Background

Disparities in Insulin Pump Use Among Spanish-Speaking Children With Type 1 Diabetes Compared to Their Non-Hispanic White Peers: Mixed Methods Study.

Objective

We aimed to investigate the use of insulin pumps and continuous glucose monitoring (CGM) devices among Spanish-language-preferring children in our clinic population and to identify specific barriers to technology use.

Methods

First, we assessed rates and patterns of diabetes technology use (eg, insulin pumps and CGM devices) in a sample of 76 children (38 Spanish-language preferring and 38 non-Hispanic White). We compared rates of technology use, average length of time between diabetes diagnosis and initiation of insulin pump or CGM device, and rates of discontinuation of these devices between the Spanish-language-preferring and non-Hispanic White children. Second, to understand specific barriers to technology use, we compared responses to a questionnaire assessing decision-making about insulin pumps.

Results

Spanish-language-preferring patients had lower rates of insulin pump use, even after controlling for age, gender, age at diagnosis, and type of health insurance. Spanish-language-preferring participants were more likely to report concerns over learning to use an insulin pump and were more likely to discontinue using an insulin pump after starting one.

Conclusions

These data confirm demographic disparities in insulin pump use among children with T1D and provide new insights about insulin pump discontinuation among Spanish-language-preferring children. Our findings suggest a need for improved patient education about insulin pump technology in general and improved support for Spanish-language-preferring families with T1D after initiation of pump therapy.

Background

Caregivers of children with newly diagnosed type 1 diabetes (T1D) maintain close contact with providers for several weeks to facilitate rapid adjustments in insulin dosing regimens. Traditionally, patient glucose values are relayed by telephone for provider feedback, but digital health technology can now enable the remote sharing of glucose data via mobile apps.

Objective

The aim of this study was to test the feasibility of remote glucose monitoring in a population of children and adolescents with newly diagnosed T1D and to explore whether remote monitoring alters habits for self-review of glucose data or perceived ease of provider contact in this population as compared to a nonrandomized control group.

Methods

Data were collected from families who chose to participate in remote monitoring (intervention group) as well as from patients receiving usual care (control group). The intervention group received Bluetooth-capable glucose meters and Apple iPod Touch devices. Patient-generated glucose data were passively relayed from the meter to the iPod Touch and then to both the electronic health record (EHR) and a third-party diabetes data platform, Tidepool. The principal investigator reviewed glucose data daily in the EHR and Tidepool and contacted the participants as needed for insulin dose adjustments during the time between hospital discharge and first clinic appointment. Families in the control group received usual care, which involved keeping written records of glucose values and contacting the diabetes team daily by telephone to relay data and receive treatment recommendations. A total of 40 families (20 for the intervention group and 20 for the control group) participated in the study. All families were surveyed at 1 month and 6 months regarding self-review of glucose data and ease of contacting the diabetes team.

Results

Patient-generated glucose data were remotely accessible for 100% of the participants via Tidepool and for 85% via the EHR. Survey data indicated that families in the intervention group were more likely than those in the control group to review their glucose data using mobile health apps after 1 month (P<.001), but by 6 months, this difference had disappeared. Perceived ease of contacting the clinical team for assistance was lower for the intervention group after 6 months (when receiving usual care) in comparison to during the intervention period (P=.48) and compared with a control group who did not have exposure to remote monitoring (P=.03).

Conclusions

Remote glucose monitoring is feasible among pediatric patients with newly diagnosed T1D and may be associated with the earlier adoption of mobile health apps for self-management. The use of broadscale remote monitoring for T1D in the future will depend on improved access to Bluetooth-enabled mobile devices for all patients, improved interoperability of mobile health apps to enable data transfer on Android as well as Apple devices, and new provider workflows to handle large-scale panel management based on patient-generated health data.

Trial registration

ClinicalTrials.gov NCT04106440; https://clinicaltrials.gov/ct2/show/NCT04106440.

