Two- vs one-hour glucose tolerance testing: Predicting prediabetes in adolescent girls with obesity.

BACKGROUND: During an oral glucose tolerance test (OGTT), morphological features of the glucose curve (monophasic curve, glucose peak >30 minutes and 1-hour glucose ≥ 155 mg/dL) maybe associated with higher prediabetes risk, but their reproducibility and predictive ability in adolescents with obesity are unknown. METHODS: Nondiabetic adolescent girls with obesity underwent a multiple-sample OGTT at baseline (n = 93), 6 weeks (n = 83), and 1 year (n = 72). Short-term reproducibility (baseline to 6 weeks) and the predictive ability for prediabetes (baseline to 1 year) for each feature were compared with standard fasting and 2-hour OGTT diagnostic criteria. RESULTS: There was fair/moderate short-term reproducibility (κ < 0.5) for all morphological features. At 1 year, compared with standard OGTT criteria, the areas under the receiver operating curve (ROC-AUCs) for glucose peak > 30 minutes, 1 hour ≥155 mg/dL or a combination of the two criteria were comparable (all P > 0.05), but the monophasic curve had the lowest ROC-AUC (P < 0.001). CONCLUSIONS: In adolescent girls with obesity, glucose peak > 30 minutes and/or glucose ≥155 mg/dL had similar reproducibility and 1-year predictive ability for prediabetes compared with standard OGTT criteria. The shortened 1-hour OGTT may provide diagnostic equivalence for prediabetes risk with the additional advantage of a less time-consuming risk assessment.

Improving paediatric residents' knowledge and perspectives regarding the insulin pump using a novel educational workshop.

OBJECTIVES: As a pilot study, we aimed to investigate the knowledge and perceptions of categorical paediatric residents (RES) at our institution regarding insulin pumps (IPs) and the impact following a targeted workshop. METHODS: All RES at our institution in attendance at a routine noon conference participated in a workshop, completing an anonymous survey before and right after the intervention to evaluate knowledge, attitudes and self-reported comfort regarding IPs. The workshop consisted of a didactic lecture followed by an insulin pump (IP) device demonstration of three commonly available brands. Knowledge score (KS) was calculated for each RES based on the total correct responses. Attitudes were assessed via 5-point Likert scale. Frequencies, t-test and McNemar tests were used to analyse data. RESULTS: Thirty four completed surveys were analysed out of 49 RES (69.3%) who attended the workshop. Among them, there were 19 first-year, 8 second-year and 7 third-year residents. Following the intervention, KS increased significantly (p<0.001) with progression in residents' attitudes. Overall, more RES reported being comfortable with handling the IP, including looking up and changing the settings (p<0.001). CONCLUSION: There is scope for improvement in the knowledge and perceptions of RES regarding IPs. Educational interventions like ours are needed to familiarise our future physicians with IPs to allow hospitals to provide their systematic and safe inpatient use.

Time to glucose peak during an oral glucose tolerance test identifies prediabetes risk.

CONTEXT: Morphological characteristics of the glucose curve during an oral glucose tolerance test (OGTT) (time to peak and shape) may reflect different phenotypes of insulin secretion and action, but their ability to predict diabetes risk is uncertain. OBJECTIVE: To compare the ability of time to glucose peak and curve shape to detect prediabetes and ß-cell function. DESIGN AND PARTICIPANTS: In a cross-sectional evaluation using an OGTT, 145 adults without diabetes (age 42±9 years (mean±SD), range 24-62 years, BMI 29.2±5.3 kg/m2 , range 19.9-45.2 kg/m2 ) were characterized by peak (30 minutes vs >30 minutes) and shape (biphasic vs monophasic). MAIN OUTCOME MEASURES: Prediabetes and disposition index (DI)-a marker of ß-cell function. RESULTS: Prediabetes was diagnosed in 36% (52/145) of participants. Peak>30 minutes, not monophasic curve, was associated with increased odds of prediabetes (OR: 4.0 vs 1.1; P<.001). Both monophasic curve and peak>30 minutes were associated with lower DI (P≤.01). Time to glucose peak and glucose area under the curves (AUC) were independent predictors of DI (adjR2 =0.45, P<.001). CONCLUSION: Glucose peak >30 minutes was a stronger independent indicator of prediabetes and ß-cell function than the monophasic curve. Time to glucose peak may be an important tool that could enhance prediabetes risk stratification.

