Low Glucose Alarms Research Articles

Continuous glucose monitoring in a patient with insulinoma presenting with unawareness of postprandial hypoglycemia.

Unawareness of postprandial hypoglycemia for 5 years was identified in a 66-year-old man at a local clinic. The patient was referred to our hospital because of this first awareness of hypoglycemia (i.e. lightheadedness and impaired consciousness) developing after lunch. In a 75 g oral glucose tolerance test, the plasma glucose concentration was decreased to 32 mg/dL (1.8 mmol/L) at 150 min with relatively high concentrations of insulin (8.1 μU/mL), proinsulin (70.3 pmol/L), and C-peptide (4.63 ng/mL). In a prolonged fasting test, the plasma glucose concentration was decreased to 43 mg/dL (2.4 mmol/L) at 66 h with an insulin concentration of 1.4 μU/mL and a C-peptide concentration of 0.49 ng/mL. Computed tomography showed an 18 mm hyperenhancing tumor in the uncinate process of the pancreas. A selective arterial calcium stimulation test showed an elevated serum insulin concentration in the superior mesenteric artery. The patient was then diagnosed with insulinoma and received pancreaticoduodenectomy. Continuous glucose monitoring (CGM) using the Dexcom G6 system showed unawareness of hypoglycemia mainly during the daytime before surgery. When the sensor glucose value was reduced to 55 mg/dL (3.1 mmol/L), the Dexcom G6 system emitted an urgent low glucose alarm to the patient four times for 10 days. Two months after surgery, an overall increase in daily blood glucose concentrations and resolution of hypoglycemia were shown by CGM. We report a case of insulinoma with unawareness of postprandial hypoglycemia in the patient. The Dexcom G6 system was helpful for assessing preoperative hypoglycemia and for evaluating outcomes of treatment by surgery. Insulinoma occasionally leads to postprandial hypoglycemia. The CGM system is useful for revealing the presence of unnoticed hypoglycemia and for evaluating treatment outcomes after surgical resection. The Dexcom G6 system has an urgent low glucose alarm, making it particularly suitable for patients who are unaware of hypoglycemia.

Intermittent-scanned continuous glucose monitoring with low glucose alarms decreases hypoglycemia incidence in middle-aged adults with type 1 diabetes in real-life setting

ObjectiveThere is limited real-life data demonstrating that hypo-/hyperglycemic alarms added to continuous glucose monitoring (CGM) improve metabolic control in adults with type 1 diabetes (T1D).We evaluated the usefulness of switching from a flash or intermittent-scanned continuous glucose monitoring (is-CGM) device without low or higher glucose alarms to a is-CGM device with alarms to prevent hypoglycemia in adults with T1D. MethodsIndividuals with T1D and fearful of hypoglycemia, prone to hypoglycemia unawareness, and/or experiencing severe hypoglycemia while using is-CGM Free Style Libre 1 (FSL1) were switched to FSL2 with individually-programmable low glucose alarms. The primary endpoint was the changes in % time below range (TBR%) <70 mg/dl [3.9 mmol/l] and <54 mg/dl [3.0 mmol/l] after 12 weeks on FSL2 compared with FSL1. Secondary endpoints were changes in % time in range (TIR% 70–180 mg/dl [3.9–10.0 mmol/l]), % time above range (TAR%) >180 [10.0 mmol/l], mean interstitial glucose, glycemic management indicator (GMI), interstitial glucose coefficient of variation (CV%), hemoglobin A1c, and sensor's scans/day. ResultsWe included 108 individuals (57.4 % men), aged 58.2 ± 17.3 [95 % CI: 55.0 to 61.5] years, with mean diabetes duration 25 ± 14.6 [95 % CI: 22.1 to 27.7] years. Among individuals, 40 (37.0 %) had hypoglycemia awareness with Clarke's score ≥4 and 19 (17.5 %) had a history of severe hypoglycemia. The median low glucose alarm threshold was 70 [IQR: 65–70] mg/dl (3.9 [IQR: 3.6–3.9] mmol/L). By comparison of first 12 weeks on FSL2 vs. last 12 weeks on FSL1, TBR% <70 mg/dl decreased from 4.5 ± 4.4 to 2.3 ± 2.8 % (p < 0.001), TBR% <54 mg/dl decreased from 1.4 ± 2.2 to 0.3 ± 0.9 % (p < 0.001). TIR% was not significantly different (51.5 ± 14.9 vs. 52.9 ± 16 % (p = 0.13)), nor was TAR% (43.8 ± 16.2 vs. 44.7 ± 16.5 % (p = 0.5)). CV% decreased from 39.4 ± 6.9 to 37.9 ± 6.1 % (p < 0.001). Those at risk for hypoglycemia (TBR >4 % and >1 %, respectively, at baseline) showed a significant decrease in the incidence of hypoglycemia <70 and <54 mg/dl (p < 0.0001). Patients' satisfaction with hypoglycemia alarms was high, since all individuals opted to pursue using individual alarm beyond the study period. ConclusionSwitching from FSL1 to FSL2 with low glucose alarms reduced the frequency of hypoglycemia in middle-age adults with T1D, particularly in those who were prone to hypoglycemia awareness or severe hypoglycemia.

