Oral Glucose Tolerance Test Glucose Peak Time Is Most Predictive of Prediabetes and Hepatic Steatosis in Obese Girls

Abstract

Obese adolescent girls are at increased risk for type 2 diabetes, characterized by defects in insulin secretion and action. We sought to determine if later glucose peak timing (>30 minutes), 1-hour glucose >155 mg/dl, or monophasic pattern of glucose excursion during an oral glucose tolerance test (OGTT) reflect a worse cardiometabolic risk profile. Post-pubertal overweight/obese adolescent girls without diabetes were studied (N = 88; age, 15.2 ± 0.2 years; body mass index percentile, 97.7 ± 0.5). All participants completed an OGTT and body composition measures. Thirty-two girls had a four-phase hyperinsulinemic euglycemic clamp with isotope tracers, vascular imaging, and muscle mitochondrial assessments. Participants were categorized by glucose peak timing (≤30 min = early; >30 min = late), 1-hour glucose concentration (±155 mg/dL) and glucose pattern (monophasic, biphasic). Girls with a late (N = 54) vs earlier peak (n = 34) timing had higher peak glucose (P < 0.001) and insulin (P = 0.023), HbA1c (P = 0.021); prevalence of hepatic steatosis (62% vs 26%; P = 0.003) and lower oral disposition index (P < 0.001) and glucagon-like peptide-1 response (P = 0.037). When classified by 1-hour glucose, group differences were similar to peak timing, but minimal when classified by glucose pattern. In the >155 mg/dL group only, peripheral insulin sensitivity and fasting free fatty acids were worse. A later glucose peak or >155 mg/dL 1-hour glucose predicts metabolic disease risk in obese adolescent girls. This may defect incretin effects and first phase insulin response, and muscle and adipose insulin resistance.

The shape of the glucose response curve during an oral glucose tolerance test heralds β–cell function in a large Chinese population

“…Our study further found that individuals with multiphasic curves whose plasma glucose concentration reached the lowest point at 60 min had better β-cell function than those with a nadir at 120 min. Consistent with previous studies [26], we found that the earlier the glucose/insulin peak in the OGTT curve, the better the β-cell function.…”

Two- vs one-hour glucose tolerance testing: Predicting prediabetes in adolescent girls with obesity

“…Importantly, we also identified the monophasic curve shape an unreliable biomarker with the lowest diagnostic sensitivity and specificity at 6-weeks and 1-year compared to all other morphological features. Though previous studies in adolescents with obesity found an association of monophasic curve (compared to the biphasic) with increased insulin resistance (11), more recent data in youth and adults suggest that the monophasic curve has high false positive rates (8, 16). When curve shape is directly compared to the time to glucose peak parameter, the mono/ biphasic curve variable mischaracterized prediabetes status in >50% of cases (8, 16) (37).…”

“…Though previous studies in adolescents with obesity found an association of monophasic curve (compared to the biphasic) with increased insulin resistance (11), more recent data in youth and adults suggest that the monophasic curve has high false positive rates (8, 16). When curve shape is directly compared to the time to glucose peak parameter, the mono/ biphasic curve variable mischaracterized prediabetes status in >50% of cases (8, 16) (37). In keeping with these analyses, this study confirms that the monophasic curve shape was associated with lowest reproducibility and modest diagnostic accuracy compared to both glucose peak and 1-hr glucose parameters.…”

“…However, the utility of these morphological features for predicting prediabetes in youth is still unclear. Although some studies examined the ability of curve shape to predict prediabetes in youth, only a few have evaluated the time to glucose peak parameter or 1-hr glucose as potential alternatives (11, 13–16). Evaluating the glucose peak and 1-hr glucose thresholds are intriguing because these parameters are relatively simple to quantify for clinical use and could be obtained during a shortened 1-hr OGTT.…”

A Tool to Explore Discrete-Time Data: The Time Series Response Analyser

“…Specifically, risk prediction models for prediabetes were shown to be reliably and independently enhanced by the addition of time-to-peak blood glucose concentration during an oral glucose tolerance test (Chung et al, 2017). Moreover, the use of this statistic in this context theoretically signified the early phase insulin response, which may have provided additional mechanistic insight beyond alternative summary statistics (Cree-Green et al, 2018). A further application of time-to-peak has been to inform methodologies that seek to identify certain responses, such as the duration and sampling frequency of an oral fat tolerance test The time taken to reach the maximum measured value.…”