Glycemia and Gluconeogenesis With Metformin and Liraglutide: A Randomized Trial in Youth-onset Type 2 Diabetes.

OBJECTIVE: Elevated rates of gluconeogenesis are an early pathogenic feature of youth-onset type 2 diabetes (Y-T2D), but targeted first-line therapies are suboptimal, especially in African American (AA) youth. We evaluated glucose-lowering mechanisms of metformin and liraglutide by measuring rates of gluconeogenesis and ß-cell function after therapy in AA Y-T2D. METHODS: In this parallel randomized clinical trial, 22 youth with Y-T2D-age 15.3 ± 2.1 years (mean ± SD), 68% female, body mass index (BMI) 40.1 ± 7.9 kg/m2, duration of diagnosis 1.8 ± 1.3 years-were randomized to metformin alone (Met) or metformin + liraglutide (Lira) (Met + Lira) and evaluated before and after 12 weeks. Stable isotope tracers were used to measure gluconeogenesis [2H2O] and glucose production [6,6-2H2]glucose after an overnight fast and during a continuous meal. ß-cell function (sigma) and whole-body insulin sensitivity (mSI) were assessed during a frequently sampled 2-hour oral glucose tolerance test. RESULTS: At baseline, gluconeogenesis, glucose production, and fasting and 2-hour glucose were comparable in both groups, though Met + Lira had higher hemoglobin A1C. Met + Lira had a greater decrease from baseline in fasting glucose (-2.0 ± 1.3 vs -0.6 ± 0.9 mmol/L, P = .008) and a greater increase in sigma (0.72 ± 0.68 vs -0.05 ± 0.71, P = .03). The change in fractional gluconeogenesis was similar between groups (Met + Lira: -0.36 ± 9.4 vs Met: 0.04 ± 12.3%, P = .9), and there were no changes in prandial gluconeogenesis or mSI. Increased glucose clearance in both groups was related to sigma (r = 0.63, P = .003) but not gluconeogenesis or mSI. CONCLUSION: Among Y-T2D, metformin with or without liraglutide improved glycemia but did not suppress high rates of gluconeogenesis. Novel therapies that will enhance ß-cell function and target the elevated rates of gluconeogenesis in Y-T2D are needed.

The accuracy of the olfactory sense in detecting alcohol intoxication in trauma patients.

INTRODUCTION: A common presentation to the emergency department (ED) is the trauma patient with altered sensorium who is presumed to be alcohol intoxicated by physicians based on their olfactory sense. ED physicians may often leave patients suspected of alcohol intoxication aside until the effects wear off, potentially missing trauma as the source of confusion. This often results in delays in diagnosing acute potentially life-threatening injuries in patients with presumed alcohol intoxication. OBJECTIVE: This study aimed to determine the accuracy of a physician's olfactory sense for diagnosing alcohol intoxication. METHODS: Patients suspected of major trauma in the ED underwent an evaluation by the examining physician for alcohol odour and a blood alcohol level. Alcohol intoxication was defined as a serum ethanol level ≥80 mg/100 ml. Data were reported as means with 95% CI or proportions with IQR 25-75%. RESULTS: 151 patients (70% men) were enrolled, with a median age of 45 years (IQR 33-56). The prevalence of alcohol intoxication was 43% (95% CI 35% to 51%). OPERATING CHARACTERISTICS: Physician assessment of alcohol intoxication: sensitivity 84% (95% CI 73% to 92%), specificity 87% (95% CI 78% to 93%), positive likelihood ratio 6.6 (95% CI 3.8 to 11.6), negative likelihood ratio 0.18 (95% CI 0.1 to 0.3) and accuracy 86% (95% CI 80% to 91%). 7.3% (95% CI 4% to 13%) of patients were falsely suspected of being intoxicated. CONCLUSIONS: Although the physicians had a high degree of accuracy in identifying patients with alcohol intoxication based on their olfactory sense, they still falsely overestimated intoxication in significant numbers of non-intoxicated trauma patients.

