Trial of Hybrid Closed-Loop Control in Young Children with Type 1 Diabetes.

BACKGROUND: Closed-loop control systems of insulin delivery may improve glycemic outcomes in young children with type 1 diabetes. The efficacy and safety of initiating a closed-loop system virtually are unclear. METHODS: In this 13-week, multicenter trial, we randomly assigned, in a 2:1 ratio, children who were at least 2 years of age but younger than 6 years of age who had type 1 diabetes to receive treatment with a closed-loop system of insulin delivery or standard care that included either an insulin pump or multiple daily injections of insulin plus a continuous glucose monitor. The primary outcome was the percentage of time that the glucose level was in the target range of 70 to 180 mg per deciliter, as measured by continuous glucose monitoring. Secondary outcomes included the percentage of time that the glucose level was above 250 mg per deciliter or below 70 mg per deciliter, the mean glucose level, the glycated hemoglobin level, and safety outcomes. RESULTS: A total of 102 children underwent randomization (68 to the closed-loop group and 34 to the standard-care group); the glycated hemoglobin levels at baseline ranged from 5.2 to 11.5%. Initiation of the closed-loop system was virtual in 55 patients (81%). The mean (±SD) percentage of time that the glucose level was within the target range increased from 56.7±18.0% at baseline to 69.3±11.1% during the 13-week follow-up period in the closed-loop group and from 54.9±14.7% to 55.9±12.6% in the standard-care group (mean adjusted difference, 12.4 percentage points [equivalent to approximately 3 hours per day]; 95% confidence interval, 9.5 to 15.3; P<0.001). We observed similar treatment effects (favoring the closed-loop system) on the percentage of time that the glucose level was above 250 mg per deciliter, on the mean glucose level, and on the glycated hemoglobin level, with no significant between-group difference in the percentage of time that the glucose level was below 70 mg per deciliter. There were two cases of severe hypoglycemia in the closed-loop group and one case in the standard-care group. One case of diabetic ketoacidosis occurred in the closed-loop group. CONCLUSIONS: In this trial involving young children with type 1 diabetes, the glucose level was in the target range for a greater percentage of time with a closed-loop system than with standard care. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases; PEDAP ClinicalTrials.gov number, NCT04796779.).

Antidiabetic treatment and COVID-19 Outcomes: A population-based cohort study in primary health care in Catalonia during the first wave of the pandemic.

AIMS: To analyse if antidiabetic treatment was associated with better COVID-19 outcomes in type 2 diabetic patients, measured by hospital admission and mortality rates as severe outcomes. METHODS: Cohort study including COVID-19 patients registered in the Primary Care electronic records, in March-June 2020, comparing exposed to metformin in monotherapy with exposed to any other antidiabetic. DATA SOURCE: SIDIAP (Information System for Research in Primary Care), which captures clinical information of 5,8 million people from Catalonia, Spain. RESULTS: We included 31,006 diabetic patients infected with COVID-19, 43.7% previously exposed to metformin, 45.5% of them in monotherapy. 16.4% were admitted to hospital and 15.1% died. Users of insulin in monotherapy (OR 1.29, 95% CI 1.11-1.50), combined with metformin (OR 1.38, 1.13-1.69) or IDPP4 alone (OR 1.29, 1.03-1.63) had higher risk of severe outcomes than those in metformin monotherapy. Users of any insulin (OR 1.61, 1.32-1.97) or combined with metformin (OR 1.69, 1.30-2.20) had a higher risk of mortality. CONCLUSIONS: Patients receiving metformin monotherapy in our study showed a lower risk of hospitalization and death in comparison to those treated with other frequent antidiabetic agents. We cannot distinguish if better outcomes are related with the antidiabetic therapy or with other factors, such as metabolic control or interventions applied during the hospital admission.

Insulin Therapy and Outcome of Coronavirus Disease 2019 (COVID-19): A Systematic Review, Meta-Analysis, and Meta-Regression.

BACKGROUND: Currently, the relationship between insulin therapy and COVID-19 outcome is not yet established. Our study aims to evaluate the possible association between insulin and the composite poor outcome of COVID-19. METHODS: We systematically searched the PubMed and Europe PMC database using specific keywords related to our aims until December 12th, 2020. All articles published on COVID-19 and insulin were retrieved. Statistical analysis was done using Review Manager 5.4 and Comprehensive Meta-Analysis version 3 software. RESULTS: Our pooled analysis showed that insulin use was associated with composite poor outcomes of COVID-19 [OR 2.06 (95% CI 1.70 - 2.48), p < 0.00001, I2 = 83%, random-effect modelling], and its subgroup which comprised of risk of COVID-19 [OR 1.70 (95% CI 1.40 - 2.08), p < 0.00001, I2 = 34%, random-effect modelling], severe COVID-19 [OR 2.30 (95% CI 1.60 - 3.30), p < 0.00001, I2 = 88%, random-effect modelling], and mortality [OR 2.14 (95% CI 1.47 - 3.10), p < 0.0001, I2 = 85%, random-effect modelling]. Meta-regression showed that the association was influenced by age (p = 0.008), but not by diabetes p = 0.423) and cardiovascular disease (p = 0.086). CONCLUSION: Physicians should be more aware and take extra precautions with diabetes patients who use insulin therapy.

