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ABSTRACT: Prepubertal African American (AA) youth compared with their Caucasian (C) peers have higher insulin secretion which correlates positively with free fatty acid (FFA) concentration. In our continued efforts to explain the racial disparity in insulinemia, and because FFAs modulate insulin secretion, we hypothesized that AA youth would have a greater response to FFA-induced β-cell insulin secretion than C youth. We compared the short-term effects of FFA elevation on fasting and glucose-stimulated C-peptide-modeled insulin secretion in prepubertal normal-weight AA versus C peers during a 2-hour hyperglycemic clamp (12.5mmol/L) on two occasions: a) infusion of normal saline (NS) and b) infusion of 20% intralipid (IL). During IL infusion, insulin sensitivity (IS) declined comparably in AA and C youth. Glucose sensitivity of 1(st) and 2(nd) phase insulin secretion showed a significant condition x race interaction being higher in AA youth. Disposition index, β-cell function relative to IS, declined with IL infusion in both AA and C youth with a significantly greater decrease in Cs compared with AAs. In conclusion, both AA and C prepubertal youth demonstrated a decline in β-cell function relative to IS during IL infusion, indicative of acute lipotoxicity. The greater decline in C youth compared with AAs may suggest that either C youth are more susceptible to β-cell lipotoxicity than AA youth, or alternatively, AA youth are hypersensitive to FFA stimulation of β-cell insulin secretion consistent with our theory.
Diabetes 04/2013; · 8.29 Impact Factor
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ABSTRACT: OBJECTIVE: Although higher rates of depression are found among individuals with type 2 diabetes, it remains unknown if the presence of depressive symptoms is associated with heightened metabolic risk for the development of type 2 diabetes among youth. The objective of this study was to evaluate whether depressive symptoms in obese adolescents are associated with impaired β-cell function relative to insulin sensitivity [oral disposition index (oDI)] and/or dysglycemia or prediabetes, predictors of type 2 diabetes development. RESEARCH DESIGN AND METHODS: Fasting and oral glucose tolerance test (OGTT)-derived indices of glucose tolerance, insulin sensitivity, secretion, and oDI were evaluated in obese youth (n = 56, age 15.0 ± 1.6 yr, 68% female). The Children's Depression Inventory was utilized to determine depressive symptomatology. RESULTS: Despite no association between depressive symptoms and measures of adiposity, youth with higher depressive symptoms had (i) significantly higher fasting and stimulated glucose levels (13% higher glucose area under the OGTT curve), (ii) ∼50% lower oDI, and (iii) a 50% frequency of prediabetes. CONCLUSIONS: These data point to an important relationship between depressive symptoms and a heightened metabolic risk for type 2 diabetes in obese adolescents, including prediabetes and impairment in β-cell function relative to insulin sensitivity. While the directionality of these relationships is unknown, it should be determined if treating one disorder improves the other or vice versa.
Pediatric Diabetes 03/2013; · 2.16 Impact Factor
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ABSTRACT: Objective:Overweight/obese (OW/OB) African American (AA) adolescents have a more diabetogenic insulin secretion/sensitivity pattern compared with their American white (AW) peers. The present study investigated β-cell lipotoxicity to test whether increased free fatty acid (FFA) levels result in greater β-cell dysfunction in AA vs AW OW/OB adolescents.Research Design and Methods:Glucose-stimulated insulin secretion was modeled, from glucose and C-peptide concentrations during a 2-hour hyperglycemic (225 mg/dL) clamp in 22 AA and 24 AW OW/OB adolescents, on 2 occasions after a 12-hour overnight infusion of either normal saline or intralipid (IL) in a random sequence. β-Cell function relative to insulin sensitivity, the disposition index (DI), was examined during normal saline and IL conditions. Substrate oxidation was evaluated with indirect calorimetry and body composition and abdominal adiposity with dual-energy X-ray absorptiometry and magnetic resonance imaging at L4-L5, respectively.Results:Age, sex, body mass index, total and sc adiposity were similar between racial groups, but visceral adiposity was significantly lower in AAs. During IL infusion, FFAs and fat oxidation increased and insulin sensitivity decreased similarly in AAs and AWs. β-Cell glucose sensitivity of first- and second-phase insulin secretion did not change significantly during IL infusion in either group, but DI in each phase decreased significantly and similarly in AAs and AWs.Conclusions:Overweight/obese AA and AW adolescents respond to an overnight fat infusion with significant declines in insulin sensitivity, DI, and β-cell function relative to insulin sensitivity, suggestive of β-cell lipotoxicity. However, contrary to our hypothesis, there does not seem to be a race differential in β-cell lipotoxicity. Longer durations of FFA elevation may unravel such race-related contrasts.
