Continuous Glucose Monitoring Study Research Articles

Journal of Diabetes News

Journal of Diabetes News

Hypoglycemia with gliclazide MR in women with type 2 diabetes. A continuous glucose monitoring study

Background Hypoglycemia is usually a limiting factor in the treatment of type 2 diabetes and it may be asymptomatic many times. Sulfonylureas are a group of anti-diabetic drugs associated with an increased risk of hypoglycemia, but, within this group, gliclazide MR seems to be associated with a fewer number of these episodes. Large-scale studies suggest that the incidence of hypoglycemia may be associated with an increase of cardiovascular risk.

A pilot study of continuous glucose monitoring in critically ill patients: Do they perform well enough for use in glycaemic control?

Glycaemic control (GC) in the intensive care unit (ICU) has proven difficult and contentious. Continuous glucose monitors (CGM) have been mooted as a solution to provide better control with less clinical effort. The aim of this study was to assess the reliability of CGM devices in critically ill patients, as well as the impact of device type (inter-device) and sensor location (inter-site) on performance. Ten patients were enrolled in this pilot trial and each patient was monitored using 3 concurrent CGM devices: a Medtronic Guardian real-time on their abdomen and Medtronic iPro2 recorders on their abdomen and thigh. The Guardian real-time had an overall MARD of 24%, compared to ~12% for the iPro2 devices. Bland Altman plots showed Guardian SG errors were associated with BG level, but iPro2 SG errors were not associated with BG level. Inter-device SG discrepancies were larger than inter-site discrepancies, when comparing concurrent data and CGM device type, or calibration method, tends to have a larger impact on SG accuracy than sensor location. Three case studies showed several interesting findings regarding CGM behaviour in critically ill patients. CGM devices are capable of performing very well in critically ill patients, but certain illnesses/conditions, as well as drugs/therapies may impact SG data. These factors require further investigation before CGMs can be implemented as standard clinical practice and/or for GC.

Benefits of Short-Term Professional Continuous Glucose Monitoring in Clinical Practice

The clinical utility of short-term professional continuous glucose monitoring (CGM) is uncertain. This is a retrospective review of 121 consecutive insulin-treated patients seen in a university-based subspecialty clinic who completed a 72-120-h professional CGM study. Based on the indications for the study, patients were divided into three groups: hyperglycemia (Hyper) (n=51), widely fluctuating glycemia (Fluctuating) (n=50), or hypoglycemia (Hypo) (n=20). Hemoglobin A1c (A1c) was compared before and 3-6 months after CGM. Hypoglycemia frequency was recorded by patients' self-report. Among the entire cohort, the A1c level dropped a small amount (0.18%; P=0.04). In the Hyper group, the A1c level fell from 9.0±1.1% to 8.6±1.2% (P<0.02). In the Fluctuating group, there was no change (from 8.0±1.0% to 8.0±0.9%). The A1c level of the Hypo group patients did not change (7.6±1.1% before and after), but 14 of 20 (70%; P<0.01) had a drop in self-reported frequency of hypoglycemia. For the whole cohort, the drop in A1c level was correlated with the initial A1c value (r=0.54, P<0.01). Patients with an initial A1c level of >9.0% saw a drop of 0.7% (from 10.2±1.1% to 9.4±1.1%; P<0.01), and those with an A1c level of >7.5% saw a drop of 0.4% (from 8.9±1.2% to 8.5±1.1%; P=0.01). Subgroup analysis showed that patients with type 1 diabetes had a drop in A1c level that was not statistically significant. However, type 1 diabetes patients in the Hypo group did have a decrease in self-reported hypoglycemia (11 of 16 [68%]; P=0.03). Professional CGM can lead to a lowering of elevated A1c levels in insulin-treated patients, especially those with type 2 diabetes. There also appears to be benefit in decreasing self-reported hypoglycemia.

