Role of NKG2D in Obesity-Induced Adipose Tissue Inflammation and Insulin Resistance

The early events that initiate inflammation in the adipose tissue during obesity are not well defined. It is unclear whether the recruitment of CD8 T cells to the adipose tissue during onset of obesity occurs through antigen-dependent or -independent processes. We have previously shown that interaction between NKG2D (natural-killer group 2, member D) and its ligand Rae-1ε is sufficient to recruit cytotoxic T lymphocytes to the pancreas and induce insulitis. Here, we tested whether NKG2D–NKG2D ligand interaction is also involved in obesity-induced adipose tissue inflammation and insulin resistance. We observed a significant induction of NKG2D ligand expression in the adipose tissue of obese mice, especially during the early stages of obesity. However, mice lacking NKG2D developed similar levels of insulin resistance and adipose tissue inflammation compared to control mice when placed on a high-fat diet. Moreover, overexpression of Rae-1ε in the adipose tissue did not increase immune cell infiltration to the adipose tissue either in the setting of a normal or high-fat diet. These results indicate that, unlike in the pancreas, NKG2D–NKG2D ligand interaction does not play a critical role in obesity-induced inflammation in the adipose tissue.     

Pleiotropic Effects of Genes for Insulin Resistance on Adiposity in Baboons

Objective: Previous research has suggested a genetic contribution to the development of insulin resistance and obesity. We hypothesized that the same genes influencing insulin resistance might also contribute to the variation in adiposity. Research Methods and Procedures: A total of 601 (200 male, 401 female) adult baboons (Papio hamadryas) from nine families with pedigrees ranging in size from 43 to 121 were used in this study. Plasma insulin, glucose, C‐peptide, and adiponectin were analyzed, and homeostasis model assessment of insulin resistance (HOMA IR) was calculated. Fat biopsies were collected from omental fat tissue, and triglyceride concentration per gram of fat tissue was determined. Body weight and length were measured, and BMI was derived. Univariate and bivariate quantitative genetic analyses were performed using SOLAR. Results: Insulin, glucose, C‐peptide, and adiponectin levels, HOMA IR, triglyceride concentration of fat tissue, body weight, and BMI were all found to be significantly heritable, with heritabilities ranging from 0.15 to 0.80. Positive genetic correlations (r_Gs) were observed for HOMA IR with C‐peptide (r_G = 0.88 ± 0.10, p = 0.01), triglyceride concentration in fat tissue (r_G = 0.86 ± 0.33, p = 0.02), weight (r_G = 0.50 ± 0.20, p = 0.03), and BMI (r_G = 0.64 ± 0.22, p = 0.02). Discussion: These results suggest that a set of genes contributing to insulin resistance also influence general and central adiposity phenotypes. Further genetic research in a larger sample size is needed to identify the common genes that constitute the genetic basis for the development of insulin resistance and obesity.     

Racial Differences in Insulin Secretion and Sensitivity in Prepubertal Children: Role of Physical Fitness and Physical Activity

Objective: To investigate in prepubertal children whether physical fitness and/or physical activity are: 1) associated with insulin secretion and sensitivity and 2) account for racial differences in insulin secretion and sensitivity. Research Methods and Procedures: Subjects included 34 African American and 34 white nondiabetic children aged 5 to 11 years. Data were divided into two sets according to the availability of VO_2max and physical activity data. Body composition was measured by dual‐energy X‐ray absorptiometry. Subcutaneous abdominal adipose tissue and intra‐abdominal adipose tissue were examined by computed tomography. Insulin sensitivity (S_I) and acute insulin response (AIR) were determined by a frequently sampled intravenous glucose tolerance test. An all‐out, progressive treadmill exercise test was used for measuring VO_2max. Physical activity data were collected by questionnaire. Results: African American children had lower S_I and higher AIR than white children, after adjusting for total body fat mass. African Americans reported higher levels of physical activity (hours/wk) than whites, but had a lower VO_2max. In multiple linear regression analysis, hours/wk of activity and hours/wk of vigorous activity, but not moderate activity, were independently related to S_I and AIR after adjusting for race, total body fat mass or fat distribution, and total lean tissue mass. VO_2max was not related to AIR, and was inversely related to S_I, after adjusting for body composition. Race remained significantly associated with both S_I and AIR, even after adjusting for body composition, fat distribution, and hours/wk of activity or hours/wk of vigorous activity. Discussion: In summary, overall physical activity and, especially, vigorous activity were associated with insulin secretion and sensitivity. However, neither physical activity nor VO_2max explained the racial difference in insulin secretion (higher in African Americans) and sensitivity (lower in African Americans). Thus, racial (African American to white) differences in aspects of insulin action seem to be due to factors other than body composition, fat distribution, cardiovascular fitness, and amount of physical activity.     

