Examining the evidence for self-monitoring of blood glucose in non-insulin Type 2 diabetes

Keywords::

• diabetes
• glucose monitoring
• glycemia
• hemoglobin A1C
• meta-analysis
• randomized controlled trial
• review
• self-monitoring of blood glucose

Self-monitoring of blood glucose (SMBG) can be a tool to provide feedback information to patients and clinicians to consider in the management of diabetes mellitus. SMBG is clearly useful to detect hypoglycemia and hyperglycemia. Practitioners utilize SMBG to create a profile of blood glucose levels and develop recommendations for nutrition and diabetes drug therapy. Records of SMBG can also be used during consultation with diabetes healthcare providers to titrate blood glucose-lowering agents and to guide physical activity and caloric intake. A lack of SBGM has been associated with hospitalization for diabetes-related complications [1]. Some practitioners are skeptical about the effectiveness of SMBG in regulating diabetes control for those Type 2 diabetes mellitus (T2DM) patients not taking insulin. There continues to be debate over the optimal frequency and timing of SMBG. SMBG in individuals with diabetes should be based on each patient’s needs [2,3].

Although the UK Prospective Diabetes Study did not specifically evaluate SMBG, this landmark study showed a 1% reduction in glycated hemoglobin (HbA1c) associated with a 21% decreased risk of microvascular complications in individuals with T2DM [4]. SMBG is integral to intensive treatment for HbA1c reduction in patients with diabetes and is widely believed to improve the control of blood glucose levels and health outcomes. Among those with Type 1 diabetes, results of the Diabetes Control and Complications Trial indicate that intensive glycemia control significantly slowed the progression of diabetes complications [5]. In this trial, daily SMBG and injections of insulin were required. In clinical practice, SMBG can be a valuable tool for patients and clinicians to regulate glucose control.

Randomized controlled trials (RCTs) have been conducted to assess the impact of SMBG on glucose control [6]. Poolsup et al. evaluated nine RCTs comparing SMBG versus non-SMBG in non-insulin-treated T2DM with HbA1c as the primary outcome measure [6]. SMBG was effective in reducing HbA1c (pooled mean difference: -0.24%; 95% CI: -0.34–0.14; p < 0.00001). A subgroup with baseline HbA1cs of 8–10% showed a reduction of -0.27 (95% CI: -0.40 to -0.14), while patients with a baseline HbA1c of greater than 10% had a reduction of -1.23 (95% CI: -2.31 to -0.14). Thus, SMBG lowered HbA1c more in the subgroup whose baseline HbA1c was 8% or more and was greatest among those with HbA1c levels above 10%. In this meta-analysis, a significant positive effect of SMBG was sustained at 6 months but not at 12 months duration or longer [6]. Some studies were statistically underpowered RCTs with small sample sizes, lack of description for compliance measures, variable dropout rates between studies and variation in primary interventions across studies.

Another meta-analysis by Towfigh et al. included RCTs of 3–12 months duration [7]. Among three RCTs (3 months), the studies were too heterogenous to pool the data. The studies of 6-month duration (n = 5) yielded a pooled effect estimate of a decrease in mean HbA1c of -0.21 (95% CI: -0.38 to -0.04). Four trials reporting outcomes of 1 year or longer had a mean HbA1c decrease of -0.16 (95% CI: -0.38–0.05%). Meta-regression analysis of baseline HbA1c levels showed higher baseline HbA1c levels were associated with reduced efficacy of SMBG. Each 1% increase in HbA1c level resulted in an estimated 0.19% decrease in efficacy of SMBG. Limitations consist of heterogeneity of studies including the differing interventions added to the SMBG, provider contact and management for adjunctive treatments, and education/counseling variability across studies.

Sarol et al. conducted a meta-analysis of eight RCTs that assessed HbA1c reduction between SMBG versus non-SMBG [8]. Interventions among the studies included education and/or treatment adjustments based on SMBG result. Therapies that included SMBG as part of a multicomponent management strategy produced a mean additional HbA1c reduction of -0.39% (95% CI: -0.54 to -0.23) under a fixed-effects model and -0.42% (95% CI: -0.63 to -0.21) using a random-effects model. The conservative random-effects approach treats studies as heterogeneous. Some studies in the analysis do not describe concealment of treatment allocation in randomization. Other trials had problems with comparability in components of care between groups meriting a low-quality score.