Hypoglycemia Observed During Continuous Glucose Monitoring in Patients with Type 2 Diabetes Mellitus Treated by Subcutaneous Insulin Injection

The relationship between hypoglycemia and the dose of insulin used in patients with type 2 diabetes mellitus was investigated by continuous glucose monitoring (CGM). In total, 83 CGM studies were performed in 70 outpatients with type 2 diabetes receiving treatment by subcutaneous insulin injection. The total dose of insulin, bolus insulin dose, and basal insulin dose used in the subjects were 32±18 units, 19±13 units, and 13±8 units, respectively. The proportion of time in the hypoglycemic range (blood glucose<3.9 mmol/L) during CGM was positively correlated with the bolus insulin ratio (bolus/total insulin dose, r=0.22, P=0.04), although it was not associated with the total dose of insulin or the hemoglobin A1c (HbA1c) level. It was negatively correlated with the mean blood glucose (r=-0.38, P<0.01), whereas it was not associated with the SD or the mean amplitude of glycemic excursions (MAGE). The proportion of time in the hypoglycemic range was significantly greater in the subjects with a bolus insulin ratio of ≥0.6 (3.2±4.4%, n=42) than a ratio of <0.6 (1.2±3.0%, n=41), although the HbA1c level, total dose of insulin, mean blood glucose, SD, and MAGE were not significantly different between the two groups. An excessive dose of bolus insulin might increase the duration of hypoglycemia, independently from the HbA1c levels, in patients with type 2 diabetes mellitus receiving subcutaneous insulin injection.

Effects of Sensor-Augmented Pump Therapy on Glycemic Variability in Well-Controlled Type 1 Diabetes in the STAR 3 Study

Compared with multiple daily injections (MDI), sensor-augmented pump (SAP) insulin therapy may reduce glycemic variability and oxidative stress in type 1 diabetes in a glycosylated hemoglobin (A1C)-independent manner. The STAR 3 study compared SAP with MDI therapy for 1 year. Week-long continuous glucose monitoring studies were conducted at baseline and 1 year for assessment of glycemic variability in both groups. Soluble CD40 ligand (CD40L), a biomarker of inflammation and thrombocyte function, was measured at baseline and 1 year. Subjects were classified according to treatment group and 1-year A1C levels (<6.5%, 6.5-6.9%, 7-7.9%, ≥8%). Glycemic parameters were compared between SAP and MDI subjects in each A1C cohort. At 1 year, sensor glucose values at A1C levels ≥6.5% were similar in the SAP and MDI groups. However, sensor glucose SD and coefficient of variation (CV) values were lower at A1C levels <8% among SAP than among MDI subjects; the overall between-group difference was significant for both SD (P<0.01) and CV (P=0.01). The overall mean amplitude of glycemic excursion was similar in MDI and SAP groups (P=0.23). CD40L levels fell over the course of the study in both groups, but the between-group difference was not significant (P=0.18). CD40L concentrations were unrelated to A1C, change in A1C from baseline, or glycemic variability. At comparable A1C levels of <8%, SAP reduced glycemic variability as measured by SD and CV compared with MDI. SAP may provide beneficial reductions in the number and severity of glycemic excursions.

Prediction of the Risk to Develop Diabetes-Related Late Complications by Means of the Glucose Pentagon Model: Analysis of Data from the Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study

By taking parameters into account that describe the variability of continuously monitored glucose and long-term metabolic control [hemoglobin A1c (HbA1c)], the glucose pentagon model (GPM) allows characterization of the glucose profile of individual patients with diabetes in a graphical format. A glycemic risk parameter (GRP) derived from this model might allow a better prognosis of the risk to develop diabetes-related complications than the HbA1c. To evaluate this hypothesis, we analyzed a subset of data from the Juvenile Diabetes Research Foundation continuous glucose monitoring (CGM) study. The values of the different parameters that are integrated in the GPM were extracted automatically from CGM profiles registered before and after 6 months by means of the Medtronic CGM system in 108 patients. In these patients, the significant reduction in HbA1c from 7.4% to 7.0% was accompanied by a reduction in glycemia from 164 to 156 mg/dl, standard deviation from 61 to 57 mg/dl, area under the curve >160 mg/dl 29.2 to 23.1, and time per day >160 mg/dl 634 to 576 min. This led to a subsequent reduction in GRP from 3.3 to 2.7; this decrease by 18.2% was significantly larger than that in HbA1c by 8.6% (p < .001). Changes in individual GPMs/GRPs support this observation. They also show the impact of high glycemic variability on GPM/GRP. Our analysis of data of a study with a considerable sample size and study duration showed that the GPM is not only helpful for rapid assessment of individual glycemic profiles and how therapeutic interventions influence these, but also appears to provide a better prognosis of the risk to develop late complications than the HbA1c per se. However, it is also clear that a true validation of such a model requires performance of a long-term study in a large number of patients with diabetes.