Mediating Effects of Inflammatory Biomarkers on Insulin Resistance Associated with Obesity

Objective: Obesity is associated with elevated levels of biomarkers of inflammation and endothelial dysfunction [including C‐reactive protein (CRP), E‐selectin, and intercellular adhesion molecule‐1], as well as insulin resistance (IR) and type 2 diabetes. We tested the hypothesis that these biomarkers mediate associations among obesity, IR, and risk of diabetes. Research Methods and Procedures: We stratified 510 initially non‐diabetic women in the Nurses’ Health Study cohort into four phenotypes above/below median BMI (27 kg/m²) and waist circumference (81 cm): low BMI‐low waist (LBLW; N = 190), low BMI‐high waist (LBHW; N = 74), high BMI‐low waist (HBLW; N = 27), and high BMI‐high waist (HBHW; N = 219). Results: In models assessing associations of weight phenotype with IR [fasting insulin (FI)], adjusted for age and diabetes risk factors, mean FI was higher comparing HBHW women (13.6 μU/mL, p < 0.0001) and LBHW (11.5 μU/mL, p = 0.02) with LBLW women (8.6 μU/mL); HBLW and LBLW women were not significantly different. Differences in FI levels were most strongly attenuated after adjustment for E‐selectin comparing LBHW with LBLW women (11.7 vs. 9.7 μU/mL, p = 0.2). Discussion: In logistic regression models, LBHW predicted diabetes (risk factor‐adjusted relative risk 2.06, 1.05 to 6.40), compared with LBLW, but was no longer significant after adjustment for E‐selectin or CRP. After adjusting for CRP and E‐selectin, only HBHW and E‐selectin were significantly associated with risk of diabetes. In women with central adiposity and low BMI, endothelial dysfunction and inflammation may mediate the relationship among central fat, IR, and incident diabetes.     

Randomized Control Trial to Improve Adiposity and Insulin Resistance in Overweight Latino Adolescents

Few randomized trials attempt to improve insulin sensitivity and associated metabolic risks in overweight Latino youth. The purpose of this study is to examine the effects of a modified carbohydrate nutrition program combined with strength training on insulin sensitivity, adiposity, and other type 2 diabetes risk factors in overweight Latino adolescents. In a 16‐week randomized trial, 54 overweight Latino adolescents (15.5 ± 1.0 years) were randomly assigned to: (i) Control (C; n = 16), (ii) Nutrition (N; n = 21), or (iii) Nutrition + Strength training (N+ST; n = 17). The N group received modified carbohydrate nutrition classes (once per week), while the N+ST received the same nutrition classes plus strength training (twice per week). The following were measured at pre‐ and postintervention: strength by 1‐repetition maximum, dietary intake by 3‐day records, body composition by dual‐energy X‐ray absorptiometry, glucose/insulin indices by oral glucose tolerance test (OGTT) and intravenous glucose tolerance test with minimal modeling. Across intervention group effects were tested using analysis of covariance with post hoc pairwise comparisons. A significant overall intervention effect was found for improvement in bench press (P < 0.001) and reductions in energy (P = 0.05), carbohydrate (P = 0.04) and fat intake (P = 0.03). There were no significant intervention effects on insulin sensitivity, body composition, or most glucose/insulin indices with the exception of glucose incremental area under the curve (IAUC) (P = 0.05), which decreased in the N and N+ST group by 18 and 6.3% compared to a 32% increase in the C group. In conclusion, this intense, culturally tailored intervention resulted in no significant intervention effects on measured risk factors with the exception of a beneficial effect on glycemic response to oral glucose.     

