Assessment of Hyperglycemia, Hypoglycemia and Inter-Day Glucose Variability Using Continuous Glucose Monitoring among Diabetic Patients on Chronic Hemodialysis

Continuous glucose monitoring (CGM) facilitates the assessment of short-term glucose variability and identification of acute excursions of hyper- and hypo-glycemia. Among 37 diabetic hemodialysis patients who underwent 7-day CGM with the iPRO2 device (Medtronic Diabetes, Northridge, CA, USA), we explored the accuracy of glycated albumin (GA) and hemoglobin A1c (HbA1c) in assessing glycemic control, using CGM-derived metrics as the reference standard. In receiver operating characteristic (ROC) analysis, the area under the curve (AUC) in diagnosing a time in the target glucose range of 70–180 mg/dL (TIR70–180) in <50% of readings was higher for GA (AUC: 0.878; 95% confidence interval (CI): 0.728–0.962) as compared to HbA1c (AUC: 0.682; 95% CI: 0.508–0.825) (p < 0.01). The accuracy of GA (AUC: 0.939; 95% CI: 0.808–0.991) in detecting a time above the target glucose range > 250 mg/dL (TAR>250) in >10% of readings did not differ from that of HbA1c (AUC: 0.854; 95% CI: 0.699–0.948) (p = 0.16). GA (AUC: 0.712; 95% CI: 0.539–0.848) and HbA1c (AUC: 0.740; 95% CI: 0.570–0.870) had a similarly lower efficiency in detecting a time below target glucose range < 70 mg/dL (TBR<70) in >1% of readings (p = 0.71). Although the mean glucose levels were similar, the coefficient of variation of glucose recordings (39.2 ± 17.3% vs. 32.0 ± 7.8%, p < 0.001) and TBR<70 (median (range): 5.6% (0, 25.8) vs. 2.8% (0, 17.9)) were higher during the dialysis-on than during the dialysis-off day. In conclusion, the present study shows that among diabetic hemodialysis patients, GA had higher accuracy than HbA1c in detecting a 7-day CGM-derived TIR70–180 < 50%. However, both biomarkers provided an imprecise reflection of acute excursions of hypoglycemia and inter-day glucose variability.

Fully automated closed-loop glucose control compared with standard insulin therapy in adults with type 2 diabetes requiring dialysis: an open-label, randomized crossover trial

We evaluated the safety and efficacy of fully closed-loop insulin therapy compared with standard insulin therapy in adults with type 2 diabetes requiring dialysis. In an open-label, multinational, two-center, randomized crossover trial, 26 adults with type 2 diabetes requiring dialysis (17 men, 9 women, average age 68 ± 11 years (mean ± s.d.), diabetes duration of 20 ± 10 years) underwent two 20-day periods of unrestricted living, comparing the Cambridge fully closed-loop system using faster insulin aspart (‘closed-loop’) with standard insulin therapy and a masked continuous glucose monitor (‘control’) in random order. The primary endpoint was time in target glucose range (5.6–10.0 mmol l−1). Thirteen participants received closed-loop first and thirteen received control therapy first. The proportion of time in target glucose range (5.6–10.0 mmol l−1; primary endpoint) was 52.8 ± 12.5% with closed-loop versus 37.7 ± 20.5% with control; mean difference, 15.1 percentage points (95% CI 8.0–22.2; P < 0.001). Mean glucose was lower with closed-loop than control (10.1 ± 1.3 versus 11.6 ± 2.8 mmol l−1; P = 0.003). Time in hypoglycemia (<3.9 mmol l−1) was reduced with closed-loop versus control (median (IQR) 0.1 (0.0–0.4%) versus 0.2 (0.0–0.9%); P = 0.040). No severe hypoglycemia events occurred during the control period, whereas one severe hypoglycemic event occurred during the closed-loop period, but not during closed-loop operation. Fully closed-loop improved glucose control and reduced hypoglycemia compared with standard insulin therapy in adult outpatients with type 2 diabetes requiring dialysis. The trial registration number is NCT04025775.

Achievement of Target Glucose Level among Newly Diagnosed Type 2 Diabetes Mellitus Patients in Public Teaching Hospitals in Addis Ababa, Ethiopia: a retrospective chart review

Background Diabetes is a chronic illness that requires continuous medical care to reach target glycaemic level to prevent complications. Most studies around the world have showed that glycaemic control among type 2 diabetes mellitus (T2DM) patients is poor using measurements taken at one point and including all patients irrespective of the duration of illness. This study aimed to assess achievement of optimal glycaemic control at different points in time in relation to the time of diagnosis and initiation of treatment and to identify associated factors among T2DM patients attending diabetes clinic of public teaching hospitals in Addis Ababa, Ethiopia. Methods A retrospective chart review was conducted from May to July 2018 among randomly selected 685 medical charts of patients who were on follow-up from January, 2013 to December, 2017. Association was assessed using Binary logistic regression, where 95% CIs for odds ratio and P-values were used for testing significance and interpretation of results. Results The prevalence of optimal glycaemic control among T2DM patients at the end of 3 months, 6 months, 1 year, 2 years, 3 years, 4 years and 5 years of diagnosis and treatment were 1.9%, 44.7%, 52.8%, 66.3%, 69.2%, 70.2% and 70.5% respectively. The significant factors were age group and type of treatment regimen. Conclusions Achievement of optimal glycaemic control increases as the follow-up duration increases; it was only 1.9% at the third month and 70.5% at the fifth year of observation. Close to one third of patients (29.5%) did not achieve target glucose even after five years and were at the verge of increased risk for diabetes related complications and death. Attention should be given to the time when patients achieve target glucoses level instead of just measuring the number of individuals who achieved glycaemic control in a short observation period.

