Validity and reliability of a novel metabolic flexibility test in children with obesity

Existing methods for diagnosing diabetes and for identifying risk of diabetes development are completed under resting conditions and based on adult data. Studying additional methods to identify metabolic risk in children is warranted. Our objective was to examine the validity and reliability of a metabolic flexibility (MetFlex) test for screening glycemia and insulin resistance (IR) in children. We hypothesized higher MetFlex during exercise would be correlated with lower fasting glucose and homeostasis model assessment of insulin resistance (HOMA-IR) and higher whole body insulin sensitivity index (WBISI) and insulin secretion-sensitivity index-2 (ISSI-2). Thirty-four children with obesity (14 boys, 20 girls) attended two visits. At visit 1, an oral glucose tolerance test (OGTT) was followed by anthropometric and aerobic fitness (V̇o_2max) assessments. Insulin and glucose during the OGTT were used to calculate HOMA-IR, WBISI, and ISSI-2. At visit 2, a ¹³C-enriched carbohydrate drink was ingested before 60 min of exercise at 45% V̇o_2max. Breath measurements were collected to calculate area under the curve exogenous carbohydrate to measure MetFlex. Pearson's r correlation showed no significant association between MetFlex during exercise with fasting glucose ( r = -0.288, P = 0.110). MetFlex was associated with log-HOMA-IR ( r = -0.597, P = 0.024), log-WBISI ( r = 0.575, P = 0.051), and log-ISSI-2 ( r = 0.605, P = 0.037) in boys but not girls. When repeated ( n = 18), MetFlex was deemed a reliable test (intraclass correlation coefficient = 0.692). MetFlex during exercise was negatively associated with IR and β-cell function in boys. Further research is required to explore clinical utility of the MetFlex test and explain the lack of association in girls. NEW & NOTEWORTHY This study is the first to investigate the validity and reliability of a novel noninvasive metabolic flexibility (MetFlex) test for identifying insulin resistance in children with obesity. MetFlex was measured during exercise using [¹³C]glucose stable isotope methodology. Findings showed that MetFlex was negatively associated with insulin resistance in boys but not in girls with obesity. Future work is required to investigate these sex differences. MetFlex test results were deemed reliable when repeated on a separate day.