Whole-Body and Hepatic Insulin Resistance in Obese Children

Background

Insulin resistance may be assessed as whole body or hepatic.

Objective

To study factors associated with both types of insulin resistance.

Methods

Cross-sectional study of 182 obese children. Somatometric measurements were registered, and the following three adiposity indexes were compared: BMI, waist-to-height ratio and visceral adiposity. Whole-body insulin resistance was evaluated using HOMA-IR, with 2.5 as the cut-off point. Hepatic insulin resistance was considered for IGFBP-1 level quartiles 1 to 3 (<6.67 ng/ml). We determined metabolite and hormone levels and performed a liver ultrasound.

Results

The majority, 73.1%, of obese children had whole-body insulin resistance and hepatic insulin resistance, while 7% did not have either type. HOMA-IR was negatively associated with IGFBP-1 and positively associated with BMI, triglycerides, leptin and mother''s BMI. Girls had increased HOMA-IR. IGFBP-1 was negatively associated with waist-to-height ratio, age, leptin, HOMA-IR and IGF-I. We did not find HOMA-IR or IGFBP-1 associated with fatty liver.

Conclusion

In school-aged children, BMI is the best metric to predict whole-body insulin resistance, and waist-to-height ratio is the best predictor of hepatic insulin resistance, indicating that central obesity is important for hepatic insulin resistance. The reciprocal negative association of IGFBP-1 and HOMA-IR may represent a strong interaction of the physiological processes of both whole-body and hepatic insulin resistance.     

Associations of Maternal Prenatal Smoking with Child Adiposity and Blood Pressure

Objective: To examine the extent to which maternal prenatal smoking is associated with adiposity, central adiposity, and blood pressure in 3‐year‐old children. Research Methods and Procedures: We studied 746 mother‐child pairs in Project Viva, a prospective cohort study, and categorized mothers as never, early pregnancy, or former smokers. Main outcome measures were overweight (BMI for age and sex > 85th percentile), BMI z‐score, sum of subscapular (SS) and triceps (TR) skinfolds, SS:TR skinfold ratio, and systolic blood pressure (SBP). Results: One hundred sixty‐one (22%) mothers quit smoking before pregnancy, 71 (10%) smoked in early pregnancy, and 514 (69%) never smoked. At age 3 years, 204 (27%) children were overweight. On multivariable analysis, compared with children of never smokers, children of early pregnancy smokers had an elevated risk for overweight [odds ratio (OR), 2.2; 95% confidence interval (CI), 1.2, 3.9] and higher BMI z‐score (0.30 units; 95% CI, 0.05, 0.55), SS + TR (2.0 mm; 95% CI, 0.9, 3.0), and SBP (2.4 mm Hg; 95% CI, ?0.1, 4.9). Children of former smokers were not more overweight (BMI z‐score, 0.02 units; 95% CI, ?0.15, 0.19) but had higher SBP (1.5 mm Hg; 95% CI, ?0.1, 3.2). We saw no relationship of smoking with central adiposity (SS:TR). Discussion: Former and early pregnancy smokers had children with somewhat higher SBP, but only early pregnancy smokers had children who were more overweight. Mechanisms linking smoking with child adiposity and blood pressure may differ. A long‐term impact of maternal smoking on offspring cardiovascular risk provides further reason to reduce smoking in women.     

