Claudia M. Toledo-Corral

Association between the Metabolic Syndrome and Serum Cortisol in Overweight Latino Youth

OBJECTIVE The purpose of this report is to investigate the associations between metabolic syndrome (MS) and levels of morning serum cortisol in a cohort of overweight Latino youth. DESIGN Subjects were 205 overweight, Latino youth (age 8-13 yr, body mass index percentile > 85, family history positive for type 2 diabetes). Measures included body composition by dual-energy x-ray absorptiometry, intraabdominal adipose tissue (IAAT) by magnetic resonance imaging, insulin sensitivity by frequently sampled iv glucose tolerance test/minimal model, fasting lipids, and serum cortisol. RESULTS Children with MS had higher body mass index percentile, total body fat mass, and IAAT and lower insulin sensitivity than those without MS. Children with MS had higher morning serum cortisol levels, whether unadjusted (10.1 +/- 3.7 vs. 9.0 +/- 2.8 microg/dl, P < 0.05) or after adjusting for age, gender, total body fat and lean tissue mass, and insulin sensitivity (10.4 +/- 0.4 vs. 8.9 +/- 0.3 microg/dl, P < 0.01). Increasing number of features of MS was associated with higher cortisol levels, after adjusting for covariates (P = 0.001). Among individual features of MS, systolic blood pressure had the strongest relationship with adjusted cortisol level (r = 0.34; P < 0.001), followed by diastolic blood pressure and fasting plasma glucose (both r = 0.23; P < 0.01). IAAT was associated with cortisol (r = 0.16; P < 0.05), whereas high-density lipoprotein, triglycerides, and waist circumference were not. CONCLUSIONS In overweight, Latino youth, MS is associated with higher morning serum cortisol levels, independent of body fat and insulin sensitivity. More studies are needed to investigate the role of relative hypercortisolism and chronic stress in obesity-related metabolic disorders in children.

Inverse relation between dietary fiber intake and visceral adiposity in overweight Latino youth

BACKGROUND To date, no studies have assessed the longitudinal changes of dietary intake on metabolic risk factors in Latino youth. OBJECTIVE We assessed the relation between changes in dietary intake, specifically sugar and fiber intakes, with changes in adiposity and risk factors for type 2 diabetes in a longitudinal analysis of overweight Latino youth. DESIGN Overweight Latino youth (n = 85; aged 11-17 y) underwent the following measures over 2 y [mean (+/-SD) time difference was 1.5 +/- 0.5 y]: dietary intake by 2-d diet recalls, body composition by dual-energy X-ray absorptiometry and magnetic resonance imaging, and glucose and insulin indexes by oral- and intravenous-glucose-tolerance tests. Partial correlations and repeated-measures analysis of covariance assessed the relation between changes in dietary intake with changes in adiposity and glucose and insulin indexes, independent of the following a priori covariates: sex, Tanner stage, time between visits, and baseline dietary and metabolic variables of interest. RESULTS Increases in total dietary fiber (g/1000 kcal) and insoluble fiber (g/1000 kcal) were associated with decreases in visceral adipose tissue (VAT) (r = -0.29, P = 0.02, and r = -0.27, P = 0.03, for total dietary and insoluble fiber, respectively), independent of baseline covariates and change in subcutaneous abdominal adipose tissue. Participants who had decreased total dietary fiber (mean decrease of 3 g . 1000 kcal(-1) x d(-1)) had significant increases in VAT compared with participants who had increased total dietary fiber (21% compared with -4%; P = 0.02). No other changes in dietary variables were related to changes in adiposity or metabolic variables. CONCLUSION Small reductions in dietary fiber intake over 1-2 y can have profound effects on increasing visceral adiposity in a high-risk Latino youth population.

