Tamara S. Hannon

Childhood obesity and type 2 diabetes mellitus.

Until recently, the majority of cases of diabetes mellitus among children and adolescents were immune-mediated type 1a diabetes. Obesity has led to a dramatic increase in the incidence of type 2 diabetes (T2DM) among children and adolescents over the past 2 decades. Obesity is strongly associated with insulin resistance, which, when coupled with relative insulin deficiency, leads to the development of overt T2DM. Children and adolescents with T2DM may experience the microvascular and macrovascular complications of this disease at younger ages than individuals who develop diabetes in adulthood, including atherosclerotic cardiovascular disease, stroke, myocardial infarction, and sudden death; renal insufficiency and chronic renal failure; limb-threatening neuropathy and vasculopathy; and retinopathy leading to blindness. Health care professionals are advised to perform the appropriate screening in children at risk for T2DM, diagnose the condition as early as possible, and provide rigorous management of the disease.

Longitudinal Study of Physiologic Insulin Resistance and Metabolic Changes of Puberty

Cross-sectional studies have shown that 1) adolescents are insulin resistant compared with prepubertal children and adults, 2) pubertal insulin resistance is likely mediated by growth hormone (GH), and 3) pubertal insulin resistance is associated with increased fat oxidation and decreased glucose oxidation. The aim of this study was to assess the validity of these cross-sectional observations by performing a longitudinal study in normal children during the prepubertal and pubertal periods. Nine healthy, normal weight, prepubertal children underwent hyperinsulinemic-euglycemic and hyperglycemic clamp studies for evaluation of insulin sensitivity and insulin secretion. Children had repeat evaluations during puberty. Consistent with cross-sectional observations, this longitudinal study demonstrated that during puberty: 1) insulin sensitivity decreased by ∼50%, 2) the decrease in insulin sensitivity was compensated by a doubling in insulin secretion, and 3) the decrease in insulin sensitivity was independent of changes in percentage of body fat. Puberty was associated with increased total body lipolysis and decreased glucose oxidation. A novel observation is the demonstration of ∼50% decrease in adiponectin levels at the pubertal time point. These metabolic changes are proposed to be partially mediated by increased GH secretion and are consistent with the Randle cycle of competition between glucose and fat oxidation.

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.

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.

Rapid Eye Movement Sleep in Relation to Overweight in Children and Adolescents

CONTEXT Short sleep duration is associated with obesity, but few studies have examined the relationship between obesity and specific physiological stages of sleep. OBJECTIVE To examine specific sleep stages, including rapid eye movement (REM) sleep and stages 1 through 4 of non-REM sleep, in relation to overweight in children and adolescents. DESIGN, SETTING, AND PARTICIPANTS A total of 335 children and adolescents (55.2% male; aged 7-17 years) underwent 3 consecutive nights of standard polysomnography and weight and height assessments as part of a study on the development of internalizing disorders (depression and anxiety). MAIN OUTCOME MEASURES Body mass index (calculated as weight in kilograms divided by height in meters squared) z score and weight status (normal, at risk for overweight, overweight) according to the body mass index percentile for age and sex. RESULTS The body mass index z score was significantly related to total sleep time (beta = -0.174), sleep efficiency (beta = -0.027), and REM density (beta = -0.256). Compared with normal-weight children, overweight children slept about 22 minutes less and had lower sleep efficiency, shorter REM sleep, lower REM activity and density, and longer latency to the first REM period. After adjustment for demographics, pubertal status, and psychiatric diagnosis, 1 hour less of total sleep was associated with approximately 2-fold increased odds of overweight (odds ratio = 1.85), 1 hour less of REM sleep was associated with about 3-fold increased odds (odds ratio = 2.91), and REM density and activity below the median increased the odds of overweight by 2-fold (odds ratio = 2.18) and 3-fold (odds ratio = 3.32), respectively. CONCLUSIONS Our results confirm previous epidemiological observations that short sleep time is associated with overweight in children and adolescents. A core aspect of the association between short sleep duration and overweight may be attributed to reduced REM sleep. Further studies are needed to investigate possible mechanisms underpinning the association between diminished REM sleep and endocrine and metabolic changes that may contribute to obesity.

Youth-Onset Type 2 Diabetes Consensus Report: Current Status, Challenges, and Priorities

Type 2 diabetes is a significant and increasing burden in adolescents and young adults. Clear strategies for research, prevention, and treatment of the disease in these vulnerable patients are needed. Evidence suggests that type 2 diabetes in children is different not only from type 1 but also from type 2 diabetes in adults. Understanding the unique pathophysiology of type 2 diabetes in youth, as well as the risk of complications and the psychosocial impact, will enable industry, academia, funding agencies, advocacy groups, and regulators to collectively evaluate both current and future research, treatment, and prevention approaches. This Consensus Report characterizes type 2 diabetes in children, evaluates the fundamental differences between childhood and adult disease, describes the current therapeutic options, and discusses challenges to and approaches for developing new treatments.

Hyperinsulinemia in African-American Adolescents Compared With Their American White Peers Despite Similar Insulin Sensitivity A reflection of upregulated β-cell function?

OBJECTIVE—African-American (AA) children are hyperinsulinemic and insulin resistant compared with American white (AW) children. Previously, we demonstrated that insulin secretion relative to insulin sensitivity was ∼75% higher in AA compared with AW children, suggesting that hyperinsulinemia in AA children is not merely a compensatory response to lower insulin sensitivity. The aim of the present investigation was to assess whether glucose-stimulated insulin response is higher in AA versus AW adolescents who have comparable in vivo insulin sensitivity. RESEARCH DESIGN AND METHODS—The hyperinsulinemic-euglycemic and hyperglycemic clamp techniques were utilized to assess first- and second-phase insulin secretion. Insulin secretion relative to insulin sensitivity was calculated as the glucose disposition index. RESULTS—AA adolescents compared with their AW peers with comparable insulin sensitivity and body composition had higher first-phase insulin concentrations. CONCLUSIONS—The quantitative relationship between insulin sensitivity and first-phase insulin appears to differ among AA and AW adolescents.

Use of markers of dyslipidemia to identify overweight youth with insulin resistance

Context:  Markers to identify overweight youth with insulin resistance are of clinical importance.

Sleep-disordered breathing in obese adolescents is associated with visceral adiposity and markers of insulin resistance

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.

Racial Differences in Sensitivity of Blood Pressure to Aldosterone

Blacks in comparison with whites are at risk for a more serious form of hypertension with high rates of complications. Greater sodium retention is thought to underlie the blood pressure (BP)-determining physiology of blacks, but specific mechanisms have not been identified. In a prospective observational study of BP, 226 black children and 314 white children (mean age, 10.6 years) were enrolled initially. Assessments were repeated in 85 blacks and 136 whites after reaching adulthood (mean age, 31 years). The relationship of BP to plasma aldosterone concentration in the context of the prevailing level of plasma renin activity was studied in blacks and whites. In a secondary interventional study, 9-&agr; fludrocortisone was administered for 2 weeks to healthy adult blacks and whites to simulate hyperaldosteronism. BP responses in the 2 race groups were then compared. Although black children had lower levels of plasma renin activity and plasma aldosterone, their BP was positively associated with the plasma aldosterone concentration, an effect that increased as plasma renin activity decreased (P=0.004). Data from black adults yielded similar results. No similar relationship was observed in whites. In the interventional study, 9-&agr; fludrocortisone increased BP in blacks but not in whites. In conclusion, aldosterone sensitivity is a significant determinant of BP in young blacks. Although its role in establishing the risk of hypertension is not known, it could be as relevant as the actual level of aldosterone.