SoJung Lee

Effects of Exercise Modality on Insulin Resistance and Functional Limitation in Older Adults: A Randomized Controlled Trial

BACKGROUND Authorities advocate that resistance and aerobic exercise are essential for reducing risk factors for chronic disease and disability in older adults. However, the incremental effects of combined resistance and aerobic exercise compared with either modality alone on risk factors for disease and disability is generally unknown. METHODS Participants were 136 sedentary, abdominally obese older men and women recruited from September 30, 2002, through November 15, 2006, at Queens University. Participants were randomized to 1 of the following 4 groups for 6 months: resistance exercise, aerobic exercise, resistance and aerobic exercise (combined exercise), or nonexercise control. Primary outcomes were analyzed by an intent-to-treat model and included changes in insulin resistance by hyperinsulinemic-euglycemic clamp and functional limitation using the average change in 4 tests combined (average z score). RESULTS After controlling for age, sex, and baseline value, insulin resistance improved compared with controls in the aerobic exercise and the combined exercise groups but not in the resistance exercise group. Improvement (mean [SE]) in the combined exercise group was greater than in the resistance exercise group (9.2 [1.3] vs 1.8 [1.3] mg/mL/microIU per kilogram of skeletal muscle per minute x100 [P < .001]) but not in the aerobic exercise group (9.2 [1.3] vs 6.5 [1.3] mg/mL/microIU per kilogram of skeletal muscle per minute x100 [P = .46]). Functional limitation improved significantly in all groups compared with the control group. Improvement in the combined exercise group was greater than in the aerobic exercise group (0.5 [0.1] vs -0.0 [0.1]; standard units, z score [P = .003]) but not in the resistance exercise group. Improvement in the resistance exercise group was not different from the aerobic exercise group. CONCLUSION The combination of resistance and aerobic exercise was the optimal exercise strategy for simultaneous reduction in insulin resistance and functional limitation in previously sedentary, abdominally obese older adults. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00520858.

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.

Effects of aerobic versus resistance exercise without caloric restriction on abdominal fat, intrahepatic lipid, and insulin sensitivity in obese adolescent boys: a randomized, controlled trial.

The optimal exercise modality for reductions of abdominal obesity and risk factors for type 2 diabetes in youth is unknown. We examined the effects of aerobic exercise (AE) versus resistance exercise (RE) without caloric restriction on abdominal adiposity, ectopic fat, and insulin sensitivity and secretion in youth. Forty-five obese adolescent boys were randomly assigned to one of three 3-month interventions: AE, RE, or a nonexercising control. Abdominal fat was assessed by magnetic resonance imaging, and intrahepatic lipid and intramyocellular lipid were assessed by proton magnetic resonance spectroscopy. Insulin sensitivity and secretion were evaluated by a 3-h hyperinsulinemic-euglycemic clamp and a 2-h hyperglycemic clamp. Both AE and RE prevented the significant weight gain that was observed in controls. Compared with controls, significant reductions in total and visceral fat and intrahepatic lipid were observed in both exercise groups. Compared with controls, a significant improvement in insulin sensitivity (27%) was observed in the RE group. Collapsed across groups, changes in visceral fat were associated with changes in intrahepatic lipid (r = 0.72) and insulin sensitivity (r = −0.47). Both AE and RE alone are effective for reducing abdominal fat and intrahepatic lipid in obese adolescent boys. RE but not AE is also associated with significant improvements in insulin sensitivity.

Metabolomic Profiling of Fatty Acid and Amino Acid Metabolism in Youth With Obesity and Type 2 Diabetes: Evidence for enhanced mitochondrial oxidation

OBJECTIVE We compared acylcarnitine (AcylCN) species, common amino acid and fat oxidation (FOX) byproducts, and plasma amino acids in normal weight (NW; n = 39), obese (OB; n = 64), and type 2 diabetic (n = 17) adolescents. RESEARCH DESIGN AND METHODS Fasting plasma was analyzed by tandem mass spectrometry, body composition by dual energy X-ray absorptiometry and computed tomography, and total-body lipolysis and substrate oxidation by [2H5]glycerol and indirect calorimetry, respectively. In vivo insulin sensitivity (IS) was assessed with a 3-h hyperinsulinemic-euglycemic clamp. RESULTS Long-chain AcylCNs (C18:2-CN to C14:0-CN) were similar among the three groups. Medium- to short-chain AcylCNs (except C8 and C10) were significantly lower in type 2 diabetes compared with NW, and when compared with OB, C2-, C6-, and C10-CN were lower. Amino acid concentrations were lower in type 2 diabetes compared with NW. Fasting lipolysis and FOX were higher in OB and type 2 diabetes compared with NW, and the negative association of FOX to C10:1 disappeared after controlling for adiposity, Tanner stage, and sex. IS was lower in OB and type 2 diabetes with positive associations between IS and arginine, histidine, and serine after adjusting for adiposity, Tanner stage, and sex. CONCLUSIONS These metabolomics results, together with the increased rates of in vivo FOX, are not supportive of defective fatty acid or amino acid metabolism in obesity and type 2 diabetes in youth. Such observations are consistent with early adaptive metabolic plasticity in youth, which over time—with continued obesity and aging—may become dysfunctional, as observed in adults.

