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Title: Indices of insulin secretion during a liquid mixed-meal test in obese youth with diabetes

Author
item BACHA, FIDA - Children'S Nutrition Research Center (CNRC)
item GUNGOR, NESLIHAN - Louisiana State University
item LEE, SOJUNG - University Of Pittsburgh Medical Center
item DE LAS HERAS, JAVIER - Hospital De Cruces
item ARSLANIAN, SILVA - University Of Pittsburgh Medical Center

Submitted to: Journal of Pediatrics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/7/2012
Publication Date: 5/1/2013
Citation: Bacha, F., Gungor, N., Lee, S., De Las Heras, J., Arslanian, S. 2013. Indices of insulin secretion during a liquid mixed-meal test in obese youth with diabetes. Journal of Pediatrics. 162(5):924-929.

Interpretive Summary: There is interest in being able to measure insulin secretion in children with diabetes and the changes in insulin production in response to different therapies, using a simple method. This study aimed to find out if an easily feasible liquid mixed meal test (using a Boost drink) can be used to distinguish insulin secretion between different groups of children with diabetes. The study found that indices of insulin secretion during this standardized mixed-meal test are reliable and could be used to assess insulin production in future trials that need to measure the pancreatic beta-cell function in youth with diabetes.

Technical Abstract: To compare indices of insulin secretion, insulin sensitivity (IS),and oral disposition index (oDI) during the liquid mixed-meal test in obese youth with clinically diagnosed type 2 diabetes mellitus (T2DM) and negative autoantibodies (Ab-) versus those with T2DM and positive autoantibodies (Ab+) to examine whether differences in beta-cell function can be detected between the 2 groups. Twenty-seven youth with Ab(-)and 15 youth with Ab(+) clinically diagnosed T2DM underwent a mixed-meal test (Boost; 55% carbohydrate, 25% protein, and 20% fat). Fasting and mixed-meal–derived insulin and C-peptide indices of IS, secretion (30-minute insulinogenic [deltaI30/DG30] and C-peptide [deltaC30/deltaG30]), and oDI were calculated. Indices of insulin secretion were ~40%-50% lower in patients with Ab(+) T2DM compared with those with Ab(-)T2DM. After controlling for body mass index, deltaI30/deltaG30, deltaC30/deltaG30, C-peptide area under the curve (AUC)/glucose AUC, and insulin AUC/glucose AUC were significantly (P < .05) lower in the Ab(+) group compared with the Ab(-)group. Sensitivity indices were significantly higher in the Ab(+) group. The oDI, 1/fasting insulin x deltaI30/deltaG30 (0.04 +/- 0.02 vs 0.12 +/- 0.02 mg/dL(-1); P = .005), and 1/fasting C-peptide x deltaC30/deltaG30 (0.02 +/- 0.009 vs 0.05 =/- 0.006 mg/dL(-1); P = .018) were lower in the Ab(+) group. Receiver operating characteristic curve analyses revealed that fasting C-peptide <3.2 ng/mL had 87% sensitivity and 74% specificity and deltaC30/deltaG30 <0.075 ng/mL per mg/dL had 93% sensitivity and 80% specificity for identifying youth with Ab(+) T2DM. During a liquid mixed-meal test, indices of beta-cell function were lower and IS was higher in patients with Ab+ T2DM versus those with Ab- T2DM, with high sensitivity and specificity for fasting and stimulated C-peptide as markers of Ab(+) status. Indices of insulin secretion during this standardized mixed-meal test could be used to assess beta-cell function in therapeutic trials of beta-cell restoration in youth with T2DM.