The Effect of Exercise Intensity on Carbohydrate Sparing Postexercise: Implications for Postexercise Hypoglycemia.

The purpose of this study was to determine the effect of exercise intensity on the proportion and rate of carbohydrate oxidation and glucoregulatory hormone responses during recovery from exercise. Six physically active participants completed 1 hr of low-intensity (LI; 50% lactate threshold) or moderate-intensity (MI; 100% lactate threshold) exercise on separate days following a randomized counterbalanced design. During exercise and for 6 hr of recovery, samples of expired air were collected to determine oxygen consumption, respiratory exchange ratio, energy expenditure, and substrate oxidation rates. Blood samples were also collected to measure glucoregulatory hormones (catecholamines, GH) and metabolites (glucose, free fatty acids, lactate, pH, and bicarbonate). During exercise, respiratory exchange ratio, energy expenditure, and the proportion and rate of carbohydrate (CHO) oxidation were higher during MI compared with LI. However, during recovery from MI, respiratory exchange ratio and the proportion and rate of CHO oxidation were lower than preexercise levels and corresponding LI. During exercise and early recovery, catecholamines and growth hormone were higher in MI than LI, and there was a trend for higher levels of free fatty acids in the early recovery from MI compared with LI. In summary, CHO oxidation during exercise increases with exercise intensity but there is a preference for CHO sparing (and fat oxidation) during recovery from MI exercise compared with LI exercise. This exercise intensity-dependent shift in substrate oxidation during recovery is explained, in part, by the pattern of change of key glucoregulatory hormones including catecholamines and growth hormone and plasma fatty acid concentrations.

A very low carbohydrate diet for minimising blood glucose excursions during ultra-endurance open-water swimming in type 1 diabetes: a case report.

Carbohydrate-restricted diets are used by people with type 1 diabetes (T1D) to help manage their condition. However, the impact of this strategy on blood glucose responses to exercise is unknown. This study describes the nutritional strategies of an athlete with T1D, who follows a very low carbohydrate diet to manage her condition during an ultra-endurance open-water swimming event. The athlete completed the 19.7 km distance in 6 h 43 min. She experienced minimal disruptions to glycaemia, reduced need for supplemental carbohydrate, and no episodes of symptomatic hypoglycaemia. This case report will hopefully encourage further experimental studies that inform and expand current clinical practice guidelines.

Questionnaires Measuring Physical Activity in Clinical Pediatric Populations: A Systematic Review.

PURPOSE: Regular physical activity (PA) is a cornerstone therapy for many childhood chronic health conditions, and questionnaires offer a simple method for monitoring PA and identifying children who do not meet clinical practice guidelines. The purpose of this systematic review is to determine which questionnaires are most efficacious for assessing PA in children with chronic health conditions. METHODS: Systematic literature searches were conducted through ProQuest, MEDLINE, Scopus, and SPORTDiscus from January 2010 to August 2020 to identify studies that measured PA with a validated questionnaire in children and adolescents aged 3-18 years old with chronic health conditions. In eligible studies, the validity and reliability of questionnaires were identified, and the modified COnsensus-based Standards for the selection of health status Measurement INstruments checklist and Grading of Recommendations, Assessment, Development, and Evaluations were used to assess the quality and strength of evidence and risk of bias. RESULTS: Four thousand four hundred and seventy-eight references were extracted, and 10 articles were included for review. From 10 eligible studies, 6 questionnaires were identified, none of which adequately measure PA in clinical pediatric populations. CONCLUSION: Questionnaires to adequately measure PA in children with chronic conditions are lacking. This compromises the identification of those who do not meet PA guidelines, limiting the opportunity to identify and address factors contributing to low PA levels.

Association between non-tea flavonoid intake and risk of type 2 diabetes: the Australian diabetes, obesity and lifestyle study.