1246-P: Reducing Hypoglycemia in the Noncritical Care Setting Using CGM Devices: The Glucose Telemetry System

Objective: In a pilot study we have previously demonstrated successful transmission of glucometric values from continuous glucose monitoring (CGM) devices to a monitoring system at the nursing station (Glucose Telemetry System-GTS). In an ongoing study, we are evaluating whether use of GTS can reduce inpatient hypoglycemia compared to point of care (POC) capillary glucose testing, without increasing hyperglycemia. Design: Twenty-four patients with DM2 at high risk for inpatient hypoglycemia were randomized to GTS (N=12 intervention group) or POC (N=12 standard of care). Nursing staff were asked to proceed with hypoglycemia preventative actions for GTS low glucose alarms set at &amp;lt;85 mg/dL. Subjects randomized to standard of care used “blinded” CGM. Mean percent time spent in hypoglycemia, hyperglycemia, and hypoglycemia event rates were evaluated. Results: Twenty-one subjects were included in the analysis, 2 subjects withdrew due to minor bleeding at CGM insertion site and 1 subject had insufficient CGM data due to sensor failure. 30 GTS hypoglycemia alarms occurred in 7 different subjects. Overall percent time spent in hypoglycemia (≤70 mg/dL) was 0.18%±0.21 versus 1.64%±1.59 (p=0.056), and clinically significant hypoglycemia (&amp;lt;54mg/dL) was 0.01%±0.01 versus 0.48%±1.07 (p=0.135), between intervention and control groups, respectively. Rate of hypoglycemic episodes per day/per patient was 0.12±0.17 vs. 0.27±0.33 (p=0.19) for GTS and POC, respectively. Percent time spent in normoglycemia (70-179 mg/dL) was 52.04%±23.65 versus 52.92%±27.37 (p=0.94), while percent time in hyperglycemia (≥180 mg/dL) was 47.80%±23.65 versus 45.43%±28.05 (p=0.84), respectively. Conclusion: In this preliminary analysis, subjects monitored by GTS had a non-statistically significant decrease in inpatient hypoglycemia compared to standard of care. Disclosure E. Spanakis: None. M. Satyarengga: None. L.G. Singh: None. L. Pinault: None. J.D. Sorkin: None. M. Zhan: None. G.E. Umpierrez: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc. Research Support; Self; AstraZeneca, Merck &amp; Co., Inc., Novo Nordisk Inc., Sanofi US. Funding U.S. Department of Veterans Affairs (1I01CX001825-01)

Hypoglycaemia unawareness in patients with type 1 diabetes

Hypoglycaemia unawareness, defined at the onset of neuroglycopenia before the appearance of autonomic warning symptoms, is an serious problem in type 1 diabetes mellitus. It is often caused by recurrent or severe hypoglycaemia, which leads to the failure of the autonomic nervous system (hypoglycaemia-associated autonomic failure - HAAF). The hypoglycaemia awareness can be restored by avoiding episodes of hypoglycaemia. Management of hypoglycaemia unawareness is complex, and can only be achieved by amultifactorial intervention of clinical care and structured patient education. In patients in whom functional intensive insulin therapy with insulin analogue, continuous subcutaneous insulin infusion using insulin pumps are ineffective in the prevention of hypoglycaemia the implementation of continuous glucose monitoring (CGM) is advisable. CGM systems equipped with low glucose alarms and prediction alarms not only significantly reduce the risk of severe hypoglycaemia, but also significantly reduce the fear of hypoglycaemia and improve the quality of life of patients and their families. The insulin pumps integrated with CGM automatically suspending insulin infusion when glucose is predicted to soon be low (PLGS) should be preferred in patient with hypoglycaemia unawareness. Hypoglycaemia management is complex and should also include structural education. Particular attention should be paid to the management of hypoglycaemia and appropriate use of modern therapy. The hypoglycaemia unawareness is very common among children under the age of 6 years who are unable to observe the early symptoms of hypoglycemia by themselves. This induces ahigh risk of frequent and severe hypoglycaemia, which can lead to structural changes in the brain, cognitive dysfunctions, poor mental abilities and behavioral disorders later in life.