The Journal of clinical endocrinology and metabolism 03/2013; · 6.50 Impact Factor
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ABSTRACT: OBJECTIVE
To 1) determine if plasma 25-hydroxyvitamin D (25[OH]D) concentrations differ among obese youth with normal glucose tolerance (NGT) versus prediabetes versus type 2 diabetes, and 2) assess the relationships between 25(OH)D and in vivo insulin sensitivity and β-cell function in this cohort.RESEARCH DESIGN AND METHODS
Plasma 25(OH)D concentrations were examined in banked specimens in 9- to 20-year-old obese youth (n = 175; male 42.3%, black 46.3%) (NGT, n = 105; impaired glucose tolerance [IGT], n = 43; type 2 diabetes, n = 27) who had in vivo insulin sensitivity and secretion measured by hyperinsulinemic-euglycemic and hyperglycemic clamp techniques and had an assessment of total body composition and abdominal adiposity.RESULTSThe mean age and BMI of the subjects were 14.3 ± 2.1 years and 35.7 ± 5.6 kg/m(2), respectively. BMI, plasma 25(OH)D, and the proportion of vitamin D-deficient and -insufficient children did not differ across the three groups. Furthermore, there was no association between 25(OH)D and in vivo insulin sensitivity or β-cell function relative to insulin sensitivity (disposition index) in all groups combined or in each group separately.CONCLUSIONS
Our data in obese youth show 1) no differences in plasma 25(OH)D concentrations across the glucose tolerance groups, and 2) no relationship between 25(OH)D and in vivo insulin sensitivity and β-cell function relative to insulin sensitivity in any of the groups. It remains uncertain if enhancement of the vitamin D status could improve pathophysiological mechanisms of prediabetes and type 2 diabetes in obese youth.
Diabetes care 01/2013; · 8.09 Impact Factor
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ABSTRACT: Context:In longitudinal studies of adults, elevated amino acid (AA) concentrations predicted future type 2 diabetes mellitus (T2DM).Objective:The aim of the present investigation was to examine whether increased plasma AA concentrations are associated with impaired β-cell function relative to insulin sensitivity [i.e. disposition index (DI)], a predictor of T2DM development.Design, Setting, and Participants:Metabolomic analysis for fasting plasma AAs was performed by tandem mass spectrometry in 139 normal-weight and obese adolescents with and without dysglycemia. First-phase insulin secretion was evaluated by a hyperglycemic (∼225 mg/dl) clamp and insulin sensitivity by a hyperinsulinemic-euglycemic clamp. DI was calculated as the product of first-phase insulin and insulin sensitivity.Results:DI was positively associated with branched-chain AAs (leucine/isoleucine and valine; r = 0.27 and 0.29, P = 0.001), neutrally transported AAs (phenylalanine and methionine; r = 0.30 and 0.35, P < 0.001), basic AAs (histidine and arginine; r = 0.28 and 0.23, P ≤ 0.007), serine (r = 0.35, P < 0.001), glycine (r = 0.26, P = 0.002), and branched-chain AAs-derived intermediates C3, C4, and C5 acylcarnitine (range r = 0.18-0.19, P ≤ 0.04).Conclusion:In youth, increased plasma AA concentrations are not associated with a heightened metabolic risk profile for T2DM; rather, they are positively associated with β-cell function relative to insulin sensitivity. These contrasting observations between adults and youth may be a reflection of developmental differences along the lifespan dependent on the combined impact of the aging process together with the impact of progressive obesity.
