Continuous glucose monitoring (CGM) is an essential part of diabetes care. Real-time CGM data are beneficial to patients for daily glucose management, and aggregate summary statistics of CGM measures ...are valuable to direct insulin dosing and as a tool for researchers in clinical trials. Yet, the various commercial systems still report CGM data in disparate, non-standard ways. Accordingly, there is a need for a standardized, free, open-source approach to CGM data management and analysis. A package titled cgmanalysis was developed in the free programming language R to provide a rapid, easy, and consistent methodology for CGM data management, summary measure calculation, and descriptive analysis. Variables calculated by our package compare well to those generated by various CGM software, and our functions provide a more comprehensive list of summary measures available to clinicians and researchers. Consistent handling of CGM data using our R package may facilitate collaboration between research groups and contribute to a better understanding of free-living glucose patterns.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The molecular mechanisms of sodium-glucose cotransporter-2 (SGLT2) inhibitors (SGLT2i) remain incompletely understood. Single-cell RNA sequencing and morphometric data were collected from research ...kidney biopsies donated by young persons with type 2 diabetes (T2D), aged 12 to 21 years, and healthy controls (HCs). Participants with T2D were obese and had higher estimated glomerular filtration rates and mesangial and glomerular volumes than HCs. Ten T2D participants had been prescribed SGLT2i (T2Di+) and 6 not (T2Di-). Transcriptional profiles showed SGLT2 expression exclusively in the proximal tubular (PT) cluster with highest expression in T2Di(-) patients. However, transcriptional alterations with SGLT2i treatment were seen across nephron segments, particularly in the distal nephron. SGLT2i treatment was associated with suppression of transcripts in the glycolysis, gluconeogenesis, and tricarboxylic acid cycle pathways in PT, but had the opposite effect in thick ascending limb. Transcripts in the energy-sensitive mTORC1-signaling pathway returned toward HC levels in all tubular segments in T2Di(+), consistent with a diabetes mouse model treated with SGLT2i. Decreased levels of phosphorylated S6 protein in proximal and distal tubules in T2Di(+) patients confirmed changes in mTORC1 pathway activity. We propose that SGLT2i treatment benefits the kidneys by mitigating diabetes-induced metabolic perturbations via suppression of mTORC1 signaling in kidney tubules.
Atherosclerotic CVD is the major cause of death in patients with type 1 diabetes mellitus (T1DM). Alterations in the HDL proteome have been shown to associate with prevalent CVD in T1DM. We therefore ...sought to determine which proteins carried by HDL might predict incident CVD in patients with T1DM. Using targeted MS/MS, we quantified 50 proteins in HDL from 181 T1DM subjects enrolled in the prospective Coronary Artery Calcification in Type 1 Diabetes study. We used Cox proportional regression analysis and a case-cohort design to test associations of HDL proteins with incident CVD (myocardial infarction, coronary artery bypass grafting, angioplasty, or death from coronary heart disease). We found that only one HDL protein—SFTPB (pulmonary surfactant protein B)—predicted incident CVD in all the models tested. In a fully adjusted model that controlled for lipids and other risk factors, the hazard ratio was 2.17 per SD increase of SFTPB (95% confidence interval, 1.12–4.21, P = 0.022). In addition, plasma fractionation demonstrated that SFTPB is nearly entirely bound to HDL. Although previous studies have shown that high plasma levels of SFTPB associate with prevalent atherosclerosis only in smokers, we found that SFTPB predicted incident CVD in T1DM independently of smoking status and a wide range of confounding factors, including HDL-C, LDL-C, and triglyceride levels. Because SFTPB is almost entirely bound to plasma HDL, our observations support the proposal that SFTPB carried by HDL is a marker—and perhaps mediator—of CVD risk in patients with T1DM.
Insulin-secreting β-cells are functionally heterogeneous. Whether there exist cells driving the first-phase calcium response in individual islets, has not been examined. We examine "first responder" ...cells, defined by the earliest Ca2+ response during first-phase Ca2+ elevation, distinct from previously identified "hub" and "leader" cells. We used islets isolated from Mip-CreER; Rosa-Stop-Lox-Stop-GCamP6s mice (β-GCamP6s) that show β-cell-specific GCamP6s expression following tamoxifen-induced CreER-mediated recombination. First responder cells showed characteristics of high membrane excitability and lower electrical coupling to their neighbors. The first-phase response time of β-cells in the islet was spatially organized, dependent on the cell's distance to the first responder cell, and consistent over time up to approximately 24 h. When first responder cells were laser ablated, the first-phase Ca2+ was slowed down, diminished, and discoordinated compared to random cell ablation. Cells that were next earliest to respond often took over the role of the first responder upon ablation. In summary, we discover and characterize a distinct first responder β-cell state, critical for the islet first-phase response to glucose.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To characterize health-related quality of life (HRQL) and functional recovery trajectories and risk factors for prolonged impairments among critically ill children receiving greater than or equal to ...3 days of invasive ventilation.
