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.

Although all types of diabetes result in hyperglycemia, the pathophysiology of each type of diabetes is different. These guidelines summarize available data specific to the comprehensive care of youth with type 2 diabetes. The objective is to enrich the recognition of type 2 diabetes in youth, its risk factors, its pathophysiology, its management, and the prevention of associated complications. PATHOPHYSIOLOGY Glucose homeostasis is maintained by a balance between insulin secretion from the pancreatic b-cells and sensitivity to insulin in skeletal muscle, adipose tissue, and liver (1). When insulin sensitivity declines, insulin secretion must increase to maintain glucose tolerance, and, in most youth, decreased insulin sensitivity due to puberty and/or obesity is compensated by increased insulin secretion. However, when b-cells cannot secrete sufficient insulin to compensate for insulin resistance, abnormalities in glucose homeostasis ensue, potentially progressing to prediabetes and type 2 diabetes as b-cell function deteriorates further (2-9). The relationship between b-cell function and insulin sensitivity in adults and youth has been demonstrated to be a hyperbolic function and can be described mathematically as the product of insulin sensitivity and b-cell function, called the disposition index (DI) (1). The DI essentially expresses the amount of insulin being secreted relative to the degree of insulin resistance and is a constant for a given degree of glucose tolerance in any one individual. Overweight and obesity are major acquired contributors to the development of insulin resistance, particularly in the face of the physiologic insulin resistance characteristic of puberty. Robust pancreatic b-cell compensatory insulin secretion maintains normal glucose homeostasis. However, in adolescents with obesity who develop type 2 diabetes, there is severe peripheral and hepatic insulin resistance, with ;50% lower peripheral insulin sensitivity than peers with obesity without diabetes, along with increased fasting hepatic glucose production and inadequate firstand second-phase insulin secretion, resulting in ;85% lower DI (2). Additional abnormalities in youth with type 2 diabetes include impaired glucose sensitivity of insulin secretion, lower serum adiponectin concentrations, and reduced incretin effect (3,9-13). While upregulation of a-cell function with hyperglucagonemia has been implicated in the pathophysiology of type 2 diabetes in adults (14,15), there are limited data in youth with type 2 diabetes, with studies showing either hyperglucagonemia or no difference from control subjects without diabetes (3,11,16,17). Cross-sectional and longitudinal studies in youth with obesity along the spectrum of glycemia from normoglycemia to prediabetes to type 2 diabetes show, as in adults, that b-cell failure with declining insulin secretion relative to insulin sensitivity results in prediabetes and type 2 diabetes in high-risk youth (5-9,18-21). Importantly, however, prior to reaching the American Diabetes Association (...

The incidence of type 2 diabetes mellitus in children is increasing with the increasing prevalence of obesity, particularly in African-American children. We hypothesized that African-American obese adolescents are more insulin resistant than their white peers, but have lower insulin secretion, thus increasing their risk of type 2 diabetes mellitus. The present study investigated insulin sensitivity and secretion, visceral adiposity (VAT), and cardiovascular disease (CVD) risk profile in black obese adolescents (BOA) vs. white obese adolescents (WOA). Twenty-four BOA and 26 WOA underwent a hyperinsulinemic-euglycemic clamp to assess insulin sensitivity, a hyperglycemic clamp to determine insulin secretion, dual energy x-ray absorptiometry for body composition and computed tomography scan at L4-L5 to measure VAT and sc abdominal adipose tissue. Fasting lipid and automated blood pressure measurements were obtained. The WOA and BOA groups were divided into low VAT and high VAT groups. BOA compared with WOA of similar body mass index and percent body fat had less visceral adiposity, lower hepatic glucose production, and lower lipid levels. Visceral adiposity was associated with lower insulin sensitivity in both groups [low vs. high VAT; BOA, 2.9 +/- 0.4 vs. 1.7 +/- 0.2 micromol/kg x min per pmol/liter (P = 0.016); WOA, 2.6 +/- 0.5 vs. 1.5 +/- 0.1 (P = 0.032)]. However, this was compensated by higher insulin secretion in whites (low VAT, 934.8 +/- 121.8; high VAT, 1590.6 +/- 232.8 pmol/liter; P = 0.037), but not in blacks (low VAT, 1398.9 +/- 214.0; high VAT, 1423.7 +/- 108.7 pmol/liter). Glucose disposition index (insulin sensitivity x first phase insulin) was lower in high VAT vs. low VAT BOA, but not in WOA. In each racial group, high VAT groups had elevation of systolic and diastolic blood pressure, but dyslipidemia was worse in WOA with high VAT. In conclusion, a given level of body mass index confers different metabolic risks for WOA vs. BOA. Although differences in fat patterning may help explain the more atherogenic risk profile in whites, the cause of the more diabetogenic insulin sensitivity/secretion profile in blacks remains unknown and needs to be investigated further.