CD44 Plays a Critical Role in Regulating Diet-Induced Adipose Inflammation,Hepatic Steatosis,and Insulin Resistance

CD44 is a multifunctional membrane receptor implicated in the regulation of several biological processes, including inflammation. CD44 expression is elevated in liver and white adipose tissue (WAT) during obesity suggesting a possible regulatory role for CD44 in metabolic syndrome. To study this hypothesis, we examined the effect of the loss of CD44 expression on the development of various features of metabolic syndrome using CD44 null mice. Our study demonstrates that CD44-deficient mice (CD44KO) exhibit a significantly reduced susceptibility to the development of high fat-diet (HFD)-induced hepatic steatosis, WAT-associated inflammation, and insulin resistance. The decreased expression of genes involved in fatty acid synthesis and transport (Fasn and Cd36), de novo triglyceride synthesis (Mogat1), and triglyceride accumulation (Cidea, Cidec) appears in part responsible for the reduced hepatic lipid accumulation in CD44KO(HFD) mice. In addition, the expression of various inflammatory and cell matrix genes, including several chemokines and its receptors, osteopontin, and several matrix metalloproteinases and collagen genes was greatly diminished in CD44KO(HFD) liver consistent with reduced inflammation and fibrogenesis. In contrast, lipid accumulation was significantly increased in CD44KO(HFD) WAT, whereas inflammation as indicated by the reduced infiltration of macrophages and expression of macrophage marker genes, was significantly diminished in WAT of CD44KO(HFD) mice compared to WT(HFD) mice. CD44KO(HFD) mice remained considerably more insulin sensitive and glucose tolerant than WT(HFD) mice and exhibited lower blood insulin levels. Our study indicates that CD44 plays a critical role in regulating several aspects of metabolic syndrome and may provide a new therapeutic target in the management of insulin resistance.     

Role of Insulin Resistance in the Alzheimer's Disease Progression

Recent studies continue to find evidence linking Type 2 diabetes (T2D) with Alzheimer's disease (AD), the most common cause of dementia, a general term for memory loss and other cognitive abilities serious enough to interfere with daily life. Insulin resistance or dysfunction of insulin signaling is a universal feature of T2D, the main culprit for altered glucose metabolism and its interdependence on cell death pathways, forming the basis of linking T2D with AD as it may exacerbate Aβ accumulation, tau hyperphosphorylation and devastates glucose transportation, energy metabolism, hippocampal framework and promulgate inflammatory pathways. The current work demonstrates the basic mechanisms of the insulin resistance mediates dysregulation of bioenergetics and progress to AD as a mechanistic link between diabetes mellitus and AD. This work also aimed to provide a potential and feasible zone to succeed in the development of therapies in AD by enhanced hypometabolism and altered insulin signaling.

     

Sex-Specific Effect of Juvenile Diet on Adult Disease Resistance in a Field Cricket

Food limitation is expected to reduce an individual’s body condition (body mass scaled to body size) and cause a trade-off between growth and other fitness-related traits, such as immunity. We tested the condition-dependence of growth and disease resistance in male and female Gryllus texensis field crickets by manipulating diet quality via nutrient content for their entire life and then subjecting individuals to a host resistance test using the live bacterium Serratia marcescens. As predicted, crickets on a high-quality diet eclosed more quickly, and at a larger body size and mass. Crickets on a high-quality diet were not in better condition at the time of eclosion, but they were in better condition 7–11 days after eclosion, with females also being in better condition than males. Despite being in better condition, however, females provided with a high-quality diet had significantly poorer disease resistance than females on a low-quality diet and in poor condition. Similarly, males on low- and high-quality diets did not differ in their disease resistance, despite differing in their body condition. A sex difference in disease resistance under diet-restriction suggests that females might allocate resources toward immunity during development if they expect harsh environmental conditions as an adult or it might suggest that females allocate resources toward other life history activities (i.e. reproduction) when food availability increases. We do not know what immune effectors were altered under diet-restriction to increase disease resistance, but our findings suggest that increased immune function might provide an explanation for the sexually-dimorphic increase in longevity generally observed in diet-restricted animals.     

