Reproducibility of the Oral Glucose Tolerance Test in Overweight Children
Children's Hospital of Pittsburgh, and Department of Epidemiology, Graduate School of Public Health, Center for Exercise and Health-Fitness Research, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. Journal of Clinical Endocrinology & Metabolism
(Impact Factor: 6.21).
09/2008; 93(11):4231-7. DOI: 10.1210/jc.2008-0801
We examined the reproducibility of the oral glucose tolerance test (OGTT) in overweight children and evaluated distinguishing characteristics between those with concordant vs. discordant results.
Sixty overweight youth (8-17 yr old) completed two OGTTs (interval between tests 1-25 d). Insulin sensitivity was assessed by the surrogate measures of fasting glucose to insulin ratio, whole-body insulin sensitivity index, and homeostasis model assessment of insulin resistance, and insulin secretion by the insulinogenic index with calculation of the glucose disposition index (GDI).
Of the 10 subjects with impaired glucose tolerance (IGT) during the first OGTT only three (30%) had IGT during the second OGTT. The percent positive agreement between the first and second OGTT was low for both impaired fasting glucose and IGT (22.2 and 27.3%, respectively). Fasting blood glucose had higher reproducibility, compared with the 2-h glucose. Youth with discordant OGTTs, compared with those with concordant results, were more insulin resistant (glucose/insulin 2.7+/-1.4 vs. 4.1+/-1.8, P=0.006, whole-body insulin sensitivity index of 1.3+/-0.6 vs. 2.2+/-1.1, P=0.003, and homeostasis model assessment of insulin resistance 10.6+/-8.1 vs. 5.7+/-2.8, P=0.001), had a lower GDI (0.45+/-0.58 vs. 1.02+/-1.0, P=0.03), and had higher low-density lipoprotein cholesterol (117.7+/-36.6 vs. 89.9+/-20.1, P=0.0005) without differences in physical characteristics.
Our results show poor reproducibility of the OGTT in obese youth, in particular for the 2-h plasma glucose. Obese youth who have discordant OGTT results are more insulin resistant with higher risk of developing type 2 diabetes mellitus, as evidenced by a lower GDI. The implications of this remain to be determined in clinical and research settings.
Available from: Marianne Bertolet
- "Finally, the slope and 95% CI of the slope for log-transformed hcDI variables was not as close to −1 in the OB-IGT group as in the other groups, which may appear to undermine the appropriateness of this method in obese children with glucose intolerance. However, this could be due to the poor reproducibility of the OGTT, whereby categorizing an individual as IGT without a second documented OGTT may not necessarily reflect the person’s true glucose tolerance status, as we previously showed (24). "
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To compare β-cell function relative to insulin sensitivity, disposition index (DI), calculated from two clamps (2cDI, insulin sensitivity from the hyperinsulinemic-euglycemic clamp and first-phase insulin from the hyperglycemic clamp) with the DI calculated from the hyperglycemic clamp alone (hcDI).RESEARCH DESIGN AND METHODS
Complete data from hyperglycemic and hyperinsulinemic-euglycemic clamps were available for 330 youth, including 73 normal weight (NW), 168 obese with normal glucose tolerance (OB-NGT), 57 obese with impaired glucose tolerance (OB-IGT), and 32 obese with type 2 diabetes (OB-T2DM). The correlation between hcDI and 2cDI and Bland-Altman analysis of agreement between the two were examined.RESULTSInsulin sensitivity and first-phase insulin from hcDI showed a hyperbolic relationship. The hcDI correlated significantly with 2cDI in the groups combined (r = 0.85, P < 0.001) and within each group separately (r ≥ 62, P < 0.001). Similar to 2cDI, hcDI showed a declining pattern of β-cell function across the glucose-tolerance groups. Overall, hcDI values were 27% greater than 2cDI, due to the hyperglycemic versus euglycemic conditions, reflected in a positive bias with Bland-Altman analysis.CONCLUSIONSβ-Cell function relative to insulin sensitivity could be accurately evaluated from a single hyperglycemic clamp, obviating the need for two separate clamp experiments, when lessening participant burden and reducing research costs are important considerations.
