Raymond J. Davey

Improving Epinephrine Responses in Hypoglycemia Unawareness With Real-Time Continuous Glucose Monitoring in Adolescents With Type 1 Diabetes

OBJECTIVE To determine whether real-time continuous glucose monitoring (CGM) with preset alarms at specific glucose levels would prove a useful tool to achieve avoidance of hypoglycemia and improve the counterregulatory response to hypoglycemia in adolescents with type 1 diabetes with hypoglycemia unawareness. RESEARCH DESIGN AND METHODS Adolescents with type 1 diabetes with hypoglycemia unawareness underwent hyperinsulinemic hypoglycemic clamp studies at baseline to determine their counterregulatory hormone responses to hypoglycemia. Subjects were then randomized to either standard therapy or real-time CGM for 4 weeks. The clamp study was then repeated. RESULTS The epinephrine response during hypoglycemia after the intervention was greater in the CGM group than in the standard therapy group. CONCLUSIONS A greater epinephrine response during hypoglycemia suggests that real-time CGM is a useful clinical tool to improve hypoglycemia unawareness in adolescents with type 1 diabetes.

The effect of a short sprint on postexercise whole-body glucose production and utilization rates in individuals with type 1 diabetes mellitus.

CONTEXT Recently we showed that a 10-sec maximal sprint effort performed before or after moderate intensity exercise can prevent early hypoglycemia during recovery in individuals with type 1 diabetes mellitus (T1DM). However, the mechanisms underlying this protective effect of sprinting are still unknown. OBJECTIVE The objective of the study was to test the hypothesis that short duration sprinting increases blood glucose levels via a disproportionate increase in glucose rate of appearance (Ra) relative to glucose rate of disappearance (Rd). SUBJECTS AND EXPERIMENTAL DESIGN: Eight T1DM participants were subjected to a euglycemic-euinsulinemic clamp and, together with nondiabetic participants, were infused with [6,6-(2)H]glucose before sprinting for 10 sec and allowed to recover for 2 h. RESULTS In response to sprinting, blood glucose levels increased by 1.2 ± 0.2 mmol/liter (P < 0.05) within 30 min of recovery in T1DM participants and remained stable afterward, whereas glycemia rose by only 0.40 ± 0.05 mmol/liter in the nondiabetic group. During recovery, glucose Ra did not change in both groups (P > 0.05), but glucose Rd in the nondiabetic and diabetic participants fell rapidly after exercise before returning within 30 min to preexercise levels. After sprinting, the levels of plasma epinephrine, norepinephrine, and GH rose transiently in both experimental groups (P < 0.05). CONCLUSION A sprint as short as 10 sec can increase plasma glucose levels in nondiabetic and T1DM individuals, with this rise resulting from a transient decline in glucose Rd rather than from a disproportionate rise in glucose Ra relative to glucose Rd as reported with intense aerobic exercise.

Contribution of an intrinsic lag of continuous glucose monitoring systems to differences in measured and actual glucose concentrations changing at variable rates in vitro.

Background: Current continuous glucose monitoring (CGM) systems measure glucose levels in the interstitial fluid to estimate blood glucose concentration. A lag time has been observed between CGM system glucose readings and blood glucose levels when glucose levels are changing. Although this lag has been attributed to the time it takes glucose to equilibrate between blood and interstitial fluid compartments, it is unclear to what extent these inaccuracies reflect an intrinsic delay of the device itself. Methods: Four Guardian® REAL-Time CGM systems (CGMSs) (Medtronic Diabetes, Minimed, CA) and eight glucose sensors were tested in glucose solutions prepared in Krebs bicarbonate buffers at 37 °C. Glucose readings obtained from CGMSs were compared with actual glucose concentrations during controlled changes in glucose concentration performed at four rates (30, 90, and 220 mg/dl/hr−1 and an instantaneous change of 110 mg/dl) using a linear gradient maker. Results: Irrespective of the rate and direction of changes in glucose concentration, the readings obtained from CGMSs were significantly different from actual glucose levels. The faster the rise or fall in actual glucose concentration, the more pronounced the mismatch with CGMS glucose readings. Furthermore, the intrinsic lag times (8.3 to 40.1 min) were high enough to account for the lags reported in previous in vivo studies. Conclusions: The lag intrinsic of the CGMS may make a significant contribution to the mismatch between CGM system readings and blood glucose concentrations.

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

Background: 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). Methods: 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. Results: 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. Conclusions: 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.

The Effect of Midday Moderate-Intensity Exercise on Postexercise Hypoglycemia Risk in Individuals With Type 1 Diabetes

CONTEXT Exercise increases the risk of hypoglycemia in type 1 diabetes. OBJECTIVE Recently we reported a biphasic increase in glucose requirements to maintain euglycemia after late-afternoon exercise, suggesting a unique pattern of delayed risk for nocturnal hypoglycemia. This study examined whether this pattern of glucose requirements occurs if exercise is performed earlier in the day. DESIGN, PARTICIPANTS, AND INTERVENTION Ten adolescents with type 1 diabetes underwent a hyperinsulinemic euglycemic glucose clamp on 2 different occasions during which they either rested or performed 45 minutes of moderate-intensity exercise at midday. Glucose was infused to maintain euglycemia for 17 hours after exercise. MAIN OUTCOME MEASURES The glucose infusion rate (GIR) to maintain euglycemia, glucose rates of appearance and disappearance, and levels of counterregulatory hormones were compared between conditions. RESULTS GIRs to maintain euglycemia were not significantly different between groups at baseline (9.8 ± 1.4 and 9.5 ± 1.6 g/h before the exercise and rest conditions, respectively) and did not change in the rest condition throughout the study. In contrast, GIR increased more than 3-fold during exercise (from 9.8 ± 1.4 to 30.6 ± 4.7 g/h), fell within the first hour of recovery, but remained elevated until 11 hours after exercise before returning to baseline levels. CONCLUSIONS The pattern of glucose requirements to maintain euglycemia in response to moderate-intensity exercise performed at midday suggests that the risk of exercise-mediated hypoglycemia increases during and for several hours after moderate-intensity exercise, with no evidence of a biphasic pattern of postexercise risk of hypoglycemia.