The Journal of clinical endocrinology and metabolism 09/2012; · 6.50 Impact Factor
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ABSTRACT: OBJECTIVE: In adults, type 2 diabetes (T2DM) is characterized with progressive deterioration in insulin secretion. Data are scanty in youth. We investigated prospectively the change in β-cell function and in insulin sensitivity in youth with T2DM. RESEARCH DESIGN AND METHODS: Six adolescents with T2DM [hemoglobin A1c (HbA1c) 6.6 ± 1.0%] underwent evaluation of hepatic glucose production (HGP; [6,6-(2) H(2) ] glucose), insulin-stimulated glucose disposal (Rd; hyperinsulinemic-euglycemic clamp), first- and second-phase insulin/C-peptide secretion (hyperglycemic clamp), body composition dual energy X-ray absorptiometry (DEXA), and abdominal adiposity (computed tomography) within 3 yr of the diagnosis of diabetes and after 12-16 months of follow-up. RESULTS: Weight, body mass index (37.1 ± 6.9), HbA1c (6.3 ± 0.7%), HGP (2.8 ± 1.2 mg/kg/min), and Rd (4.9 ± 3.4 mg/kg/min) did not change significantly from baseline. However, first-phase insulin and C-peptide declined (152.6 ± 261.2 vs. 75.9 ± 108.5 μU/mL, p = 0.028; 8.0 ± 6.3 vs. 5.9 ± 4.4 ng/mL, p = 0.048, respectively) with no significant change in second-phase insulin/C-peptide. The rate of decline in β-cell function was ∼20% per year. CONCLUSIONS: After a median duration of 20 months of diabetes, youth with T2DM manifest a rapid decline in β-cell function with no significant changes in peripheral or hepatic insulin sensitivity. Interventions to retard this deterioration in β-cell function should be investigated.
Pediatric Diabetes 08/2012; · 2.16 Impact Factor
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ABSTRACT: OBJECTIVE
The recommended HbA(1c) diagnostic categories remain controversial and their utility in doubt in pediatrics. We hypothesized that alterations in the pathophysiologic mechanisms of type 2 diabetes may be evident in the American Diabetes Association recommended at-risk/prediabetes category (HbA(1c) 5.7 to <6.5%).RESEARCH DESIGN AND METHODS
We compared in vivo hepatic and peripheral insulin sensitivity by [6,6-(2)H(2)] glucose and a 3-h hyperinsulinemic-euglycemic clamp and β-cell function by a 2-h hyperglycemic clamp (∼225 mg/dL) in overweight/obese (BMI ≥85th percentile) adolescents with prediabetes (HbA(1c) 5.7 to <6.5%) (n = 160) to those with normal HbA(1c) (<5.7%) (n = 44). β-Cell function was expressed relative to insulin sensitivity (i.e., the disposition index = insulin sensitivity × first-phase insulin).RESULTSIn the prediabetes versus normal HbA(1c) category, fasting glucose, insulin, and oral glucose tolerance test (OGTT) area under the curve for glucose and insulin were significantly higher; hepatic and peripheral insulin sensitivity were lower; and β-cell function relative to insulin sensitivity was lower (366 ± 48 vs. 524 ± 25 mg/kg/min; P = 0.005). A total of 27% of youth in the normal HbA(1c) category and 41% in the prediabetes HbA(1c) category had dysglycemia (impaired fasting glucose and/or impaired glucose tolerance) by a 2-h OGTT.CONCLUSIONS
Overweight/obese adolescents with HbA(1c) in the at-risk/prediabetes category demonstrate impaired β-cell function relative to insulin sensitivity, a metabolic marker for heightened risk of type 2 diabetes. Thus, HbA(1c) may be a suitable screening tool in large-scale epidemiological observational and/or interventional studies examining the progression or reversal of type 2 diabetes risk.
