Anthropometric Equations to Predict Visceral Adipose Tissue in European and American Youth.

OBJECTIVE: To investigate whether prediction equations including a limited but selected number of anthropometrics that consider differences in subcutaneous abdominal adipose tissue may improve prediction of the visceral adipose tissue (VAT) in youth. STUDY DESIGN: Anthropometrics and abdominal adipose tissue by MRI were available in 7-18 years old youth with overweight or obesity: 181 White Europeans and 186 White and Black Americans. Multivariable regressions were performed to develop and validate the VAT anthropometric predictive equations in a cross-sectional study. RESULTS: A model with both waist circumference (WaistC) and hip circumference (HipC) (VAT = [1.594 × WaistC] - [0.681 × HipC] + [1.74 × Age] - 48.95) more strongly predicted VAT in girls of White European ethnicity (R2 = 50.8%; standard error of the estimate [SEE] = 13.47 cm2), White American ethnicity (R2 = 41.9%; SEE, 15.63 cm2), and Black American ethnicity (R2 = 25.1%; SEE, 16.34 cm2) (P < .001), than WaistC or BMI. In boys, WaistC was the strongest predictor of VAT; HipC did not significantly improve VAT prediction. CONCLUSIONS: A model including both WaistC and HipC that considers differences in subcutaneous abdominal adipose tissue more accurately predicts VAT in girls and is superior to commonly measured anthropometrics used individually. In boys, other anthropometric measures did not significantly contribute to the prediction of VAT beyond WaistC alone. This demonstrates that selected anthropometric predictive equations for VAT can be an accessible, cost-effective alternative to imaging methods that can be used in both clinics and research.

Sex and Ethnic Differences in the Relationship between Changes in Anthropometric Measurements and Visceral Fat in Adolescents with Obesity.

OBJECTIVE: To examine sex and ethnic differences in how baseline and changes in anthropometric measures relate with change in visceral fat with interventions in adolescents. STUDY DESIGN: Black and white adolescents (n = 143: body mass index [BMI] ≥85th percentile, 12-18 years) who participated in intervention studies (3-6 months) were included and had assessments of anthropometric measures (weight, BMI, waist circumference, waist-to-hip ratio [WHR], and waist-to-thigh ratio) and visceral fat at L4-L5 by magnetic resonance imaging before and after interventions. RESULTS: At baseline, all of the anthropometric measures were positively associated with visceral fat (P < .05), with weight, waist circumference, and WHR having the largest variance explained (model adjusted R2 = 0.35-0.47 vs 0.32-0.35). Blacks had 11.5-23.3 cm2 less visceral fat compared with whites for a given anthropometric value. Girls tended to have less visceral fat for a given anthropometric value, but the sex differences were not consistently significant (range: 0.7-12.9 cm2). Changes in waist circumference, BMI, and weight, but not WHR, remained significantly associated with changes in visceral fat. There were no sex differences, and much more minimal ethnic differences (<4.9 cm2). CONCLUSIONS: At baseline, there are sex and ethnic differences in how anthropometric measures correlate with visceral fat. However, there were minimal sex and ethnic differences in how changes in anthropometric measures related with changes in visceral fat. Although all of the anthropometric measures were associated with visceral fat at baseline, waist circumference, BMI, and weight, but not WHR were associated with changes in visceral fat. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00739180, NCT01323088, and NCT01938950.

Effects of Exercise Modality on Insulin Resistance and Ectopic Fat in Adolescents with Overweight and Obesity: A Randomized Clinical Trial.

OBJECTIVE: To examine whether a combined aerobic exercise and resistance exercise is more effective than either aerobic exercise or resistance exercise alone in improving insulin sensitivity and reducing total adiposity and ectopic fat in adolescents. STUDY DESIGN: A total of 118 sedentary adolescents with overweight/obesity (body mass index >85th percentile, 12-17 years) were recruited from October 2013 through April 2017 at Children's Hospital of Pittsburgh. Participants were randomized to 1 of the following 6-month exercise groups (3 d/wk, 180 min/wk): aerobic exercise (n = 38), resistance exercise (n = 40), and combined aerobic exercise and resistance exercise (n = 40). The primary outcome was the change in insulin-stimulated glucose disposal by a 3-hour hyperinsulinemic-euglycemic clamp. The secondary outcomes were changes in liver fat by proton magnetic resonance spectroscopy and intermuscular adipose tissue by computed tomography. RESULTS: Of the 118 participants randomized, 85 participants (72%) completed the study with 90% exercise attendance. Total adiposity reduced similarly in all groups (-2%, P < .05). After adjusting for age and sex, insulin-stimulated glucose disposal increased (P < .05) in all groups, with the increase in the aerobic exercise group being greater than the resistance exercise group (1.7 ± 0.1 vs 0.7 ± 0.1 mg/kg/min, P < .05) but not different from the combined group (1.2 ± 0.1 mg/kg/min). Liver fat was reduced (P < .05) in the aerobic exercise (-0.6%) and combined (-0.6%) groups but not in the resistance exercise group (-0.3%, P > .05). Intermuscular adipose tissue decreased (P < .05) similarly in all groups. CONCLUSION: Combined aerobic exercise and resistance exercise and aerobic exercise alone are similarly beneficial in improving insulin sensitivity and reducing ectopic fat in adolescents with obesity. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01938950.