Studies examining the association between flavonoid intake and measures of insulin resistance and ß-cell dysfunction, as markers of type 2 diabetes (T2DM) across the adult lifespan, may provide insights into how flavonoids influence T2DM risk. This study examined the cross-sectional associations between flavonoid intakes, from dietary sources other than tea, and biomarkers of glucose tolerance and insulin sensitivity in adults aged 25 years and older participating in the Australian diabetes, obesity and lifestyle (AusDiab) study. Additionally, longitudinal associations between non-tea flavonoid intakes and incident T2DM over 12 years were explored. Eligible participants (n = 7675) had no previous history of T2DM and had completed a food-frequency questionnaire at baseline (1999-2000) from which flavonoid intakes were calculated using United States Department of Agriculture Databases. Restricted cubic splines in regression models were used to examine cross-sectional associations between intakes of total non-tea flavonoids and selected flavonoid subclasses and measures of glucose tolerance and insulin sensitivity including glycated haemoglobin (HbA1c), homeostasis model assessment of ß-cell function (HOMA2-% ß) and insulin sensitivity (HOMA2-% S), 2-hour post load plasma glucose (PLG), fasting plasma glucose (FPG) and fasting insulin levels. Associations between flavonoid intakes and T2DM risk were estimated using Cox proportional hazards models. Cross-sectionally, significant beneficial associations were observed for intakes of total flavonoids and the flavan-3-ol-monomer, proanthocyanidin, flavonol and anthocyanidin subclasses with measures of glucose tolerance and insulin sensitivity (P < 0.05 for all), except fasting plasma glucose. During follow-up, 344 incident T2DM cases were recorded. Participants with the highest total flavonoid intake had a 21% lower risk of T2DM over 12 years, although this was not statistically significant in multivariable adjusted models [HR (95% CI): 0.79 (0.57, 1.09)]. This study provides some evidence that consuming flavonoid-rich foods may be protective against T2DM through mechanisms related to glucose tolerance and insulin sensitivity.

Higher Habitual Flavonoid Intakes Are Associated with a Lower Incidence of Diabetes.

BACKGROUND: Higher flavonoid intakes are hypothesized to confer protection against type 2 diabetes mellitus. OBJECTIVES: We aimed to 1) investigate associations between flavonoid intakes and diabetes, 2) examine the mediating impact of body fat, and 3) identify subpopulations that may receive the greatest benefit from higher flavonoid intakes in participants of the Danish Diet, Cancer, and Health Study followed up for 23 y. METHODS: Cross-sectional associations between baseline flavonoid intake, estimated using FFQs and the Phenol Explorer database, and body fat, estimated by bioelectrical impedance, were assessed using multivariable-adjusted linear regression models. Nonlinear associations between flavonoid intake and incident diabetes were examined using restricted cubic splines with multivariable-adjusted Cox proportional hazards models. RESULTS: Among 54,787 participants (median age: 56 y; IQR: 52-60 y; 47.3% men), 6700 individuals were diagnosed with diabetes. Participants in the highest total flavonoid intake quintile (median, 1202 mg/d) had a 1.52 kg lower body fat (95% CI: -1.74, -1.30 kg) and a 19% lower risk of diabetes (HR: 0.81; 95% CI: 0.75, 0.87) after multivariable adjustments and compared with participants in the lowest intake quintile (median: 174 mg/d). Body fat mediated 57% (95% CI: 42, 83%) of the association between flavonoid intake and incident diabetes. Of the flavonoid subclasses, moderate to high intakes of flavonols, flavanol monomers, flavanol oligo + polymers, and anthocyanins were significantly associated with a lower risk of diabetes. Although associations were not modified by sex, smoking status, BMI, or physical activity (Pinteraction > 0.05 for all), findings on an absolute scale suggest that those at a higher risk (those with obesity) may benefit the most from a higher flavonoid intake. CONCLUSIONS: The findings reported in this study suggest that a diet abundant in flavonoid-rich foods may help ameliorate diabetes risk, in part through a reduction in body fat.

Associations Between Fruit Intake and Risk of Diabetes in the AusDiab Cohort.