Brain injury is the most serious and most extensively studied complication of pediatric DKA. Lifethreatening brain injury occurs in 0.5-1% of pediatric DKA episodes (1), however, more subtle injury occurs frequently, causing cognitive deficits that are detectable after even a single DKA episode. Similarly, renal failure is an infrequent consequence of DKA, however, recent data demonstrate that less severe acute kidney injury (AKI) occurs commonly (2). These data suggest that organ injuries during DKA may not occur as isolated events but instead reflect a form of multiple organ dysfunction syndrome. Importantly, patterns of organ involvement in DKA largely mirror patterns of chronic organ dysfunction that are characteristic of T1D in adulthood. Data from other brain and kidney diseases suggests that inflammatory processes triggered during acute injury may persist chronically and contribute to long-term organ dysfunction. Understanding the processes leading to organ dysfunction during DKA in childhood therefore may have far-reaching implications, extending beyond the acute time frame associated with DKA.

Introduction

Diabetic ketoacidosis (DKA) causes acute and chronic neuroinflammation that may contribute to cognitive decline in patients with type 1 diabetes. We evaluated the effects of agents that reduce neuroinflammation (triarylmethane-34 (TRAM-34) and minocycline) during and after DKA in a rat model.

Research design and methods

Juvenile rats with DKA were treated with insulin and saline, either alone or in combination with TRAM-34 (40 mg/kg intraperitoneally twice daily for 3 days, then daily for 4 days) or minocycline (45 mg/kg intraperitoneally daily for 7 days). We compared cytokine and chemokine concentrations in brain tissue lysates during DKA among the three treatment groups and in normal controls and diabetic controls (n=9-15/group). We also compared brain inflammatory mediator levels in these same groups in adult diabetic rats that were treated for DKA as juveniles.

Results

Brain tissue concentrations of chemokine (C-C) motif ligand (CCL)3, CCL5 and interferon (IFNγ) were increased during acute DKA, as were brain cytokine composite scores. Both treatments reduced brain inflammatory mediator levels during acute DKA. TRAM-34 predominantly reduced chemokine concentrations (chemokine (C-X-C) motif ligand (CXCL-1), CCL5) whereas minocycline had broader effects, (reducing CXCL-1, tumor necrosis factor (TNFα), IFNγ, interleukin (IL) 2, IL-10 and IL-17A). Brain inflammatory mediator levels were elevated in adult rats that had DKA as juveniles, compared with adult diabetic rats without previous DKA, however, neither TRAM-34 nor minocycline treatment reduced these levels.

Conclusions

These data demonstrate that both TRAM-34 and minocycline reduce acute neuroinflammation during DKA, however, treatment with these agents for 1 week after DKA does not reduce long-term neuroinflammation.

Introduction

Management of type 1 diabetes (T1D) is labor-intensive, requiring multiple daily blood glucose measurements and insulin injections. Patients are seen quarterly by providers, but evidence suggests more frequent contact is beneficial. Current technology allows secure, remote sharing of diabetes data and video-conferencing between providers and patients in their home settings.

Methods

Home-based video visits were provided for six months to pediatric T1D patients with poor glycemic control, indicated by a hemoglobin A1c (HbA1c) ≥8% at enrollment. Video visits were conducted every 4-8 weeks in addition to regularly scheduled clinic visits. Dates of clinic visits and HbA1c values were abstracted from the medical record at baseline and six months. Patients were surveyed at video visits regarding technical issues, and after six months a standardized survey was administered to assess satisfaction with video-based care.

Results

A total of 57 patients enrolled and 36 completed six months of video visits. Patients completing six months averaged 4.0 video visits (SD 1.1). Their frequency of in-person care also increased from 3.2 clinic visits/year at baseline to 3.7 clinic visits/year during the study (P = 0.04). Mean HbA1c reduction among patients completing six months was 0.8% (95% CI 0.2-1.4%); 94% of these patients were "very satisfied" while 6% were "somewhat satisfied" with the experience.

Discussion

This study demonstrates that home-based video visits are feasible and satisfactory for pediatric patients with poorly controlled T1D. Furthermore, use of video visits can improve frequency of subspecialty care and resulting glycemic control in this population.

Background

Diabetic ketoacidosis (DKA) causes brain injuries in children ranging from subtle to life-threatening. Previous studies suggest that DKA-related brain injury may involve both stimulation of Na-K-Cl cotransport and microglial activation. Other studies implicate the Na-K-Cl cotransporter and the Ca-activated K channel KCa3.1 in activation of microglia and ischemia-induced brain edema. In this study, we determined whether inhibiting cerebral Na-K-Cl cotransport or KCa3.1 could reduce microglial activation and decrease DKA-related inflammatory changes in the brain.

