Effects of an Intravenous Lipid Challenge and Free Fatty Acid Elevation on In Vivo Insulin Sensitivity in African American Versus Caucasian Adolescents

OBJECTIVE—African American youth have lower insulin sensitivity than their Caucasian peers, but the metabolic pathways responsible for this difference remain unknown. Free fatty acids (FFAs) are associated with insulin resistance through the Randle cycle. The present investigation determined whether elevating FFA is more deleterious to insulin sensitivity in African American than in Caucasian adolescents

The Changing Face of Diabetes in Youth: Lessons Learned from Studies of Type 2 Diabetes

The incidence of youth type 2 diabetes (T2D), linked with obesity and declining physical activity in high-risk populations, is increasing. Recent multicenter studies have led to a number of advances in our understanding of the epidemiology, pathophysiology, diagnosis, treatment, and complications of this disease. As in adult T2D, youth T2D is associated with insulin resistance, together with progressive deterioration in β cell function and relative insulin deficiency in the absence of diabetes-related immune markers. In contrast to adult T2D, the decline in β cell function in youth T2D is three- to fourfold faster, and therapeutic failure rates are significantly higher in youth than in adults. Whether the more aggressive nature of youth T2D is driven by genetic heterogeneity or physiology/metabolic maladaptation is yet unknown. Besides metformin, the lack of approved pharmacotherapeutic agents for youth T2D that target the pathophysiological mechanisms is a major barrier to optimal diabetes management. There is a significant need for effective therapeutic options, in addition to increased prevention, to halt the projected fourfold increase in youth T2D by 2050 and the consequences of heightened diabetes-related morbidity and mortality at younger ages

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

Depressive symptoms and metabolic markers of risk for type 2 diabetes in obese adolescents

OBJECTIVE: Although higher rates of depression are found among individuals with type 2 diabetes, it remains unknown if the presence of depressive symptoms is associated with heightened metabolic risk for the development of type 2 diabetes among youth. The objective of this study was to evaluate whether depressive symptoms in obese adolescents are associated with impaired β-cell function relative to insulin sensitivity [oral disposition index (oDI)] and/or dysglycemia or prediabetes, predictors of type 2 diabetes development. RESEARCH DESIGN AND METHODS: Fasting and oral glucose tolerance test (OGTT)-derived indices of glucose tolerance, insulin sensitivity, secretion, and oDI were evaluated in obese youth (n = 56, age 15.0 ± 1.6 yr, 68% female). The Children's Depression Inventory was utilized to determine depressive symptomatology. RESULTS: Despite no association between depressive symptoms and measures of adiposity, youth with higher depressive symptoms had (i) significantly higher fasting and stimulated glucose levels (13% higher glucose area under the OGTT curve), (ii) ∼50% lower oDI, and (iii) a 50% frequency of prediabetes. CONCLUSIONS: These data point to an important relationship between depressive symptoms and a heightened metabolic risk for type 2 diabetes in obese adolescents, including prediabetes and impairment in β-cell function relative to insulin sensitivity. While the directionality of these relationships is unknown, it should be determined if treating one disorder improves the other or vice versa

Morning Blood Pressure is Associated with Sleep Quality in Obese Adolescents

Objective To examine relationships between blood pressure (BP), adiposity, and sleep quality using overnight polysomnography (PSG) in obese adolescents. Study design Overnight PSG and morning BP measurements were performed in obese (BMI >97th %ile) non-diabetic adolescents (eligible age range 12-18 years, n=49). Subjects were stratified into two groups, one with normal BP, and one with elevated BP, and demographic and clinical characteristics compared between the groups. Multiple linear regression analysis was used to assess the BP effects of sleep quality measures. Results Participants (n=27) had normal morning BP, and 22 (44.9%) had elevated morning BP. There were no differences in age (p=0.53), sex (p=0.44), race (p=0.58) or BMI (p=0.56) between the two BP groups. The group with elevated BP spent shorter percentages of time in rapid eye movement (REM; p=0.006) and slow-wave sleep (SWS; p=0.024). Multiple linear regression analysis showed a lower percent of both REM and SWS were associated with increased morning BP, after adjusting for pubertal stage, sex, race, and BMI. Conclusion Lack of deeper stages of sleep, REM sleep and SWS, is associated with higher morning BP in obese adolescents, independent of BMI. Poor sleep quality should be considered in the work-up of obese youth with hypertension. Intervention studies are needed to evaluate whether improving the quality of sleep will reduce blood pressure elevation

