Role of continuous glucose monitoring for type 2 in diabetes management and research
Introduction
Among the major advances in the field of diabetes has been the development of accurate methods of self-monitoring of blood glucose (BG). The Diabetes Control and Complications Trial which began recruiting in 1983 was the first large clinical trial to use self-monitoring of blood glucose (SMBG) with either a reflectance meter or visual observation of the color changes of a glucose-oxidase embedded strip (Diabetes Control and Complications Trial Research Group, 1993). Although primitive by today's standards, these BG measurements permitted intensive insulin administration. The next advance in glucose measurement technology occurred in 1987 when a biosensor system was developed employing artificial electron acceptors (i.e., electron mediators or redox dyes) instead of oxygen (Clarke & Foster, 2012). The resultant current was read amperometrically, permitting the development of smaller and more accurate BG meters. Subsequent improvements in this technology afforded faster results in devices that require less blood.
Essentially the same glucose-oxidase methodology developed for BG meters has been adapted for use in most continuous glucose monitoring (CGM) systems. The first of these CGM systems using a glucose-oxidase sensor for venous blood was contained in an artificial pancreas system over 40Ā years ago (Albisser et al., 1974). Devices using other methodologies such as microdialysis (Dehennis et al., 2015, Schierenbeck et al., 2013, Valgimigli et al., 2010) and fluorescence (Dehennis et al., 2015) have been developed for both subcutaneous and intravenous use but neither is currently commercially available. The advantage of CGM over SMBG by fingerstick is that CGM displays interstitial glucose readings every 5Ā min. As a result, CGM can show the effects of diet, exercise, medications, sleep, and stress on glucose levels and makes a āvital sign.ā With 288 glucose measurements a day, CGM has enabled investigators to develop new metrics of glycemic control that were not feasible with BG monitoring alone. This enhanced our understanding of how diabetes interventions affect glycemic control beyond the surrogate metric for mean glucose, hemoglobin A1C (HbA1C). These include the percent time-in-range, in hypo- and hyperglycemic ranges, the intensity of the hypo- and hyperglycemic excursion (area-under-the-curve), and glycemic variability (e.g., standard deviation [SD], Mean Amplitude of Glucose Excursion [MAGE], continuous overlapping net glycemic action [CONGA], and mean of daily differences [MODD]) within and between days. The value of these glucose measurements was demonstrated by the FDA accepting for labeling purposes the area-under-the-curve of nocturnal low sensor glucose values as the primary outcome metric in the in-home trial evaluating the threshold suspend insulin pump (Bergenstal et al., 2013).
Section snippets
Use cases of CGM
The two major use cases for CGM are professional (retrospective or diagnostic) CGM in which the patient does not see the display in real-time and personal (real-time) in which the patient can observe the changes and also be alerted to values that cross a preset or predicted high or low glucose threshold (Table 1). These use cases apply to patients with both type 1 diabetes (T1D) and type 2 diabetes (T2D) with or without insulin therapy in those with T2D. A new approach to glucose monitoring
Evidence for use of professional CGM in patients with type 2 diabetes
Professional and real-time CGM has been used primarily in patients with T1D and most of the evidence for its benefit is in that group (Floyd, Liebl). However, there has been growing evidence that those with T2D may benefit from the use of this technology by CGM's ability to uncover previously unknown hypoglycemia particularly in those with hypoglycemic unawareness and/or during sleep as well as unrecognized hyperglycemia particularly post-prandially. The evidence for use of professional and
Randomized controlled trials
Several studies (Table 2) have been performed to determine whether or not professional CGM can reduce HbA1C (Allen et al., 2008, Blackberry et al., 2014, Cosson et al., 2001, Leinung et al., 2013, Mohan et al., 2016, Murphy et al., 2008, Pepper et al., 2012, Young et al., 2015). Five randomized controlled trials showed that 3ā7Ā days of professional CGM results in improvement in HbA1C (0.6%ā2.3%). Two of these involve patients who were not taking insulin. Allen et al. (2008) used the CGM report
Evidence for use of personal (real-time) CGM in patients with type 2 diabetes
There have been a limited number of trials using personal CGM in patients with T2D. In a short-term trial, Garg et al. (2006) studied 91 patients with diabetes which included 15 insulin-requiring type 2 diabetic patients in a randomized controlled trial of 9Ā days of CGM. All patients wore the CGM in professional (retrospective) mode for the first 3Ā days and then were randomly assigned to either personal (real-time) or professional mode for the next 6Ā days. Those who had access to real-time days
Use of CGM in drug research
HbA1C is considered a gold standard for diabetes control as it is a proxy for glycation of proteins in the body and is used as a measurable link between glucose levels potential complications (Diabetes Control and Complications Trial Research Group, 1993). Since it is metric reflecting long-term glycemic control, it is inadequate for measurement of short-term drug response nor does it capture hypoglycemic exposure or the pharmacodynamic and pharmacokinetic responses to agents which are often a
Professional societies' statements on the use of CGM in type 2 diabetes
Four major professional societies have developed positions related to the use of CGM in those with T2D (Table 3). The Endocrine Society recently updated its Clinical Practice Guideline on diabetes technology (Peters et al., 2016). They use the GRADE method for developing recommendations (Andrews et al., 2013, Brozek et al., 2013). This method is used by more than 80 entities including professional societies (Endocrine Society. American College of Physicians), governmental agencies (Agency for
Conclusion
The development of continuous glucose monitoring technology has created an opportunity to improve glycemic control and thereby reduce the complications of diabetes due to its ability to provide robust data not available through SMBG. While initially applied to those with T1D, recent studies have demonstrated that there is a role for its use in both the professional and personal forms in the management of those with T2D. While there is considerable debate among diabetologists about what are the
References (52)
- et al.