The Shape of the Glucose Response Curve During an Oral Glucose Tolerance Test Heralds Biomarkers of Type 2 Diabetes Risk in Obese Youth.

OBJECTIVE: The shape of the glucose response curve during an oral glucose tolerance test (OGTT), monophasic versus biphasic, identifies physiologically distinct groups of individuals with differences in insulin secretion and sensitivity. We aimed to verify the value of the OGTT-glucose response curve against more sensitive clamp-measured biomarkers of type 2 diabetes risk, and to examine incretin/pancreatic hormones and free fatty acid associations in these curve phenotypes in obese adolescents without diabetes. RESEARCH DESIGN AND METHODS: A total of 277 obese adolescents without diabetes completed a 2-h OGTT and were categorized to either a monophasic or a biphasic group. Body composition, abdominal adipose tissue, OGTT-based metabolic parameters, and incretin/pancreatic hormone levels were examined. A subset of 106 participants had both hyperinsulinemic-euglycemic and hyperglycemic clamps to measure in vivo insulin sensitivity, insulin secretion, and ß-cell function relative to insulin sensitivity. RESULTS: Despite similar fasting and 2-h glucose and insulin concentrations, the monophasic group had significantly higher glucose, insulin, C-peptide, and free fatty acid OGTT areas under the curve compared with the biphasic group, with no differences in levels of glucagon, total glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide, and pancreatic polypeptide. Furthermore, the monophasic group had significantly lower in vivo hepatic and peripheral insulin sensitivity, lack of compensatory first and second phase insulin secretion, and impaired ß-cell function relative to insulin sensitivity. CONCLUSIONS: In obese youth without diabetes, the risk imparted by the monophasic glucose curve compared with biphasic glucose curve, independent of fasting and 2-h glucose and insulin concentrations, is reflected in lower insulin sensitivity and poorer ß-cell function, which are two major pathophysiological biomarkers of type 2 diabetes in youth.

Effect of Aerobic versus Resistance Exercise on Pulse Wave Velocity, Intima Media Thickness and Left Ventricular Mass in Obese Adolescents.

A cardiovascular comorbidity in obese adolescents is increased aortic pulse wave velocity (aPWV), carotid intima-media thickness (cIMT) and left ventricular mass (LVM). We investigated in obese adolescents 1) the risk factors associated with aPWV, cIMT and LVM, and 2) the effects of aerobic (AE) versus resistance (RE) exercise alone (without calorie restriction) on aPWV, cIMT, LVM index (LVMI) and cardiometabolic risk factors. Eighty-one obese adolescents (12-18 yrs, BMI ≥95th percentile) were randomized to 3 months of AE (n = 30), RE (n = 27) or a control group (n = 24). Outcome measures included aPWV, cIMT, LVMI, body composition, cardiorespiratory fitness (CRF), blood pressure (BP) and lipids. At baseline, the strongest correlates of aPWV were body weight (r = .31) and diastolic BP (r = .28); of cIMT were body weight (r=0.26) and CRF (r=-0.25); and of LVMI was CRF (r=0.32) after adjusting for sex and race (p < .05 for all). Despite significant reductions in total fat and improvements in CRF in the AE and RE groups, aPWV, cIMT, LVMI, BP, lipids and body weight did not change as compared with controls (p > .05 for all). Interventions of longer duration or together with weight loss may be required to improve these early biomarkers of CVD in obese adolescents.

ß-cell function, incretin effect, and incretin hormones in obese youth along the span of glucose tolerance from normal to prediabetes to type 2 diabetes.