Precision and Accuracy of Hyperglycemic Clamps in a Multicenter Study

Background: Application of glucose clamp methodologies in multicenter studies brings challenges for standardization. The Restoring Insulin Secretion (RISE) Consortium implemented a hyperglycemic clamp protocol across seven centers using a combination of technical and management approaches to achieve standardization. Methods: Two- stage hyperglycemic clamps with glucose targets of 200 mg/dL and >450 mg/dL were performed utilizing a centralized spreadsheet-based algorithm that guided dextrose infusion rates using bedside plasma glucose measurements. Clamp operators received initial and repeated training with ongoing feedback based on surveillance of clamp performance. The precision and accuracy of the achieved stage-specific glucose targets were evaluated, including differences by study center. We also evaluated robustness of the method to baseline physiologic differences and on-study treatment effects. Results: The RISE approach produced high overall precision (3-9% variance in achieved plasma glucose from target at various times across the procedure) and accuracy (SD <10% overall). Statistically significant but numerically small differences in achieved target glucose concentrations were observed across study centers, within the magnitude of the observed technical variability. Variation of the achieved target glucose over time in placebo-treated individuals was low (<3% variation), and the method was robust to differences in baseline physiology (youth vs adult, IGT vs diabetes status) and to differences in physiology induced by study treatments. Conclusions: The RISE approach to standardization of the hyperglycemic clamp methodology across multiple study centers produced technically excellent standardization of achieved glucose concentrations. This approach provides a reliable method for implementing glucose clamp methodology across multiple study centers.

Assessing the efficacy, safety and utility of closed-loop insulin delivery compared with sensor-augmented pump therapy in very young children with type 1 diabetes (KidsAP02 study): an open-label, multicentre, multinational, randomised cross-over study protocol

IntroductionDiabetes management in very young children remains challenging. Glycaemic targets are achieved at the expense of high parental diabetes management burden and frequent hypoglycaemia, impacting quality of life for the whole family. Our objective is to assess whether automated insulin delivery can improve glycaemic control and alleviate the burden of diabetes management in this particular age group.Methods and analysisThe study adopts an open-label, multinational, multicentre, randomised, crossover design and aims to randomise 72 children aged 1–7 years with type 1 diabetes on insulin pump therapy. Following screening, participants will receive training on study insulin pump and study continuous glucose monitoring devices. Participants will be randomised to 16-week use of the hybrid closed-loop system (intervention period) or to 16-week use of sensor-augmented pump therapy (control period) with 1–4 weeks washout period before crossing over to the other arm. The order of the two study periods will be random. The primary endpoint is the between-group difference in time spent in the target glucose range from 3.9 to 10.0 mmol/L based on sensor glucose readings during the 16-week study periods. Analyses will be conducted on an intention-to-treat basis. Key secondary endpoints are between group differences in time spent above and below target glucose range, glycated haemoglobin and average sensor glucose. Participants’ and caregivers’ experiences will be evaluated using questionnaires and qualitative interviews, and sleep quality will be assessed. A health economic analysis will be performed.Ethics and disseminationEthics approval has been obtained from Cambridge East Research Ethics Committee (UK), Ethics Committees of the University of Innsbruck, the University of Vienna and the University of Graz (Austria), Ethics Committee of the Medical Faculty of the University of Leipzig (Germany) and Comité National d’Ethique de Recherche (Luxembourg). The results will be disseminated by peer-reviewed publications and conference presentations.Trial registration numberNCT03784027.

SAFETY AND EFFICACY OF GLUCOSTABILIZER IN THE MANAGEMENT OF DIABETIC KETOACIDOSIS

Objective: To evaluate the safety and efficacy of GlucoStabilizer software intravenous insulin (IV) dosing in comparison to American Diabetes Association protocol-directed provider-guided insulin dose adjustment (PGIA). Methods: GlucoStabilizer calculates the dose of IV insulin required to reach a prescribed target glucose range. GlucoStabilizer has not been fully studied in DKA. This retrospective study compared outcomes in patients with DKA before and after the implementation of GlucoStabilizer. Insulin doses were administered based on GlucoStabilizer calculations or PGIA. The analysis evaluated before-after changes in the amount of insulin used, time to target, hypoglycemia or hypokalemia events, and the time to DKA resolution. Results: We studied 77 patients with insulin doses calculated by GlucoStabilizer and 69 patients with PGIA dosing. GlucoStabilizer was superior to PGIA. Patients treated with GlucoStabilizer-calculated doses did not experience hypoglycemia (N = 0 versus N = 10; P<.001). The 10 unique PGIA patients had a total of 18 episodes with 17 between 55 to 69 mg/dL; 1 <54 mg/dL, and no episodes <40 mg/dL. The GlucoStabilizer group required less insulin to reach DKA resolution (59.2 versus 101.2 units; P<.001). Time to glycemic target and DKA resolution were similar (6.7 versus 4.6 hours; P = .132) and (9.8 versus 9.9 hours; P = .803), respectively. No difference in the incidence of hypokalemia was seen (N = 9 versus N = 11; P = .48). Conclusion: This study demonstrates the Gluco Stabilizer settings that can be successfully used in the management of DKA with the avoidance of hypoglycemia. Patients treated with GlucoStabilizer-calculated doses experienced no hypoglycemia and required less insulin as compared to those managed with PGIA. Abbreviations: ADA = American Diabetes Association; DKA = diabetic ketoacidosis; ED = emergency department; eGMS = electronic glycemic management systems; ICU = intensive care unit; IV = intravenous; PGIA = protocol-directed provider-guided insulin dose adjustment