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Continuous subcutaneous glucose monitoring in children with type 1 diabetes mellitus: a single-blind, randomized, controlled trial.

BACKGROUND: Tight glycemic control delays the long-term complications of type 1 diabetes mellitus (T1DM) but increases the risk for hypoglycemia. The continuous glucose-monitoring system (CGMS) provides blood glucose (BG) readings every 5 min, and its accuracy and reliability has been established in adults. However, there are limited data on its efficacy and safety in children. The purpose of this study was to determine if CGMS use improves metabolic control in children with T1DM. METHODS: Twenty-seven children (12 male) with T1DM participated in this single-blind, randomized, controlled trial. Participants (age: 11.4 +/- 3.7 (mean +/- SD) yr, range: 7-17 yr) were randomized to an intervention group (n = 18) or a control group (n = 9). Both groups wore the CGMS for 72-h periods at 0, 2, and 4 months. Adjustments in therapy for the intervention group were based on both CGMS and self-monitoring of BG (SMBG) data, while only SMBG data were used for the control group. Hemoglobin A1c (HbA1c) was determined at 0, 2, 4, and 6 months. The change in HbA1c from 0 to 6 months (HbA1c(Delta1-4)) and mean daily area under the CGMS curve for glucose <70 mg/dL area under the curve (AUC(<70)) were compared between groups. RESULTS: At study entry, HbA1c levels were similar in the intervention and control groups (8.4 +/- 0.98 and 8.8 +/- 0.86%, respectively; p = 0.12) but were significantly lower in the intervention group compared with the control group at study completion (7.8 +/- 0.88 and 8.6 +/- 0.95%, respectively; p = 0.02). The decrease in HbA1c of 0.61 +/- 0.68% in the intervention group was statistically significant (p = 0.03), whereas the decrease in HbA1c of 0.28 +/- 0.78% in the control group was not. Nonetheless, the differences in HbA1c(Delta1-4) between groups did not reach statistical significance (p = 0.13). There was no statistically significant difference in AUC(<70) between study groups (p = 0.18). CONCLUSION: CGMS use may improve metabolic control in children with T1DM without increasing the risk for hypoglycemia.

Adolescent↗

[Continuous blood glucose monitoring and infusion in freely mobile dogs (author's transl)].

With the system recently developed, continuous glucose determinations and programmed infusions are also possible in the freely mobile dog. The animal is kept in a dog box and wears a dog jacket to which a plastic plate is fitted. A bite- and twist-proof flexible hollow pipeline is connected rigidly to this plate. The pipeline goes through a hole in the centre of the roof of the dog box to a newly developed rotary adaptor system for three catheters. The rotary adaptor is fitted to a vertical sliding bar system with counter movement. The three catheters run along the inside of the hollow pipeline down to the animal's back where two of them connect to a double-lumen catheter (DLC) inserted in the jugular vein. Through one tube, heparin solution is transported to the tip of the DLC. There it is sucked back together with blood through the second tube and transported to the glucose analyser. Through the third catheter, insulin or glucose is infused into the other jugular vein. The flow of the extracorporeally heparinized blood is regular. Occlusion of the DLC does not occur. During a 24-h study period, 70 ml of blood are taken from the animal. The DLC is simple to manufacture and, if suitably developed, might also be used in humans instead of the usual rigid double-lumen plastic cannular system.

Animals↗

Acute mild cold exposure with shivering reduces 24 h glucose levels in individuals with type 2 diabetes but not prediabetes.