Vitamin D Status, Adiposity, and Lipids in Black American and Caucasian Children

OBJECTIVE The aim of the study was to examine the relationship between vitamin D status, total and abdominal adiposity, and lipids in black and white children. METHODS Plasma 25-hydroxyvitamin D [25(OH)D], adiposity [body mass index (BMI), percentage of total body fat, visceral adipose tissue (VAT), sc adipose tissue (SAT)], and fasting lipids were assessed in healthy obese and nonobese 8- to 18-yr-old black and white children. RESULTS We studied 237 children (mean ± sd age, 12.7 ± 2.2 yr; 47% black, 47% obese, and 43% male). Mean 25(OH)D concentration for the entire cohort was 19.4 ± 7.4 ng/ml. The majority of the children were vitamin D deficient [25(OH)D < 20 ng/ml; 73% blacks, 40% whites]. Plasma 25(OH)D was associated inversely with BMI, BMI percentile, percentage of total body fat, VAT, and SAT and positively with HDL cholesterol in the entire cohort. VAT was higher in vitamin D-deficient whites, and SAT was higher in vitamin D-deficient blacks compared with their respective vitamin D-nondeficient counterparts. Race, season, pubertal status, and VAT were independent significant predictors of 25(OH)D status. CONCLUSIONS In black and white youth examined together, lower levels of 25(OH)D are associated with higher adiposity measures and lower HDL. Furthermore, vitamin D deficiency is associated with higher VAT in whites and greater SAT in blacks. Besides therapeutic interventions to correct the high rates of vitamin D deficiency in youth, benefits of vitamin D optimization on adiposity measures and lipid profile need to be explored.

Insulin Resistance: Link to the components of the metabolic syndrome and biomarkers of endothelial dysfunction in youth

OBJECTIVE—We examined the relationship of in vivo insulin sensitivity to the components of the metabolic syndrome and biomarkers of endothelial dysfunction in youth. RESEARCH DESIGN AND METHODS—Subjects included 216 youths (8–19 years of age) who participated in a 3-h hyperinsulinemic-euglycemic clamp. RESULTS—Independent of race, the frequencies of central obesity, high triglycerides, low HDL, high blood pressure, impaired fasting glucose, and impaired glucose tolerance were significantly higher (P < 0.05) in the lowest versus highest quartile of insulin sensitivity. BMI, abdominal adiposity, systolic blood pressure, and triglycerides increased and adiponectin and HDL decreased significantly (P for trend for all <0.05), with decreasing insulin sensitivity in both races. After controlling for BMI, insulin resistance remained associated (P < 0.05) with visceral adipose tissue in both races (P for trend = 0.01 in blacks and 0.08 in whites). In whites but not blacks, lower insulin sensitivity was associated (P < 0.05) with higher intercellular adhesion molecule-1 (ICAM-1) and E-selectin levels; however, these relationships did not remain significant (P > 0.05) once visceral adipose tissue was controlled for. CONCLUSIONS—The prevalence of the individual components of metabolic syndrome increases with decreasing insulin sensitivity in black and white youth. In whites but not blacks, insulin resistance is associated with increased circulating endothelial biomarkers. It remains to be determined if lower abdominal adiposity and triglycerides in blacks underlies the racial differences in risk translation.

From Pre-Diabetes to Type 2 Diabetes in Obese Youth: Pathophysiological characteristics along the spectrum of glucose dysregulation

OBJECTIVE Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) are considered pre-diabetes states. There are limited data in pediatrics in regard to their pathophysiology. We investigated differences in insulin sensitivity and secretion among youth with IFG, IGT, and coexistent IFG/IGT compared with those with normal glucose tolerance (NGT) and type 2 diabetes. RESEARCH DESIGN AND METHODS A total of 24 obese adolescents with NGT, 13 with IFG, 29 with IGT, 11 with combined IFG/IGT, and 30 with type 2 diabetes underwent evaluation of hepatic glucose production ([6,6-2H2]glucose), insulin-stimulated glucose disposal (Rd, euglycemic clamp), first- and second-phase insulin secretion (hyperglycemic clamp), body composition (dual-energy X-ray absorptiometry), abdominal adiposity (computed tomography), and substrate oxidation (indirect calorimetry). RESULTS Adolescents with NGT, pre-diabetes, and type 2 diabetes had similar body composition and abdominal fat distribution. Rd was lower (P = 0.009) in adolescents with type 2 diabetes than in those with NGT. Compared with adolescents with NGT, first-phase insulin was lower in those with IFG, IGT, and IFG/IGT with further deterioration in those with type 2 diabetes (P < 0.001), and β-cell function relative to insulin sensitivity (glucose disposition index [GDI]) was also lower in those with IFG, IGT, and IFG/IGT (40, 47, and 47%, respectively), with a further decrease (80%) in those with type 2 diabetes (P < 0.001). GDI was the major determinant of fasting and 2-h glucose levels. CONCLUSIONS Obese adolescents who show signs of glucose dysregulation, including abnormal fasting glucose, glucose intolerance or both, are more likely to have impaired insulin secretion rather than reduced insulin sensitivity. Given the impairment in insulin secretion, they are at high risk for progression to type 2 diabetes. Further deterioration in insulin sensitivity or secretion may enhance the risk for this progression.

