Faculty Bibliography

OBJECTIVE:The Diabetes in Children, Adolescents, and Young Adults (DiCAYA) network seeks to create a nationwide electronic health record (EHR)-based diabetes surveillance system. This study aimed to develop a DiCAYA-wide EHR-based computable phenotype (CP) to identify prevalent cases of diabetes. RESEARCH DESIGN AND METHODS/METHODS:We conducted network-wide chart reviews of 2,134 youth (aged <18 years) and 2,466 young adults (aged 18 to <45 years) among people with possible diabetes. Within this population, we compared the performance of three alternative CPs, using diabetes diagnoses determined by chart review as the gold standard. CPs were evaluated based on their accuracy in identifying diabetes and its subtype. RESULTS:The final DiCAYA CP requires at least one diabetes diagnosis code from clinical encounters. Subsequently, diabetes type classification was based on the ratio of type 1 diabetes (T1D) or type 2 diabetes (T2D) diagnosis codes in the EHR. For both youth and young adults, the sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) in finding diabetes cases were >90%, except for the specificity and NPV in young adults, which were slightly lower at 83.8% and 80.6%, respectively. The final DiCAYA CP achieved >90% sensitivity, specificity, PPV, and NPV in classifying T1D, and demonstrated lower but robust performance in identifying T2D, consistently maintaining >80% across metrics. CONCLUSIONS:The DiCAYA CP effectively identifies overall diabetes and T1D in youth and young adults, though T2D misclassification in youth highlights areas for refinement. The simplicity of the DiCAYA CP enables broad deployment across diverse EHR systems for diabetes surveillance.

OBJECTIVE:To compare hospitalization rates between African American (AA) and European American (EA) deceased-donor (DD) kidney transplant (KT) recipients during over a10-year period. METHOD/METHODS:Data from the Scientific Registry of Transplant Recipients and social determinants of health (SDoH), measured by the Social Deprivation Index, were used. Hospitalization rates were estimated for kidney recipients from AA and EA DDs who had one kidney transplanted into an AA and one into an EA, leading to four donor/recipient pairs (DRPs): AA/AA, AA/EA, EA/AA, and EA/EA. Poisson-Gamma models were fitted to assess post-transplant hospitalizations. RESULT/RESULTS:Unadjusted hospitalization rates (95% confidence interval) were higher among all DRP involving AA, 131.1 (122.5, 140.3), 134.8 (126.3, 143.8), and 102.4 (98.9, 106.0) for AA/AA, AA/EA, and EA/AA, respectively, compared to 97.1 (93.7, 100.6) per 1000 post-transplant person-years for EA/EA pairs. Multivariable analysis showed u-shaped relationships across SDoH levels within each DRP, but findings varied depending on recipients' race, i.e., AA recipients in areas with the worst SDoH had higher hospitalization rates. However, EA recipients in areas with the best SDoH had higher hospitalization rates than their counterparts. CONCLUSIONS:Relationship between healthcare utilization and SDoH depends on DRP, with higher hospitalization rates among AA recipients living in areas with the worst SDoH and among EA recipients in areas with the best SDoH profiles. SDoH plays an important role in driving disparities in hospitalizations after kidney transplantation.

In critically ill patients, fluid resuscitation with balanced crystalloids close to plasma osmolarity have a lower risk of electrolyte imbalances and demonstrated better clinical outcomes compared to normal saline (NS). While lactated ringer's (LR) has shown benefit over NS, plasma-lyte (PL) with a higher osmolarity and different electrolyte formulation is hypothesized to be superior. We performed a retrospective observational cohort study over 37 months at a tertiary hospital. Inclusion criteria were hospitalization in the surgical intensive care unit (SICU), trauma indication, ≥18 years old, and received either PL or LR. All PL administrations and every fifth patient with LR as resuscitation were included in order to match the sample size in each group. Primary outcomes were SICU length of stay (LOS), hospital LOS, and mortality. Secondary outcomes were biomarker changes from baseline. There were 113 patients in both PL and LR groups. The PL arm had higher APACHE II scores (16 vs 13, P = .033) and were more likely ventilated (39.3% vs 20.4%, P = .002) compared to LR. Median hospital LOS (12.0 vs 8.0, P < .001) and SICU LOS (6.0 vs 3.0, P < .001) are significantly longer in PL group compared to the LR group. However, there was no difference in in-hospital mortality (5.3% vs 3.5% P = .519) and SICU mortality (9.7% vs 5.3%, P > .208) between PL and LR. Overall, PL use was associated with prolonged hospital and SICU LOS. PL use did not demonstrate mortality benefit. However, patients were more critically ill in PL group based on higher APACHE II scores and higher rates of mechanical ventilation, which could be contributing to these unfavorable outcomes.

Plasma lipids are mainly carried in apolipoprotein B (apoB) containing lipoproteins. High levels of these lipoproteins are associated with several metabolic diseases and lowering their plasma levels are associated with reduced incidence of atherosclerotic cardiovascular disease. MicroRNAs (miRs) are small non-coding RNAs that reduce protein expression of their target mRNAs and are potential therapeutic agents. Here, we identified a novel miR-615-3p that interacts with human 3'-UTR of apoB mRNA, induces post-transcriptional mRNA degradation, and reduces cellular and secreted apoB100 in human hepatoma Huh-7 cells. Reducing cellular miR-615-3p levels by CRISPR-sgRNA increased cellular and secreted apoB100 indicating endogenous miR regulates apoB expression. Overexpression of miR-615-3p along with or without palmitic acid treatment decreased cellular and media apoB and increased cellular triglyceride levels without inducing endoplasmic reticulum stress. These studies have identified miR-615-3p as a negative regulator of apoB expression in human liver derived cells. It is likely that there are more miRs that regulate apoB-containing lipoprotein assembly and secretion. Discovery of additional miRs may uncover novel mechanisms that control lipoprotein assembly and secretion.