AIMS/HYPOTHESIS: Repeated cold exposure with shivering has been proposed as a potential strategy to enhance glucose metabolism by increasing energy expenditure and substrate utilisation. However, acute effects/benefits of cold-induced shivering on glucose homeostasis in metabolically compromised individuals are unknown. Here, we aimed to determine whether cold exposure at two different intensities improves 24 h glucose homeostasis in individuals with prediabetes and type 2 diabetes. METHODS: In a randomised crossover trial conducted in the South Limburg/Maastricht region of the Netherlands, men and postmenopausal women with prediabetes (n=12) and stable type 2 diabetes (n=12), aged 40-75 years, body mass index &#x2265;27 and &#x2264;35 kg/m2, non-smoking and sedentary, underwent two whole-body cold exposure sessions using a water-perfused suit. Session order was randomised using an online randomisation tool (randomizer.org); participants were masked to the cold exposure intensity received, but investigators were not. Sessions were designed to elicit ~1.5-fold (mild, 15&#xb0;C) and ~2.5-fold (moderate, 4&#xb0;C) increases in resting metabolic rate (RMR). Continuous glucose monitoring assessed interstitial glucose concentrations over 24 h periods before and after each intervention, with controlled diet and activity. Shivering was confirmed via indirect calorimetry and electromyography. RESULTS: In both study groups and periods, RMR increased significantly vs baseline (p<0.001 for all). In prediabetes, the increase in the final 1 h of cold was 1.53&#xa0;&#xd7;&#xa0;RMR in mild and 1.94&#xa0;&#xd7;&#xa0;RMR in moderate cold. In type 2 diabetes, the increase was 1.57&#xa0;&#xd7;&#xa0;RMR and 2.09&#xa0;&#xd7;&#xa0;RMR in the final 1 h of mild and moderate cold, respectively. In prediabetes, neither mild nor moderate cold exposure altered mean 24 h glucose levels. In contrast, after mild cold exposure the type 2 diabetes group exhibited a significant reduction in mean 24 h glucose levels (-0.6&#xa0;&#xb1;&#xa0;0.5 mmol/l, p=0.003) and fasting glucose (-0.6&#xa0;&#xb1;&#xa0;0.8 mmol/l, p=0.019), as well as an increase in time in normal range (+8.8&#xa0;&#xb1;&#xa0;10.3%, p=0.013) and reduced time in hyperglycaemia (-10.9&#xa0;&#xb1;&#xa0;12.9%, p=0.014). Moderate cold did not significantly affect any of the glucose outcomes in type 2 diabetes. Baseline fasting glucose, age and ALT levels were predictors of the glucose-lowering response, suggesting greater benefits in individuals who have higher baseline glucose levels, are younger and/or have more optimal liver health, i.e. lower ALT. CONCLUSIONS/INTERPRETATION: Acute mild cold exposure with shivering reduced 24 h glucose levels in individuals with type 2 diabetes. No changes were observed in prediabetes. The observed effects appear to depend on baseline metabolic status rather than acute substrate utilisation during cold exposure. These findings support the potential of cold exposure as an adjunct non-pharmacological therapy for type 2 diabetes, although further mechanistic studies and validation in larger cohorts are warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT05576025 FUNDING: Dutch Organisation for Knowledge and Innovation in Health, Healthcare and Well-being (ZonMw): 09120012010062.

Humans↗

A novel approach to mitigating the physiological lag between blood and interstitial fluid glucose measurements.

BACKGROUND: Lag between blood and interstitial fluid (ISF) glucose levels can contribute significantly to accuracy error in current and anticipated continuous glucose monitoring systems. Mitigating this physiological lag can be an important and useful means for improving the accuracy, and hence the clinical utility, of continuous glucose monitors. METHODS: In a test of 22 subjects with diabetes in which a glucose excursion was induced through oral ingestion of a glucose load, glucose levels in finger blood and forearm dermal ISF were monitored over a 5-6-h period. ISF was sampled from two types of sites: sites at which local blood perfusion was elevated through modulated pressure application (test ISF), and control sites at which no perfusion elevation technique was employed (control ISF). RESULTS: Average lag times (mean +/- SD values) between the two ISF samples and finger capillary blood glucose were determined to be 38.3 +/- 11.5 and 2.5 +/- 6.6 min, respectively, for the control and test ISF samples. Modulated pressure application mitigated the ISF physiological error by an average of 95% in this test. CONCLUSIONS: The methodology presented here of using a pressure modulation technique to create an elevation in blood flow holds promise for significantly mitigating one of the most significant components of accuracy error for continuous monitoring systems.