Re‐examining a measure of diabetes‐related burden in parents of young people with Type 1 diabetes: the Problem Areas in Diabetes Survey – Parent Revised version (PAID‐PR)

In a pediatric patients, the burden of diabetes lies within the family. In the current era of intensive insulin therapy, perceived parental burden may affect the family's efforts at effective diabetes management. The aims of this study were to re-examine and revise a measure of perceived parental burden associated with caring for a child with diabetes in the current era. A geographically diverse population of young people (N = 376) with Type 1 diabetes and their parents included participants in the Juvenile Diabetes Research Foundation continuous glucose monitoring study and patients from the Joslin Diabetes Center. Participants provided data on demographics, diabetes management, diabetes-specific family conflict, and quality of life at baseline and after 6 months of follow-up. Young people were 12.9 ± 2.7 years old with diabetes duration of 6.3 ± 3.5 years. Mean HbA(1C) was 8.0 ± 1.2%(64 mmol/mol), 58% received insulin pump therapy, and young people monitored blood glucose 5.2 ± 2.3 times/day. Factor analysis yielded two factors, 'Immediate Burden' and 'Theoretical Burden'. The Problem Areas in Diabetes Survey - Parent Revised version (PAID-PR) demonstrated excellent internal consistency (Cronbach's α = 0.87; factor 1 α = 0.78; factor 2 α = 0.83). Greater parental burden was associated with more frequent blood glucose monitoring, higher HbA(1C) levels, greater diabetes-specific family conflict, and lower quality of life. Test-retest analysis was acceptable (r = 0.62). The PAID-PR demonstrated excellent internal consistency, good test-retest reliability, and associations with diabetes-specific family conflict and quality of life. This brief measure may have both clinical and research utility in the management of young people with Type 1 diabetes.

Insulin in the Medical Management of Postprandial Hypoglycemia in a Patient with Type 2 Diabetes after Gastric Bypass Surgery

Objective. We evaluated a 47-year-old woman with a history of type 2 diabetes and severe obesity who developed postprandial hypoglycemia after undergoing Roux-en-Y gastric bypass surgery and losing 60% of her total body weight. We studied her insulin secretion and blood glucose dynamics and were able to tailor a therapeutic regimen involving insulin that eliminated episodes of hypoglycemia. Methods. We studied blood glucose levels during a prolonged fast, performed continuous glucose monitoring studies using a subcutaneous glucose sensor, and evaluated regional pancreatic insulin secretion using selective arterial calcium stimulation. Results. Continuous glucose monitoring revealed that the patient had early (1-2 hr) postprandial hyperglycemia followed by late (3-4 hr) postprandial hypoglycemia. Biochemical studies confirmed endogenous pancreatogenous insulin secretion as the cause of episodic hypoglycemia, but imaging studies and selective arterial calcium stimulation failed to localize an insulinoma. The patient was treated with preprandial doses of insulin aspart in order to attenuate the early postprandial hyperglycemia, and the late hypoglycemic episodes were avoided. Conclusion. We describe an interesting and novel nonsurgical approach to the prevention of postprandial hypoglycemia in a patient with noninsulinoma pancreatogenous hypoglycemia after gastric bypass.

Effectiveness of sensor-augmented pump therapy in children and adolescents with type 1 diabetes in the STAR 3 study

Maintenance of appropriate A1C values and minimization of hyperglycemic excursions are difficult for many pediatric patients with type 1 diabetes. Continuous glucose monitoring (CGM) sensor-augmented pump (SAP) therapy is an alternative to multiple daily injection (MDI) therapy in this population. Sensor-augmented pump therapy for A1C reduction (STAR 3) was a 1-yr trial that included 82 children (aged 7-12) and 74 adolescents (aged 13-18) with A1C values ranging from 7.4 to 9.5% who were randomized to either SAP or MDI therapy. Quarterly A1C values were obtained from all subjects. CGM studies were carried out at baseline, 6 months, and 12 months to quantify glycemic excursions [calculated as area under the glucose concentration-time curve (AUC)] and variability. In the SAP group, sensor compliance was recorded. Baseline A1C values were similar in subjects randomized to the SAP (8.26 ± 0.55%) and MDI groups (8.30 ± 0.53%). All subsequent A1C values showed significant (p < 0.05) treatment group differences favoring SAP therapy. Compared with the MDI group, subjects in the SAP group were more likely to meet age-specific A1C targets and had lower AUC values for hyperglycemia with no increased risk of hypoglycemia. Glucose variability improved in the SAP group compared to the MDI group. Children wore CGM sensors more often and were more likely to reach age-specific A1C targets than adolescents. SAP therapy allows both children and adolescents with marginally or inadequately controlled type 1 diabetes to reduce A1C values, hyperglycemic excursions, and glycemic variability in a rapid, sustainable, and safe manner.