Safety of Nighttime 2-Hour Suspension of Basal Insulin in Pump-Treated Type 1 Diabetes Even in the Absence of Low Glucose

OBJECTIVEAn integrated sensor-augmented pump system has been introduced that interrupts basal insulin infusion for 2 h if patients fail to respond to low-glucose alarms. It has been suggested that such interruptions of basal insulin due to falsely low glucose levels detected by sensor could lead to diabetic ketoacidosis. We hypothesized that random suspension of basal insulin for 2 h in the overnight period would not lead to clinically important increases in blood β-hydroxybutyrate levels despite widely varying glucose values prior to the suspension.RESEARCH DESIGN AND METHODSSubjects measured blood glucose and blood β-hydroxybutyrate levels using a meter each night at 9:00 p.m., then fasted until the next morning. On control nights, the usual basal rates were continued; on experimental nights, the basal insulin infusion was reprogrammed for a 2-h zero basal rate at random times after 11:30 p.m.RESULTSIn 17 type 1 diabetic subjects (mean age 24 ± 9 years, diabetes duration 14 ± 11 years, A1C level 7.3 ± 0.5% [56 mmol/mol]), blood glucose and blood β-hydroxybutyrate levels were similar at 9:00 p.m. on suspend nights (144 ± 63 mg/dL and 0.09 ± 0.07 mmol/L) and nonsuspend nights (151 ± 65 mg/dL and 0.08 ± 0.06 mmol/L) (P = 0.39 and P = 0.47, respectively). Fasting morning blood glucose levels increased after suspend nights compared with nonsuspend nights (191 ± 68 vs. 141 ± 75 mg/dL, P < 0.0001), and the frequency of fasting hypoglycemia decreased the morning following suspend nights (P < 0.0001). Morning blood β-hydroxybutyrate levels were slightly higher after suspension (0.13 ± 0.14 vs. 0.09 ± 0.11 mmol/L, P = 0.053), but the difference was not clinically important.CONCLUSIONSSystems that suspend basal insulin for 2 h are safe and do not lead to clinically significant ketonemia even if the blood glucose level is elevated at the time of the suspension.

Hypoglycaemia documented with real‐time continuous glucose sensing in a case of ‘dead in bed’ syndrome

AbstractThe objective of this observational case report was to present the first case consistent with the ‘dead in bed’ syndrome in which hypoglycaemia has been documented by real‐time glucose monitoring at the time of death.We report the case of a 41‐year‐old male with type 1 diabetes. Diagnosed at age 14, he had poor glycaemic control during his teen years and suffered from severe hypoglycaemia unawareness. His diabetes was complicated by nephropathy, neuropathy and retinopathy. He was last seen alive and well by the family seven days before he was found dead in bed with his insulin pump and sensor in situ. The last recorded interaction between the patient and the pump system was seven days previously with evidence of prolonged hypoglycaemia around the time. Post‐mortem examination showed no specific cause of death.The findings in this case report are consistent with the hypothesis that hypoglycaemia is a precipitant of the ‘dead in bed’ syndrome in diabetes and indicate that the presence of low glucose alarms does not provide complete protection against such an event. Copyright © 2013 John Wiley &amp; Sons.

The effect of short-term use of the Guardian RT continuous glucose monitoring system on fear of hypoglycaemia in patients with type 1 diabetes mellitus

