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Objective: 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 β-cell function can be detected between the 2 groups., Study Design: 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 [ΔI(30)/ΔG(30)] and C-peptide [ΔC(30)/ΔG(30)]), and oDI were calculated., Results: 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, ΔI(30)/ΔG(30), ΔC(30)/ΔG(30), 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 × ΔI(30)/ΔG(30) (0.04 ± 0.02 vs 0.12 ± 0.02 mg/dL(-1); P = .005), and 1/fasting C-peptide × ΔC(30)/ΔG(30) (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 ΔC(30)/ΔG(30) <0.075 ng/mL per mg/dL had 93% sensitivity and 80% specificity for identifying youth with Ab(+) T2DM., Conclusion: During a liquid mixed-meal test, indices of β-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 β-cell function in therapeutic trials of β-cell restoration in youth with T2DM., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objective: To evaluate clinically useful measures of beta-cell function derived from the oral glucose tolerance test (OGTT) or mixed-meal (ie, Boost) tolerance test to assess insulin secretion in comparison with the gold standard, the hyperglycemic clamp (Hyper-C) test., Study Design: We hypothesized that OGTT/Boost-derived measures are useful estimates of beta-cell function and correlate well with insulin secretion measured by the Hyper-C test. This study was designed to assess the correlation between the ratio of the early incremental insulin/glucose responses at 15 and 30 minutes (DeltaI(15)/DeltaG(15) and DeltaI(30)/DeltaG(30)) of the OGTT and the Boost test with insulin secretion measured during the Hyper-C test (225 mg/dL). The same indices were evaluated using C-peptide. A total of 26 children (14 males, 12 females; mean age, 9.9 +/- 0.2 years; mean body mass index = 22.1 +/- 1.2 kg/m(2)) underwent a 2-hour Hyper-C test (225 mg/dL) and 3-hour OGTT and Boost tests with measurements of glucose, insulin, and C-peptide., Results: Correlations between Hyper-C- and OGTT-derived measures of insulin secretion were stronger for the 15-minute index than for the 30-minute index of insulin secretion and stronger for C-peptide levels than for insulin levels (r = .7, P < .001 for first-phase C-peptide vs both OGTT and Boost, DeltaC(15)/DeltaG(15))., Conclusions: In children with normal glucose tolerance, C-peptide rather than insulin level measured after 15 minutes of the OGTT or Boost test provides a reliable estimate of beta-cell function that correlates well with Hyper-C-derived insulin secretion.

Objectives: To examine the prevalence of the metabolic syndrome using different pediatric definitions reported in the literature and its relationship to abdominal adipose tissue (AT), in vivo insulin resistance, and inflammatory biomarkers in children and adolescents, as well as the utility of fasting insulin and adiponectin as predictors of the metabolic syndrome., Study Design: Cross-sectional measurements were obtained from 122 African Americans and 129 Caucasians age 8 to 19 years. Insulin sensitivity (IS) was measured by a 3-h hyperinsulinemic-euglycemic clamp. Blood pressure, fasting lipids, adiponectin, interleukin (IL)-6, adhesion molecules (intercellular adhesion molecule [ICAM]-1, vascular cell adhesion molecule [VCAM]-1, and E-selectin), and abdominal AT were measured., Results: Regardless of the metabolic syndrome criteria used, the prevalence of the metabolic syndrome was higher in overweight (24% approximately 51%) compared with non-overweight youths (1% approximately 3%) in both African Americans and Caucasians (P <.01). Youths with the metabolic syndrome had higher visceral AT and fasting insulin and lower IS and adiponetin independent of race (P < .01). In Caucasians, youths with the metabolic syndrome had higher levels of inflammatory biomarkers (IL-6, ICAM-1, and E-selectin). The area under the receiver operating curve (AUC) for insulin was 0.86 approximately 0.89 in African Americans and 0.86 approximately 0.89 in Caucasians, depending on the metabolic syndrome criteria used. For adiponetin, the AUC was 0.73 approximately 0.78 in African Americans and 0.81 approximately 0.86 in Caucasians., Conclusions: The prevalence of metabolic syndrome varies depending on the definition used in the literature. Thus, there is a need for a unified definition of this syndrome in children and adolescents to streamline the research in this area. Independent of race, visceral obesity, insulin resistance, hyperinsulinemia, and hypoadiponectinemia are the common characteristics of youths with the metabolic syndrome. In Caucasians but not in African Americans, the metabolic syndrome is associated with increased inflammatory markers; however, the translation of such findings remains to be determined based on long-term longitudinal outcome studies in different racial groups.

Objectives: We examined how well waist circumference (WC) reflects total and abdominal fat and whether WC predicts insulin resistance independent of body mass index (BMI) percentile in youths., Study Design: Body composition was measured by dual-energy x-ray absorptiometry and abdominal adiposity by computed tomography. Insulin sensitivity was measured by the hyperinsulinemic-euglycemic clamp., Results: Both BMI percentile and WC were significantly associated (P < .01) with total and abdominal fat and insulin sensitivity. WC remained a significant (P < .01) correlate of total and abdominal fat and insulin sensitivity after controlling for BMI percentile. By contrast, BMI percentile did not remain a significant correlate of visceral fat and markers of insulin resistance after controlling for WC. Without exception, WC explained a greater variance in abdominal fat and metabolic profiles than did BMI percentile., Conclusions: Our findings suggest that the prediction of health risks associated with obesity in youths is improved by the additional inclusion of WC measure to the BMI percentile. Such observations would reinforce the importance of including WC in the assessment of childhood obesity to identify those at increased metabolic risk due to excess abdominal fat.

The pathophysiology of type 2 diabetes mellitus (T2DM) involves insulin resistance and insulin deficiency. We report the progression in insulin sensitivity and secretion over a 6-year period in an adolescent with T2DM. This report further demonstrates that the earliest abnormality in youth T2DM is insulin resistance followed by progressive beta-cell failure.

Objectives: To compare insulin sensitivity and pancreatic beta-cell function measured by the euglycemic and the hyperglycemic clamp, with simple estimates of insulin sensitivity and pancreatic beta-cell function in youth. Study design We measured insulin sensitivity with a euglycemic clamp and first- and second-phase insulin secretion with a hyperglycemic clamp in 156 AA and white youths. Estimates of insulin sensitivity (fasting insulin level [I(F)], the ratio of fasting glucose [G(F)] to I(F) [G(F)/I(F)], homeostasis model assessment estimate of insulin sensitivity [HOMA IS], and quantitative insulin sensitivity check index [QUICKI]) and estimates of pancreatic beta-cell function (I(F), the ratio of I(F) to G(F) [I(F)/G(F)], and homeostasis model assessment estimate of pancreatic beta-cell function [HOMA %B]) were derived from fasting measurements., Results: In the total group, IS(Eu) correlated strongly with I(F) (r=-0.92), G(F)/I(F) (r=0.92), HOMA IS (r=0.91), and QUICKI (r=0.91) (P<.01). First-phase and second-phase insulin secretion correlated with I(F), I(F)/G(F), and HOMA %B (first-phase insulin secretion: r=0.76, 0.79, 0.82; second-phase insulin secretion: r=0.83, 0.86, 0.86, respectively; P<.01)., Conclusions: Simple estimates of insulin sensitivity and pancreatic beta-cell function using fasting insulin and glucose levels serve as surrogate measures of insulin sensitivity and secretion in nondiabetic youths. The validity of these conclusions in children with impaired glucose tolerance and type 2 diabetes mellitus remains to be determined.