Blood Glucose↗

Fasting and post-prandial glycemia and their correlation with glycated hemoglobin in Type 2 diabetes.

OBJECTIVE: The relative contribution of fasting and post-prandial glucose to glycated hemoglobin (HbA1c) is controversial. In the present study, we assessed the relationship with HbA1c of fasting and post-prandial glucose measured in a more naturalistic setting, through home glucose self-monitoring or with a continuous glucose monitoring system (CGM). MATERIALS AND METHODS: A consecutive series of 300 patients with Type 2 diabetes were enrolled in the study, provided that they performed blood glucose self-monitoring. HbA1c and fasting plasma glucose (FPG) were measured at enrolment. RESULTS: Both fasting plasma and capillary glucose showed a significant correlation with HbA1c (r=0.66 and 0.61, respectively; p<0.001). When home glucose monitoring was considered, both mean fasting and post-prandial glucose showed a significant correlation with HbA1c (r=0.71 and 0.73, respectively). In patients in the lower tertile of body mass index (BMI), HbA1c showed a significant correlation at multivariate analysis with post-prandial glucose, but not with fasting glucose. In patients with HbA1c >7%, both fasting and post-prandial glucose showed a significant correlation, after adjustment for age and BMI, with HbA1c (both p<0.01); conversely, in those with HbA1c < or =7%, such a correlation could be observed for fasting (p<0.01), but not for post-prandial glucose. CONCLUSION: In conclusion, both fasting and post-prandial glucose contribute to the determination of HbA1c . Home glucose self-monitoring appears to provide a more accurate assessment of metabolic control than a single plasma glucose measurement in experimental conditions. Fasting glucose could provide a greater contribution to HbA1c in patients with lower HbA1c, while post-prandial glucose seems to play a major role in leaner Type 2 diabetic subjects.

Aged↗

[Continuous blood glucose monitoring: the acute effect of acarbose on blood glucose variations].

BACKGROUND: Acarbose, a pseudo-tetrasaccharid, inhibits intestinal alpha-glucosidases, effects a reduction of postprandial hyperglycemia and is particularly used in the treatment of patients with type-2 diabetes mellitus. The aim of the study is to analyse by a continuous blood glucose measurement the acute effect of acarbose after a carbohydrate loading and during a 12 hours period. PATIENTS AND METHODS: We examined 10 patients with type-2 diabetes mellitus (mean age 59.2 +/- 3.79, HbA1 9.2 +/- 0.26%) treated with sulfonylureas and/or insulin after a carbohydrate meal and 12 hours during daytime, to test whether the first application of acarbose influences the mean blood glucose or the blood glucose amplitudes. Four measurements were enrolled using a portable continuous blood glucose sensor (Glucosensor, unitec Ulm). A measurement after a carbohydrate loading (Fresubin, 500 kcal, 69 g carbohydrate) with 100 mg acarbose (Glucobay) was followed by a 12-hour measurement during daytime with 3 x 100 mg acarbose and standard diet. These measurements were repeated without acarbose. RESULTS: After a carbohydrate loading, the mean blood glucose level (AUC 44,320 +/- 10,660 with acarbose vs. 61,390 +/- 12,590 without acarbose; mean + SD; p = 0.004) decreased by 28%. During daytime blood glucose levels were not significantly decreased (165.7 +/- 50.3 mg/dl vs 183.7 + 67.4 mg/dl; p = 0.1) although the postprandial blood glucose amplitudes after the 3 meals were reduced significantly (85.90 +/- 24.6 mg/dl vs 106.5 +/- 20.5 mg/dl; p = 0.02). CONCLUSIONS: Continuous blood glucose monitoring indicated that acarbose diminished mean blood glucose levels after a carbohydrate loading in patients with type-2 diabetes mellitus, but not during 12 hours of standard diet, although blood glucose amplitudes decreased. Long-term improvements of metabolism by acarbose may therefore be related to the reduction of blood glucose amplitudes which is likely to reduce toxic effects of glucose on islet cell function.