AimThis study examines whether the short-term use of a continuous glucose monitor (CGM) can reduce the fear of hypoglycaemia in individuals with type 1 diabetes mellitus (T1DM). MethodsTwelve participants with T1DM were fitted with a Guardian® REAL-Time CGM and assigned to either an alarm (low glucose alarm set at 4.5mmol/L) or no alarm condition for 3 days, with both treatments administered following a counterbalanced study design. The participants completed the Hypoglycaemia Fear Survey on three separate occasions, before their CGM was fitted as well as following the alarm and no alarm conditions. ResultsThe alarm treatment reduced the incidence of hypoglycaemic episodes (CGM readings≤3.5mmol/L; 1.1±0.5 versus 1.9±0.5; mean±SEM) and the relative time spent below this hypoglycaemic threshold (0.9±0.4% versus 2.6±1.0%) but did not alter the fear of hypoglycaemia (78.6±7.0, 75.8±5.2 and 79.3±5.8 at baseline and following the alarm and no alarm treatments, respectively; p>0.05). CGM overestimated blood glucose levels by 0.8±0.2mmol/L for blood glucose readings less than, or equal to, 5mmol/L. ConclusionsShort-term use of the Guardian® REAL-Time CGM has no clinically significant effect on fear of hypoglycaemia possibly due, in part, to the inaccuracies of CGMs at low blood glucose levels.

Increasing the Low-Glucose Alarm of a Continuous Glucose Monitoring System Prevents Exercise-Induced Hypoglycemia Without Triggering Any False Alarms

The use of continuous glucose monitoring systems (CGMSs) with low-glucose alarms is advocated as a means to decrease the risk of hypoglycemia in type 1 diabetes. Unfortunately, marked mismatches between CGMS readings and actual blood glucose (BG) concentrations limit the usefulness of CGMS in preventing hypoglycemia (1). Although we showed recently that raising the alarm level to compensate for this mismatch decreases the incidence and duration of hypoglycemic episodes, this results in an unacceptably high rate of false alarms (1), defined as an alarm triggered when BG levels are greater than the alarm threshold. This is an important issue because repeated exposure to false alarms can discourage individuals from using their CGMSs (2). Given that CGMSs overestimate BG levels when they rapidly decline (3,4), we propose that raising the CGMS alarm …

Effect of Short-Term Use of a Continuous Glucose Monitoring System with a Real-Time Glucose Display and a Low Glucose Alarm on Incidence and Duration of Hypoglycemia in a Home Setting in Type 1 Diabetes Mellitus

The objective of this study was to examine whether setting the low glucose alarm of a Guardian® REAL-Time continuous glucose monitoring system (CGMS) to 80 mg/dl for 3 days and providing instructions to users reduce the risk of hypoglycemia under free-living conditions in individuals with type 1 diabetes mellitus (T1DM). Fourteen participants with T1DM aged 26.1±6.0 years (mean±standard deviation) were fitted with a CGMS and assigned for 3 days to either an alarm [low and high blood glucose (BG) alarms set at 80 and 200 mg/dl, respectively] or no alarm condition, with each treatment administered to all participants following a counterbalanced design. All participants were given detailed instructions on how to respond appropriately to low glucose alarms. The CGMS with alarm reduced the incidence of hypoglycemia (CGMS readings≤65 mg/dl) by 44% as well as the time spent below this hypoglycemic threshold by 64% without increasing average BG levels. However, the CGMS with alarm had no effect on the incidence of symptomatic hypoglycemia. Short-term use of the CGMS with alarm, together with appropriate instructions for users, reduces the incidence and duration of hypoglycemia, but only to a limited extent, in part because it overestimates BG in the low glucose range.

Alarm Characterization for Continuous Glucose Monitors Used as Adjuncts to Self-Monitoring of Blood Glucose

Continuous glucose monitoring (CGM) devices available in the United States are approved for use as adjuncts to self-monitoring of blood glucose (SMBG). Alarm evaluation in the Clinical and Laboratory Standards Institute (CLSI) guideline for CGM does not specifically address devices that employ both CGM and SMBG. In this report, an alarm evaluation method is proposed for these devices. The proposed method builds on the CLSI method using data from an in-clinic study of subjects with type 1 diabetes. CGM was used to detect glycemic events, and SMBG was used to determine treatment. To optimize detection of a single glucose level, such as 70 mg/dl, a range of alarm threshold settings was evaluated. The alarm characterization provides a choice of alarm settings that trade off detection and false alarms. Detection of a range of high glucose levels was similarly evaluated. Using low glucose alarms, detection of 70 mg/dl within 30 minutes increased from 64 to 97% as alarm settings increased from 70 to 100 mg/dl, and alarms that did not require treatment (SMBG >85 mg/dl) increased from 18 to 52%. Using high glucose alarms, detection of 180 mg/dl within 30 minutes increased from 87 to 96% as alarm settings decreased from 180 to 165 mg/dl, and alarms that did not require treatment (SMBG <180 mg/dl) increased from 24 to 42%. The proposed alarm evaluation method provides information for choosing appropriate alarm thresholds and reflects the clinical utility of CGM alarms.