Using Baysian meta-analysis, pooled change from baseline of studies with no intervention or SMBG resulted in a random-effects model of -0.47% (95% CI: -0.66 to -0.28) for HbA1c. The pooled change from baseline for studies with SMBG interventions was -0.87% (95% CI: -1.14 to -0.58) for HbA1c. For SMBG interventions with feedback, a -1.48% (95% CI: -2.06 to -0.89) for HbA1c reduction was found [9]. The interventions of each study was considered and detailed in the meta-analysis. St John et al. conducted a meta-analysis of RCTs and showed a modest but significant benefit of -0.22% (95% CI: -0.34 to -0.11) reduction in HbA1c associated with SMBG in T2DM [10]. Another meta-analysis of 15 RCT including 12 studies of SMBG versus non-SMBG used the random-effects model [11]. Data showed that SMBG was associated with a significantly lower HbA1c weighted mean difference (WMD) of -0.31% (95% CI: -0.44 to -0.17). A higher mean baseline HbA1c of 8% or more was associated with larger effects of SMBG compared with a baseline HbA1c of less than 8% (WMD: -0.38%; 95% CI: -0.58 to -0.18 vs WMD: -0.21%; 95% CI: -0.37 to -0.05).

Other evidence from a systemic review of RCTs in T2DM patients taking oral agents or treated with diet alone indicated that of ten clinical trials of SMBG versus no SMBG, there was a reduction in HbA1c of -0.21 (95% CI: -0.31 to -0.10; p < 0.0001) [12]. Evaluation of four trials that included interventions (including education and feedback) for the patient showed an HbA1c reduction of -0.52 (95% CI: -0.98 to -0.06; p = 0.03) for SMBG versus non-SMBG. In a separate analysis of five studies that compared an educational or feedback intervention to SMBG, there was an HbA1c reduction of 0.2% that was not significant. The frequency of hypoglycemia among the different studies was inconsistent with no adjustment for medication in SMBG versus no SMBG in the trials evaluated. Another systemic review was reported evaluating cross-sectional (n = 9) and longitudinal (n = 9) studies that found inconclusive evidence for SMBG and glucose control [13]. This article also evaluated RCTs of SMBG (n = 11) and found that SMBG might help lower HbA1c levels.

A Cochrane review by Welschen et al. of RCTs (n = 6) evaluated T2DM patients not taking insulin. SMBG was found to be an effective tool in self-management of patient’s glucose values to adjust diet and lifestyle [14]. There was insufficient evidence to suggest that SMBG was beneficial for improving quality of life, wellbeing, patient satisfaction or decreasing the number of hypoglycemic episodes. The authors then published the same data as a systematic review and meta-analysis concluding a statistically significant decrease of 0.39% in HbA1c (95% CI: -0.56 to -0.21%) in favor of SMBG compared with the control group [15].

The International Diabetes Federation Clinical Guidelines Taskforce in conjunction with the SMBG International Working Group has developed a ‘Guideline on Self-Monitoring of Blood Glucose in Non-Insulin Treated Type 2 Diabetes’ [16]. Recommendations include the following summary points: SMBG should be considered at time of diagnosis but should only be used when patients, their caregivers and/or their healthcare providers have the knowledge and willingness to incorporate findings into the diabetes management plan; SMBG should be considered a part of ongoing diabetes self-management education; SMBG protocols should be individualized; patients and their healthcare providers should agree on how to use SMBG data; and tools used to measure SMBG must be accurate and easy to use.

Other consensus groups include the ‘Coalition for Clinical Research Self-Monitoring of Blood Glucose Scientific Board’, consisting of clinicians and scientists from the USA and Europe who outlined skills needed by the patient to perform, interpret and act on SMBG results and those needed by the clinician to evaluate SMBG appropriately [17]. Specifically, protocols assessing the performance of SMBG in noninsulin-treated T2DM should provide the intervention along with instructions on how to respond to SMBG values. Intervention subjects in clinical trials should aggressively titrate therapeutic response to hyperglycemia. Control subjects in clinical trials should be isolated from the intervention group for SMBG. End points for T2DM in clinical trials for SMBG will have to include Δ HbA1c levels, hyper- and hypoglycemic events, time to titrate noninsulin therapy to maximum necessary doses and quality-of-life indices.

Multidisciplinary groups have published recommendations to include technological, clinical, behavioral, policy and research considerations [18]. It was noted there is variability among protocols for SMBG. Consideration should be given to the performance of monitoring equipment as well as the manner in which patients are taught to take action on the results from SMBG and the physiological, behavioral and social circumstances under which SMBG is carried out.

Overall, a multitude of RCTs and meta-analyses have been conducted evaluating the effect of SMBG with the primary outcome of HbA1c control. Controversy exists in studying SMBG as a primary outcome. The clinical significance of the HbA1c reduction found among studies is debatable and the average estimated decrease is less than 0.5%. Difficulties in studying the impact of SMBG will remain challenging as it is unclear if SMBG and reinforcing self-management along with behavior modification contribute to the conceptual framework when studying SMBG outcomes. SMBG may be beneficial in improving HbA1c when values exceed 8% if there is education for patients and healthcare providers about data interpretation and self-adjustment of treatments. SMBG facilitates modification in diet, lifestyle and therapeutic regimens but insufficient evidence exists about quality of life, wellbeing or patient satisfaction. There is also concern that in newly diagnosed T2DM, SMBG may have little effect on HbA1c and there may be an association with higher scores on a depression subscale [19].