Acarbose↗

Continuous monitoring of the subcutaneous glucose level in freely moving normal and diabetic rats and in humans with type 1 diabetes.

Laboratory animals are extensively used in diabetic research. However, it is not known whether the glucose dynamics in laboratory animals are similar to the dynamics in humans. The aim of the present study is to see whether the Medtronic MiniMed continuous subcutaneous glucose monitoring system can be used to record fluctuations of the glucose level in freely moving normal and insulin-treated diabetic rats. The monitoring system was applied during 3 days to normal and diabetic hyperglycemic and hypoglycemic rats treated with insulin implants. Corresponding data from type 1 diabetic patients with poor glycemic control were selected retrospectively in order to note the similarities and differences. In normal rats the subcutaneous glucose level varied slightly (median = 111 mg/dL). In hyperglycemic rats the subcutaneous glucose values fluctuated markedly around a median of 226 mg/dL. The fluctuations formed a short-wave pattern with a low amplitude, superimposed on a long-wave pattern with a high amplitude. The subcutaneous glucose profile seen in type 1 diabetic patients (median = 180 mg/dL) was similar to that observed in hyperglycemic rats. In hypoglycemic rats, the subcutaneous glucose level fluctuated moderately around a median of 55 mg/dL. In these rats the fluctuations formed a short-wave pattern with low amplitude, without any obvious long-wave pattern. The subcutaneous glucose values conformed to corresponding blood glucose measurements. We conclude that the Medtronic MiniMed continuous glucose monitoring system can be used to record the subcutaneous glucose level over time in freely moving rats.

Adolescent↗

Macrosomia despite good glycaemic control in Type I diabetic pregnancy; results of a nationwide study in The Netherlands.

AIMS/HYPOTHESIS: To investigate the incidence of foetal macrosomia (i.e. birth weight >90th percentile) in a non-selected nationwide cohort of women with Type I (insulin-dependent) diabetes mellitus in The Netherlands and to identify risk indicators predictive for macrosomia. METHODS: We conducted a prospective nationwide cohort based survey regarding the outcome of Type I diabetic pregnancy in The Netherlands. Data of 289 women who gave birth to a live singleton infant without major congenital malformations at more than or equal to 28 weeks of gestation are shown. RESULTS: The incidence of foetal macrosomia was very high (48.8%), with 26.6% of infants weighing more than 97.7th percentile. Glycaemic control during pregnancy was good (i.e. mean HbA(1c) <or=7.0%), in almost all (84%) women. Multiple logistic regression analysis resulted in a predictive model for macrosomia that incorporated five variables: third trimester HbA(1c) (Odds Ratio [95% Confidence Interval]: (1.6[1.1-2.4]), absence of third trimester severe hypoglycaemia (3.0[1.2-7.3]), the use of insulin lispro (3.1[0.9-10.4]), weight gain during pregnancy (1.1[1.0-1.2]) and non-smoking (2.8[0.9-9.3]). Third trimester HbA(1c) was the most powerful predictor for the occurrence of macrosomia, but its predictive capacity was weak (explained variance <5%). CONCLUSION/INTERPRETATION: Despite apparent good glycaemic control, the incidence of foetal macrosomia in this non-selected prospective nationwide cohort of 289 Type I diabetic women was very high. Third trimester HbA(1c) was the most powerful predictor, but its predictive capacity was weak. Thus, future research should focus on new more detailed glucose monitoring techniques (such as a continuous glucose monitoring system) as well as to alternative factors to reduce macrosomia.

Adult↗

What's ahead in glucose monitoring? New techniques hold promise for improved ease and accuracy.