Prospective cohort study.
Quaternary children's hospital PICU.
Children without a preexisting tracheostomy who received greater than or equal to 3 days of invasive ventilation, survived hospitalization, and completed greater than or equal to 1 postdischarge data collection.
None.
We evaluated 144 children measuring HRQL using proxy-report Pediatric Quality of Life Inventory and functional status using the Functional Status Scale (FSS) reflecting preillness baseline, PICU and hospital discharge, and 1, 3, 6, and 12 months after hospital discharge. They had a median age of 5.3 years (interquartile range, 1.1-13.0 yr), 58 (40%) were female, 45 (31%) had a complex chronic condition, and 110 (76%) had normal preillness FSS scores. Respiratory failure etiologies included lung disease ( n = 49; 34%), neurologic failure ( n = 23; 16%), and septic shock ( n = 22; 15%). At 1-month postdischarge, 68 of 122 (56%) reported worsened HRQL and 35 (29%) had a new functional impairment compared with preillness baseline. This improved at 3 months to 54 (46%) and 24 (20%), respectively, and remained stable through the remaining 9 months of follow-up. We used interaction forests to evaluate relative variable importance including pairwise interactions and found that therapy consultation within 3 days of intubation was associated with better HRQL recovery in older patients and those with better preillness physical HRQL. During the postdischarge year, 76 patients (53%) had an emergency department visit or hospitalization, and 62 (43%) newly received physical, occupational, or speech therapy.
Impairments in HRQL and functional status as well as health resource use were common among children with acute respiratory failure. Early therapy consultation was a modifiable characteristic associated with shorter duration of worsened HRQL in older patients.
Pharmacological Na
-glucose linked cotransporter (SGLT)2 inhibition is being examined as a renal protection strategy in nondiabetic chronic kidney disease. We quantified renal SGLT mRNA expression in ...healthy controls (HC), glomerulonephritis (GN), and diabetic kidney disease (DKD) to identify differences in expression across a spectrum of renal diseases. mRNA expression of SGLT1 and SGLT2 in renal tubules and glomeruli, obtained using microdissection and microarray techniques, was evaluated in two large cohorts. The European Renal cDNA bank included HC, GN, and DKD (98 glomeruli and 93 tubulointerstitium). The Nephrotic Syndrome Study Network cohort included 124 adults with membranous nephropathy, minimal change disease, focal segmental glomerulosclerosis, and IgA nephropathy. Within the European Renal cDNA bank, SGLT2 tubular and glomerular log
mRNA expression significantly differed across HC, GN, and DKD (
= 0.0009 and
= 0.0004), with the highest expression in HC. Within the Nephrotic Syndrome Study Network, there were no differences in SGLT log
mRNA expression across GN subtypes. Tubular SGLT2 log
mRNA expression positively correlated with estimated glomerular filtration rate (by the Modification of Diet in Renal Disease Study equation) and glycated hemoglobin (
= 0.33 and 0.34,
< 0.05) and inversely correlated with interstitial fibrosis (
= -0.21,
< 0.05). In conclusion, SGLT2 mRNA expression was lower in DKD compared with HC or GN and inversely related to interstitial fibrosis. The relationships between SGLT mRNA, protein expression, and transporter activity require further elucidation.
The objective of this study was to compare the ratio of renal oxygen availability (RO
) to glomerular filtration rate (GFR), a measure of relative renal hypoxia, in adolescents with and without type ...1 diabetes (T1D) and relate the ratio to albuminuria, renal plasma flow (RPF), fat mass, and insulin sensitivity (
). RO
was estimated by blood oxygen level-dependent MRI; fat mass was estimated by DXA; GFR and RPF were estimated by iohexol and
-aminohippurate clearance; albuminuria was estimated by urine albumin-to-creatinine ratio (UACR); and
was estimated from steady-state glucose infusion rate/insulin (mg/kg/min) by hyperglycemic clamp in 50 adolescents with T1D (age 16.1 ± 3.0 years, HbA
8.6 ± 1.2%) and 20 control patients of similar BMI (age 16.1 ± 2.9 years, HbA
5.2 ± 0.2%). The RO
:GFR (ms/mL/min) was calculated as RO
(T2*, ms) divided by GFR (mL/min). Whole-kidney RO
:GFR was 25% lower in adolescents with T1D versus control patients (
< 0.0001). In adolescents with T1D, lower whole-kidney RO
:GFR was associated with higher UACR (
= -0.31,
= 0.03), RPF (
= -0.52,
= 0.0009), and fat mass (
= -0.33,
= 0.02). Lower medullary RO
:GFR was associated with lower
(
= 0.31,
= 0.03). In conclusion, adolescents with T1D exhibited relative renal hypoxia that was associated with albuminuria and with increased RPF, fat mass, and insulin resistance. These data suggest a potential role of renal hypoxia in the development of diabetic kidney disease.