Persistence of Pre-Diabetes in Overweight and Obese Hispanic Children: Association With Progressive Insulin Resistance, Poor β-Cell Function, and Increasing Visceral Fat

OBJECTIVE—To examine changes in risk factors in overweight and obese Hispanic children at high risk of developing type 2 diabetes. RESEARCH DESIGN AND METHODS—We recruited 128 overweight/obese Hispanic children with a family history of type 2 diabetes primarily from clinics in East Los Angeles. Children were evaluated annually for 4 years with an oral glucose tolerance test, applying American Diabetes Association criteria to define diabetes and pre-diabetes. Insulin sensitivity (Si), acute insulin response (AIR) to glucose, and β-cell function (BCF) were determined from frequently sampled intravenous glucose tolerance tests, and total body fat by dual-energy X-ray absorptiometry and intra-abdominal and subcutaneous abdominal adipose tissue (IAAT and SAAT) by magnetic resonance imaging were assessed in years 1, 2, and 4. RESULTS—No subjects developed type 2 diabetes, 40% never had pre-diabetes, 47% had intermittent pre-diabetes with no clear pattern over time, and 13% had persistent pre-diabetes. At baseline, those with persistent pre-diabetes had lower BCF and higher IAAT. In repeated measures, Si deteriorated regardless of pre-diabetes, and there was a significant effect of pre-diabetes on AIR (42% lower in pre-diabetes; P = 0.01) and disposition index (34% lower in pre-diabetes; P = 0.021) and a significant interaction of pre-diabetes and time on IAAT (greater increase over time in those with pre-diabetes; P = 0.034). CONCLUSIONS—In this group of Hispanic children at high risk of type 2 diabetes, 1) pre-diabetes is highly variable from year to year; 2) the prevalence of persistent pre-diabetes over 3 years is 13%; and 3) children with persistent pre-diabetes have lower BCF, due to a lower AIR, and increasing visceral fat over time.

Dietary Intake and the Metabolic Syndrome in Overweight Latino Children

Little is known about the relationship between diet and metabolic health in Latino children, a population at increased risk for diabetes. The present study evaluates diet composition and the metabolic syndrome in a cross-sectional sample of 109 overweight Latino children aged 10 to 17 years with a family history of type 2 diabetes. Dietary intake was assessed by two 24-hour recalls. Associations between nutrients and features of the metabolic syndrome were examined using multiple linear regression and analysis of covariance. Log cholesterol intake was positively associated with log systolic blood pressure (beta=0.034, P=0.017) and log soluble dietary fiber intake was inversely associated with log waist circumference (beta=-0.069, P=0.036). Log soluble fiber intake was significantly higher in participants with 0 features compared to those with 3+ features of the metabolic syndrome (P=0.046), which translates to 5.2 g vs 4.1 g soluble fiber daily. No other significant associations were found between dietary variables and either the individual features of the metabolic syndrome or the clustering of metabolic syndrome components. Increases in soluble fiber through the daily consumption of fruits, vegetables, and beans may improve metabolic health in Latino children.

Pubertal Changes of Insulin Sensitivity, Acute Insulin Response, and β-Cell Function in Overweight Latino Youth

OBJECTIVE To examine changes in insulin sensitivity (SI), compensatory acute insulin response (AIR), and β-cell function/disposition index (DI) across puberty in overweight Latino boys and girls. STUDY DESIGN Latino children (n = 253) were followed annually for up to 5 years. Longitudinal modeling was used to examine changes in SI, AIR, DI, and fasting and 2-hour glucose and insulin across Tanner stage. RESULTS In boys, SI decreased in early puberty with a recovery by late puberty. The compensatory increase in AIR was appropriate in early maturation, but after Tanner stage 3, AIR declined by more than that predicted from the recovery in SI. For girls, SI decreased in early puberty and across all stages of maturation. In early maturation, there was an appropriate compensatory increase in AIR, but after Tanner stage 3, AIR decreased. Thus, DI deteriorated across puberty in boys and girls. CONCLUSIONS In overweight Hispanic youth, compensatory changes in insulin secretion fails after Tanner stage 3 in both sexes, indicating β-cell deterioration during this critical period of development, thus increasing risk for type 2 diabetes.