Advances in blood glucose monitoring have made it easier, more comfortable, and more practical for patients to monitor frequently. The new meters for intermittent monitoring are smaller and less dependent on technical aptitude than older models. They require less blood, and many provide downloadable information for glucose analysis. Data systems used with new meters provide valuable information that can dramatically improve glycemic control. Continuous glucose sensing (figure 4) is another major breakthrough in management of diabetes. Current systems allow only retrospective analyses, but real-time readings should be available in the near future. Such technological advances hold promise for preventing both hypoglycemia and hyperglycemia and for reducing the risk of long-term complications associated with diabetes. An artificial, mechanical islet cell may be the big next step toward bringing this disease under control. By combining continuous glucose monitoring data with continuous insulin delivery via an external or an implantable insulin pump, the outlook promises to be much brighter for patients with type 1 diabetes.

Adult↗

A microdialysis technique for continuous subcutaneous glucose monitoring in diabetic patients (part 2).

The aim of this study was to evaluate the reproducibility, the accuracy and the reliability of a continuous subcutaneous glucose measuring system. The GlucoDay system (A. Menarini I.F.R. S.r.l.-Florence, Italy) is a portable instrument provided with a micro-pump and a biosensor, coupled to a microdialysis system (see part 1). This instrument has demonstrated high reliability coupled with a low degree of invasivity. The profiles of glucose monitoring allow to achieve an excellent knowledge of the real variation of glucose in diabetic patients. The reproducibility study showed a bias lower than 10% between instruments. The accuracy study showed a difference from the reference method lower than 15%.

Biosensing Techniques↗

Insulin lispro: in-vivo potency determination by intravenous administration in conscious rabbits.

Insulin lispro is a monomeric analogue of human insulin, produced by genetic engineering, and has been reported to have a more rapid absorption following subcutaneous injection than insulin. Since it has been shown to have a similar hypoglycaemic action to insulin in clinical studies and comparable properties in radioimmunoassay, the feasibility of using a bioassay which was designed originally for insulin, to measure insulin lispro potency was evaluated in this investigation. A random-dose bioassay protocol, in which insulin lispro and two insulin standards were administered intravenously in a random sequence, was used and validated in nine conscious healthy rabbits. The decline in blood-glucose levels, following the intravenous injection of a dose of insulin or its lispro analogue, was monitored by a continuous glucose monitoring system. A glucose response curve was generated, from which various pharmacodynamic parameters were determined. Compared with the insulin standards, the potencies of insulin lispro determined from nadir, basal glucose normalized nadir, glycaemic reduction and ABGC (area of the blood-glucose response curve under baseline) were observed to have mean (95% confidence limits) values of 97.0 (69.5-124.6)%, 106.3 (72.4-140.2)%, 949 (51.8-138.0)% and 102.4 (76.3-128.5)%, respectively. In addition, the coefficients of variation for correspondent parameters were 36.9, 41.5, 59.1 and 33.2%, respectively. The results indicated that the hypoglycaemic potency calculated from the ABGC values was the most accurate (102.4%) with the least coefficient of variation (33.2%). In conclusion, the potency of insulin lispro can be determined accurately from the ABGC values measured by the random-dose bioassay used.

Animals↗

Continuous blood glucose monitoring and characteristics of diabetes in patients on maintenance haemodialysis treatment.

The glucose metabolism of diabetes mellitus during maintenance haemodialysis treatment was studied in four patients with endstage renal failure. There was a large day-to-day variation in the predialysis blood glucose levels, which it was difficult to control by adjusting the insulin dose. In spite of very high blood glucose levels, blood lactate and beta-hydroxybutyrate were not elevated. Triglycerides were markedly and constantly elevated, in no apparent association with the predialysis blood glucose level. The patients were shown to release moderate amounts of glucose, beta-hydroxybutyrate and lactate into the dialysate during the dialysis period. A technique of continuous blood glucose monitoring during the haemodialysis period was applied. With this technique blood sugar levels were accurately determined during the whole dialysis period. A rapid drop in the blood glucose level was found in apparent association with an aggravation of symptoms. A very marked tendency to hypoglycaemia was also revealed. It is concluded that the technique is a valuable aid in the proper management of diabetes in these cases.