Pre-diabetes in overweight youth and early atherogenic risk

PURPOSE: To compare atherogenic lipoprotein particles and vascular smooth muscle biomarkers in overweight youth with pre-diabetes (PD) vs. normal glucose tolerance (NGT). METHODS: 144 adolescents (60 black, 84 white; 102 female; PD=45, NGT=99) aged 10-19 years underwent a fasting blood draw and 2-h OGTT. Lipoprotein particle size and subclass concentration and vascular smooth muscle biomarkers (ICAM-1, VCAM-1 and E-selectin) were compared between youth with PD and NGT. RESULTS: Compared with NGT, PD adolescents had smaller LDL (mean±SE: 20.5±0.1 vs. 21.0±0.1 nm; P=0.002) and HDL (8.62±0.05 vs. 8.85±0.04 nm; P=0.013) size and elevated medium small (159.2±10.3 vs. 123.8±6.4 nmol/L; P=0.037) and very small (626.3±45.4 vs. 458.5±26.4 nmol/L; P=0.032) LDL particle concentrations, after adjustment for race and BMI. Further adjusting for fasting insulin or visceral adiposity obviated these differences between the groups except for LDL size. ICAM-1 and E-selectin did not differ in youth with PD but correlated with LDL and HDL size, and small LDL particle concentrations. CONCLUSIONS: Overweight adolescents with PD have an atherogenic lipoprotein profile of small LDL and HDL size and increased concentrations of small LDL, moderated by insulin resistance and visceral adiposity, but independently driven by dysglycemia for LDL size. Associations between smooth muscle biomarkers and lipoproteins could be an early signal heralding the atherogenic process. It remains to be determined if correction of dysglycemia and associated lipoprotein abnormalities in obese youth could prove effective in halting this process

Phenotypic Type 2 Diabetes in Obese Youth: Insulin Sensitivity and Secretion in Islet Cell Antibody–Negative Versus –Positive Patients

OBJECTIVE— Some obese youth with a clinical diagnosis of type 2 diabetes have evidence of islet cell autoimmunity with positive autoantibodies. In this study, we investigated the differences in insulin sensitivity and secretion between autoantibody-negative (Ab−) and -positive (Ab+) youth with clinically diagnosed type 2 diabetes in comparison with control subjects

Clot Characterization in Acute Ischemic Stroke

Background: In the treatment of acute ischemic stroke (AIS) with mechanical thrombectomy, revascularization depends upon integration of the thrombus into the retrieval device. The histologic and mechanical characteristics of thrombi are key determinants of effective thrombus-device interaction. Thrombi with greater calcium and fibrin content have been associated with more challenging thrombus retrievals. Objective: To develop thrombus analogs with histologic and mechanical characteristics similar to those of challenging clinical thrombi for thrombectomy device testing. Methods: Fifty thrombi were retrieved from twenty-nine patients with AIS. Clinical thrombi underwent histologic analysis to determine erythrocyte and fibrin content. Nine clinical thrombi underwent dynamic mechanical analysis to determine thrombus stiffness, which was defined as a function of stress variation at low and high strains. Results from the clinical thrombi were used to determine the key mechanical characteristics of the challenging thrombus analogs, the calcium apatite-rich and fibrin-rich thrombus analogs. Results: Of the twenty-nine AIS cases, fifteen required multiple pass attempts. The average histologic composition of the challenging clinical thrombi was 26% erythrocyte, 54% fibrin, and 20% mixed. The average stiffness of the challenging clinical thrombi was found to be similar to that of the fibrin-rich thrombus analogs. Addition of calcium apatite increased the stiffness of the thrombus analogs at low strain approximately five-fold. Conclusions: Thrombus analogs with mechanical characteristics similar to those of challenging clinical thrombi were successfully developed. The calcium apatite-rich thrombus analogs were found to be stiffer than the fibrin-rich red thrombus analogs

Insulin autoantibodies as determined by competitive radiobinding assay are positively correlated with impaired beta-cell function — The Ulm-Frankfurt population study

Out of a random population of 4208 non-diabetic pupils without a family history of Type I diabetes 44 (1.05%) individuals had islet cell antibody (ICA) levels greater or equal to 5 Juvenile Diabetes Foundation (JDF) units. 39 of these ICA-positives could be repeatedly tested for circulating insulin autoantibodies (CIAA) using a competitive radiobinding assay. The results were compared with the insulin responses in the intravenous glucose tolerance tests (IVGTT) and with HLA types. Six pupils were positive for CIAA. All of them had complement-fixing ICA, and 5 of them were HLA-DR4 positive. Three of the 6 showed a first-phase insulin response below the first percentile of normal controls. Our data indicate that in population-based studies CIAA can be considered as a high risk marker for impaired beta-cell function in non-diabetic ICA-positive individuals