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Enhanced Predictive Capability of a 1-Hour Oral Glucose Tolerance Test

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Enhanced Predictive Capability of a 1-Hour Oral Glucose Tolerance Test Diabetes Care 1 Enhanced Predictive Capability Manan Pareek,1,2,3 Deepak L. Bhatt,1 Mette L. Nielsen,2 Ram Jagannathan,4 of a 1-Hour Oral Glucose Tolerance Karl-Fredrik Eriksson,5 Peter M. Nilsson,5 Michael Bergman,6 and Test: A Prospective Population- Michael H. Olsen2,3 Based Cohort Study https://doi.org/10.2337/dc17-1351 OBJECTIVE To examine whether the 1-h blood glucose measurement would be a more suitable screening tool for assessing the risk of diabetes and its complications than the 2-h measurement. RESEARCH DESIGN AND METHODS We conducted a prospective population-based cohort study of 4,867 men, randomly selected from prespecified birth cohorts between 1921 and 1949, who underwent an oral glucose tolerance test with blood glucose measurements at 0, 1, and 2 h. Sub- jects were followed for up to 39 years, with registry-based recording of events. Discriminative abilities of elevated 1-h (‡8.6 mmol/L) versus 2-h (‡7.8 mmol/L) 1Brigham and Women’s Hospital Heart & Vascu- glucose for predicting incident type 2 diabetes, vascular complications, and mortality lar Center, Harvard Medical School, Boston, MA 2 were compared using Kaplan-Meier analysis, Cox proportional hazards regression, Cardiovascular and Metabolic Preventive Clinic, fi Department of Endocrinology, Centre for Individ- and net reclassi cation improvement. ualized Medicine in Arterial Diseases, Odense University Hospital, Odense, Denmark RESULTS 3Cardiology Section, Department of Internal CARDIOVASCULAR AND METABOLIC RISK Median age was 48 years (interquartile range [IQR] 48–49). During follow-up (median Medicine, Holbaek Hospital, Holbaek, Denmark 4 33 years [IQR 24–37]), 636 (13%) developed type 2 diabetes. Elevated 1-h glucose Department of Population Health, Center for – P < Healthful Behavior Change, New York University was associated with incident diabetes (hazard ratio 3.40 [95% CI 2.90 3.98], 0.001) School of Medicine, New York, NY and provided better risk assessment than impaired glucose tolerance (C index 0.637 5Department of Clinical Sciences and Lund Uni- vs. 0.511, P < 0.001). Addition of a 1-h measurement in subjects stratified by fasting versity Diabetes Centre, Lund University, Skane˚ fi University Hospital, Malmo,¨ Sweden glucose provided greater net reclassi cation improvement than the addition of a 2-h 6 fi Division of Endocrinology and Metabolism, measurement (0.214 vs. 0.016, respectively). Finally, the 1-h glucose was signi cantly Department of Medicine, New York University associated with vascular complications and mortality. School of Medicine, New York University Lan- gone Diabetes Prevention Program, New York, CONCLUSIONS NY The 1-h blood glucose level is a stronger predictor of future type 2 diabetes than the Corresponding author: Manan Pareek, mpareek@ 2-h level and is associated with diabetes complications and mortality. bwh.harvard.edu and [email protected]. Received 6 July 2017 and accepted 4 October 2017. Type 2 diabetes is associated with significant morbidity and mortality and represents a This article contains Supplementary Data online major burden on health care systems worldwide (1,2). Several randomized clinical trials at http://care.diabetesjournals.org/lookup/ provide evidence that type 2 diabetes can be prevented or at least postponed with suppl/doi:10.2337/dc17-1351/-/DC1. lifestyle modification and drug therapy, which makes identifying high-risk individuals © 2018 by the American Diabetes Association. particularly important (3–6). Traditionally, prediabetes has been defined as impaired Readers may use this article as long as the work is properly cited, the use is educational and not fasting glucose (IFG) or impaired glucose tolerance (IGT) during a 2-h oral glucose for profit, and the work is not altered. More infor- tolerance test (OGTT), and interventional studies thus far have predominantly included mation is available at http://www.diabetesjournals subjects with IGT (7,8). However, not all subjects with prediabetes develop type 2 .org/content/license. Diabetes Care Publish Ahead of Print, published online November 14, 2017 2 One-Hour Oral Glucose Tolerance Test Diabetes Care diabetes, and conversely, a significant the final study population consisted of [IQR]) (non–normally distributed vari- number without prediabetes progress to 4,867 men (Supplementary Fig. 1). In ad- ables). Categorical variables are presented type 2 diabetes (9). Accumulating longitu- dition, 132 women recruited between as counts and corresponding percentages. dinal evidence, pioneered in particular by 25 January 1977 and 6 January 1984 un- Kaplan-Meier analysis with the log-rank Abdul-Ghani et al. (10–18), suggests that derwent baseline OGTT. One was excluded test and Cox proportional hazards regres- the 1-h postload glucose level during owing to known diabetes and 3 owing to sion with Harrell concordance index (C in- OGTT with a cutoff $8.6 mmol/L (155 