Self-monitoring of blood glucose has been evaluated using a schedule of testing once versus four-times per week. Weekly SMBG was found to be sufficient to maintain HbA1c close to the metabolic target in T2DM on oral hyperglycemic medication [20]. There was higher compliance with weekly SMBG testing and more cost savings. SMBG once per week is an attractive schedule for patients who are able to maintain target HbA1c. Limitations to this study are lack of a control group and results generalizable only to individuals with stable control without medication changes.

Self-monitoring of blood glucose can have a positive trend for HbA1c improvement compared with baseline in the RCTs evaluated. Limitations for the studies include methodological quality, dropout rates and lack of intervention. Observational trials form part of the evidence for SMBG and, while the populations studied are often highly heterogenous, there has been improvement noted in glycemic control. One of the largest registeries evaluating the effectiveness of SMBG is the Northern California Kaiser Permante data [21]. Using a group model, SMBG was associated with a 0.4-point lower HbA1c level among 24,312 adults nonpharmacologically treated for T2DM. However, results from observational studies of SMBG are inconsistent and do not provide information about causality, but rather they capture routine patient care. Patient preferences and overall motivation to SMBG can impact the external validity of SMBG trials. Furthermore, the inability to blind SMBG is impracticable and if patients are randomized to the ‘nonpreferred’ arm of a study there can be an effect on nonadherence. Strong patient preferences in nonblinded studies should be controlled to prevent unwanted crossover of patients to the preferred arm of the study and observational validity [16].

The role of SMBG for patients who have poor metabolic control (i.e., HbA1c >9%) is a point for discussion. Traditional RCTs of SMBG are very difficult to design and if patients randomized to perform SMBG are not committed to carrying the procedure through, the results are at risk of error. The other issue is that SMBG is not a treatment and therefore RCTs targeting a change in HbA1c can be difficult with regard to establishing a cause and effect relationship. The impact of medication and other lifestyle interventions on HbA1c movement can also be a tremendous factor to consider. No change in HbA1c when patients are reasonably controlled warrants evaluation prior to study design. External validity that involves the patient’s past experiences and attitude should also be examined. The ideal study for SMBG would control for the limitations discussed previously as well as baseline intensity of SMBG already achieved by the patient. Some advocate randomization by study site rather than the individual patient to prevent subject contamination of the SMBG intervention [16]. It is challenging to assess SMBG in isolation when several concommittant factors can contribute to improving HbA1c among non-insulin-dependent T2DM. The RCT design for SMBG has many caveats. The variables of human behavior as well as the dynamic results of SMBG for patients to modify regimens make quantification related to HbA1c change challenging.

The optimal SMBG frequency among oral-treated T2DM is also confounded by cost of supplies and insurance coverage [22]. Some research has shown that providing SMBG devices at no charge can improve the rate of testing [23]. The ideal amount of SMBG is individualized and is probably linked to patient motivation for using this information to inform self-management. Diabetes requires self-management and adherence to treatment guidelines including SMBG to monitor success with the diabetes treatment plan [2,18]. SMBG can serve an important role in improving patient knowledge of glucose levels and the effects of different behaviors on blood glucose outcomes.

Self-monitoring of blood glucose is currently the only method available for patients with diabetes to monitor blood sugar levels and make necessary day-to-day changes in disease self-management. The pivotal role for utilization of SMBG is recognition of self-management for patients with any type of diabetes to enhance the success of medical nutrition therapy, activity and pharmacotherapy [5]. SMBG will continue to play a role for diabetes management in those individuals using insulin. Non-insulin-treated T2DM patients can use SMBG data to adjust diet and make lifestyle modifications. The cost–effectiveness of SMBG has been evaluated in T2DM patients receiving noninsulin regimens and was found to be associated with higher cost and a negative impact on quality of life [24]. While evidence shows that SMBG may be effective in improving glucose control, there are insufficient data to show it is beneficial for improving quality of life, wellbeing or patient satisfaction. Incorporating SMBG into a diabetes self-management plan requires an uncomplicated procedure complemented by an accurate device that produces individualized feedback.

Until there is a cure, the use of SMBG will remain the mainstay of guiding self-care managment of glucose values for patients. SMBG provides information regarding an individual’s dynamic blood glucose profile. These data can help with the appropriate scheduling of food, physical activity and pharmacotherapy. Timing of blood glucose variations can be captured through SMBG. This information can be an essential tool for people with diabetes who are taking insulin or for those who experience fluctuations in blood glucose levels, especially hypoglycemia. For others receiving oral medication, profiling glucose trends and the confirmation of high or low blood glucose can be a useful addendum to successful management. SMBG facilitates modification in diet, lifestyle and therapeutic regimens, but insufficient evidence exists about quality of life, wellbeing or patient satisfaction.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.