Response to Swinnen et al.

Response to Swinnen et al.

Continuous glucose monitoring study does not demonstrate benefit in children and adolescents

Continuous glucose monitoring study does not demonstrate benefit in children and adolescents

JDRF Randomized Clinical Trial to Assess the Efficacy of Real-Time Continuous Glucose Monitoring in the Management of Type 1 Diabetes: Research Design and Methods

While real-time (RT) continuous glucose monitoring (CGM) systems may revolutionize treatment of type 1 diabetes (T1D), there is insufficient evidence currently available to support widespread utilization of these devices. The Juvenile Diabetes Research Foundation (JDRF) CGM Study Group developed a randomized clinical trial to determine if RT-CGM can improve glycemic control and quality of life in children and adults with T1D. This paper presents the research design and methods that are being employed in this study. The JDRF CGM Study Group trial is a randomized, parallel group, efficacy and safety study. Subjects with T1DM who meet eligibility criteria are randomized to either standard self-monitoring of blood glucose (SMBG) alone or use of any of the three current RT-CGM systems as a supplement to SMBG. After the 6-month randomized period, the Control Group is offered use of RT-CGM, and both groups are studied for an additional 6 months. Subjects are divided into two cohorts: the Main Study Cohort includes subjects with baseline glycosylated hemoglobin (HbA1c) 7.0-10.0% inclusive, and the Exploratory Pilot Study Cohort includes subjects with HbA1c<7.0%. Difference in HbA1c is the primary outcome in the Main Study. Other outcomes include the percentage of sensor glucose values within the 70-180 mg/dL range, scores on questionnaires that assess the impact of RT-CGM on living with T1D, and the cost-effectiveness of RT-CGM. Recruitment for the study was completed on December 15, 2007. Results of this clinical trial should help establish whether or not current RT-CGM devices are beneficial to patients with T1D.

Continuous Glucose Monitoring and Diabetes Health Outcomes: A Critical Appraisal

This paper presents a critical review of continuous glucose monitoring studies that address accuracy, utility in assessing glucose variability, detection of hypoglycemia for improved metabolic control or reduced glucose variability, impact on quality of life, reduced fear of hypoglycemia, and applicability in helping patients to overcome their reluctance to intensify insulin therapy. This analysis can be used to delineate the evidence that is still missing when considering continuous glucose monitoring as an established tool in clinical practice and for reimbursement of the system and services.

Changes in the Glycemic Profiles of Women With Type 1 and Type 2 Diabetes During Pregnancy

To examine the changes in glycemic excursions that occur during pregnancy using continuous glucose monitoring and to compare patterns of glycemia in pregnant women with type 1 and type 2 diabetes. An observational data analysis was performed from a prospective randomized study of continuous glucose monitoring in 57 women with pregestational type 1 (n = 40) or type 2 (n = 17) diabetes with 7-day continuous glucose monitoring system profiles during each trimester. Serial glucose measurements were divided into periods of euglycemia (70-140 mg/dl), hyperglycemia (>140 mg/dl), and hypoglycemia (<70 mg/dl). Generalized linear mixed effects models were fitted to the repeated measures data to determine how these glycemic characteristics varied during gestation and by diabetes type. A total of 180 continuous glucose profiles were examined (140 type 1 diabetes, 40 type 2 diabetes), providing 20,433 h of data for analysis (16,117 h type 1 diabetes, 4,316 type 2 diabetes). Women with type 2 diabetes spend approximately 33% less time hyperglycemic throughout pregnancy than women with type 1 diabetes (P = 0.005), with a significantly more rapid reduction in time spent hyperglycemic in early pregnancy (P = 0.02). Although women with type 2 diabetes spend less overall time hypoglycemic (P = 0.04), their risk of nocturnal hypoglycemia is equivalent to that of women with type 1 diabetes (blood glucose level <70 mg/dl, P = 0.9; blood glucose level <50 mg/dl, P = 0.2). Continuous glucose monitoring reveals clear differences in the level of glycemic control that exist in women with type 1 and type 2 diabetes. These data will guide therapeutic interventions aimed at optimizing glycemic control and improving the pregnancy outcomes of both type 1 and type 2 diabetes.