Race and Gender Differences in the Relationships Between Anthropometrics and Abdominal Fat in Youth

Objective: We examined the influence of race and gender on abdominal adipose tissue (AT) distribution for a given anthropometric measure including waist circumference (WC), waist‐to‐hip ratio (WHR) and waist‐to‐height (W/Ht) in youth.

In Vivo Insulin Sensitivity and Secretion in Obese Youth What are the differences between normal glucose tolerance, impaired glucose tolerance, and type 2 diabetes?

OBJECTIVE—Impaired glucose tolerance (IGT) represents a pre-diabetic state. Controversy continues in regards to its pathophysiology. The aim of this study was to investigate the differences in insulin sensitivity (IS) and secretion in obese adolescents with IGT compared with those with normal glucose tolerance (NGT) and type 2 diabetes. RESEARCH DESIGN AND METHODS—A total of 12 obese adolescents with NGT, 19 with IGT, and 17 with type 2 diabetes underwent evaluation of insulin sensitivity (3-h hyperinsulinemic [80mu/m2/min]–euglycemic clamp), first-phase insulin and second-phase insulin secretion (2-h hyperglycemic clamp), body composition, and abdominal adiposity. Glucose disposition index (GDI) was calculated as the product of first-phase insulin × insulin sensitivity. RESULTS—Insulin-stimulated glucose disposal was significantly lower in subjects with type 2 diabetes compared with subjects with NGT and IGT, with no difference between the latter two. However, compared with youth with NGT, youth with IGT have significantly lower first-phase insulin and C-peptide levels and GDI (P = 0.012), whereas youth with type 2 diabetes have an additional defect in second-phase insulin. Fasting and 2-h glucose correlated with GDI (r = −0.68, P < 0.001 and r = −0.73, P < 0.001, respectively) and first-phase insulin but not with insulin sensitivity. CONCLUSIONS—Compared with youth with NGT, obese adolescents with IGT have evidence of a β-cell defect manifested in impaired first-phase insulin secretion, with a more profound defect in type 2 diabetes involving both first- and second-phase insulin. GDI shows a significantly declining pattern: it is highest in NGT, intermediate in IGT, and lowest in type 2 diabetes. Such data suggest that measures to prevent progression or conversion from pre-diabetes to type 2 diabetes should target improvement in β-cell function.

Surrogate Estimates of Insulin Sensitivity in Obese Youth along the Spectrum of Glucose Tolerance from Normal to Prediabetes to Diabetes

CONTEXT In epidemiological studies of childhood obesity, simple and reliable surrogate estimates of insulin sensitivity are needed because the gold standard, the hyperinsulinemic-euglycemic clamp, is not feasible on a large scale. OBJECTIVE To examine the correlation of fasting and oral glucose tolerance test (OGTT)-derived surrogate indices of insulin sensitivity with the hyperinsulinemic-euglycemic clamp in obese adolescents with normal glucose tolerance, prediabetes, and diabetes. PATIENTS AND DESIGN A total of 188 overweight/obese adolescents (10 to <20 yr old) who completed a standard 2-h OGTT and 3-h hyperinsulinemic-euglycemic clamp were included. Fasting-derived surrogates [fasting glucose (G(F)), fasting insulin (I(F)), 1/I(F), G(F)/I(F), homeostasis model assessment and quantitative insulin sensitivity check index] and OGTT-derived surrogates [whole-body insulin sensitivity index and the ratio of glucose and insulin areas under the curve (Gluc(AUC)/Ins(AUC))] were calculated. MAIN OUTCOME MEASURES We evaluated the correlations between the clamp-measured insulin sensitivity and the surrogate estimates and area under the receiver operating characteristic curves. RESULTS Fasting indices (1/I(F), G(F)/I(F), homeostasis model assessment of insulin sensitivity, and quantitative insulin sensitivity check index) correlated significantly with clamp insulin sensitivity (r = 0.82, 0.78, 0.81, and 0.80, respectively), with lower correlations between the OGTT surrogates and clamp (whole-body insulin sensitivity index, r = 0.77; Gluc(AUC)/Ins(AUC), r = 0.62). The area under the receiver operating characteristic curves was more than or equal to 0.94 for all surrogates except Gluc(AUC)/Ins(AUC.) Across quartiles of clamp-measured insulin sensitivity, there was a significant overlap in individual values of I(F), 1/I(F), and G(F)/I(F). CONCLUSION In obese adolescents with normal or impaired glucose tolerance or diabetes, OGTT-derived surrogates do not offer any advantage over the simpler fasting indices, which correlate strongly with clamp insulin sensitivity. Surrogate indices of insulin sensitivity could be used in epidemiological studies but not to define insulin resistance in individual patients or research subjects.