Development of a pharmacist-managed protocol for the transition from intravenous to subcutaneous insulin in critically ill adults.

PURPOSE: To evaluate the efficacy and safety of a pharmacist-managed protocol for transitioning critically ill patients from intravenous (IV) to subcutaneous insulin. METHODS: This single-center, retrospective, observational study included patients admitted to the medical or surgical/trauma intensive care unit who received a continuous infusion of IV insulin from January 2019 to April 2021. Patients were excluded if they were less than 18 years old, pregnant, or incarcerated or received IV insulin for the diagnosis of diabetic ketoacidosis, hyperglycemic hyperosmolar state, calcium channel blocker or ß-blocker overdose, or hypertriglyceridemia. The primary outcome was to evaluate the percentage of blood glucose (BG) concentrations within the target range of 70 to 150 mg/dL within 48 hours of the transition to subcutaneous insulin. Secondary outcomes included the percentage of BG concentrations within the goal range following transition at 0 to 12 hours and 12 to 24 hours, the incidence of hypo- and hyperglycemia, and the percentage of patients requiring dose adjustments after the initial transition. RESULTS: Pharmacists were able to achieve BG concentrations in the target range for 53% of transitions at 12 hours, 40% of transitions at 24 hours, and 47% of transitions at 48 hours. With respect to safety endpoints, the pharmacist-managed group had a low rate of hypoglycemia (1.0%) and no severe hypoglycemia. Hyperglycemia was reported for 28% of BG concentrations while severe hyperglycemia was reported for 27%. Pharmacists transitioned patients to an average of 63% of the 24-hour total daily dose of insulin as basal insulin. CONCLUSION: Pharmacists can effectively and safely transition critically ill patients from IV to subcutaneous insulin utilizing a standardized protocol.

No effects of the COVID-19 pandemic on the prescription of insulin in Germany.

AIMS: The aim of the study was to investigate the change of insulin doses in Germany between 2017 and 2021. METHODS: This retrospective study used data from the longitudinal prescription LRx database (IQVIA) and included all patients with at least two insulin prescriptions per year in 2017-2021. Calculated daily dose (CDD) was assessed in 2017, 2018, 2019, 2020, and 2021, separately. RESULTS: The number of patients was comprised between 1,079,894 in 2021 and 1,132,839 in 2018. Median (interquartile range) CDD of basal insulin was relatively stable across the years and ranged between 27.9 (18.5-38.8) in 2021 and 28.3 (18.7-39.5) in 2020. In terms of short-acting insulin, median (interquartile range) CDD slightly decreased from 40.1 (28.2-54.3) in 2017 to 38.1 (27.2-52.2) in 2021. A slight decrease was also observed for mix insulin, from 39.4 (27.5-55.3) in 2017 to 37.9 (26.5-54.2) in 2021. These results were corroborated in most age and sex subgroups. CONCLUSIONS: COVID-19 had no substantial effects on insulin doses in Germany. Further data are warranted to corroborate or refute these findings in other settings and countries.

Practical implementation of remote continuous glucose monitoring in hospitalized patients with diabetes.

PURPOSE: Inpatient diabetes management involves frequent assessment of glucose levels for treatment decisions. Here we describe a program for inpatient real-time continuous glucose monitoring (rtCGM) at a community hospital and the accuracy of rtCGM-based glucose estimates. METHODS: Adult inpatients with preexisting diabetes managed with intensive insulin therapy and a diagnosis of coronavirus disease 2019 (COVID-19) were monitored via rtCGM for safety. An rtCGM system transmitted glucose concentration and trending information at 5-minute intervals to nearby smartphones, which relayed the data to a centralized monitoring station. Hypoglycemia alerts were triggered by rtCGM values of ≤85 mg/dL, but rtCGM data were otherwise not used in management decisions; insulin dosing adjustments were based on blood glucose values measured via fingerstick blood sampling. Accuracy was evaluated retrospectively by comparing rtCGM values to contemporaneous point-of-care (POC) blood glucose values. RESULTS: A total of 238 pairs of rtCGM and POC data points from 10 patients showed an overall mean absolute relative difference (MARD) of 10.3%. Clarke error grid analysis showed 99.2% of points in the clinically acceptable range, and surveillance error grid analysis showed 89.1% of points in the lowest risk category. It was determined that for 25% of the rtCGM values, discordances in rtCGM and POC values would likely have resulted in different insulin doses. Insulin dose recommendations based on rtCGM values differed by 1 to 3 units from POC-based recommendations. CONCLUSION: rtCGM for inpatient diabetes monitoring is feasible. Evaluation of individual rtCGM-POC paired values suggested that using rtCGM data for management decisions poses minimal risks to patients. Further studies to establish the safety and cost implications of using rtCGM data for inpatient diabetes management decisions are warranted.

Does Insulin Use Worsen the Prognosis of COVID-19 Patients with Type 2 Diabetes Mellitus? A Current Update.

