Search

Background: Excess carbohydrate intake during hypoglycemia can lead to rebound hyperglycemia (RH). We investigated associations between RH and use of real-time continuous glucose monitoring (rtCGM) and an rtCGM system’s predictive alert. Methods: RH events were series of sensor glucose values (SGVs) >180 mg/dL starting within two hours of an antecedent SGV 180 mg/dL × five minutes), and severity (area under the glucose concentration-time curve). To assess the impact of rtCGM, data gathered during the four-week baseline phase (without rtCGM) and four-week follow-up phase (with rtCGM) from 75 participants in the HypoDE clinical trial (NCT02671968) of hypoglycemia-unaware individuals were compared. To assess the impact of predictive alerts, we identified a convenience sample of 24 518 users of an rtCGM system without predictive alerts who transitioned to a system whose predictive alert signals an SGV ≤55 mg/dL within 20 minutes (Dexcom G5 and G6, respectively). RH events from periods of blinded versus unblinded rtCGM wear and from periods of G5 and G6 wear were compared with paired t tests. Results: Compared to RH events in the HypoDE baseline phase, the mean frequency, duration, and severity of events fell by 14%, 12%, and 23%, respectively, in the follow-up phase (all P < .05). Compared to RH events during G5 use, the mean frequency, duration, and severity of events fell by 7%, 8%, and 13%, respectively, during G6 use (all P < .001). Conclusions: Rebound hypreglycemia can be objectively quantified and mitigated with rtCGM and rtCGM-based predictive alerts.

Symptomatic hypoglycemia is an incentive for carbohydrate intake which, in excess, can lead to rebound hyperglycemia (RH) and contribute to high glycemic variability. We examined whether an optional "urgent low soon" (ULS) alert triggered by impending hypoglycemia could mitigate RH in the real world. Sensor glucose values (SGVs) were from the G5 and G6 continuous glucose monitoring (CGM) systems (Dexcom). G5 does not offer the ULS feature; all G6 usage was with the ULS alert enabled. An RH event was defined as any series of SGVs >180 mg/dL preceded within 2 hours by a low SGV (180 mg/dL. Data from a convenience sample of 24,518 anonymized G5 users who transitioned to G6 and uploaded ≥30 days of data from each system in 2018 were analyzed. RH events preceded by an SGV Disclosure G. Acciaroli: Employee; Self; Dexcom, Inc. A. Parker: Employee; Self; Dexcom, Inc. Stock/Shareholder; Self; Dexcom, Inc. J. Welsh: Employee; Self; CSL Behring. S. Puhr: Employee; Self; Dexcom, Inc. T.C. Walker: Employee; Self; Dexcom, Inc. H.K. Akturk: Advisory Panel; Self; Sanofi US. Research Support; Self; Eli Lilly and Company, REMD Biotherapeutics, Senseonics.

Activation of “suspend before low” in the Medtronic PLGM algorithm stops insulin delivery when sensor glucose (SG) is predicted to reach or fall below a preset low glucose limit in 30min. Basal insulin delivery automatically resumes once the algorithm detects an increasing SG trend. We evaluated the “suspend before low” feature of the MiniMed™ 670G with SmartGuard™ technology in children with T1D. Participants (N=105, aged 7-13 years) underwent an overnight in-clinic evaluation. Hypoglycemia was defined as 2 or more consecutive events of YSI or fingerstick blood glucose reference values ≤65 mg/dL (≤3.6 mmol/L). Children had exercise in the afternoon, no increase in basal insulin delivery, and were not in Auto Mode. Of the 1experiments, there were 79 with PLGM activation. Hypoglycemia was prevented 79.7% of the time (63/79). Mean duration of a suspension was 85.6±32.4min. The Table shows mean reference glucose values with respect to the start of automated insulin suspension and resumption, as well as 2 and 4 hours after insulin resumption. Rates of change (ROC) at insulin suspension and resumption start are also shown. All were evaluated by TDD and duration of diabetes, and stratified in quartiles. The “suspend before low” feature of the MiniMed™ 670G system reduced hypoglycemia events without rebound hyperglycemia in children with T1D regardless of TDD or duration of diabetes. Disclosure D.I. Shulman: Other Relationship; Self; Novo Nordisk Inc.. Research Support; Self; Medtronic MiniMed, Inc.. Board Member; Self; Pediatric Endocrine Society. Research Support; Self; Versartis, Inc. M.A. Wood: Research Support; Self; Medtronic MiniMed, Inc. G.P. Forlenza: Advisory Panel; Self; Dexcom, Inc.. Research Support; Self; Medtronic, Tandem Diabetes Care, Inc., Insulet Corporation, Dexcom, Inc., Novo Nordisk Inc., Bigfoot Biomedical. B. Buckingham: Advisory Panel; Self; Novo Nordisk Inc., ConvaTec Inc.. Research Support; Self; Medtronic, Insulet Corporation, Dexcom, Inc., Tandem Diabetes Care, Inc.. Consultant; Self; Tandem Diabetes Care, Inc., Becton, Dickinson and Company. T.S. Bailey: Research Support; Self; Abbott. Consultant; Self; Abbott. Speaker's Bureau; Self; Abbott. Research Support; Self; Ambra BioScience, Ascensia Diabetes Care, Becton, Dickinson and Company. Consultant; Self; Becton, Dickinson and Company. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Calibra Medical. Consultant; Self; Calibra Medical. Research Support; Self; Companion Medical, Dexcom, Inc., Glooko, Inc., GlySens Incorporated, Lexicon Pharmaceuticals, Inc., Eli Lilly and Company. Consultant; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Research Support; Self; Medtronic MiniMed, Inc.. Consultant; Self; Medtronic MiniMed, Inc.. Speaker's Bureau; Self; Medtronic MiniMed, Inc.. Research Support; Self; Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc.. Research Support; Self; Sanofi. Consultant; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Research Support; Self; Senseonics. Consultant; Self; Intarcia Therapeutics, Inc.. Research Support; Self; Versartis, Inc., Xeris Pharmaceuticals, Inc., MannKind Corporation. T.L. Cordero: Employee; Self; Medtronic. B.W. Bode: Research Support; Self; Abbott. Advisory Panel; Self; ADOCIA. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Janssen Pharmaceuticals, Inc.. Research Support; Self; GlaxoSmithKline plc., Lexicon Pharmaceuticals, Inc., Medtronic MiniMed, Inc., Novo Nordisk Inc., Diasome Pharmaceuticals, Inc., Sanofi US, Eli Lilly and Company, MannKind Corporation, Dexcom, Inc., OmniPod, Senseonics. X. Chen: Employee; Self; Medtronic. J. Shin: Employee; Self; Medtronic.