Adult↗

Interstitial glucose concentration and glycemia: implications for continuous subcutaneous glucose monitoring.

The changes in plasma glucose concentration and in interstitial glucose concentration, determined with a miniaturized subcutaneous glucose sensor, were investigated in anesthetized nondiabetic rats. Interstitial glucose was estimated through two different calibration procedures. First, after a glucose load, the magnitude of the increase in interstitial glucose, estimated through a one-point calibration procedure, was 70% of that in plasma glucose. We propose that this is due to the effect of endogenous insulin on peripheral glucose uptake. Second, during the spontaneous secondary decrease in plasma glucose after the glucose load, interstitial glucose decreased faster than plasma glucose, which may also be due to the effect of insulin on peripheral glucose uptake. Third, during insulin-induced hypoglycemia, the decrease in interstitial glucose was less marked than that of plasma glucose, suggesting that hypoglycemia suppressed transfer of glucose into the interstitial tissue; subsequently, interstitial glucose remained lower than plasma glucose during its return to basal value, suggesting that the stimulatory effect of insulin on peripheral glucose uptake was protracted. If these observations obtained in rats are relevant to human physiology, such discrepancies between plasma and interstitial glucose concentration may have major implications for the use of a subcutaneous glucose sensor in continuous blood glucose monitoring in diabetic patients.

Animals↗

Fiber-optic flow-through sensor for online monitoring of glucose.

A new microdialysis-based glucose-sensing system with an integrated fiber-optic hybrid sensor is presented. Design and dimensions of the cell are adapted for its coupling with commercially available microdialysis techniques, thereby providing a new system for continuous glucose monitoring. The glucose level is detected via oxygen consumption which occurs as a consequence of enzymatic reaction between immobilized glucose oxidase and glucose. The use of gas-permeable Tygon tubing ensures complete and constant air-saturation of the measuring fluid in the cell. Nevertheless, a reference oxygen optode is used to detect and to compensate response changes caused by events like bacterial growth, temperature fluctuations, or failure of the peristaltic pump. In contrast to widely used electrochemical sensors, the response of the microdialysis-based fiber-optic glucose sensor is highly selective, making this sensor approach particularly advantageous for continuous glucose monitoring of patients in intensive care units. The effects of flow rate, pH, temperature, and common interferences on the sensor response are presented and discussed in detail. The sensor is evaluated in vitro using a 3-day continuous test in glucose-spiked plasma. The ability to measure glucose in humans is demonstrated by coupling the flow-through cell and commercially available microdialysis catheter CMA60. A 24-h monitoring test using this setup is successfully applied to a healthy volunteer.

Enzymes, Immobilized↗

Glycemic characteristics in continuously monitored patients with type 1 and type 2 diabetes: normative values.

OBJECTIVE: The purpose of this study was to generate normative values for periods of euglycemia as well as for daily patterns of glycemic excursions in patients with type 1 and type 2 diabetes monitored continuously for a maximum period of 21 days and blinded to glucose levels. RESEARCH DESIGN AND METHODS: This was a multicenter, prospective observational study in which 101 consecutive patients with type 1 (n = 60) or type 2 (n = 41) diabetes underwent blinded continuous glucose monitoring. Serial glucose measurements were divided into periods of euglycemia (70-180 mg/dl), hyperglycemia (>180 mg/dl), and hypoglycemia (<70 mg/dl). The proportions of time patients were hypoglycemic, euglycemic, and hyperglycemic and the total areas under the curves (AUCs) were determined. RESULTS: During the observation period the 101 subjects contributed an average 287 +/- 132 h of continuous glucose values. Subjects remained in the euglycemic range for approximately 63% of the total day, were hypoglycemic 8%, and were hyperglycemic 29%. Hypoglycemia was more prevalent nocturnally (11 vs. 7%) and hyperglycemia diurnally (31 vs. 25%). Compared with subjects with type 2 diabetes, type 1 diabetic subjects had more frequent hypoglycemic episodes per day (2.1 vs. 1.0; P < 0.001) that were of longer duration (1.1 vs. 0.7 h; P < 0.0001), reflecting a greater number of hours per day in the hypoglycemic range (2.3 vs. 1.0 h; P < 0.0001). The mean hypoglycemic AUC values were >150% higher for type 1 compared with type 2 diabetic subjects (41 vs. 16, respectively; P < 0.0001). CONCLUSIONS: These normative data will assist in study and sample size planning for future investigations of continuous glucose monitoring and allow for qualitative comparisons with trials of therapeutic interventions aimed at reducing the occurrence of glycemic excursions.