Available from: Lama Farchoukh
- "On a separate occasion, 1 to 3 weeks apart, and in random order, a 2-h hyperglycemic clamp (∼225 mg/dL) was performed (12,13,22). Either the day preceding one of the clamp procedures or on a separate visit within a 1- to 3-week period, a 2-h OGTT (1.75 g/kg glucola, maximum 75 g) was performed in 142 participants (23,24). Normal versus impaired glycemia was defined according to standards for fasting or 2-h OGTT glucose (2). "
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The recommended HbA(1c) diagnostic categories remain controversial and their utility in doubt in pediatrics. We hypothesized that alterations in the pathophysiologic mechanisms of type 2 diabetes may be evident in the American Diabetes Association recommended at-risk/prediabetes category (HbA(1c) 5.7 to <6.5%).RESEARCH DESIGN AND METHODS
We compared in vivo hepatic and peripheral insulin sensitivity by [6,6-(2)H(2)] glucose and a 3-h hyperinsulinemic-euglycemic clamp and β-cell function by a 2-h hyperglycemic clamp (∼225 mg/dL) in overweight/obese (BMI ≥85th percentile) adolescents with prediabetes (HbA(1c) 5.7 to <6.5%) (n = 160) to those with normal HbA(1c) (<5.7%) (n = 44). β-Cell function was expressed relative to insulin sensitivity (i.e., the disposition index = insulin sensitivity × first-phase insulin).RESULTSIn the prediabetes versus normal HbA(1c) category, fasting glucose, insulin, and oral glucose tolerance test (OGTT) area under the curve for glucose and insulin were significantly higher; hepatic and peripheral insulin sensitivity were lower; and β-cell function relative to insulin sensitivity was lower (366 ± 48 vs. 524 ± 25 mg/kg/min; P = 0.005). A total of 27% of youth in the normal HbA(1c) category and 41% in the prediabetes HbA(1c) category had dysglycemia (impaired fasting glucose and/or impaired glucose tolerance) by a 2-h OGTT.CONCLUSIONS
Overweight/obese adolescents with HbA(1c) in the at-risk/prediabetes category demonstrate impaired β-cell function relative to insulin sensitivity, a metabolic marker for heightened risk of type 2 diabetes. Thus, HbA(1c) may be a suitable screening tool in large-scale epidemiological observational and/or interventional studies examining the progression or reversal of type 2 diabetes risk.
Available from: Stephanie A Atkinson
- "Dysglycemia was common (20.8%) and IGT was identified in 16.2% of the participants, comparable to the findings of several American studies (2,25). Silent T2DM was relatively rare in this population (1 of 259) but was identified on a 2-h blood glucose alone. "
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ABSTRACT: To examine the performance of current screening recommendations for detecting dysglycemia in children and adolescents with obesity.
In a cross-sectional study, an oral glucose tolerance test and demographic (age, sex, family history of diabetes, and ethnicity), clinical (BMI z score, waist circumference, and pubertal stage), and laboratory variables used in current pediatric screening criteria for type 2 diabetes mellitus were measured in 259 overweight or obese youth aged 5-17 years. Glycemic status was based on American Diabetes Association (ADA) thresholds. The performance (sensitivity and specificity) of current screening criteria and newly developed models to identify isolated IGT were compared.
Dysglycemia was present in 20.8% of the cohort. Of the 54 participants with dysglycemia, 68% had a normal fasting glucose and were identified with the 2-h glucose test. Current ADA criteria had low sensitivity (41.7% [95% CI 25.6-57.8]) and moderate specificity (69.5% [63.5-75.6]) to identify IGT. In receiver operating characteristic (ROC) analysis, the addition of hemoglobin A(1c) (HbA(1c)) or FPG did not improve the ROC area under the curve (AUC) (HbA(1c): 0.64 vs. 0.63; P = 0.54; HbA(1c) + FPG: 0.66; P = 0.42), but adding triglyceride level did (AUC 0.72 vs. 0.63; P = 0.03). A simple model with fasting triglyceride level >1.17 mmol/L improved AUC compared with ADA screening criteria (0.68 vs. 0.57; P = 0.04).
The prevalence of IGT is high among obese children and youth. Current screening criteria have low sensitivity to detect isolated IGT. Although adding nonfasting laboratory values to history and physical measures does not improve diagnostic accuracy, adding fasting lipid profile improves predictive value.
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