Objectives To compare complex quantitative magnetic resonance imaging (MRI) with MR spectroscopy (MRS) for quantification of hepatic steatosis (HS) and determine clinically significant MRI-based thresholds of HS in female youths. Methods This prospective, cross-sectional study was conducted in 132 healthy females (11–22 years, mean 13.3 ± 2). Proton density fat-fraction (PDFF) was measured using complex quantitative MRI and MRS. Body mass index (BMI), fasting labs [glucose, insulin, alanine aminotransferase (ALT), and other metabolic markers] were obtained. Outcomes were measured using regression analysis, Spearman-rank correlation, and receiver operator characteristics (ROC) analysis. HS was defined as MRI-PDFF >5.6 %. Results HS was detected by MRI-PDFF in 15 % of all subjects. Linear regression demonstrated excellent correlation and agreement [r2 = 0.96, slope = 0.97 (95 %CI: 0.94–1.00), intercept = 0.78 % (95 %CI: 0.58–0.98 %)] between MRI-PDFF and MRS-PDFF. MRI-PDFF had a sensitivity of 100 % (95 %CI: 0.79–1.00), specificity of 96.6 % (95 %CI: 0.91–0.99), and a kappa index of 87 % (95 %CI: 0.75-0.99) for identifying HS. In overweight subjects with HS, MRI-PDFF correlated with ALT (r = 0.84, p < 0.0001) and insulin (r = 0.833, p < 0.001), but not with BMI or WC. ROC analysis ascertained an optimal MRI-PDFF threshold of 3.5 % for predicting metabolic syndrome (sensitivity = 76 %, specificity = 83 %). Conclusion Complex quantitative MRI demonstrates strong correlation and agreement with MRS to quantify hepatic triglyceride content in adolescent girls and young women. A low PDFF threshold is predictive of metabolic syndrome in this population.
Purpose of review Recombinant human growth hormone (hGH) therapy in children with Prader–Willi syndrome (PWS) improves linear growth, body composition, physical strength and agility, and other metabolic parameters. These benefits must be weighed against potential adverse effects, including rare occurrences of sudden death. This review summarizes recent evidence important to a benefit–risk analysis of hGH use in children with PWS. Recent findings Studies consistently show that hGH improves stature, body composition, fat percentage and distribution, and other metabolic markers in children with PWS. Preliminary reports of improved cognitive development during hGH have also emerged. Scoliosis progression is influenced by growth rate, but frequency of occurrence and severity are not increased by hGH exposure. PWS genotype does not appear to affect response to hGH. Concerns about hGH-associated sudden death persist, but recent studies show either absence of change in sleep-disordered breathing or improved sleep cardiovascular function during hGH therapy. Summary Recent studies confirm and expand reported benefits of hGH therapy in children with PWS, including a possible salutary role in cognitive development. These findings support previous assertions that hGH can reduce morbidity and improve function in children with PWS, and suggest that potential risks of such treatment are favorably balanced by its benefits.
Objectives To develop a risk assessment model for early detection of hepatic steatosis using common anthropometric and metabolic markers. Study design Cross-sectional study of 134 girls, age 11–22 years (mean 13.3±2), Ethnicity: 27% Hispanic, 73% Non-Hispanic; Race: 64% Caucasian, 31% African-American, 5% Asian, from a middle school and clinics (Madison, WI). Fasting glucose, fasting insulin, alanine aminotransferase (ALT), body mass index (BMI), waist circumference (WC) and other metabolic markers were assessed. Hepatic fat was quantified using magnetic resonance proton density fat fraction (MR-PDFF). Hepatic steatosis was defined as MR-PDFF >5.5%. Outcome measures were sensitivity, specificity, and positive predictive value (PPV) of BMI, WC, ALT, fasting insulin and ethnicity as predictors of hepatic steatosis, individually and combined, in a risk assessment model. Classification and regression tree methodology constructed a decision tree for predicting hepatic steatosis. Results MR-PDFF revealed hepatic steatosis in 16% of subjects (27% overweight, 3% non-overweight). Hispanic ethnicity conferred an odds ratio of 4.26 (CI 1.65–11.04, p=0.003) for hepatic steatosis. BMI and ALT did not independently predict hepatic steatosis. A BMI > 85% combined with ALT > 65 U/L had 9% sensitivity, 100% specificity and 100% PPV. Lowering ALT to 24 U/L increased sensitivity to 68%, but reduced PPV to 47%. A risk assessment model incorporating fasting insulin, total cholesterol, WC, and ethnicity increased sensitivity to 64%, specificity to 99% and PPV to 93%. Conclusions A risk assessment model can increase specificity, sensitivity, and PPV for identifying risk of hepatic steatosis and guide efficient use of biopsy or imaging for early detection and intervention.
