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.

OBJECTIVEThe shape of the glucose response curve during an oral glucose tolerance test (OGTT), monophasic versus biphasic, identifies physiologically distinct groups of individuals with differences in insulin secretion and sensitivity. We aimed to verify the value of the OGTT-glucose response curve against more sensitive clamp-measured biomarkers of type 2 diabetes risk, and to examine incretin/pancreatic hormones and free fatty acid associations in these curve phenotypes in obese adolescents without diabetes.RESEARCH DESIGN AND METHODSA total of 277 obese adolescents without diabetes completed a 2-h OGTT and were categorized to either a monophasic or a biphasic group. Body composition, abdominal adipose tissue, OGTT-based metabolic parameters, and incretin/pancreatic hormone levels were examined. A subset of 106 participants had both hyperinsulinemic-euglycemic and hyperglycemic clamps to measure in vivo insulin sensitivity, insulin secretion, and β-cell function relative to insulin sensitivity.RESULTSDespite similar fasting and 2-h glucose and insulin concentrations, the monophasic group had significantly higher glucose, insulin, C-peptide, and free fatty acid OGTT areas under the curve compared with the biphasic group, with no differences in levels of glucagon, total glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide, and pancreatic polypeptide. Furthermore, the monophasic group had significantly lower in vivo hepatic and peripheral insulin sensitivity, lack of compensatory first and second phase insulin secretion, and impaired β-cell function relative to insulin sensitivity.CONCLUSIONSIn obese youth without diabetes, the risk imparted by the monophasic glucose curve compared with biphasic glucose curve, independent of fasting and 2-h glucose and insulin concentrations, is reflected in lower insulin sensitivity and poorer β-cell function, which are two major pathophysiological biomarkers of type 2 diabetes in youth.

Using the hyperglycemic and euglycemic clamp, we demonstrated impaired β-cell function in obese youth with increasing dysglycemia. Herein we describe oral glucose tolerance test (OGTT)-modeled β-cell function and incretin effect in obese adolescents spanning the range of glucose tolerance. β-Cell function parameters were derived from established mathematical models yielding β-cell glucose sensitivity (βCGS), rate sensitivity, and insulin sensitivity in 255 obese adolescents (173 with normal glucose tolerance [NGT], 48 with impaired glucose tolerance [IGT], and 34 with type 2 diabetes [T2D]). The incretin effect was calculated as the ratio of the OGTT-βCGS to the 2-h hyperglycemic clamp-βCGS. Incretin and glucagon concentrations were measured during the OGTT. Compared with NGT, βCGS was 30 and 65% lower in youth with IGT and T2D, respectively; rate sensitivity was 40% lower in T2D. Youth with IGT or T2D had 32 and 38% reduced incretin effect compared with NGT in the face of similar changes in GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) in response to oral glucose. We conclude that glucose sensitivity deteriorates progressively in obese youth across the spectrum of glucose tolerance in association with impairment in incretin effect without reduction in GLP-1 or GIP, similar to that seen in adult dysglycemia.

Objective This study examined adherence to a personalized, community-based exercise intervention by sedentary adolescents with type 1 or type 2 diabetes or those with obesity. Research design and Methods We conducted a pretest–posttest investigation to explore the application of an individualized exercise prescription based upon current fitness level for 39 adolescents (20 with type 1 diabetes, 9 with type 2 diabetes, and 10 obese) over 16 weeks in community settings. Subjects were recruited from a university-based pediatric endocrinology clinic in the southwestern United States. Adherence to the exercise prescription was monitored using accelerometers over the entire intervention period. Results Moderate-to-vigorous physical activity (MVPA) levels significantly increased over sedentary baseline values (p < .001), but the average of 42.5 ± 22.1 min/day of MVPA determined at the end of the study was still less than the recommended 60 min/day. Perceptions of health were significantly increased for the total group following the intervention (p = .008). For those with type 1 diabetes, there was a significant association between MVPA duration and percentage change in HbA1c (r = −.526, p = .02). Conclusions Recruitment and retention of adolescent participation in daily exercise is challenging. Personalized approaches that include adolescent choices with family support and ongoing motivation can improve individual exercise adherence and a sense of personal health.