Methods

Using immunohistochemistry, we investigated cellular alterations in brain specimens from juvenile rats with DKA before, during and after insulin and saline treatment. We compared findings in rats treated with and without bumetanide (an inhibitor of Na-K-Cl cotransport) or the KCa3.1 inhibitor TRAM-34.

Results

Glial fibrillary acidic protein (GFAP) staining intensity was increased in the hippocampus during DKA, suggesting reactive astrogliosis. OX42 staining intensity was increased during DKA in the hippocampus, cortex and striatum, indicating microglial activation. Treatment with TRAM-34 decreased both OX42 and GFAP intensity suggesting a decreased inflammatory response to DKA. Treatment with bumetanide did not significantly alter OX42 or GFAP intensity.

Conclusions

Inhibiting KCa3.1 activity with TRAM-34 during DKA treatment decreases microglial activation and reduces reactive astrogliosis, suggesting a decreased inflammatory response.

Background

Severe hypocapnia reduces cerebral blood flow (CBF) and is known to be a risk factor for diabetic ketoacidosis (DKA)-related cerebral edema and cerebral injury in children. Reductions in CBF resulting from hypocapnia alone, however, would not be expected to cause substantial cerebral injury. We hypothesized that either hyperglycemia or ketosis might alter the effects of hypocapnia on CBF and/or cerebral edema associated with CBF reduction.

Methods

We induced hypocapnia (pCO₂ 20 ± 3 mmHg) via mechanical ventilation in three groups of juvenile rats: 25 controls, 22 hyperglycemic rats (serum glucose 451 ± 78 mg/dL), and 15 ketotic rats (β-hydroxy butyrate 3.0 ± 1.0 mmol/L). We used magnetic resonance imaging to measure CBF and apparent diffusion coefficient (ADC) values in these groups and in 17 ventilated rats with normal pCO₂ (40 ± 3 mmHg). In a subset (n = 35), after 2 h of hypocapnia, pCO₂ levels were normalized (40 ± 3 mmHg) and ADC and CBF measurements were repeated.

Results

Declines in CBF with hypocapnia occurred in all groups. Normalization of pCO₂ after hypocapnia resulted in hyperemia in the striatum. These effects were not substantially altered by hyperglycemia or ketosis. Declines in ADC (suggesting brain cell swelling) during hypocapnia, however, were greater during both hyperglycemia and ketosis.

Conclusions

We conclude that brain cell swelling associated with hypocapnia is increased by both hyperglycemia and ketosis, suggesting that these metabolic conditions may make the brain more vulnerable to injury during hypocapnia.

Cognitive decline is common in patients with type 1 diabetes and has been attributed to the effects of chronic hyperglycemia and severe hypoglycemia. Diabetic ketoacidosis (DKA) has only recently been suspected to be involved in causing cognitive decline. We hypothesized that DKA triggers both acute and chronic neuroinflammation, contributing to brain injury. We measured concentrations of cytokines, chemokines and matrix metalloproteinases (MMP) in serum and brain tissue lysates in juvenile rats during and after DKA (during acute DKA, 24 hours and 7 days after DKA), and compared these to healthy controls and hyperglycemic controls. We also measured cytokine, chemokine and MMP concentrations in serum and brain tissue of adult rats (70 days) that had experienced DKA as juveniles and compared these measurements to those of adult diabetic rats without exposure to DKA. During acute DKA in the juvenile rats, serum concentrations of CCL3, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and MMP-9 were significantly increased. Serum concentrations of IL-2 and IL-17A increased 7 days after DKA recovery. In brain tissue lysates, concentrations of CCL3, CCL5, interferon (IFN)-γ and MMP-9 were significantly elevated during acute DKA. In adult rats that had DKA as juveniles (28 days previously), serum concentrations of IL-1ß and brain concentrations of IL-10 and IL-12p70 were elevated in comparison to diabetic rats without prior DKA. Composite scores for highly correlated cytokines and chemokines (mean z-scores for IL-10, IL-1ß, TNF-α, IL-17A, IFN-γ, CXCL-1 and CCL5) were also significantly elevated in adult rats with prior DKA. These data confirm that DKA causes acute systemic inflammation and neuroinflammation in a rat model. Importantly, the neuroinflammatory response triggered by DKA is long-lasting, suggesting the possibility that DKA-induced chronic neuroinflammation could contribute to long-term cognitive decline in individuals with diabetes.