To evaluate the contemporary prevalence of diabetic peripheral neuropathy (DPN) in participants with type 1 diabetes in the T1D Exchange Clinic Registry throughout the U.S. RESEARCH DESIGN AND METHODSDPN was assessed with the Michigan Neuropathy Screening Instrument Questionnaire (MNSIQ) in adults with ‡5 years of type 1 diabetes duration. A score of ‡4 defined DPN. Associations of demographic, clinical, and laboratory factors with DPN were assessed. RESULTSAmong 5,936 T1D Exchange participants (mean 6 SD age 39 6 18 years, median type 1 diabetes duration 18 years [interquartile range 11, 31], 55% female, 88% non-Hispanic white, mean glycated hemoglobin [HbA 1c ] 8.1 6 1.6% [65.3 6 17.5 mmol/mol]), DPN prevalence was 11%. Compared with those without DPN, DPN participants were older, had higher HbA 1c , had longer duration of diabetes, were more likely to be female, and were less likely to have a college education and private insurance (all P < 0.001). DPN participants also were more likely to have cardiovascular disease (CVD) (P < 0.001), worse CVD risk factors of smoking (P 5 0.008), hypertriglyceridemia (P 5 0.002), higher BMI (P 5 0.009), retinopathy (P 5 0.004), reduced estimated glomerular filtration rate (P 5 0.02), and Charcot neuroarthropathy (P 5 0.002). There were no differences in insulin pump or continuous glucose monitor use, although DPN participants were more likely to have had severe hypoglycemia (P 5 0.04) and/or diabetic ketoacidosis (P < 0.001) in the past 3 months. CONCLUSIONSThe prevalence of DPN in this national cohort with type 1 diabetes is lower than in prior published reports but is reflective of current clinical care practices. These data also highlight that nonglycemic risk factors, such as CVD risk factors, severe hypoglycemia, diabetic ketoacidosis, and lower socioeconomic status, may also play a role in DPN development.Diabetic neuropathy is a prevalent complication in patients with diabetes and a major cause of morbidity and mortality (1). Among the various forms of diabetic neuropathy, distal symmetric polyneuropathy (DPN) and diabetic autonomic neuropathies are by far the most studied (1).
Purpose-To determine whether waist circumference (WC) is a better predictor of insulin resistance (IR) compared with body mass index (BMI) in US adolescents 12-18 years.Methods-Using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2002, we evaluated an ethnically diverse sample of 1571 adolescents with BMI, WC, and fasting glucose and insulin levels. Children were classified as having IR if they had a homeostasis model assessment of insulin resistance (insulin (μU/ml) × glucose (mmol/l))/22.5) greater than 4.39. We created receiver operating characteristic (ROC) curves predicting IR across various thresholds of WC and BMI, and area under the curve (AUC) was compared.Results-The prevalence of IR for the population was 11.8%. Measures of test performance (sensitivity and specificity) for predicting IR were similar for abnormal BMI and WC thresholds; i.e. thresholds of BMI 85 th % and WC 75 th %, and thresholds of BMI 95 th % and WC 90 th % were quite similar. There were no significant differences in AUC for WC versus BMI 0.85 (95% CI 0.83-0.88) (p=0.84) for the overall population or for specific racial groups.Conclusions-WC does not appear to provide a distinct advantage over BMI for identifying adolescents with IR.
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