On Real-Time Estimates of Blood Glucose Levels

In the comment from Trevino (1), three articles are cited as having “emphasized the need for real-time assessment of blood glucose levels.” Two of the cited articles (2,3) indeed relate to real-time assessment of blood glucose levels using new technology referred to as continuous glucose monitoring (CGM). The third article Trevino refers to, by Farmer et al. (4), relates to the use of traditional finger-stick blood analysis that is communicated to a nurse via telemedicine. We are engaged in the study of CGM, so further comments will be related only to continuous sensors (2,3) and not to telemedicine. Trevino further states that “[r]eal-time analysis is motivated by the belief that the random time series being analyzed manifests average properties that change with the passage of time. Results of such analyses are presented to patients as means (μ) ± SD.” In regard to our study (2), this statement is completely false. We do not rely on averaged properties of time series data. Patients received actual glucose concentration values transmitted every 5 min. Under no circumstances were patients presented with the mean and SD of the data in real time. Trevino further describes an equation for determining mean and SD and …

Clinical experience with an integrated continuous glucose sensor/insulin pump platform: A feasibility study

The recent US Food and Drug Administration approval of an integrated real-time continuous glucose monitoring (CGM) system and insulin pump (Medtronic Mini-Med Paradigm REAL-Time System; Medtronic MiniMed, Inc., Northridge, Calif) is the most recent breakthrough paving the way toward the development of a closedloop insulin delivery system that could revolutionize diabetes care. An early prototype of the MiniMed Paradigm REAL-Time System--which provided both realtime CGM and insulin pump therapy but was not yet fully integrated--was tested in 20 volunteer subjects with type 1 diabetes who wore the device for up to 2 y. Subjects were instructed on the technical use of the device but were provided no additional support, aside from their usual diabetes care. Participation in the trial averaged 317 d (minimum, 88 d; maximum, 618 d). Five participants prematurely dropped out of the study (2 because of the inconvenience of carrying 2 devices). Data from all subjects were analyzed. Subjects reduced their A1C by a mean of 1.1% (standard deviation, 0.8). After 3 mo of device use, the number of participants who achieved A1C <7% increased by more than 3-fold. Individuals with baseline A1C >or= 7% had a 67% likelihood of achieving an A1C <7% by the first follow-up assessment. This observational study of combined CGM and insulin pump therapy suggests that this innovative device can help people achieve improved glycemic control. Given that only about one third of individuals with diabetes are achieving glycemic control targets, more effective methods to help patients avoid the devastating consequences of uncontrolled diabetes are desperately needed.

Preliminary study of continuous glucose monitoring with a microdialysis technique and a null method--a numerical analysis.

Monitoring of the subcutaneous tissue glucose concentration is an attractive method for continuous monitoring of the glucose concentration in diabetic patients. Several researchers have studied this, but no satisfactory method has been developed. We have proposed a new method, which can measure the glucose concentration of subcutaneous tissue continuously, even as the efficiency of membrane perfusion and sensor performance decline. Two reference solutions were prepared with concentrations higher and lower than the objective solution. They were perfused alternately for different ratios of perfusion times. The glucose concentration, after perfusing microdialysis, was detected and the trend of changes in the concentration was used to control the ratio of the two perfusion solutions. When the trend was a unity, the glucose concentration was calculated from the ratio of the two perfusion solutions. The numerical study was performed with a compartment model and a basic control theory. In simulation, the 90% response time to step change was approximately 7 min, which is fast enough when compared with the fluctuation of glucose in the electrolyte. This result suggested that this new system might be useful for continuous monitoring of the glucose concentration in subcutaneous tissue.