CONTEXT: Fruit, but not fruit juice, intake is inversely associated with type 2 diabetes mellitus (T2DM). However, questions remain about the mechanisms by which fruits may confer protection. OBJECTIVE: The aims of this work were to examine associations between intake of fruit types and 1) measures of glucose tolerance and insulin sensitivity and 2) diabetes at follow-up. METHODS: Among participants of the Australian Diabetes, Obesity and Lifestyle Study, fruit and fruit juice intake was assessed by food frequency questionnaire at baseline. Associations between fruit and fruit juice intake and 1) fasting plasma glucose, 2-hour postload plasma glucose, updated homeostasis model assessment of insulin resistance of ß-cell function (HOMA2-%ß), HOMA2 of insulin sensitivity (HOMA2-%S), and fasting insulin levels at baseline and 2) the presence of diabetes at follow-up (5 and 12 years) were assessed using restricted cubic splines in logistic and linear regression models. RESULTS: This population of 7675 Australians (45% males) had a mean ±â€…SD age of 54 ±â€…12 years at baseline. Total fruit intake was inversely associated with serum insulin and HOMA2-%ß, and positively associated with HOMA2-%S at baseline. Compared to participants with the lowest intakes (quartile 1), participants with moderate total fruit intakes (quartile 3) had 36% lower odds of having diabetes at 5 years (odds ratio, 0.64; 95% CI, 0.44-0.92), after adjusting for dietary and lifestyle confounders. Associations with 12-year outcomes were not statistically significant. CONCLUSION: A healthy diet including whole fruits, but not fruit juice, may play a role in mitigating T2DM risk.

Exploration of the Performance of a Hybrid Closed Loop Insulin Delivery Algorithm That Includes Insulin Delivery Limits Designed to Protect Against Hypoglycemia.

BACKGROUND: Hypoglycemia remains a risk for closed loop insulin delivery particularly following exercise or if the glucose sensor is inaccurate. The aim of this study was to test whether an algorithm that includes a limit to insulin delivery is effective at protecting against hypoglycemia under those circumstances. METHODS: An observational study on 8 participants with type 1 diabetes was conducted, where a hybrid closed loop system (HCL) (Medtronic™ 670G) was challenged with hypoglycemic stimuli: exercise and an overreading glucose sensor. RESULTS: There was no overnight or exercise-induced hypoglycemia during HCL insulin delivery. All daytime hypoglycemia was attributable to postmeal bolused insulin in those participants with a more aggressive carbohydrate factor. CONCLUSION: HCL systems rely on accurate carbohydrate ratios and carbohydrate counting to avoid hypoglycemia. The algorithm that was tested against moderate exercise and an overreading glucose sensor performed well in terms of hypoglycemia avoidance. Algorithm refinement continues in preparation for long-term outpatient trials.

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.

Effect of Exercise Intensity on Glucose Requirements to Maintain Euglycemia During Exercise in Type 1 Diabetes.

CONTEXT: No recommendations exist to inform the carbohydrate amount required to prevent hypoglycemia associated with exercise of different intensities in individuals with type 1 diabetes (T1D). OBJECTIVE: The relationship between exercise intensity and carbohydrate requirements to maintain stable euglycemia in individuals with T1D remains to be determined. It was predicted that an "inverted-U" relationship exists between exercise intensity and the amount of glucose required to prevent hypoglycemia during exercise at basal insulinemia. Our objective was to investigate this relationship and elucidate the underlying glucoregulatory mechanisms. DESIGN, PARTICIPANTS, AND INTERVENTION: We subjected nine individuals (mean ± SD age, 21.5 ± 4.0 years; duration of disease, 11.4 ± 6.4 years; glycated hemoglobin, 7.9 ± 0.8% [60 mmol/mol]; body mass index, 25.4 ± 5.5 kg/m(2); VO2peak, 34.8 ± 5.1 mL·kg(-1)·min(-1); and lactate threshold, 59.9 ± 5.9% VO2peak) with T1D to a euglycemic clamp, whereby euglycemia was maintained by infusing basal insulin rates with concomitant infusion of [6,6-(2)H2]glucose for determining glucose kinetics. Glucose was infused to maintain euglycemia during and for 2 hours after exercise of different intensities (35, 50, 65, and 80% VO2peak). MAIN OUTCOME MEASURES: The glucose infusion rate (GIR), levels of glucoregulatory hormones, and rates of endogenous glucose appearance and disappearance were compared between conditions. RESULTS: The mean GIR to maintain euglycemia during exercise increased with intensity up to 50% (4.0 ± 1.6 g/h; P < .05) and 65% (4.1 ± 1.7 g/h), but no glucose was required at 80% VO2peak. Glucose rate of appearance and disappearance increased with intensity and, together with plasma catecholamines, reached higher levels at 80% VO2peak. CONCLUSION: Our findings support the predicted inverted-U relationship between exercise intensity and glucose requirement. However, the relationship between iv and oral glucose requirements needs to be investigated to translate these GIR data to clinical practice.