BACKGROUND: Insulin has recently received special attention concerning its use in COVID-19 patients. Although controversial, insulin can be able to worsen the prognosis of COVID-19 patients with Type 2 Diabetes Mellitus (T2DM) through an inflammatory pathway. This uncertain aspect brings a new perspective related to insulin use in this pandemic era. OBJECTIVE: We tried to collect and analyze various studies related to this issue to provide a complete picture of the prognosis of insulin use in COVID-19 patients with T2DM. METHODS: We comprehensively searched PubMed, Cochrane CENTRAL, Embase, EBSCO CINAHL, MEDLINE, and grey literature databases for studies investigating the effect of insulin on COVID-19 outcomes, including mortality, hospitalization, disease progression, other prognostic surrogates. Records were screened against the eligibility criteria. RESULTS: 2556 articles were retrieved and were screened. A total of 8 studies were included in the final analysis. There are no studies with solid evidence supporting the effect of insulin treatment on the worsening of the prognosis of COVID-19 patients with T2DM. Although several studies have shown that insulin is associated with a poor prognosis, most studies have not considered confounders. This certainly makes it challenging to analyze the effects of insulin independently. CONCLUSION: We propose that COVID-19 patients with T2DM continue to receive insulin, but with careful observation of the risk of disease progression.

Glycemic Profile of Intravenous Dexamethasone-Induced Hyperglycemia Using Continuous Glucose Monitoring.

BACKGROUND Intravenous (IV) dexamethasone is widely used in critical illness, chemotherapy, or severe COVID-19. Although glucocorticoid-induced hyperglycemia (GCIH) is well-known, there is no report describing the glycemic profile following a single dose of IV dexamethasone as captured on continuous glucose monitoring (CGM) in a patient with diabetes treated with insulin. CASE REPORT A 70-year-old woman with diabetes and pancreatic adenocarcinoma was treated with chemotherapy containing dexamethasone every other week. CGM data of 23 cycles revealed a reproducible triphasic glycemic pattern consisting of a constant hyperglycemia period, followed by a transient improvement, and ending with another hyperglycemic plateau. Given this recurrent pattern, basal insulin and correction insulin were adjusted with subsequent GCIH attenuation. CONCLUSIONS This is the first report of CGM glycemic profile following recurring doses of IV dexamethasone in a patient with diabetes treated with basal-bolus insulin. The understanding of triphasic glycemic pattern allows optimal glycemic management.

Treatment of Severe Hypertriglyceridemia With Insulin Infusions in Severe COVID-19: A Case Series.

PURPOSE: Rapid onset of severe hypertriglyceridemia was quickly recognized in critical COVID-19 patients. Associated causes have been due to secondary hemophagocytic lymphohystiocytosis (HLH) syndrome, medication-induced, or acute liver failure. Statins, omega-3 polyunsaturated acids, niacin, and fibrates are common oral lipid lowering therapy options in patients at risk for hypertriglyceridemia. The severity of hypertriglyceridemia in COVID-19 patients with triglyceride values reaching greater than 1,000 mg/dL put them at a heightened risk of pancreatitis and therefore an essential need to acutely lower their levels. We present a case series of 5 patients who achieved rapid triglyceride lowering through continuous insulin infusion therapy. METHODS: A retrospective chart review of 48 critical COVID-19 patients who were admitted from March 22 to April 15, 2020 was conducted. Inclusion criteria consisted of mechanical ventilation and continuous insulin infusion to treat severe hypertriglyceridemia resulting with 5 eligible patients in this case report. RESULTS AND CONCLUSION: In addition to standard oral lipid lowering therapies, continuous insulin infusion successfully treated severe hypertriglyceridemia in critically ill COVID-19 patients. None of the patients experienced pancreatitis or hypoglycemia necessitating cessation of insulin. Further studies are needed to show the optimum dose and duration of insulin infusion as monotherapy and in combination with oral therapies.

Evaluation of severe hypoglycemia and common mental disorders in patients receiving insulin analogues for treatment of type 1 diabetes.

This is a retrospective report of the frequency of severe hypoglycemia and the association between common mental disorders and type 1 diabetes mellitus treated with insulin analogues. Patients with severe hypoglycemia compared with those without this complication had a higher prevalence of positive screening for common mental disorders (88% vs. 77%, respectively, p = 0.03).

Treating type 2 diabetes in COVID-19 patients: the potential benefits of injective therapies.

The coronavirus disease 2019 (COVID-19) has been declared as pandemic by the World Health Organization and is causing substantial morbidity and mortality all over the world. Type 2 diabetes, hypertension, and cardiovascular disease significantly increase the risk for hospitalization and death in COVID-19 patients. Hypoglycemia and hyperglycemia are both predictors for adverse outcomes in hospitalized patients. An optimized glycemic control should be pursued in patients with diabetes and SARS-CoV-2 infection in order to reduce the risk of severe COVID-19 course. Both insulin and GLP-1RAs have shown optimal glucose-lowering and anti-inflammatory effects in type 2 diabetic patients and may represent a valid therapeutic option to treat asymptomatic and non-critically ill COVID-19 diabetic patients.