Adult↗

Factors Associated With Progression From Level 1 to Level 2 Sensor-Detected Hypoglycaemia in People With Type 1 and Insulin-Treated Type 2 Diabetes: A Post Hoc Analysis From the Hypo-METRICS Study.

AIMS: We investigated the proportion of sensor-detected hypoglycaemic (SDH) events progressing to level 2, and associated variables. MATERIALS AND METHODS: We used data from Hypo-METRICS, which recruited people with type 1 (pwT1D) and insulin-treated type 2 diabetes (pwT2D) with &#x2265;&#x2009;1 hypoglycaemic event in preceding 3&#x2009;months, wearing blinded continuous glucose monitoring devices (CGM), additional to usual monitoring modality, and FitBits for 10&#x2009;weeks. We defined: L1: SDH <&#x2009;3.9&#x2009;mmol/L for &#x2265;&#x2009;15&#x2009;min but &#x2265;&#x2009;3.0&#x2009;mmol/L; L2: SDH <&#x2009;3.9&#x2009;mmol/L with &#x2265;&#x2009;15&#x2009;min of sensor glucose <&#x2009;3.0&#x2009;mmol/L; L2 ratio&#x2009;=&#x2009;L2/(L1&#x2009;+&#x2009;L2), restricted to participants with both event types during the study period. Associations of selected variables on L2 ratio was assessed using beta regression and purposeful variable selection. RESULTS: We analysed 23&#x2009;768 SDH events from 212 pwT1D and 213 pwT2D. PwT1D were predominantly female (53% vs. 42% in T2D, p&#x2009;=&#x2009;0.023) and younger (median age 49 vs. 62&#x2009;years, p&#x2009;<&#x2009;0.001), with a higher L2 ratio (16% vs. 14%, p&#x2009;=&#x2009;0.03). Coefficient of variation (CV), OR&#x2009;=&#x2009;1.07, 95% CI&#x2009;=&#x2009;1.06-1.09 (p&#x2009;<&#x2009;0.001), and mean sensor glucose, OR&#x2009;=&#x2009;1.13, 95% CI&#x2009;=&#x2009;1.08-1.18 (p&#x2009;<&#x2009;0.001) were the principal predictors in T1D and T2D respectively; mean L1-SDH duration, weekly L1-SDH frequency, personal CGM usage, impaired awareness were not. Progression was higher during sleep than wakefulness (21% vs. 11%, p&#x2009;<&#x2009;0.001); L2 ratios during sleep did not differ by awareness status. CONCLUSIONS: Approximately one sixth of SDH events progressed to L2, with a higher proportion in T1D than T2D. The principal determinants were CV in T1D and mean glucose in T2D. Awareness status was not associated with progression risk during sleep.

Humans↗

Association of hypoglycemia and cardiac ischemia: a study based on continuous monitoring.