Introduction. Treatment with a glucagon-like peptide 1 (GLP-1) analog fails in some patients due to rebound hyperglycemia caused by tachyphylaxis (GLP-1 tachyphylaxis). We investigated the efficacy of basal-supported oral therapy (BOT) with insulin glargine and sitagliptin for counteracting GLP-1 tachyphylaxis.Materials and Methods. The subjects were 12 men and 3 women aged59.9±10.0years who had been treated with GLP-1 analogs. All of them had developed rebound hyperglycemia caused by GLP-1 tachyphylaxis. Their GLP-1 analog-based therapy was switched to BOT with insulin glargine plus sitagliptin and other medications. The primary outcomes were whether switching of therapy was associated with a change of hemoglobinA1c(HbA1c) and whether weight gain occurred.Results. BaselineHbA1cwas8.0±0.9%. It decreased to7.3±0.9% at 3 months after switching (P<0.01) and to7.2±0.9% at 4 months (P<0.05). Weight gain was 1.1 kg after 1 month (P<0.01) and 2.3 kg after 5 months (P<0.01).Conclusion. Switching to BOT with insulin glargine and sitagliptin improved glycemic control. The significant decrease ofHbA1cdemonstrated that this combination can counteract deterioration of glycemic control due to rebound hyperglycemia secondary to GLP-1 tachyphylaxis. However, weight gain remains a problem.

Medical records of 38 patients undergoing anesthesia and surgery for removal of an insulinoma were reviewed to determine 1) the safety of avoiding intraoperative glucose, 2) the appropriate frequency of plasma glucose analysis, and 3) the accuracy of using rebound hyperglycemia as an indication of tumor removal. Plasma glucose was determined approximately every 15 min during operative and recovery-room periods. The changes in plasma glucose concentrations before tumor removal were compared with those occurring after the resection in each patient by separate linear regressions of glucose concentration versus time. The slopes of the preresection regression lines averaged +0.196 (+/- SD 0.577) mg X dl-1 X min-1. The mean of the postresection slopes was +0.624 (+/- SD 0.339) mg X dl-1 X min-1. The mean difference in slope (post- minus pre-) was +0.426 (+/- SD 0.748) mg X dl-1 X min-1, indicating that a significant (P less than 0.02) increase in post-resection slope had occurred. In no case did a preresection plasma glucose concentration decrease to less than 50 mg X dl-1 if the previous value had been 60 mg X dl-1 or greater. Nonetheless, there were nine patients whose plasma glucose did decrease to less than 50 mg X dl-1 at some time during the operative course. Only 39% of patients showed a rebound of 20 mg X dl-1 or more in the first 30 min after resection. The authors conclude that intermittent sampling is safe as long as plasma glucose is kept above 60 mg X dl-1 by infusing glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Simple rapid polyethylene glycol precipitation of serum makes it possible to measure free (FI) and total insulin (TI) in insulin-treated patients by standard radioimmunoassay. Six diabetics, ages 8-19 years, were studied because of suspected overinsulinization with rebound hyperglycemia. Patients were hospitalized and received their usual insulin and dietary regimen. Blood was sampled hourly, for 24 hours, for glucose, free and total insulin. FI varied between patients from 3-12% of TI. Neither TI nor FI correlated positively with insulin dose. FI did not correlate with TI in individual patients, but data suggests that binding of administered insulin is instantaneous; equilibrium between bound and free insulin pools is variable and slow. A better understanding of those variables is required for rational adjustment of insulin therapy.

To the Editor.— The study by Brodows et al 1 in the Dec 28,1984, issue of JAMA is a long-awaited formal documentation of what those of us who use pure glucose for treating hypoglycemia have known for many years— gram for gram, glucose raises blood glucose levels faster than any other oral agent. It is unfortunate that the study did not report the blood glucose levels measured two hours after treatment with different foods. We routinely ask our new insulin-using patients to measure their blood glucose responses to candy, orange juice, and other sources of mixed slow- and fast-acting carbohydrate that they had previously been using to treat hypoglycemia. As a rule, they observe that when consuming enough of such foods to normalize blood glucose levels within a half hour, after two hours levels are very high. Thus, "rebound hyperglycemia" can be explained as a consequence of overconsumption of carbohydrate