emigration, but none of them underwent dex), assuming an uncensored policy for mg/dL) may be an early marker of IGT intervention, leaving a total of 128 female handling ties, were used for assessment and subsequent type 2 diabetes that is subjects. The Malmo¨ Preventive Project of discriminative ability for postload glu- potentially more useful than either fast- was approved by the ethics committee cose measurements, including compari- ing or 2-h glucose levels. Furthermore, of Lund University and conducted in ac- sons between predefined risk groups from a pathophysiological perspective, cordance with the Declaration of Helsinki. (27). Hazard ratios (HRs) were reported the 1-h glucose level is intriguing owing All participants gave informed consent. unadjusted and adjusted for age, BMI, to its seemingly strong correlation with IFG, triglycerides, and family history of markers of both insulin secretion and sen- Baseline Variables diabetes. Furthermore, the ability of 1-h sitivity (10,19,20). However, practical clin- Participants used a self-administered and 2-h postload glucose measurements ical implications of using a 1-h glucose questionnaire to provide information on to enhance prognostication in addition to measurement for prediction of type 2 di- lifestyle and medical history, including a fasting blood glucose was tested with cat- fi abetes and its associated complications history of diabetes in rst-degree relatives, egorical net reclassification improvement are less clear. Therefore, the aim of this cardiovascular disease, and current medi- (28). All glucose measurements were as- fi study was to examine whether the 1-h cation. Prevalent diabetes was de ned as sessed in a binary fashion, using the fol- blood glucose measurement would be a self-reported diabetes or according to the lowing cut points: IFG, fasting blood more suitable screening tool for risk assess- 1985WorldHealthOrganizationcriteria(24). glucose $5.6 mmol/L (100 mg/dL); ele- ment than the 2-h blood glucose alone. Blood glucose and serum lipids were ob- vated 1-h blood glucose, $8.6 mmol/L $ tained after an overnight ( 10 h) fast. (155 mg/dL); and IGT, 2-h BG $7.8 RESEARCH DESIGN AND METHODS Blood glucose was analyzed using the glu- mmol/L (140 mg/dL) (7,10). Analyses – All subjects were participants of the cose oxidase (1974 1977) or the hexoki- were performed at 12 years and at max- – Malmo¨ Preventive Project (1974–1992), nase (1977 1992) method. Serum lipids imal available follow-up, respectively. ’ a population-based case-finding program were analyzed using the local laboratory s This was because of the possibility of standard methods. A 2-h OGTT was per- with the objective of identifying high-risk 2 the intervention among high-risk individ- adults suitable for preventive measures. formed by ingestion of 30 g glucose/m uals during the first 12 years after recruit- Inhabitants of Malmo,¨ Sweden, belonging body surface area (DuBois formula), with ment affecting the study outcomes to prespecified birth cohorts (1921–1949) glucose levels determined at 0, 20, 40, 60, 90, because even though we attempted to were invited for an examination of cardio- and 120 min (25). Analyses of postload minimize the implications of the interven- vascular risk factors, alcohol abuse, and glucose levels were focused on measure- tion by excluding individuals who were breast cancer. Progressively older men ments at 1 h and 2 h. subjected to it, there may have been a were recruited later during the course Outcomes spillover effect to the control subjects, of the study. The participation rate was We used national and local registries to given the population-based nature of – 71% (21 23). During the initial phase of record clinical end points. Besides the di- the study. Results obtained from the the study (9 September 1974 to 31 May agnosis itself, the date of diagnosis is also women were reported separately. There- 1978 [both inclusive]), 7,200 men were coded in these registries. All events (type 2 fore, unless explicitly stated otherwise, all consecutively included, of whom 5,364 diabetes, myocardial infarction, diabetic analyses and conclusions were based on fi underwent baseline OGTT. After exclu- retinopathy, and diabetes with peripheral the larger male population. The signi - sion of subjects with a missing or invalid vascular complications, including ulcer) cance level was 5% (two sided), and no 1-h glucose measurement (7 of 5,364) or were defined according to the relevant adjustments for multiple comparisons known diabetes (100 of 5,364), and those ICD-7 to ICD-10 codes (Supplementary were made, as the study was considered who emigrated (71 of 5,364), 5,182 indi- Table 1). Reported validities in the Swed- exploratory. All analyses were performed viduals were left. Of these, a subset of ish National Inpatient Register were high with IBM SPSS Statistics 23 (IBM, Armonk, d individuals at high risk including those for all diagnoses (26). Mortality follow-up NY) and Stata/IC 15 (StataCorp, College with hypertension, hyperlipidemia, diabe- was based on the national registry on Station, TX).
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