Persistence of the metabolic syndrome and its influence on carotid artery intima media thickness in overweight Latino children

OBJECTIVE The objective of this study was to examine the influence of persistence of the metabolic syndrome (Mets) and its individual components over a 3-year period on carotid intima media thickness (CIMT) in overweight Latino children. METHODS Ninety-seven healthy male and female overweight Latino children (mean age at baseline: 11.0+/-1.8 years) were assessed for MetS on four annual evaluations and classified according to the persistence of MetS: NEVER (0 annual visits with the MetS, n=53), INTERMITTENT (1 or 2 visits with the MetS, n=28), and PERSISTENT (3 or 4 visits with the MetS, n=16). CIMT was measured with high-resolution B-mode ultrasound (7.9+/-0.7 months after the most recent MetS assessment; mean age: 14.6+/-1.8 years). RESULTS PERSISTENT MetS was associated with significantly higher CIMT (0.647+/-0.018mm compared to 0.600+/-0.007mm in those who NEVER had MetS, p<0.01). This difference remained significant after controlling for gender, baseline age, total fat mass, total lean tissue mass and insulin sensitivity. PERSISTENT high waist circumference and PERSISTENT high blood pressure were also significantly associated with higher mean CIMT, but these differences were no longer significant after controlling for total fat and lean tissue mass. Baseline systolic blood pressure and 2-h glucose were significantly related to CIMT independent of all other MetS components (p<0.05). CONCLUSIONS Persistence of the MetS over a 3-year period was uniquely associated with increased CIMT during childhood. Children with hypertension, persistent abdominal adiposity or impaired glucose tolerance may also be at higher risk for elevated CIMT.

Randomized Controlled Trial to Improve Adiposity, Inflammation, and Insulin Resistance in Obese African-American and Latino Youth

The purpose of this study was to examine ethnic differences in the metabolic responses to a 16‐week intervention designed to improve insulin sensitivity (SI), adiposity, and inflammation in obese African‐American and Latino adolescents. A total of 100 participants (African Americans: n = 48, Latino: n = 52; age: 15.4 ± 1.1 years, BMI percentile: 97.3 ± 3.3) were randomly assigned to interventions: control (C; n = 30), nutrition (N; n = 39, 1×/week focused on decreasing sugar and increasing fiber intake), or nutrition + strength training (N+ST; n = 31, 2×/week). The following were measured at pre‐ and postintervention: strength, dietary intake, body composition (dual‐energy X‐ray absorptiometry/magnetic resonance imaging) and glucose/insulin indexes (oral glucose tolerance test (OGTT)/intravenous glucose tolerance test (IVGTT)) and inflammatory markers. Overall, N compared to C and N+ST reported significant improvements in SI (+16.5% vs. −32.3% vs. −6.9% respectively, P < 0.01) and disposition index (DI: +15.5% vs. −14.2% vs. −13.7% respectively, P < 0.01). N+ST compared to C and N reported significant reductions in hepatic fat fraction (HFF: −27.3% vs. −4.3% vs. 0% respectively, P < 0.01). Compared to N, N+ST reported reductions in plasminogen activator inhibitor‐1 (PAI‐1) (−38.3% vs. +1.0%, P < 0.01) and resistin (−18.7% vs. +11.3%, P = 0.02). There were no intervention effects for all other measures of adiposity or inflammation. Significant intervention by ethnicity interactions were found for African Americans in the N group who reported increases in total fat mass, 2‐h glucose and glucose incremental areas under the curve (IAUC) compared to Latinos (Ps < 0.05). These interventions yielded differential effects with N reporting favorable improvements in SI and DI and N+ST reporting marked reductions in HFF and inflammation. Both ethnic groups had significant improvements in metabolic health; however some improvements were not seen in African Americans.

Cortisol Is Negatively Associated with Insulin Sensitivity in Overweight Latino Youth

CONTEXT AND OBJECTIVE The purpose of the present study was to investigate the cross-sectional and longitudinal associations of serum morning cortisol and aspects of insulin action in Latino children and adolescents (8-13 yr) at risk for type 2 diabetes. DESIGN AND PARTICIPANTS The present study includes a cross-sectional analysis in 211 participants and a longitudinal analysis in a subset of 143 participants. RESULTS At baseline, cortisol was negatively associated with fasting glucose (r = 0.23; P < 0.01), β-cell function (disposition index, r = -0.24; P < 0.05), and acute insulin response to glucose (r = -0.27; P < 0.05). Baseline cortisol was also significantly related to the change in insulin sensitivity over 1 yr (r = -0.23; P < 0.05). These results did not differ by Tanner stage or sex. CONCLUSIONS Cortisol contributes to the reduction in insulin sensitivity at an early age in Latino children and adolescents. Specifically, cortisol is negatively associated with potential compensatory mechanisms for insulin resistance, such as increased β-cell function and increased insulin release to a glucose challenge, by exacerbating the progression toward insulin resistance in this population. The results underline the relevance of glucocorticoid reduction for the prevention of metabolic disease in Latino children and adolescents.

