Who Should Return for an Oral Glucose Tolerance Test? A Proposed Clinical Pathway Based on Retrospective Analysis of 332 Children

Abstract

Purpose: Fasting plasma glucose (FPG) or oral glucose tolerance test (OGTT) is the traditional diagnostic tool for type 2 diabetes (T2DM). Primary barrier to performing FPG or OGTT in asymptomatic patients is the requirement of fasting, and thus the need for another scheduled visit. For OGTT, at least 2 blood draws would be needed, making the test inconvenient and labour-intensive. These barriers may lead to lower testing rate and possibly under-diagnosis. In a busy clinic setting with increasing number of referrals for children with obesity, a more practical and simpler clinical pathway to stratify those at higher risk of having abnormal OGTT results from the lower risk ones is needed. This study thus aimed to identify simple non-fasting parameters which can be used to formulate a clinical pahtway to stratify subjects according to their risk of abnormal OGTT. Methods: This retrospective study included subjects with overweight or obesity who had undergone OGTT in tertiary paediatric unit from 2012–2018. The optimal haemoglobin A1c (HbA1c) cutoff that predicts abnormal OGTT was evaluated. Other non-fasting parameters, in combination with this HbA1c cutoff, were also explored as predictors of abnormal OGTT. Results: Three hundred and thirty-two subjects (boys: 54.2%, Chinese: 97.3%) were included for analysis, of which, 272 (81.9%) subjects had normal OGTT while 60 (18.0%) subjects had abnormal OGTT (prediabetes or T2DM). The mean age was 15.4 ± 2.3 years and the mean BMI z-score was 2.7 ± 0.6. The mean HbA1c level was significantly higher in the abnormal OGTT group than normal OGTT group (5.6% vs 5.3%, P<0.001). In our cohort, using the ADA criteria for prediabetes with a HbA1c cutoff of ≥ 5.7% only yielded a sensitivity of 41.7% and a specificity of 86% in identifying abnormal OGTT (prediabetes or T2DM), meaning that a substantial proportion of subjects with prediabetes or diabetes will be missed. From Receivers operating characteristic (ROC) curves analysis, optimal HbA1c predicting abnormal OGTT was 5.5% (AUC 0.71; sensitivity of 66.7% and specificity of 71%). When HbA1c ≥ 5.5% was combined with positive family history and abnormal alanine transaminase (ALT) level, the positive predictive value for abnormal OGTT was increased from 33.6% to 61.6%. Conclusion: In our cohort, over 97% were Chinese and close to 60% had family history of T2DM, thus fulfilling the ‘high-risk’ group criteria as suggested by American Diabetes Association to have FPG or OGTT screening. Nevertheless, only 18% of subjects had prediabetes or diabetes based on OGTT results. Our study showed that HbA1c, family history of T2DM and ALT level could be used to derive a clinical pathway to stratify children who have high risk of abnormal OGTT. These high risk individuals can go for further diagnostic tests, while those at lower risk of prediabetes/T2DM can avoid unnecessary tests and additional clinic visits.