Use of the Cygnus GlucoWatch Biographer at a Diabetes Camp

Detection and prevention of nocturnal hypoglycemia is a major medical concern at diabetes camps. We conducted an open-label trial of the Cygnus GlucoWatch biographer to detect nocturnal hypoglycemia in a diabetes camp, a nonclinical environment with multiple activities. Forty-five campers (7-17 years old) wore a biographer. The biographer was placed on the arm at 6:00 PM, with the low alarm set to 85 mg/dL (4.7 mmol/L). Overnight glucose monitoring occurred per usual camp protocol. Counselors were to check and record blood glucose values if the biographer alarmed. Biographers were worn for 154 nights by 45 campers. After a 3-hour warm-up period, 67% of biographers were calibrated, of which 28% were worn the entire night (12 hours). Thirty-four percent of readings were skipped because of: "data errors" (65%), sweat (20%), and temperature change (16%). Reported biographer values correlated with meter glucose values measured 11 to 20 minutes later (r = 0.90). Of 20 low-glucose alarms with corresponding meter values measured within 20 minutes, there were 10 true-positive alarms, 10 false-positive alarms, and no false-negative alarms. Campers reported sleep disruption 32% of the nights, and 74% found the biographer helpful. Campers reported they would wear the biographer 4 to 5 nights each week. Half of the biographer low-glucose alarms that had corresponding blood meter values were true-positive alarms, and the remaining were false-positive alarms. There was close correlation between the biographer and meter glucose values. The majority of campers found the biographer helpful and would use it at home.

A non‐invasive frequent home blood glucose monitor

AbstractAttaining near‐normoglycaemia in patients with diabetes is essential if diabetes‐related complications are to be minimised. Attempts to optimise glycaemic control are often limited by the infrequent nature of current home blood glucose monitoring systems and fear of hypoglycaemia. We evaluated the potential benefit of the GlucoWatch® Biographer, a non‐invasive glucose monitoring device designed to give a frequent measure of blood glucose and provide early warning of hypoglycaemia or hyperglycaemia, in five subjects with type 1 diabetes over a three week period.Subjects found the device easy to use, obtaining 762 usable readings out of a possible 1168 (65%) although all experienced some degree of skin irritation. They felt that the device facilitated continuous blood glucose monitoring and thought that high and low glucose alarms were helpful. Subjects experienced between one and six hypoglycaemia alarms per day, usually 20 to 60 min before the appearance of clinical symptoms, and between zero and four hyperglycaemia alarms per day. The degree to which the device can improve glycaemic control remains to be evaluated. Copyright © 2002 John Wiley &amp; Sons, Ltd.

New developments in type 1 (insulin-dependent) diabetes.

The Diabetes Control and Complications Trial has conclusively demonstrated that improved metabolic control leads to reduction in the rate of microvascular complications of diabetes. In order to allow patients to achieve improved metabolic control, much research has focused on improved methods of glucose monitoring and more physiologic ways of insulin delivery. The 2 most promising methods of minimally invasive blood glucose monitoring are the Glucowatch, using the technique of reverse iontophoresis to measure interstitial fluid glucose levels every twenty minutes and an implantable sensor, in which a catheter resembling that used for insulin delivery through a pump is impregnated with glucose oxidase at the tip. This device monitors blood sugars every few minutes, but like a holter monitor, must be downloaded in the physician's office. Still under development are (1) implantable subcutaneous sensors with a high and low blood glucose alarm and (2) sensors in which the patient will be able to download the data using a home PC. Advances in insulin delivery have included the availability of new insulin analogs which more closely simulate endogenous insulin release, with rapid acting analogs simulating the increase in insulin production that normally occurs after meals. Phase III clinical trials are in progress of a long-acting basal insulin without peak actions to simulate the low dose continuous production of the insulin which normally inhibits hepatic glucose production. In addition, use of the insulin pump has increased markedly since publication of the DCCT with the greatest increase being among adolescents. In addition to advances in treatment of diabetes, research has continued on curing the disease using islet cell transplantation and preventing the disease with agents such as insulin (DPT-1 Trial) and nicotinamide (ENDIT). This article provides an overview of recent advances in diabetes management and prevention.