PARENTAL HISTORY AND RISK OF TYPE 2 DIABETES IN OVERWEIGHT LATINO ADOLESCENTS: A LONGITUDINAL ANALYSIS.

OBJECTIVE— The purpose of this article was to examine metabolic risk factors for type 2 diabetes in children and adolescents as a function of maternal versus paternal family history of type 2 diabetes and to examine whether differences in these risk factors emerge during adolescent growth. RESEARCH DESIGN AND METHODS— A total of 247 overweight Latino children (baseline age = 11.1 ± 1.7 years) with a parental history of type 2 diabetes were followed annually for 5 years (2.2 ± 1.2 observations/child) with measures of insulin sensitivity, acute insulin response to glucose, and disposition index. Longitudinal linear mixed-effects modeling was used to evaluate the influence of maternal versus paternal family history of type 2 diabetes on changes in diabetes risk factors over age. RESULTS— Insulin sensitivity and the disposition index decreased over age (β = −0.052 and β = −0.033, P < 0 0.01). Acute insulin response to glucose and fasting and 2-h glucose increased (β = 0.019, β = 0.002, and β = 0.003, P < 0.01). Declines in insulin sensitivity were significantly greater in participants whose maternal grandmothers had a history of type 2 diabetes (β = −0.03, P = 0.03). Declines in the disposition index (β = −0.02, P = 0.04) and increases in fasting glucose were significantly influenced by a maternal history of type 2 diabetes (β = 0.60, P < 0.05). CONCLUSIONS— Maternal but not paternal family history for diabetes may have a significant impact on insulin dynamics, becoming more pronounced during growth in overweight Latino adolescents. Further research is clearly warranted.

Ectopic fat deposition in prediabetic overweight and obese minority adolescents.

CONTEXT Optimizing effective prevention and treatment of type 2 diabetes in youth is limited by incomplete understanding of its pathophysiology and how this varies across ethnicities with high risk. OBJECTIVE The aim of this study was to examine the contribution of visceral adipose tissue (VAT), hepatic fat fraction (HFF), and pancreatic fat fraction (PFF) to prediabetes in overweight/obese African American (AA) and Latino youth. DESIGN AND SETTING We conducted a cross-sectional study in an academic pediatric care facility. SUBJECTS A total of 148 healthy, overweight/obese adolescents (56 AA, 92 Latino; 72 males, 76 females; age, 15.5 ± 1.2 y; BMI z-score, 2.1 ± 0.5) participated in the study. They were normal glucose tolerant (n = 106) and prediabetic (n = 42), based on fasting glucose of 100-125 mg/dL and/or 2-hour glucose of 140-199 mg/dL, and/or hemoglobin A1C 6.0-6.4%. MAIN OUTCOME MEASURES We measured sc abdominal adipose tissue, VAT, HFF, and PFF by 3-Tesla magnetic resonance imaging and measured total body fat by dual-energy x-ray absorptiometry. RESULTS Adolescents with prediabetes had 30% higher HFF (P = .001) and 31% higher PFF (P = .042), compared to those with normal glucose tolerance after controlling for age, sex, pubertal stage, ethnicity, total percentage body fat, and VAT. Logistic regression showed that PFF predicted prediabetes in AAs and HFF predicted prediabetes in Latinos, with the odds of having prediabetes increased by 66% for every 1% increase in PFF in African Americans, and increased by 22% for every 1% increase in HFF in Latinos. CONCLUSION These data demonstrate that ectopic fat phenotypes associated with prediabetes are established by adolescence. Ethnic differences in the deposition of ectopic fat in adolescents with prediabetes may differ, with pancreatic fat in AAs, vs hepatic fat in Latino adolescents, being associated with diabetes risk.