- 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. Annals of internal medicine. 2010 Jun 15; 152(12):770-7.
- 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 (Burbank, Los Angeles County, Calif.). 2010 Jun 1; 26(6):641-7.
- 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 1; 33(5):958-63.
- 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 1; 33(1):e10.
- 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 1; 33(1):49-54.
- 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 1; 52(9):1798-807.
- Phillips LS, Olson DE. Diabetes: normal glucose levels should be the goal. Nature reviews. Endocrinology.. 2012 Sep 1; 8(9):510-2.
- Olson DE, Rhee MK, Herrick K, Ziemer DC, Twombly JG, Phillips LS. Screening for diabetes and prediabetes with proposed A 1c-based diagnostic criteria: Response to Buse. Diabetes Care. 2010 Dec 1; 33(12):e175.
- Jackson SL, Olson DE, Mohan A, Tomolo A, Barb D, Zhu M, Long Q, Phillips LS. Characterizing Veterans with Diabetes who are Missed by A1c Screening. Poster session presented at: VA HSR&D / QUERI National Meeting; 2012 Jul 16; National Harbor, MD.
- Jackson SL, Olson DE, Mohan A, Tomolo A, Barb D, Dubowitz N, Watson-Williams P, Ownby J, Rhee M, Phillips LS. Who is missed by A1c screening for diabetes? Poster session presented at: American Diabetes Association Annual Scientific Session; 2012 Jun 8; Philadelphia, PA.
- Jackson SL, Olson DE, Wilson P, Venkat Narayan KM, Weaver J, Michaels JA, Varughese R, Jasien C, Byrd-Sellers J, Phillips LS. Screening Detects Highly Prevalent Undiagnosed Diabetes and Prediabetes in Veterans Receiving Primary Care, but A1c Misclassifies Patients. Paper presented at: American Diabetes Association Annual Scientific Session; 2011 Jun 24; San Diego, CA.
Health Systems, Diabetes and Related Disorders
Clinical Diagnosis and Screening, Diabetes, Primary care, Screening