Objective

Remote patient monitoring (RPM) holds potential to enable more individualized and effective care for patients with type 1 diabetes (T1D), but requires population analytics to focus limited clinical resources on patients most in need. We explored the feasibility of RPM from patient and provider standpoints using a commercially available data analytic platform (glooko Population Health) among a cohort of youth with T1D.

Study design

Patients aged 1-20 years with established T1D (≥12 months) and CGM use (≥3 months) were recruited to participate. Participants' CGM devices were connected to the glooko app and linked to the research team's glooko account during a one-month baseline period. This was followed by a six-month intervention period during which participants with >15% of glucose values >250 mg/dl or >5% of values <70 mg/dl each month were contacted with personalized diabetes management recommendations. Participants were surveyed about their experiences, and effects on glycemic control were estimated via change in glucose management indicator (GMI) generated from CGM data at baseline and completion. Changes in time spent within various glucose ranges were also evaluated, and all glycemic metrics were compared to a non-randomized control group via difference-in-difference regression, adjusting for baseline characteristics.

Results

Remote data-sharing was successful for 36 of 39 participants (92%). Between 33%-66% of participants merited outreach each month, and clinician outreach required a median of 10 minutes per event. RPM was reported to be helpful by 94% of participants. RPM was associated with a GMI change of -0.25% (P=0.047) for the entire cohort, and stratified analysis revealed greatest treatment effects among participants with baseline GMI of 8.0-9.4% (GMI change of -0.68%, P=0.047; 19.84% reduction in time spent >250 mg/dl, P=0.005).

Conclusions

This study demonstrates the feasibility of RPM for patients with T1D using a commercially available population health platform, and suggests that RPM with clinician-initiated outreach may be particularly beneficial for patients with suboptimal glycemic control at entry. However, larger randomized studies are needed to fully explore the glycemic impact of RPM.

Clinical trial registration

https://clinicaltrials.gov/ct2/show/NCT04696640, identifier NCT04696640.

Objective

Cerebral edema is a life-threatening complication of diabetic ketoacidosis (DKA) in children. Recent data suggest that cerebral hypoperfusion and activation of cerebral ion transporters may be involved, but data describing cerebral metabolic alterations during DKA are lacking.

Research design and methods

We evaluated 50 juvenile rats with DKA and 21 normal control rats using proton and phosphorus magnetic resonance spectroscopy (MRS). MRS measured cerebral intracellular pH and ratios of metabolites including ATP/inorganic phosphate (Pi), phosphocreatine (PCr)/Pi, N-acetyl aspartate (NAA)/creatine (Cr), and lactate/Cr before and during DKA treatment. We determined the effects of treatment with insulin and intravenous saline with or without bumetanide, an inhibitor of Na-K-2Cl cotransport, using ANCOVA with a 2 x 2 factorial study design.

Results

Cerebral intracellular pH was decreased during DKA compared with control (mean +/- SE difference -0.13 +/- 0.03; P < 0.001), and lactate/Cr was elevated (0.09 +/- 0.02; P < 0.001). DKA rats had lower ATP/Pi and NAA/Cr (-0.32 +/- 0.10, P = 0.003, and -0.14 +/- 0.04, P < 0.001, respectively) compared with controls, but PCr/Pi was not significantly decreased. During 2-h treatment with insulin/saline, ATP/Pi, PCr/Pi, and NAA/Cr declined significantly despite an increase in intracellular pH. Bumetanide treatment increased ATP/Pi and PCr/Pi and ameliorated the declines in these values with insulin/saline treatment.

Conclusions

These data demonstrate that cerebral metabolism is significantly compromised during DKA and that further deterioration occurs during early DKA treatment--consistent with possible effects of cerebral hypoperfusion and reperfusion injury. Treatment with bumetanide may help diminish the adverse effects of initial treatment with insulin/saline.