Postpartum women with overweight/obesity and a history of adverse pregnancy outcomes are at elevated risk for cardiometabolic disease. Postpartum weight loss and lifestyle changes can decrease these ...risks, yet traditional face-to-face interventions often fail. We adapted the Diabetes Prevention Program into a theory-based mobile health (mHealth) program called Fit After Baby (FAB) and tested FAB in a randomized controlled trial.
The FAB program provided 12 weeks of daily evidence-based content, facilitated tracking of weight, diet, and activity, and included weekly coaching and gamification with points and rewards. We randomized women at 6 weeks postpartum 2:1 to FAB or to the publicly available Text4baby (T4B) app (active control). We measured weight and administered behavioral questionnaires at 6 weeks, and 6 and 12 months postpartum, and collected app user data.
81 eligible women participated (77% White, 2% Asian, 15% Black, with 23% Hispanic), mean baseline BMI 32±5 kg/m2 and age 31±5 years. FAB participants logged into the app a median of 51/84 (IQR 25,71) days, wore activity trackers 66/84 (IQR 43,84) days, logged weight 17 times (IQR 11,24), and did coach check-ins 5.5/12 (IQR 4,9) weeks. The COVID-19 pandemic interrupted data collection for the primary 12-month endpoint, and impacted diet, physical activity, and body weight for many participants. At 12 months postpartum women in the FAB group lost 2.8 kg 95% CI -4.2,-1.4 from baseline compared to a loss of 1.8 kg 95% CI -3.8,+0.3 in the T4B group (p = 0.42 for the difference between groups). In 60 women who reached 12 months postpartum before the onset of the COVID-19 pandemic, women randomized to FAB lost 4.3 kg 95% CI -6.0,-2.6 compared to loss in the control group of 1.3 kg 95% CI -3.7,+1.1 (p = 0.0451 for the difference between groups).
There were no significant differences between groups for postpartum weight loss for the entire study population. Among those unaffected by the COVID pandemic, women randomized to the FAB program lost significantly more weight than those randomized to the T4B program. The mHealth FAB program demonstrated a substantial level of engagement. Given the scalability and potential public health impact of the FAB program, the efficacy for decreasing cardiometabolic risk by increasing postpartum weight loss should be tested in a larger trial.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Enterovirus D68 (EV-D68) causes cyclical outbreaks of respiratory disease and acute flaccid myelitis. EV-D68 is primarily transmitted through the respiratory route, but the duration of shedding in ...the respiratory tract is unknown. We prospectively enrolled 9 hospitalized children with EV-D68 respiratory infection and 16 household contacts to determine EV-D68 RNA shedding dynamics in the upper respiratory tract through serial midturbinate specimen collections and daily symptom diaries. Five (31.3%) household contacts, including 3 adults, were EV-D68–positive. The median duration of EV-D68 RNA shedding in the upper respiratory tract was 12 (range 7–15) days from symptom onset. The most common symptoms were nasal congestion (100%), cough (92.9%), difficulty breathing (78.6%), and wheezing (57.1%). The median illness duration was 20 (range 11–24) days. Understanding the duration of RNA shedding can inform the expected rate and timing of EV-D68 detection in associated acute flaccid myelitis cases and help guide public health measures.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To identify postdischarge outcome phenotypes and risk factors for poor outcomes using insurance claims data.
Retrospective cohort study.
Single quaternary center.
Children without preexisting ...tracheostomy who required greater than or equal to 3 days of invasive mechanical ventilation, survived the hospitalization, and had postdischarge insurance eligibility in Colorado's All Payer Claims Database.
None.
We used unsupervised machine learning to identify functional outcome phenotypes based on claims data representative of postdischarge morbidities. We assessed health trajectory by comparing change in the number of insurance claims between quarters 1 and 4 of the postdischarge year. Regression analyses identified variables associated with unfavorable outcomes. The 381 subjects had median age 3.3 years (interquartile range, 0.9-12 yr), and 147 (39%) had a complex chronic condition. Primary diagnoses were respiratory (41%), injury (23%), and neurologic (11%). We identified three phenotypes: lower morbidity (n = 300), higher morbidity (n = 62), and 1-year nonsurvivors (n = 19). Complex chronic conditions most strongly predicted the nonsurvivor phenotype. Longer PICU stays and tracheostomy placement most strongly predicted the higher morbidity phenotype. Patients with high but improving postdischarge resource use were differentiated by high illness severity and long PICU stays. Patients with persistently high or increasing resource use were differentiated by complex chronic conditions and tracheostomy placement.
New morbidities are common after prolonged mechanical ventilation. Identifying phenotypes at high risk of postdischarge morbidity may facilitate prognostic enrichment in clinical trials.
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