Purpose This exploratory study tested the feasibility of conducting a novel, personalized exercise intervention based upon the current fitness levels of adolescents with type 1 diabetes (T1DM). The relationships of perceptions of benefits and barriers to exercise, exercise self-efficacy and family support to exercise adherence and changes in cardiovascular (CV) fitness, quality of life (QOL), and glycemic control were studied. Methods Adolescents who were sedentary received a graded exercise test to determine their current fitness level (VO2peak). A 16-wk personalized exercise program was developed for each adolescent based upon individual fitness level and exercise preferences. Pretest and posttest measures of exercise self-efficacy, benefits and barriers to exercise, family support, and diabetes QOL were completed. A1c levels were obtained using the DCA2000®. Adherence to exercise was measured using the Actigraph™ Accelerometer. Results Twelve adolescents completed the study. Accelerometry data revealed adherence to 60 min of moderate-to-vigorous physical activity (MVPA) per day for a mean of 45.5 (SD = 23.9)% of the days the accelerometer was worn. Adolescents’ perceptions of family support for exercise improved following the intervention (p = 0.03). Adolescents who had more daily bouts of exercise lasting 60 min increased their CV fitness (r = 0.59, p = 0.04). A1c remained unchanged. Conclusions Encouraging 60 min of accumulated exercise bouts/d can improve fitness levels in adolescents with T1DM, minimizing future CV risks. Although physical activity increased in adolescents, family based strategies are required to promote current physical activity recommendations.

The purpose of this study was to describe the associations between levels of physical activity measured by accelerometry and changes in fitness, body composition, lipids, and glucose control (i.e., glycosolated hemoglobin [A1C]) in a sample of 16 adolescents with type 1 diabetes participating in a personalized exercise program. More sedentary activity was associated with lower fitness and fat free mass and increased total cholesterol, low-density lipoprotein (LDL-c), and triglycerides (p < .05). Greater amounts of moderate to vigorous activity were associated with higher fitness and fat free mass, and decreased total cholesterol, LDL-c, triglycerides, and A1C (p < .05). Findings support the beneficial effects of increased moderate activity and decreased sedentary behavior to reduce cardiovascular risks and improve glucose control in adolescents with type 1 diabetes.

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.

Adipose tissue insulin resistance is one of the pathophysiological components of type 2 diabetes. Herein we investigated: 1) adipose insulin resistance index (Adipose-IR) (calculated as fasting insulin 3 free fatty acids [FFAs]) in youth across the spectrum of adiposity from normal weight to obese and the spectrum from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) to type 2 diabetes, 2) the relationship of Adipose-IR with physical and metabolic characteristics, and 3) the predictive power of Adipose-IR for determining dysglycemia in youth. RESEARCH DESIGN AND METHODS A total of 205 youth had fasting glucose, insulin, FFA, Adipose-IR, body composition, visceral adipose tissue (VAT), leptin, and adiponectin evaluated. RESULTS Adipose-IR was 2.2-fold higher in obese NGT, 4.3-fold higher in IGT, and 4.6-fold higher in type 2 diabetes compared with that in normal-weight peers (all P < 0.05). Females with dysglycemia (IGT and type 2 diabetes) had higher Adipose-IR than their male counterparts (P < 0.001). Adipose-IR correlated positively with total body and visceral adiposity, fasting glucose, HOMA-IR, and leptin and negatively with adiponectin. Receiver operating characteristic curve analysis yielded an optimal cutoff for Adipose-IR of 9.3 mU/mL 3 mmol/L for determining dysglycemia with 80% predictive power. CONCLUSIONS Adipose-IR is a simple surrogate estimate that reflects pathophysiological alterations in adipose tissue insulin sensitivity in youth, with progressive deterioration from normal weight to obese and from NGT to IGT to type 2 diabetes. Adipose-IR can be applied in large-scale epidemiological/observational studies of the natural history of youth-onset type 2 diabetes and its progression or reversal with intervention strategies.