Dysregulation of the Autonomic Nervous System Can Be a Link between Visceral Adiposity and Insulin Resistance

Objective: To evaluate the interplay among abdominal adipose tissue distribution, the cortisol axis, the autonomic nervous system, and insulin resistance. Research Methods and Procedures: Two age‐, sex‐, and BMI‐matched groups were studied. Fifteen subjects were first‐degree relatives of patients with type 2 diabetes (R), and 15 had no family history of diabetes (controls, C). A hyperinsulinemic euglycemic clamp, cortisol measurements, and analysis of heart rate variability (HRV) were performed. Computed tomography was performed in a subgroup (n = 9 + 9) to determine abdominal adipose tissue distribution. Results: R tended to be less insulin‐sensitive than C (M value 9.2 ± 1.0 vs 10.3 ± 0.7 mg/kg per minute, not significant). Stimulation with tetracosactin or corticotropin releasing hormone yielded lower peak serum cortisol levels in R (p = 0.03 and p = 0.06, respectively). The amount of visceral abdominal fat (VAT) tended to be greater in R. In all subjects, VAT was negatively correlated to insulin sensitivity (r = ?0.93, p < 0.001). There was a positive association between VAT and resting heart rate (r = 0.70, p = 0.003) and sympathetic/parasympathetic ratio in HRV assessment after tilt (r = 0.53, p = 0.03). Subcutaneous abdominal tissue was not associated with insulin sensitivity or any of the hormonal or HRV assessments. Discussion: Subjects genetically predisposed for type 2 diabetes had a tendency toward a larger amount of VAT and to lower insulin sensitivity compared with control subjects. The amount of visceral fat was strongly associated with insulin resistance and signs of a high ratio of sympathetic vs. parasympathetic reactivity. A large amount of visceral fat may act in concert with sympathetic/parasympathetic imbalance to promote the development of insulin resistance, and this may be partly independent of genetic background.     

Renal Lipotoxicity-Associated Inflammation and Insulin Resistance Affects Actin Cytoskeleton Organization in Podocytes

In the last few decades a change in lifestyle has led to an alarming increase in the prevalence of obesity and obesity-associated complications. Obese patients are at increased risk of developing hypertension, heart disease, insulin resistance (IR), dyslipidemia, type 2 diabetes and renal disease. The excess calories are stored as triglycerides in adipose tissue, but also may accumulate ectopically in other organs, including the kidney, which contributes to the damage through a toxic process named lipotoxicity. Recently, the evidence suggests that renal lipid accumulation leads to glomerular damage and, more specifically, produces dysfunction in podocytes, key cells that compose and maintain the glomerular filtration barrier. Our aim was to analyze the early mechanisms underlying the development of renal disease associated with the process of lipotoxicity in podocytes. Our results show that treatment of podocytes with palmitic acid produced intracellular accumulation of lipid droplets and abnormal glucose and lipid metabolism. This was accompanied by the development of inflammation, oxidative stress and endoplasmic reticulum stress and insulin resistance. We found specific rearrangements of the actin cytoskeleton and slit diaphragm proteins (Nephrin, P-Cadherin, Vimentin) associated with this insulin resistance in palmitic-treated podocytes. We conclude that lipotoxicity accelerates glomerular disease through lipid accumulation and inflammation. Moreover, saturated fatty acids specifically promote insulin resistance by disturbing the cytoarchitecture of podocytes. These data suggest that renal lipid metabolism and cytoskeleton rearrangements may serve as a target for specific therapies aimed at slowing the progression of podocyte failure during metabolic syndrome.     