National Survey Assessment of the United States' Pediatric Residents' Knowledge, Attitudes, and Practices Regarding Newborn Screening.

A pediatrician's approach to newborn screening (NBS) impacts patient care. Some physicians have reported not being well prepared to inform families about a positive NBS and recommend further follow-up. The knowledge and approach of categorical pediatric residents (RES) in the United States regarding NBS is not known. They were anonymously surveyed via listserv maintained by American Academy of Pediatrics. A total of 655 responses were analyzed. The mean composite knowledge score (CKS) was 17.7 (SD 1.8), out of maximum 21. Training level (p = 0.001) and completing NICU rotation (p < 0.001) predicted higher CKS. Most RES agreed that NBS is useful and pediatricians play an important role in the NBS process, however, only 62% were comfortable with counseling. Higher level RES were more likely to follow NBS results in clinic (p = 0.0027) and know the contact agency for results (p < 0.001). Most RES wanted more NBS training during residency and were not aware of clinical algorithms like ACTion sheets developed by American College of Medical Genetics. We concluded that although RES have sufficient knowledge about NBS, there is a need for earlier RES education on available tools for NBS to enhance their comfort level and improve practices such as educating parents about the NBS process.

Gluconeogenesis and risk for fasting hyperglycemia in Black and White women.

Black women, compared with White women, have high rates of whole-body insulin resistance but a lower prevalence of fasting hyperglycemia and hepatic steatosis. This dissociation of whole-body insulin resistance from fasting hyperglycemia may be explained by racial differences in gluconeogenesis, hepatic fat, or tissue-specific insulin sensitivity. Two groups of premenopausal federally employed women, without diabetes were studied. Using stable isotope tracers, [2H2O] and [6,62-H2]glucose, basal glucose production was partitioned into its components (gluconeogenesis and glycogenolysis) and basal whole-body lipolysis ([2H5]glycerol) was measured. Indices of insulin sensitivity, whole-body (SI), hepatic (HISIGPR), and adipose tissue, were calculated. Hepatic fat was measured by proton magnetic resonance spectroscopy. Black women had less hepatic fat and lower fractional and absolute gluconeogenesis. Whole-body SI, HISIGPR, and adipose tissue sensitivity were similar by race, but at any given level of whole-body SI, Black women had higher HISIGPR. Therefore, fasting hyperglycemia may be a less common early pathological feature of prediabetes in Black women compared with White women, because gluconeogenesis remains lower despite similar whole-body SI.

Cushing Disease in a patient with Multiple Endocrine Neoplasia type 2B.

CONTEXT: Multiple endocrine neoplasia type 2B (MEN2B) is a rare autosomal-dominant cancer syndrome characterized in part by metastatic medullary thyroid cancer (MTC) and pheochromocytoma. Cushing disease is a rare cause of endogenous hypercortisolism in children. CASE DESCRIPTION: We describe a 21-year-old African-American male who was diagnosed at age 10 with an ACTH-secreting pituitary microadenoma. At age 16 he developed medullary thyroid cancer and was found to have multiple endocrine neoplasia type 2B with the characteristic M918T mutation of the RET proto-oncogene. Following thyroidectomy, he was initiated on Vandetanib, a tyrosine kinase inhibitor, and has since had stable disease over the last 5 years. CONCLUSIONS: Our patient is the first individual with MEN2B to be described with Cushing disease. The RET oncogene may play a role in pituitary tumorigenesis; alternatively, the coexistence of these two entities may represent an extremely rare coincidence.