Continuous glucose monitoring counseling improves physical activity behaviors of individuals with type 2 diabetes: a randomized clinical trial
Diabetes Research and Clinical Practice
(2008) - et al.
An exploratory trial of basal and prandial insulin initiation and titration for type 2 diabetes in primary care with adjunct retrospective continuous glucose monitoring: INITIATION study
Diabetes Research and Clinical Practice
(2014) - et al.
Continuous glucose monitoring: A consensus conference of the American Association of Clinical Endocrinologists and American College of Endocrinology
Endocrine Practice
(2016) - et al.
Proceedings from the American Association of Clinical Endocrinologists and American College of Endocrinology consensus conference on glucose monitoring
Endocrine Practice
(2015) - et al.
Blood glucose fluctuations in hemodialysis patients with end stage diabetic nephropathy
Journal of Diabetes and its Complications
(2015) - et al.
Effectiveness of continuous glucose monitoring in dialysis patients with diabetes: The DIALYDIAB pilot study
Diabetes Research and Clinical Practice
(2015) - et al.
Effects of vildagliptin twice daily vs. sitagliptin once daily on 24-hour acute glucose fluctuations
Journal of Diabetes and its Complications
(2010) - et al.
Use of the continuous glucose monitoring system to guide therapy in patients with insulin-treated diabetes: A randomized controlled trial
Mayo Clinic Proceedings
(2004) - et al.
Use of a real time continuous glucose monitoring system as a motivational device for poorly controlled type 2 diabetes
Diabetes Research and Clinical Practice
(2008) - et al.
Personalized nutrition by prediction of glycemic response
Cell
(2015)
An artificial endocrine pancreas
Diabetes
Prevention or delay of type 2 diabetes
Diabetes Care
GRADE guidelines 15: Going from evidence to recommendation ā Determinants of a recommendation's direction and strength
Journal of Clinical Epidemiology
Reduction in hemoglobin A1C with real-time continuous glucose monitoring: Results from a 12-week observational study
Diabetes Technology & Therapeutics
Threshold-based insulin-pump interruption for reduction of hypoglycemia
The New England Journal of Medicine
GRADE guidelines: 15. Going from evidence to recommendation-determinants of a recommendation's direction and strength
Journal of Clinical Epidemiology
Continuous subcutaneous glucose monitoring in children with type 1 diabetes
Pediatrics
Risk of cardiac arrhythmias during hypoglycemia in patients with type 2 diabetes and cardiovascular risk
Diabetes
A history of blood glucose meters and their role in self-monitoring of diabetes mellitus
British Journal of Biomedical Science
Multicentre-randomized controlled study of the impact of continuous subcutaneous glucose monitoring on glycaemic control in type 1 and 2 diabetes
Diabetes & Metabolism
Multisite study of an implanted continuous glucose sensor over 90Ā days in patients with diabetes mellitus
Journal of Diabetes Science and Technology
The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus
The New England Journal of Medicine
The effect of real-time continuous glucose monitoring on glycemic control in patients with type 2 diabetes mellitus
Journal of Diabetes Science and Technology
Heterogeneity of responses to real-time continuous glucose monitoring (RT-CGM) in patients with type 2 diabetes and its implications for application
Diabetes Care
Improvement in glycemic excursions with a transcutaneous, real-time continuous glucose sensor: A randomized controlled trial
Diabetes Care
Hypoglycemia in type 2 diabetesāMore common than you think: A continuous glucose monitoring study
Journal of Diabetes Science and Technology
Cited by (76)
Effect of structured individualized education on continuous glucose monitoring use in poorly controlled patients with type 1 diabetes: A randomized controlled trial
2022, Diabetes Research and Clinical PracticeImpact of blinded retrospective continuous glucose monitoring on clinical decision making and glycemic control in persons with type 2 diabetes on insulin therapy
2021, Nutrition, Metabolism and Cardiovascular DiseasesCitation Excerpt :On the other hand, sporadic self-monitoring of capillary blood glucose (SMBG) provides limited information, and is not routinely performed in people with type 2 diabetes. In recent years, advances in technology have facilitated the access to a more extensive picture of daily glycaemia profiles, namely through retrospective continuous glucose monitoring (rCGM) systems [10]. The main uses have been to evaluate overall glycaemic control and glycaemic patterns, detection of hypoglycaemia episodes, identification of glucose variability, and incorporation in lifestyle management and motivation support.
Clinically relevant stratification of patients with type 2 diabetes by using continuous glucose monitoring data
2024, Diabetes, Obesity and Metabolism
Conflict of interest: Both authors are full time employees of Medtronic Diabetes.
- 1
Tel.: +Ā 1 763 526 3509.