Diabetes care 08/2012; · 8.09 Impact Factor
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ABSTRACT: OBJECTIVES: To determine if the ratio of triglycerides to high-density lipoprotein cholesterol (TG/HDL) and non-HDL cholesterol concentration could identify youth with small dense low-density lipoprotein (LDL). STUDY DESIGN: One hundred forty-one (75 black and 66 white) overweight adolescents (9 to <18 years) had a fasting measurement of plasma lipids and LDL particle concentrations and size. Receiver operating characteristic curves were used to indicate the ability of different TG/HDL ratios and non-HDL cholesterol concentrations to identify overweight youth with atherogenic LDL concentration and size. RESULTS: Youth with a TG/HDL ratio of ≥3 vs <3 had higher concentrations of small dense LDL (1279.5 ± 60.1 vs 841.8 ± 24.2 nmol/L, P < .001) and smaller LDL particle size (20.3 ± 0.1 vs 21.2 ± 0.1 nm, P < .001). In receiver operating characteristic analyses a TG/HDL cut-point of 3 best predicted LDL concentration in white youth, and 2.5 in black youth. Non-HDL cholesterol cut-point of 120 mg/dL and 145 mg/dL predicted LDL particle concentration in white and in black youth, respectively. TG/HDL ratio with body mass index or waist circumference explained 71% and 79% of the variance, respectively, in total small LDL. CONCLUSIONS: TG/HDL ratio and non-HDL cholesterol can identify overweight youth with atherogenic LDL particles. These easily obtained clinical lipid markers, in combination with body mass index and waist circumference, could be cost effective, in observational or interventional studies, for screening and follow-up of youth at heightened risk for atherogenic LDL.
The Journal of pediatrics 07/2012; · 4.02 Impact Factor
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ABSTRACT: 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.
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 [(2)H(5)]glycerol and indirect calorimetry, respectively. In vivo insulin sensitivity (IS) was assessed with a 3-h hyperinsulinemic-euglycemic clamp.
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.
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.
Diabetes care 03/2012; 35(3):605-11. · 8.09 Impact Factor
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ABSTRACT: To examine the relationships between plasma 25-hydroxyvitamin D [25(OH)D] and in vivo insulin sensitivity and β-cell function relative to insulin sensitivity, disposition index (DI), in black and white youth.
Plasma 25(OH)D concentrations were analyzed in banked specimens in healthy youth aged 8 to 18 years who had existing data on hyperinsulinemic-euglycemic and hyperglycemic clamp to assess insulin sensitivity and secretion, and measurements of body composition, and abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT).
A total of 183 research volunteers (mean ± SD; age, 12.6 ± 2.2 years; 98 white, 98 male, 92 obese) were studied. Analysis of HbA(1c), fasting glucose and insulin, insulin sensitivity, and DI across quartiles of plasma 25(OH)D revealed no differences among whites. In blacks, the observed significance of higher insulin sensitivity and DI in the highest quartile of 25(OH)D disappeared after adjusting for any of the adiposity measures (BMI or fat mass or VAT or SAT). The difference in insulin sensitivity (9.4 ± 1.2 vs. 5.6 ± 0.5 mg/kg/min per μU/mL; P = 0.006) between 25(OH)D nondeficient (≥20 ng/mL) versus deficient (<20 ng/mL) black youth also was negated when adjusted for adiposity.
In healthy youth, plasma 25(OH)D concentrations bear no independent relationship to parameters of glucose homeostasis and in vivo insulin sensitivity and β-cell function relative to insulin sensitivity. It remains to be determined whether in youth with dysglycemia the relationships are different and whether vitamin D optimization enhances insulin sensitivity and β-cell function.