Effect of antecedent moderate-intensity exercise on the glycemia-increasing effect of a 30-sec maximal sprint: a sex comparison.

This study investigated whether a prior bout of moderate-intensity exercise attenuates the glycemia-increasing effect of a maximal 30-sec sprint. A secondary aim was to determine whether the effect of antecedent exercise on the glucoregulatory response to sprinting is affected by sex. Participants (men n = 8; women n = 7) were tested on two occasions during which they either rested (CON) or cycled for 60-min at a moderate intensity of ~65% V ˙ O 2 peak (EX) before performing a 30-sec maximal cycling effort 195 min later. In response to the sprint, blood glucose increased to a similar extent between EX and CON trials, peaking at 10 min of recovery, with no difference between sexes (P > 0.05). Blood glucose then declined at a faster rate in EX, and this was associated with a glucose rate of disappearance (R d) that exceeded the glucose rate of appearance (R a) earlier in EX compared with CON, although the overall glucose R a and R d profile was higher in men compared with women (P < 0.05). The response of growth hormone was attenuated during recovery from EX compared with CON (P < 0.05), with a lower absolute response in women compared with men (P < 0.05). The response of epinephrine and norepinephrine was also lower in women compared with men (P < 0.05) but similar between trials. In summary, a prior bout of moderate-intensity exercise does not affect the magnitude of the glycemia-increasing response to a 30-sec sprint; however, the subsequent decline in blood glucose is more rapid. This blood glucose response is similar between men and women, despite less pronounced changes in glucose R a and R d, and a lower response of plasma catecholamines and growth hormone to sprinting in women.

Antecedent hypoglycaemia does not diminish the glycaemia-increasing effect and glucoregulatory responses of a 10 s sprint in people with type 1 diabetes.

AIMS/HYPOTHESIS: A 10 s sprint has been reported to provide a means to prevent acute post-exercise hypoglycaemia in young adults with type 1 diabetes because of its glycaemia-raising effect, but it is unclear whether this effect is impaired by antecedent hypoglycaemia. The purpose of this study was to investigate whether antecedent hypoglycaemia impairs the glycaemia-raising effect of a 10 s sprint in individuals with type 1 diabetes. METHODS: Eight individuals underwent a hyperinsulinaemic-hypoglycaemic or hyperinsulinaemic-euglycaemic clamp on two separate mornings. Thereafter, the participants underwent a basal insulin-euglycaemic clamp before performing a 10 s sprint on a cycle ergometer. The levels of blood glucose and glucoregulatory hormones and rates of glucose appearance (Ra) and disappearance (Rd) were compared between conditions. RESULTS: During the morning clamps, blood glucose levels were significantly different between conditions of hypoglycaemia (2.8 ± 0.1 mmol/l) and euglycaemia (5.4 ± 0.2 mmol/l; p < 0.001). Mean glycaemia prior to sprinting was similar (5.6 ± 0.4 and 5.5 ± 0.3 mmol/l for hypoglycaemic and euglycaemic conditions, respectively; p = 0.83). In response to the afternoon sprint, the pattern of increase in blood glucose levels did not differ between conditions, reaching similar maximal levels 45 min after exercise (6.5 ± 0.4 and 6.6 ± 0.3 mmol/l, respectively; p = 0.43). The early post-exercise patterns in glucose Ra and Rd and increases in plasma adrenaline (epinephrine), growth hormone and cortisol levels did not differ between conditions. CONCLUSIONS/INTERPRETATION: Hypoglycaemia in the morning does not diminish the glycaemia-raising effect of an afternoon 10 s sprint in young adults with type 1 diabetes, suggesting that sprinting is a useful strategy for opposing hypoglycaemia, regardless of prior hypoglycaemia.

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.

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.

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.

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.

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.