OBJECTIVE: In some studies intensive diabetes treatment in patients with type 2 diabetes may be associated with increased cardiovascular events. It is not clear whether these events are related to hypoglycemic episodes. To determine whether episodes of hypoglycemia were more likely to be associated with cardiac ischemia than normoglycemia or hyperglycemia, we carried out a study in 21 patients with coronary artery disease (CAD) and type 2 diabetes treated with insulin who had good glycemic control. RESEARCH DESIGN AND METHODS: We carried out 72-h continuous glucose monitoring along with simultaneous cardiac Holter monitoring for ischemia. Patients also recorded symptoms of cardiac ischemia (chest pain) and symptoms of hypoglycemia. RESULTS: Satisfactory continuous glucose monitoring system recordings were obtained in 19 patients. We recorded 54 episodes of hypoglycemia (blood glucose <70 mg/dl; 26 of these were symptomatic) and 59 episodes of hyperglycemia (blood glucose >200 mg/dl; none symptomatic). Of the 54 episodes of hypoglycemia, 10 were associated with symptoms of chest pain, during 4 of which electrocardiographic abnormalities were documented. In contrast, only 1 episode of chest pain occurred during 59 episodes of hyperglycemia. No chest pain or electrocardiographic abnormalities occurred when the blood glucose was within the normal range. The difference between the frequency of ischemia during hypoglycemia and the frequency during both hyperglycemia and normoglycemia was statistically significant (P < 0.01). There were 50 episodes during which the blood glucose changed by >100 mg over a 60-min period, and ischemic symptoms occurred during 9 of these episodes (P < 0.01 compared with stable normoglycemia or hyperglycemia). CONCLUSIONS: Hypoglycemia is more likely to be associated with cardiac ischemia and symptoms than normoglycemia and hyperglycemia, and it is particularly common in patients who experience considerable swings in blood glucose. These data may be important in the institution of insulin treatment and attempting near-normal glycemia in patients with known CAD. Further research is needed to determine strategies to prevent ischemia associated with hypoglycemia.

Blood Glucose↗

Continuous subcutaneous insulin infusion (CSII) of insulin aspart versus multiple daily injection of insulin aspart/insulin glargine in type 1 diabetic patients previously treated with CSII.

OBJECTIVE: Multiple daily injection (MDI) therapy of bolus insulin aspart and basal insulin glargine was compared with continuous subcutaneous insulin infusion (CSII) with aspart in type 1 diabetic patients previously treated with CSII. RESEARCH DESIGN AND METHODS: One hundred patients were enrolled in a randomized, multicenter, open-label, crossover study. After a 1-week run-in period with aspart by CSII, 50 subjects were randomly assigned to MDI therapy (aspart immediately before each meal and glargine at bedtime) and 50 subjects continued CSII. After 5 weeks of the first treatment, subjects crossed over to the alternate treatment for 5 weeks. During the last week of each treatment period, subjects wore a continuous glucose monitoring system for 48-72 h. RESULTS: Mean serum fructosamine levels were significantly lower after CSII therapy than after MDI therapy (343 +/- 47 vs. 355 +/- 50 micromol/l, respectively; P = 0.0001). Continuous glucose monitoring profiles over a 24-h time period showed that glucose exposure was 24 and 40% lower for CSII than MDI as measured by area under the curve (AUC) glucose >/=80 mg/dl (1,270 +/- 742 vs. 1,664 +/- 1,039 mg . h . dl(-1); P < 0.001) and AUC glucose >/=140 mg/dl (464 +/- 452 vs. 777 +/- 746 mg . h . dl(-1), CSII vs. MDI, respectively; P < 0.001). Similar percentages of subjects reported hypoglycemic episodes (CSII: 92%, MDI: 94%) and nocturnal (12:00 a.m. to 8:00 a.m.) hypoglycemic episodes (CSII: 73%, MDI: 72%). Major hypoglycemia was infrequent (CSII: two episodes, MDI: five episodes). CONCLUSIONS: In a trial of short duration, CSII therapy with insulin aspart resulted in lower glycemic exposure without increased risk of hypoglycemia, as compared with MDI with insulin aspart and glargine.

Adult↗