No abstract

OBJECTIVE -Adiponectin is an adipose tissue protein that enhances insulin sensitivity and has antiatherogenic properties. The present study investigated the relationship of adiponectin levels in adolescents to 1) obesity and body fat distribution and 2) insulin sensitivity and the components of syndrome X.RESEARCH DESIGN AND METHODS -Twenty-three normal-weight and 26 obese adolescents had fasting adiponectin, lipid profile, and proinsulin measurements performed. Hepatic and peripheral insulin sensitivity were assessed with constant-rate [6,6-2 H 2 ]glucose infusion and a 3-h hyperinsulinemic-euglycemic clamp, respectively. Body composition was evaluated by dual-energy X-ray absorptiometry, and visceral adipose tissue (VAT) and subcutaneous adipose tissue were measured by computed tomography scan at the L 4 -L 5 level.RESULTS -Obese adolescents had ϳ50% lower adiponectin than normal-weight adolescents. Moreover, obese adolescents with high (111.8 Ϯ 9.3 cm 2 ) versus low (55.4 Ϯ 2.1 cm 2 ) VAT had lower adiponectin levels (6.2 Ϯ 0.9 vs. 9.0 Ϯ 1.0 g/ml, P ϭ 0.05). Plasma adiponectin correlated positively with peripheral and hepatic insulin sensitivity (r ϭ 0.67, P Ͻ 0.001 and r ϭ 0.54, P Ͻ 0.001, respectively) and HDL (r ϭ 0.52, P Ͻ 0.001) and negatively with fasting proinsulin and the proinsulin-to-insulin ratio (r ϭ Ϫ0.64, P Ͻ 0.001 and r ϭ Ϫ0.43, P ϭ 0.003, respectively). In a multiple regression analysis, adiponectin, independently and together with BMI, explained 73% (R 2 ϭ 0.73, P Ͻ 0.001) of the variance in insulin sensitivity. Adiponectin, but not adiposity, was the significant independent determinant of the proinsulin-to-insulin ratio (R 2 ϭ 0.18, P ϭ 0.008) and of HDL (R 2 ϭ 0.45, P Ͻ 0.001).CONCLUSIONS -In summary, hypoadiponectinemia in youth is a strong and independent correlate of insulin resistance, ␤-cell dysfunction, visceral adiposity, and syndrome X. The antidiabetogenic and antiatherogenic properties of adiponectin are evident early in life and compromised in youth-onset obesity.

OBJECTIVEWe compared acylcarnitine (AcylCN) species, common amino acid and fat oxidation (FOX) byproducts, and plasma amino acids in normal weight (NW; n = 39), obese (OB; n = 64), and type 2 diabetic (n = 17) adolescents.RESEARCH DESIGN AND METHODSFasting plasma was analyzed by tandem mass spectrometry, body composition by dual energy X-ray absorptiometry and computed tomography, and total-body lipolysis and substrate oxidation by [2H5]glycerol and indirect calorimetry, respectively. In vivo insulin sensitivity (IS) was assessed with a 3-h hyperinsulinemic-euglycemic clamp.RESULTSLong-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.CONCLUSIONSThese 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.

No abstract

OBJECTIVE -This study evaluates insulin sensitivity, pancreatic ␤-cell function (BCF), and the balance between the two in youth with type 2 diabetes and assesses the relationship of diabetes duration and HbA 1c to insulin sensitivity and BCF.RESEARCH DESIGN AND METHODS -The subjects were 14 adolescents with type 2 diabetes and 20 obese control subjects of comparable age, BMI, body composition, and puberty. Insulin sensitivity was evaluated with a 3-h hyperinsulinemic (80 mU ⅐ m -2 ⅐ min -1 ) euglycemic clamp. First-phase insulin secretion (FPIS) and second-phase insulin secretion (SPIS) were evaluated with a 2-h hyperglycemic (12.5 mmol/l) clamp. Fasting glucose rate of appearance was determined with the use of [6,6-2 H 2 ]glucose.RESULTS -Fasting glucose rate of appearance was higher in type 2 diabetic patients than in obese control subjects (16.5 Ϯ 1.1 vs. 12.3 Ϯ 0.5 mol ⅐ kg -1 ⅐ min -1 ; P ϭ 0.002). Insulin sensitivity was lower in type 2 diabetic patients than in obese control subjects (1.0 Ϯ 0.1 vs. 2.0 Ϯ 0.2 mol ⅐ kg -1 ⅐ min -1 per pmol/l; P ϭ 0.001). Fasting insulin was higher in type 2 diabetic patients than in obese control subjects (289.8 Ϯ 24.6 vs. 220.2 Ϯ 18.0 pmol/l; P ϭ 0.007), and FPIS and SPIS were lower (FPIS: 357.6 Ϯ 42.0 vs. 1,365.0 Ϯ 111.0 pmol/l; SPIS: 652.2 Ϯ 88.8 vs. 1,376.4 Ϯ 88.8 pmol/l; P Ͻ 0.001 for both). The glucose disposition index (GDI ϭ insulin sensitivity ϫ FPIS) was ϳ86% lower in type 2 diabetic patients than in obese control subjects. HbA 1c correlated with FPIS (r ϭ Ϫ0.61, P ϭ 0.025) with no relationship to insulin sensitivity.CONCLUSIONS -Despite the impairment in both insulin sensitivity and BCF in youth with type 2 diabetes, the magnitude of the derangement is greater in BCF than insulin sensitivity when compared with that in obese control subjects. The inverse relationship between BCF and HbA 1c may either reflect the impact of deteriorating BCF on glycemic control or be a manifestation of a glucotoxic phenomenon on BCF. Future studies in youth type 2 diabetes should target the natural course of ␤-cell failure and means of retarding and/or preventing it. Diabetes Care 28:638 -644, 2005D espite the increasing rate of type 2 diabetes in youth, the information on its pathophysiology is mostly derived from adult studies (1). Decreased insulin sensitivity and impaired ␤-cell function (BCF) are the two key components in type 2 diabetes pathogenesis (2-4). The development sequence of these abnormalities has been long debated. Several studies in adults proposed that insulin resistance with compensatory hyperinsulinemia is the initial step in type 2 diabetes pathogenesis (2,4). This is an implication of the hyperbolic relationship between insulin sensitivity and BCF, which calls for an increase in insulin secretion when insulin sensitivity decreases (4). The subsequent step in type 2 diabetes pathogenesis is impaired early insulin secretion, leading to postprandial and, later, fasting hyperglycemia (at which time clinical diabetes becomes evident). This sequence has also been do...