The Role of IGF-system in Vascular Insulin Resistance

Insulin and IGF-I are closely related peptides, which interact by several mechanisms. In high supraphysiological concentrations (>/=10 (-8) M), they cross-react with each other's receptors with 100- to 1000-fold lower affinity than with their cognate receptors. This can cause confusion, since in many in vitro studies, insulin has been used in high unphysiological concentrations, which activate IGF-I receptors. Due to the differences in affinity, insulin and IGF-I probably do not activate each other's receptors in vivo. IGF-I receptors are several-fold more abundant than insulin receptors in human micro- and macrovascular endothelial cells and in human vascular smooth muscle cells. Both insulin and IGF-I receptor protein can be demonstrated and they are activated by their cognate ligand at physiological concentrations of 10 (-9)-10 (-10) M. In vascular smooth muscle cells, IGF-I but not insulin stimulates metabolism and growth. IGF-I stimulates DNA-synthesis and growth in microvascular endothelial cells, but neither insulin nor IGF-I have any effect on macrovascular endothelial cells. Both insulin and IGF-I have been shown to stimulate nitric oxide production in endothelial cells, but only the effect of IGF-I was obtained at a physiological concentration. In both endothelial and vascular smooth muscle cells, insulin and IGF-I receptors occur as insulin/IGF-I hybrid receptors with high affinity to IGF-I and low for insulin. Due to the low number of insulin receptors and the presence of hybrid receptors the insulin receptor signal is probably too attenuated to elicit biological effects, explaining the insulin resistance of vascular cells in vitro. In vivo both insulin and IGF-I have been reported to increase muscle blood flow in physiological concentrations. Whether this is due to direct effects on endothelial cells or indirectly induced is not clear. The effect of insulin is attenuated by insulin resistance. In conclusion, the in vitro data suggest that endothelial cells and vascular smooth muscle cells are sensitive to IGF-I, but insensitive to insulin, and this is due to a preponderance of IGF-I receptors and the presence of insulin/IGF-I hybrid receptors.     

Effects of Changes in Adiposity and Physical Activity on Preadolescent Insulin Resistance: The Australian LOOK Longitudinal Study

Background

In a previous longitudinal analysis of our cohort as 8 to 10 year-olds, insulin resistance (IR) increased with age, but was not modified by changes in percent body fat (%BF), and was only responsive to changes in physical activity (PA) in boys. We aimed to determine whether these responses persisted as the children approached adolescence.

Methods

In this prospective cohort study, 256 boys and 278 girls were assessed at ages 8, 10 and 12 years for fasting blood glucose and insulin, %BF (dual energy X-ray absorptiometry); PA (7-day pedometers), fitness (multistage run); and pubertal development (Tanner stage).

Results

From age 8 to 12 years, the median homeostatic model of IR (HOMA-IR) doubled in boys and increased 250% in girls. By age 12, 23% of boys and 31% of girls had elevated IR, as indicated by HOMA-IR greater than 3. Longitudinal relationships, with important adjustments for covariates body weight, PA, %BF, Tanner score and socioeconomic status showed that, on average, for every 1 unit reduction of %BF, HOMA-IR was lowered by 2.2% (95% CI 0.04–4) in girls and 1.6% (95% CI 0–3.2) in boys. Furthermore, in boys but not girls, HOMA-IR was decreased by 3.5% (95%CI 0.5–6.5) if PA was increased by 2100 steps/day.

Conclusion

Evidence that a quarter of our apparently healthy 12 year-old Australians possessed elevated IR suggests that community-based education and prevention strategies may be warranted. Responsiveness of IR to changes in %BF in both sexes during late preadolescence and to changes in PA in the boys provides a specific basis for targeting elevated IR. That body weight was a strong covariate of IR, independent of %BF, points to the importance of adjusting for weight in correctly assessing these relationships in growing children.     

Relation of Leptin to Insulin Resistance Syndrome in Children

Objectives: To examine the relation of leptin to insulin resistance, as measured by euglycemic insulin clamp, and insulin resistance syndrome factors in thin and heavy children. Research Methods and Procedures: Anthropometrics, insulin, blood pressure, and leptin were measured in 342 11‐ to 14‐year‐old children (189 boys, 153 girls, 272 white, 70 black). Insulin sensitivity (M) was determined by milligrams glucose uptake per kilogram per minute and expressed as M/lean body mass (M_lbm). Children were divided by median BMI (boys = 20.5 kg/m²; girls = 21.4 kg/m²) into below‐median (thin) and above‐median (heavy) groups. Correlation coefficients between log‐leptin and components of insulin resistance syndrome were adjusted for Tanner stage, gender, and race. Results: BMI was related to leptin in boys (r = 0.70, p < 0.001) and girls (r = 0.75, p < 0.001). Leptin was higher in girls than boys (32.6 vs. 12.3 ng/mL, p = 0.0001). Leptin levels increased in girls and decreased in boys during puberty, paralleling the changes in body fat. Leptin was significantly correlated with insulin, M_lbm, triglycerides, and blood pressure in heavy children and only with insulin in thin children. After adjustment for body fat, the correlations remained significant for insulin and M_lbm in heavy children and with insulin in thin children. Discussion: Significant associations were found between leptin and insulin resistance in children, and these associations were attenuated by adjustment for adiposity. These findings at age 13 likely have long‐term consequences in the development of the obesity‐insulin resistance‐related cardiovascular risk profile.     