Diabetes care 03/2012; 35(3):627-33. · 8.09 Impact Factor
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ABSTRACT: Evidence supports the importance of parental involvement for youth's ability to manage weight. This study utilized the stages of change (SOC) model to assess readiness to change weight control behaviors as well as the predictive value of SOC in determining BMI outcomes in forty adolescent-parent dyads (mean adolescent age = 15 ± 1.84 (13-20), BMI = 37 ± 8.60; 70% white) participating in a weight management intervention for adolescent females with polycystic ovary syndrome (PCOS). Adolescents and parents completed a questionnaire assessing their SOC for the following four weight control domains: increasing dietary portion control, increasing fruit and vegetable consumption, decreasing dietary fat, and increasing usual physical activity. Linear regression analyses indicated that adolescent change in total SOC from baseline to treatment completion was not predictive of adolescent change in BMI from baseline to treatment completion. However, parent change in total SOC from baseline to treatment completion was predictive of adolescent change in BMI, (t(24) = 2.15, p = 0.043). Findings support future research which carefully assesses adolescent and parent SOC and potentially develops interventions targeting adolescent and parental readiness to adopt healthy lifestyle goals.
Journal of obesity 01/2012; 2012:298067.
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ABSTRACT: To explore associations between measures of obstructive sleep apnea (OSA) and sleep quality, anthropometrics, and neurocognitive functioning in severely obese adolescents.
This was a cross-sectional pilot study performed at an academic medical center in 37 severely obese (body mass index [BMI] >97th percentile) adolescents. Study evaluations included polysomnography, BMI, waist circumference, and standardized neurocognitive tests to assess memory, executive functioning, psychomotor efficiency, academic achievement, and an approximation of full-scale IQ. Outcome data were evaluated categorically, based on clinical criteria for the diagnosis of OSA, and continuously to quantify associations between sleep parameters, anthropometrics, and neurocognitive test results.
Sleep fragmentation and poorer sleep quality were associated with reduced psychomotor efficiency, poorer memory recall, and lower scores on standardized academic tests. Having evidence of OSA was associated with lower math scores, but not with other neurocognitive measures. BMI and waist circumference were negatively associated with oxygen saturation.
Our pilot study findings suggest that sleep fragmentation and poorer sleep quality have implications for neurocognitive functioning in obese adolescents. The epidemic of childhood obesity has dire implications, not only for increasing cardiometabolic pathology, but also for possibly promoting less readily apparent neurologic alterations associated with poor sleep quality.
The Journal of pediatrics 12/2011; 160(5):732-5. · 4.02 Impact Factor
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ABSTRACT: Little is known about racial differences in androgen levels among obese children. The objective of this pilot study was to compare basal and stimulated androgen levels in a cross-sectional sample of obese black and white pubertal females. STUDY DESIGN, SETTING, AND PARTICIPANTS: This was cross-sectional study of obese (body mass index ≥ 95th percentile) but otherwise healthy female adolescents (10 black and 12 white; age range 8.8-13.9 y) who underwent adrenocorticotropic hormone stimulation testing at an academic medical center as part of a protocol for the study of obesity-related conditions.
Basal and stimulated androgen levels.
White and black participants were similar with regard to pubertal stage, body mass index, percentage body fat, and fasting glucose and insulin levels. Black girls had lower stimulated levels of 17-hydroxyprogesterone, and the differences between basal and stimulated levels of 17-hydroxyprogesterone and androstenedione were lower in black girls. Body mass index was negatively correlated with stimulated cortisol in blacks only (r = -0.69, P = .03).
There appear to be race-related differences in stimulated androgen levels in obese adolescent females. These differences deserve further study, as measurements of androgen levels are commonly used in clinical practice and research.
Journal of pediatric and adolescent gynecology 11/2011; 25(1):82-5. · 0.90 Impact Factor
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ABSTRACT: Non-diabetic African American (AA) youth have an upregulated insulin secretion relative to insulin sensitivity (IS) compared with their American White (AW) peers. We investigated if similar racial differences exist in youth with T2DM.
Fourteen AAs and 14 AWs T2DM adolescents underwent evaluation of IS and clearance (hyperinsulinemic-euglycemic clamp), first- and second-phase insulin and C-peptide secretion (hyperglycemic clamp); body composition (DEXA); and abdominal adiposity (CT).