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 …

A 10-s Sprint Performed After Moderate-Intensity Exercise Neither Increases nor Decreases the Glucose Requirement to Prevent Late-Onset Hypoglycemia in Individuals With Type 1 Diabetes

OBJECTIVE To determine whether performing a 10-s sprint after moderate-intensity exercise increases the amount of carbohydrate required to maintain euglycemia and prevent late-onset postexercise hypoglycemia relative to moderate-intensity exercise alone. RESEARCH DESIGN AND METHODS Seven individuals with type 1 diabetes underwent a hyperinsulinemic-euglycemic clamp and performed 30 min of moderate-intensity exercise on two separate occasions followed by either a 10-s maximal sprint effort or no sprint. During the following 8 h, glucose infusion rate to maintain euglycemia and rates of glucose appearance and disappearance were measured continuously. RESULTS In response to exercise and throughout the 8-h recovery period, there were no differences in glucose infusion rate, blood glucose levels, plasma insulin concentrations, and rates of glucose appearance and disappearance between the two experimental conditions (P > 0.05). CONCLUSIONS A 10-s sprint performed after 30 min of moderate-intensity exercise does not affect the amount of carbohydrate required to maintain euglycemia postexercise in individuals with type 1 diabetes.

Is the response of continuous glucose monitors to physiological changes in blood glucose levels affected by sensor life

BACKGROUND None of the studies concerned with the performance of a continuous glucose monitor (CGM) over time has examined the extent to which extended periods of wear affect the responses of both CGM accuracy and lag time to rapid changes in blood glucose levels. Here we propose a novel approach to address these issues. METHODS Eight participants without diabetes were each fitted with two CGMs (Paradigm(®) 722 Real-Time [Medtronic, Northridge, CA]; abdominal and triceps regions) and completed fasted oral glucose challenges (OGCs) on six occasions over a 9-day period, while the CGMs were worn without removal. Arterialized blood samples were collected for comparison with CGM values. RESULTS There were marked mismatches and lag times between blood glucose and CGM values in response to all OGCs, most notably during the initial rapid increase in glucose levels. Abdominal and triceps CGMs consistently underestimated peak blood glucose by an average of 2.7±0.2 and 2.9±0.2 mM, respectively, and were associated with a peak blood glucose lag of 21.6±1.8 and 18.1±1.6 min, respectively. CGM accuracy did not deteriorate over 9 days of wear in OGCs for either the abdominal or triceps sensor. All participants found the triceps sensor site more comfortable than the abdominal site (P<0.05). CONCLUSIONS The current CGM sensor tested here may be used for extended periods, providing added economic benefits for the wearer. However, the marked inaccuracy and lag time of CGM readings when blood glucose levels change rapidly within the physiological range must be considered for optimal CGM use in glycemic management.

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

AIM This 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). METHODS Twelve participants with T1DM were fitted with a Guardian® REAL-Time CGM and assigned to either an alarm (low glucose alarm set at 4.5 mmol/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. RESULTS The alarm treatment reduced the incidence of hypoglycaemic episodes (CGM readings≤3.5 mmol/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±0.2 mmol/L for blood glucose readings less than, or equal to, 5 mmol/L. CONCLUSIONS Short-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.

Effectiveness of a Predictive Algorithm in the Prevention of Exercise-Induced Hypoglycemia in Type 1 Diabetes

BACKGROUND Sensor-augmented pump therapy (SAPT) with a predictive algorithm to suspend insulin delivery has the potential to reduce hypoglycemia, a known obstacle in improving physical activity in patients with type 1 diabetes. The predictive low glucose management (PLGM) system employs a predictive algorithm that suspends basal insulin when hypoglycemia is predicted. The aim of this study was to determine the efficacy of this algorithm in the prevention of exercise-induced hypoglycemia under in-clinic conditions. METHODS This was a randomized, controlled cross-over study in which 25 participants performed 2 consecutive sessions of 30 min of moderate-intensity exercise while on basal continuous subcutaneous insulin infusion on 2 study days: a control day with SAPT alone and an intervention day with SAPT and PLGM. The predictive algorithm suspended basal insulin when sensor glucose was predicted to be below the preset hypoglycemic threshold in 30 min. We tested preset hypoglycemic thresholds of 70 and 80 mg/dL. The primary outcome was the requirement for hypoglycemia treatment (symptomatic hypoglycemia with plasma glucose <63 mg/dL or plasma glucose <50 mg/dL) and was compared in both control and intervention arms. RESULTS Results were analyzed in 19 participants. In the intervention arm with both thresholds, only 6 participants (32%) required treatment for hypoglycemia compared with 17 participants (89%) in the control arm (P = 0.003). In participants with a 2-h pump suspension on intervention days, the plasma glucose was 84 ± 12 and 99 ± 24 mg/dL at thresholds of 70 and 80 mg/dL, respectively. CONCLUSIONS SAPT with PLGM reduced the need for hypoglycemia treatment after moderate-intensity exercise in an in-clinic setting.