Regulation of Adipose Tissue Inflammation and Insulin Resistance by MAPK Phosphatase 5

Obesity and metabolic disorders such as insulin resistance and type 2 diabetes have become a major threat to public health globally. The mechanisms that lead to insulin resistance in type 2 diabetes have not been well understood. In this study, we show that mice deficient in MAPK phosphatase 5 (MKP5) develop insulin resistance spontaneously at an early stage of life and glucose intolerance at a later age. Increased macrophage infiltration in white adipose tissue of young MKP5-deficient mice correlates with the development of insulin resistance. Glucose intolerance in MKP5-deficient mice is accompanied by significantly increased visceral adipose weight, reduced AKT activation, enhanced p38 activity, and increased inflammation in visceral adipose tissue when compared with wild-type (WT) mice. Deficiency of MKP5 resulted in increased inflammatory activation in macrophages. These findings thus demonstrate that MKP5 critically controls inflammation in white adipose tissue and the development of metabolic disorders.     

Dietary Fat Intake and Insulin Resistance in Black and White Children

Objective: The purpose of this study was to determine whether dietary fat intake above current Acceptable Macronutrient Distribution Range (AMDR) guidelines was associated with greater insulin resistance in black and white children. Research Methods and Procedures: We studied 142 healthy children (n = 81 whites, n = 61 blacks), 6.5 to 14 years old. Dietary composition was determined by repeated 24‐hour dietary recall, body composition by DXA, visceral fat by computed tomography, and insulin sensitivity (SI) and acute insulin response to glucose (AIRg) by frequently sampled intravenous glucose tolerance test. Subjects were categorized by ethnicity (white/black) and dietary fat intake (above‐AMDR/within‐AMDR guidelines), and differences were analyzed by 2 × 2 analysis of covariance, adjusting for covariates. Results: After adjusting for total body fat, gender, and Tanner stage, subjects consuming dietary fat above AMDR intake guidelines had lower SI and higher AIRg. This effect was specific to black children (32% lower SI and 62% higher AIRg in above‐AMDR compared with within‐AMDR blacks) and was not seen in whites. Discussion: In black, but not white, children, those with dietary fat intake above current AMDR guidelines had lower SI and higher AIRg than those who met AMDR guidelines. These findings support current AMDR guidelines for dietary fat in black children and adolescents. The mechanism(s) underlying the ethnic differences in the relationship between dietary fat intake and SI in children require further investigation.     

Chronobiologic Evaluation of Blood Pressure in School Children

Blood pressure (BP) and heart rate (HR) data were collected over 24 h with an ambulatory BP monitor to (a) determine the existence of 12-, 24-, and combined 12- and 24-h BP patterns in children as previously noted for adults; (b) provide MESOR (an acronym for midline estimating statistics of rhythm), amplitude, and acrophase data for subgroups of students by race and gender; and (c) determine the influence of HR (as an estimate of activity) on BP and BP patterns for 100 normal, healthy students 9-12 years of age. We found no statistically significant differences between various racial groups or between gender for MESOR, amplitude, acrophase, or degree of sinusoidality of circadian rhythmicity (R² values) for BP; clinically interesting differences were observed, including lower MESOR BPs in Hispanic males when compared with their female counterparts and slightly higher MESOR BPs in blacks of both genders when compared with whites. In addition, we demonstrated subgroups of students who exhibited specific 24-h and combined 12- and 24-h patterns. Also, 67% of subjects showed stable or nonrhythmic BP patterns, perhaps related to BP sampling intervals. Differences in HR, as a surrogate measure of activity, accounted for 56% of the variation in systolic BP but only 26% in diastolic BP over the 24 h.