AA and AW T2DM had similar HbA1c, diabetes duration, BMI, and % body fat, with lower visceral fat in AAs (p = 0.013). While insulin-stimulated glucose disposal was similar in AA and AW (7.5 ± 1.0 vs. 7.3 ± 0.9 mg/kg FFM/min), IS tended to be lower (2.5 ± 0.4 vs. 3.8 ± 0.6 mg/kg FFM/min per µU/mL, p = 0.081). First-phase insulin (175.7 ± 52.9 vs. 66.6 ± 10.8 µU/mL, p = 0.01) and second-phase insulin (236.2 ± 40.7 vs. 105.1 ± 17.9 µU/mL, p = 0.008), and first-phase C-peptide (8.2 ± 1.2 vs. 5.0 ± 0.3 ng/mL, p = 0.02) and second-phase C-peptide (10.8 ± 0.9 vs. 7.6 ± 0.6 ng/mL, p = 0.012) were higher in AA. β-Cell function relative to IS was higher in AA vs. AW (259.5 ± 35.3 vs. 168.8 ± 25.1 mg/kg FFM/min, p = 0.043).
Racial differences in insulin secretion can be demonstrated with the clamp technique in obese adolescents with T2DM. Similar to non-diabetic youth, AA adolescents with T2DM compared with their AW counterparts have an upregulated β-cell function relative to IS, the reasons for which remain to be investigated.
Pediatric Diabetes 09/2011; 13(3):259-65. · 2.16 Impact Factor
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ABSTRACT: Overweight in youth is associated with the risk of developing type 2 diabetes. We hypothesized that β-cell function relative to insulin sensitivity decreases with increasing 2-h glucose levels based on an oral glucose tolerance test (OGTT) in overweight youth. RESEARCH DESIGN AND METHODS A total of 147 overweight (BMI ≥85th percentile for age and sex) youth, aged 8 to <20 years, undertook three tests: 1) a 3-h hyperinsulinemic-euglycemic clamp; 2) a 2-h hyperglycemic clamp; and 3) a 2-h OGTT. Participants were categorically assigned to five groups according to their OGTT 2-h plasma glucose level, ranging from <120 to ≥200 mg/dL. β-Cell function relative to insulin sensitivity, assessed by clamp disposition index (DI) and oral disposition index (DI(O)), were compared among groups.
Insulin sensitivity, first-phase insulin, and DI declined significantly as 2-h glucose concentrations increased. The highest DI was found in youth with 2-h plasma glucose concentrations <120 mg/dL, with a significant decline of ~40% in those with glucose concentrations between 120 and <140 mg/dL, and an ~75% decline, the lowest DI, in youth with glucose concentrations ≥200 mg/dL. Data were similar with regard to the OGTT DI(O).
These data in overweight youth demonstrate that impairment in insulin secretion relative to insulin sensitivity is apparent even with normal glucose tolerance. Below the current cutoff of 140 mg/dL for impaired glucose tolerance, there is a >30% decline in β-cell function relative to insulin sensitivity. Against this back drop of metabolically heightened risk for type 2 diabetes, preventive measures should target the β-cell alongside insulin sensitization.
Diabetes care 07/2011; 34(9):2033-40. · 8.09 Impact Factor
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ABSTRACT: Sleep-disordered breathing is associated with obesity, insulin resistance, and the metabolic syndrome in adults. Similar data in children is limited and conflicting. This pilot study examined the relationships between sleep-disordered breathing, visceral adiposity, and cardiometabolic risk factors in obese adolescents. Twenty obese (body mass index ≥ 95(th) percentile), otherwise healthy adolescents (age 14.9 ± 2 years) underwent polysomnogram studies, fasting lipid profile and oral glucose tolerance tests, and measures of body composition (dual-energy X-ray absorptiometry) and visceral adiposity (abdominal computed tomography). The severity of sleep-disordered breathing (as measured by apnea-hypopnea index) was positively associated with visceral adipose tissue (r = 0.73, p < 0.001) but not with other measures of body composition. After controlling for body mass index, the severity of sleep-disordered breathing was positively associated with markers of insulin resistance (homeostasis model assessment and fasting insulin). Further study to allow for critical assessment of the relationships between sleep-disordered breathing and cardiometabolic risk factors in obese youth remains necessary.