OBJECTIVES/OBJECTIVE:Detecting and treating severe hypoglycemia promptly after birth is crucial due to its association with adverse long-term neurodevelopmental outcomes. However, limited data are available on the optimal timing of glucose screening in asymptomatic high-risk neonates prone to hypoglycemia. Risk factors associated with asymptomatic high-risk neonates include late prematurity ≥35 and <37 weeks gestation (LPT), small-for-gestational-age (SGA), large-for-gestational-age (LGA), and infant-of-a-diabetic mother (IDM). This study aims to determine the incidence and the impact of individual risk factors on early hypoglycemia (defined as blood glucose ≤25 mg/dL in the initial hour after birth) in asymptomatic high-risk neonates. METHODS:All asymptomatic high-risk neonates ≥35 weeks gestation underwent early blood glucose screening within the first hour after birth (n=1,690). A 2-year retrospective analysis was conducted to assess the incidence of early neonatal hypoglycemia in this cohort and its association with hypoglycemia risk factors. RESULTS:Out of the 9,919 births, 1,690 neonates (17 %) had risk factors for neonatal hypoglycemia, prompting screening within the first hour after birth. Incidence rates for blood glucose ≤25 mg/dL and ≤15 mg/dL were 3.1 and 0.89 %, respectively. Of concern, approximately 0.5 % of all asymptomatic at-risk neonates had a blood glucose value of ≤10 mg/dL. LPT and LGA were the risk factors significantly associated with early neonatal hypoglycemia. CONCLUSIONS:Asymptomatic high-risk neonates, particularly LPT and LGA neonates, may develop early severe neonatal hypoglycemia identified by blood glucose screening in the first hour of life. Additional investigation is necessary to establish protocols for screening and managing asymptomatic high-risk neonates.

Introduction: COVID-19, in combination with steroid treatment, is known to propagate hyperglycemia in diabetic patients. The purpose of this study was to establish a new insulin protocol for diabetic patients with COVID-19 on the dexamethasone protocol for better glycemic control. Research Design and Methods: This was a retrospective cohort study conducted at NYU Langone Long Island Hospital from 1 July 2020 to 1 July 2021. Eligible cases had to meet the following inclusion criteria: age of 18 years or greater, history of or new-onset diabetes, diagnosis of COVID-19 and receiving the 10 day dexamethasone treatment, length of stay of at least 3 days with a minimum of 48 h of glucose monitoring, and requiring basal and prandial insulin with correction during hospital stay. Data were collected using the hospital"™s electronic record system. The total basal, prandial, and daily doses of insulin on the day at which glycemic control was achieved, or if glycemic control was not achieved by the discharge date, then on the completion date of the dexamethasone treatment, were collected and assessed. Results: A total of 145 patient cases were analyzed. About 46% of patients achieved glycemic control. The average insulin dose required was 0.67 (0.61"“0.74) unit/kg. The mean total dose of insulin was 59 units. The mean total basal dose was 21 units. The mean total prandial dose was 38 units. The average prandial doses were higher than the basal doses for all participants. Conclusions: Diabetic patients with COVID-19 on dexamethasone should be initiated on at least 0.6"“0.7 u/kg of insulin to achieve glycemic control.

We assessed our institutional practice of individualized insulin dosing for patients with type 2 diabetes receiving preoperative carbohydrate loading (CHO-L) within an enhanced recovery after surgery (ERAS®) protocol. Patients enrolled in an ERAS® protocol with concomitant type 2 diabetes received rapid acting insulin (Novolog®[insulin aspart]) prior to 50 g CHO-L on the day of surgery. Following CHO-L and the administration of insulin, no hypoglycemic episodes occurred with preoperative POC glucose values between 6.8 and 12.3 mmol/L (123 and 221 mg/dL). Our experience demonstrates that administering rapid acting insulin prior to CHO-L in patients with type 2 diabetes is feasible and targets the potentially negative influence CHO-L may impose on preoperative glycemia in this population. Important considerations of this approach are highlighted and an insulin dosing algorithm designed for non-specialty providers is suggested.

Hyperlipidemia predisposes individuals to cardio-metabolic diseases, the most common cause of global mortality. Microsomal triglyceride transfer protein (MTP) transfers multiple lipids and is essential for the assembly of apoB-containing lipoproteins. MTP inhibition lowers plasma lipids but causes lipid retention in the liver and intestine. Previous studies suggested two lipid transfer domains in MTP and that specific inhibition of triglycerides (TG) and not phospholipids (PL) transfer can lower plasma lipids without significant tissue lipid accumulation. However, how MTP transfers different lipids and the domains involved in these activities are unknown. Here, we tested a hypothesis that two different β-sandwich domains in MTP transfer TG and PL. Mutagenesis of charged amino acids in β2-sandwich had no effect on PL transfer activity indicating that they are not critical. In contrast, amino acids with bulky hydrophobic side chains in β1-sandwich were critical for both TG and PL transfer activities. Substitutions of these residues with smaller hydrophobic side chains or positive charges reduced, while negatively charged side chains severely attenuated MTP lipid transfer activities. These studies point to a common lipid transfer domain for TG and PL in MTP that is enriched with bulky hydrophobic amino acids. Furthermore, we observed a strong correlation in different MTP mutants with respect to loss of both the lipid transfer activities, again implicating a common binding site for TG and PL in MTP. We propose that targeting of areas other than the identified common lipid transfer domain might reduce plasma lipids without causing cellular lipid retention.