Using the hyperglycemic and euglycemic clamp, we demonstrated impaired ß-cell function in obese youth with increasing dysglycemia. Herein we describe oral glucose tolerance test (OGTT)-modeled ß-cell function and incretin effect in obese adolescents spanning the range of glucose tolerance. ß-Cell function parameters were derived from established mathematical models yielding ß-cell glucose sensitivity (ßCGS), rate sensitivity, and insulin sensitivity in 255 obese adolescents (173 with normal glucose tolerance [NGT], 48 with impaired glucose tolerance [IGT], and 34 with type 2 diabetes [T2D]). The incretin effect was calculated as the ratio of the OGTT-ßCGS to the 2-h hyperglycemic clamp-ßCGS. Incretin and glucagon concentrations were measured during the OGTT. Compared with NGT, ßCGS was 30 and 65% lower in youth with IGT and T2D, respectively; rate sensitivity was 40% lower in T2D. Youth with IGT or T2D had 32 and 38% reduced incretin effect compared with NGT in the face of similar changes in GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) in response to oral glucose. We conclude that glucose sensitivity deteriorates progressively in obese youth across the spectrum of glucose tolerance in association with impairment in incretin effect without reduction in GLP-1 or GIP, similar to that seen in adult dysglycemia.

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

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 ß-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 ß-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 ß-cell function in therapeutic trials of ß-cell restoration in youth with T2DM.

Oral disposition index in obese youth from normal to prediabetes to diabetes: relationship to clamp disposition index.

OBJECTIVE: We sought to assess the glucose disposition index using an oral glucose tolerance test (OGTT; oDI) compared with the glucose disposition index measured from the combination of the euglycemic-hyperinsulinemic and hyperglycemic clamps (cDI) in obese pediatric subjects spanning the range of glucose tolerance. STUDY DESIGN: Overweight/obese adolescents (n = 185) with varying glucose tolerance (87 normal, 54 impaired, 31 with type 2 diabetes, and 13 with type 1 diabetes) completed an OGTT and both a hyperinsulinemic-euglycemic and a hyperglycemic clamp study. Indices of insulin sensitivity and ß-cell function were calculated, and 4 different oDI estimates were calculated as the products of insulin and C-peptide-based sensitivity and secretion indices. RESULTS: Mirroring the differences across groups by cDI, the oDI estimates were greatest in normal glucose tolerance adolescents and lowest in type 2 diabetes mellitus and obese with type 1 diabetes mellitus adolescents. The insulin-based oDI estimates correlated with cDI overall (r ≥ 0.74, P < .001) and within each glucose tolerance group (r ≥ 0.40, P < .001). Also, oDI and cDI predicted 2-hour OGTT glucose similarly. CONCLUSIONS: The oDI is a simple surrogate estimate of ß-cell function relative to insulin sensitivity that can be applied to obese adolescents with varying glucose tolerance in large-scale epidemiological studies where the applicability of clamp studies is limited due to feasibility, cost, and labor intensiveness.

Comparison of different definitions of pediatric metabolic syndrome: relation to abdominal adiposity, insulin resistance, adiponectin, and inflammatory biomarkers.

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.

Waist circumference, blood pressure, and lipid components of the metabolic syndrome.

OBJECTIVES: To examine whether waist circumference (WC) predicts blood pressure (BP) and lipid components of the metabolic syndrome independent of body mass index (BMI) percentile in youths. STUDY DESIGN: The study group comprised 70 African-American youths and 97 Caucasian youths. Outcome measures included BP, lipid profile, and abdominal adipose tissue (AT). RESULTS: Both BMI percentile and WC were significantly (P < .05) associated with daytime and nighttime systolic and diastolic BP, triglycerides (TG), high-density lipoprotein (HDL), and TG/HDL ratio independent of race. In African-Americans and Caucasians, WC remained a significant (P < .05) correlate of daytime (r = .50 and .59, respectively) and nighttime (r = .49 and .62, respectively) systolic BP, and in Caucasians, TG, HDL, TG/HDL, and very-low-density lipoprotein after controlling for BMI percentile. After accounting for age, sex, and race, the addition of WC to BMI percentile increased the variance (R(2)) in systolic BP by 15% (P < .05). The inclusion of WC with BMI percentile explained an additional 3% and 7% of the variance in TG and HDL, respectively (P < .05). CONCLUSIONS: The prediction of childhood obesity-related health risks is significantly improved by the inclusion of WC in addition to BMI percentile. This observation supports the notion that WC should be included in the evaluation of childhood obesity along with BMI percentile to identify those at increased health risks due to excess abdominal fat.

Waist circumference is an independent predictor of insulin resistance in black and white youths.

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.