International journal of pediatric obesity: IJPO: an official journal of the International Association for the Study of Obesity 04/2011; 6(2):157-60. · 2.00 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
The Journal of clinical endocrinology and metabolism 03/2011; 96(5):1560-7. · 6.50 Impact Factor
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ABSTRACT: It is unknown whether measurement site of visceral adipose tissue (VAT) influences the relationship between VAT and associated health risk in youth and if so, whether ethnic differences exist in this relationship. We examined the influence of the measurement site of VAT on the relationships between VAT and metabolic syndrome (MetS) in African-American (AA) and American-White (AW) youth.
Healthy AA (n = 54) and AW (n = 54) children and adolescents (age: 8-18 yr; BMI: 15.3-42.5 kg/m(2)).
VAT mass was derived using a series of five transverse images measured by magnetic resonance imaging, extending from 5 cm below to 15 cm above L4-L5. MetS was defined using a modified IDF criteria.
In AA, VAT measure at 5 cm above L4-L5 (R(2) = 0.93) was most strongly (p < 0.05) correlated with VAT mass and was a significantly (p < 0.05) stronger correlate as compared to L4-L5 (R(2) = 0.84). In AW, VAT measures at 5 cm (R(2) = 0.93) and 10 cm (R(2) = 0.93) above L4-L5 were most strongly (p < 0.05) correlated with VAT mass; however, these were not stronger correlates as compared to L4-L5 (R(2) = 0.91). In AW, all VAT measures were significantly (p < 0.05) associated with an increased odds ratio (OR) for prevalent MetS, wherein the VAT mass [OR = 5.32(1.9-15.0)] and VAT at L4-L5[OR = 5.99(1.9-18.4)] were most strongly associated with MetS. In contrast, only VAT at 10 cm above L4-L5 [OR = 4.39 (1.1-18.1)] was significantly (p < 0.05) associated with MetS in AA.
In AA and AW youth, the measurement site for VAT has impact on the estimation of total VAT and the magnitude of the association with obesity-related health risks.
Pediatric Diabetes 12/2010; 12(3 Pt 2):250-7. · 2.16 Impact Factor
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ABSTRACT: 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.
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-(2)H(2)]glucose), insulin-stimulated glucose disposal (R(d), 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).
Adolescents with NGT, pre-diabetes, and type 2 diabetes had similar body composition and abdominal fat distribution. R(d) 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.
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.
Diabetes care 10/2010; 33(10):2225-31. · 8.09 Impact Factor
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ABSTRACT: We evaluated the efficacy of family-based, behavioral weight control in the management of severe pediatric obesity.
Participants were 192 children 8.0 to 12.0 years of age (mean +/- SD: 10.2 +/- 1.2 years). The average BMI percentile for age and gender was 99.18 (SD: 0.72). Families were assigned randomly to the intervention or usual care. Assessments were conducted at baseline, 6 months, 12 months, and 18 months. The primary outcome was percent overweight (percent over the median BMI for age and gender). Changes in blood pressure, body composition, waist circumference, and health-related quality of life also were evaluated. Finally, we examined factors associated with changes in child percent overweight, particularly session attendance.
Intervention was associated with significant decreases in child percent overweight, relative to usual care, at 6 months. Intent-to-treat analyses documented that intervention was associated with a 7.58% decrease in child percent overweight at 6 months, compared with a 0.66% decrease with usual care, but differences were not significant at 12 or 18 months. Small significant improvements in medical outcomes were observed at 6 and 12 months. Children who attended > or =75% of intervention sessions maintained decreases in percent overweight through 18 months. Lower baseline percent overweight, better attendance, higher income, and greater parent BMI reduction were associated with significantly greater reductions in child percent overweight at 6 months among intervention participants.
Intervention was associated with significant short-term reductions in obesity and improvements in medical parameters and conferred longer-term weight change benefits for children who attended > or =75% of sessions.
PEDIATRICS 10/2009; 124(4):1060-8. · 4.47 Impact Factor