Continuous glucose monitoring systems for type 1 diabetes mellitus

Type 1 diabetes is a disease in which the pancreas has lost its ability to make insulin. A deficit in insulin leads to increases in blood glucose levels, these elevated blood glucose levels can lead to complications which may affect the eyes, kidneys, nerves and the heart and blood vessels. Since there is no cure for type 1 diabetes, patients need to check their blood glucose levels often by fingerprick and use these blood glucose values to decide on their insulin dosages. Fingerpricks are often regarded as cumbersome and uncomfortable by patients. In addition, fingerprick measurements only provide information about a single point in time, so it is difficult to discern trends in decline of rises in blood glucose levels.

Continuous glucose monitoring systems (CGM) measure blood glucose levels semi-continuously. Most modern CGM systems consist of a small needle which is inserted in the abdominal subcutaneous fat. The tip of the needle houses a small glucose sensor which can measure glucose levels in the fluid which surrounds the fatty tissue. Here we explore whether CGM systems help the patient to increase quality of life and her glycaemic control, which reflects how well the patient's diabetes is treated.

In this review 22 studies were included. These studies randomised 2883 patients with type 1 diabetes to receive a form of CGM or to use self measurement of blood glucose (SMBG) using fingerprick. The duration of follow-up varied between 3 and 18 months; most studies reported results for six months of CGM use. This review shows that CGM helps in lowering the glycosylated haemoglobin A1c (HbA1c) value (a measure of glycaemic control). In most studies the HbA1c value decreased (denoting improvement of glycaemic control) in both the CGM and the SMBG users, but more in the CGM group. The difference in change in HbA1c levels between the groups was on average 0.7% for patients starting on an insulin pump with integrated CGM and 0.2% for patients starting with CGM alone. The most important adverse events, severe hypoglycaemia and ketoacidosis did not occur frequently in the studies, and absolute numbers were low (9% of the patients, measured over six months). Diabetes complications, death from any cause and costs were not measured. There are no data on pregnant women with diabetes type 1 and patients with diabetes who are not aware of hypoglycaemia.

Authors' conclusions: 

There is limited evidence for the effectiveness of real-time continuous glucose monitoring (CGM) use in children, adults and patients with poorly controlled diabetes. The largest improvements in glycaemic control were seen for sensor-augmented insulin pump therapy in patients with poorly controlled diabetes who had not used an insulin pump before. The risk of severe hypoglycaemia or ketoacidosis was not significantly increased for CGM users, but as these events occurred infrequent these results have to be interpreted cautiously.There are indications that higher compliance of wearing the CGM device improves glycosylated haemoglobin A1c level (HbA1c) to a larger extent. 

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Background: 

Self-monitoring of blood glucose is essential to optimise glycaemic control in type 1 diabetes mellitus. Continuous glucose monitoring (CGM) systems measure interstitial fluid glucose levels to provide semi-continuous information about glucose levels, which identifies fluctuations that would not have been identified with conventional self-monitoring. Two types of CGM systems can be defined: retrospective systems and real-time systems. Real-time systems continuously provide the actual glucose concentration on a display. Currently, the use of CGM is not common practice and its reimbursement status is a point of debate in many countries.

Objectives: 

To assess the effects of CGM systems compared to conventional self-monitoring of blood glucose (SMBG) in patients with diabetes mellitus type 1.

Search strategy: 

We searched The Cochrane Library, MEDLINE, EMBASE and CINAHL for the identification of studies. Last search date was June 8, 2011.

Selection criteria: 

Randomised controlled trials (RCTs) comparing retrospective or real-time CGM with conventional self-monitoring of blood glucose levels or with another type of CGM system in patients with type 1 diabetes mellitus. Primary outcomes were glycaemic control, e.g. level of glycosylated haemoglobin A1c (HbA1c) and health-related quality of life. Secondary outcomes were adverse events and complications, CGM derived glycaemic control, death and costs.

Data collection and analysis: 

Two authors independently selected the studies, assessed the risk of bias and performed data-extraction. Although there was clinical and methodological heterogeneity between studies an exploratory meta-analysis was performed on those outcomes the authors felt could be pooled without losing clinical merit.

Main results: 

The search identified 1366 references. Twenty-two RCTs meeting the inclusion criteria of this review were identified. The results of the meta-analyses (across all age groups) indicate benefit of CGM for patients starting on CGM sensor augmented insulin pump therapy compared to patients using multiple daily injections of insulin (MDI) and standard monitoring blood glucose (SMBG). After six months there was a significant larger decline in HbA1c level for real-time CGM users starting insulin pump therapy compared to patients using MDI and SMBG (mean difference (MD) in change in HbA1c level -0.7%, 95% confidence interval (CI) -0.8% to -0.5%, 2 RCTs, 562 patients, I2=84%). The risk of hypoglycaemia was increased for CGM users, but CIs were wide and included unity (4/43 versus 1/35; RR 3.26, 95% CI 0.38 to 27.82 and 21/247 versus 17/248; RR 1.24, 95% CI 0.67 to 2.29). One study reported the occurrence of ketoacidosis from baseline to six months; there was however only one event. Both RCTs were in patients with poorly controlled diabetes.

For patients starting with CGM only, the average decline in HbA1c level six months after baseline was also statistically significantly larger for CGM users compared to SMBG users, but much smaller than for patients starting using an insulin pump and CGM at the same time (MD change in HbA1c level -0.2%, 95% CI -0.4% to -0.1%, 6 RCTs, 963 patients, I2=55%). On average, there was no significant difference in risk of severe hypoglycaemia or ketoacidosis between CGM and SMBG users. The confidence interval however, was wide and included a decreased as well as an increased risk for CGM users compared to the control group (severe hypoglycaemia: 36/411 versus 33/407; RR 1.02, 95% CI 0.65 to 1.62, 4 RCTs, I2=0% and ketoacidosis: 8/411 versus 8/407; RR 0.94, 95% CI 0.36 to 2.40, 4 RCTs, I2=0%).

Health-related quality of life was reported in five of the 22 studies. In none of these studies a significant difference between CGM and SMBG was found. Diabetes complications, death and costs were not measured.

There were no studies in pregnant women with diabetes type 1 and in patients with hypoglycaemia unawareness.