US Pharm. 2011;36(5)(Diabetes suppl):16-19. 

Type 2 diabetes mellitus (T2DM) is an extremely common problem in the United States and around the world. It is estimated that by the year 2030, there will be approximately 366 million individuals with diabetes.1 This article will provide an overview of T2DM; discuss the current glycemic and self-monitoring blood glucose (SMBG) recommendations; discuss the effectiveness of and the adherence to SMBG regimens; and discuss a recently proven, relatively simple SMBG method that was shown to improve the level of glycemic control in patients with T2DM.

Overview of T2DM

The occurrence of T2DM has reached epidemic proportions. As the incidence increases, so do the health care costs associated with the management of T2DM and its complications. The most recent estimates claim that more than 23 million adults and children in the U.S. are presently diagnosed with diabetes.2 This figure will be driven upward in the future due to the fact that 1.6 million new cases of diabetes are diagnosed annually in Americans aged 20 years or older. Approximately 6 million Americans currently have T2DM but have not been diagnosed.2 These large-scale missed diagnoses will ultimately generate a great deal of morbidity and mortality secondary to the unrecognized and unmanaged hyperglycemia. In the past, T2DM was considered a disease of adults. In fact, one of the diagnostic clues was the age of onset, and the condition itself was called adult onset diabetes mellitus. The past two decades have witnessed a dramatic shift in this historic pattern because young adults and children are now frequently being diagnosed with T2DM. This trend is expected to continue, and an American Academy of Pediatrics committee anticipates that the prevalence of T2DM among American children will, for the first time in history, exceed that of T1DM in the next few years.3

Several landmark trials have demonstrated the importance of strict glycemic control in patients with T2DM. These studies have shaped the guidelines that are presented in the next section. Strict glycemic control (as well as control of lipids and blood pressure) correlates with a reduction in diabetes-related complications.

It is clear that the negative metabolic/physiologic effects of chronic, prolonged hyperglycemia are grave. The sixth leading cause of death in the U.S. is diabetes.4 Microvascular disease includes retinopathy and nephropathy, while peripheral arterial disease (PAD), cerebrovascular disease, and cardiovascular disease fall under the rubric of macrovascular disease.5 The vast majority of patients (80%) with diabetes die secondary to heart disease.4 Rates of heart disease-related death in adult patients with T2DM are two to four times greater than in similar individuals without diabetes.4 It is estimated that 60% to 70% of patients with diabetes have some form of neuropathy.4 Diabetes is the leading cause of nontraumatic lower limb amputation in the U.S., due to the impact of PAD and neuropathy. The number-one cause of renal failure in the U.S. is diabetes. Lastly, the most common etiology of new-onset blindness in working-aged Americans is diabetes.

Glycemic Goals and Monitoring

Unfortunately, there is not universal consensus regarding the glycemic goals and SMBG use and methods in patients with T2DM. There are, however, two widely accepted and scientifically based sets of guidelines that address these issues. One is published by the American Diabetes Association (ADA) in collaboration with the European Association for the Study of Diabetes (EASD), and the other is published by the American Association of Clinical Endocrinologists (AACE) in collaboration with the American College of Endocrinology (ACE).5-8

The ADA/EASD suggests the following glycemic goals for patients with type 2 diabetes: glycated hemoglobin (A1C) levels of <7%, premeal glucose levels of 70 to 130 mg/dL, and postmeal levels (1-2 hours after the beginning of the meal) of less than 180 mg/dL.6 The AACE/ACE glycemic guidelines are slightly more strict than the ADA/EASD recommendations: A1C £6.5%, fasting plasma glucose levels of <110 mg/dL, and 2-hour postmeal glucose concentrations of <140 mg/dL.5

Recommendations regarding SMBG by these two collaborative sets of guidelines do offer some guidance; however, every patient is different and must have the SMBG regimen tailored to his or her specific situation. Selected AACE/ACE guidelines for glucose monitoring in patients with T2DM are shown in TABLE 1.5 The ADA/EASD guidelines for SMBG in patients with T2DM are less specific than the AACE/ACE guidelines, and some of the more salient recommendations from these organizations are shown in TABLE 2.7 The guidelines listed in these tables are purposefully vague and are intended to be applicable to multiple situations. They do not, however, offer a comprehensive method for managing and interpreting testing values.

Is SMBG Useful or Cost-Effective in T2DM?

The efficacy and cost data supporting the use of SMBG in patients with T2DM are mixed. Generally speaking, there is much less controversy regarding the utility SMBG in patients with T2DM who are using insulin. Conversely, the literature regarding the use, frequency, appropriate pattern, and cost-effectiveness of SMBG in non-insulin-treated patients is much more conflict-ridden and ambiguous. Some studies support and some do not support the use of SMBG in patients with T2DM. The more recent and salient of these studies are mentioned below.

One study in the United Kingdom evaluated 453 non-insulin-using patients with T2DM.9 The patients were randomized to standardized usual care without SMBG, usual care plus SMBG with advice to contact their provider for interpretation of results, or usual care plus SMBG with instruction on interpretation and application of the results to their lifestyle. At 12 months there were no statistically significant differences in A1C among the three groups. The authors concluded that the evidence was not convincing on the effect of SMBG on glycemic control with or without instructions for incorporating findings into self-care when compared to usual care without SMBG. There were, however, several limitations of the trial. The mean A1C level upon enrollment was 7.5% and, therefore, was already fairly well controlled. Additionally, it appears that the patients were instructed not to measure glucose in a systematic fashion but to choose various days of the week instead.

In another evaluation, researchers evaluated the cost-effectiveness and quality of life associated with SMBG in the population from the trial above.10 They concluded that SMBG with or without additional training in incorporating the results into self-care was associated with higher costs and lower quality of life in patients with non-insulin-treated T2DM. The same limitations that were mentioned above also apply to this trial.

Another recent trial in Ireland evaluated 184 newly diagnosed patients with diabetes over a period of 1 year.11 These patients were randomized to SMBG or no SMBG and were all treated with usual care. Usual care in this study included an algorithm-driven escalation of oral agents and insulin. Baseline A1C values were 8.8% and 8.6%, respectively, in the SMBG and the no-SMBG groups. At the end of the trial, both groups had a mean A1C of 6.9%. Additionally, the patients in the SMBG groups had a 6% higher depression score (out of a 100-point scale). The investigators concluded that the addition of SMBG had no impact on glycemic control and was associated with a higher depression score in newly diagnosed patients. This study, however, was severely limited. First, all of the patients were managed very aggressively with an escalating dose/medication algorithm. Following this approach, virtually any patient could have a reduced A1C. However, using this approach without monitoring can result in more hypoglycemia and undetected or unconfirmed hypoglycemia. Based purely on self-reporting from the non-SMBG group, this did occur.

A large study of over 20,000 Kaiser Permanente Diabetes Registry patients with T2DM evaluated the correlation between SMBG frequency and A1C.12 Patients who monitored more frequently had A1C levels that were statistically lower than those who monitored less frequently. The researchers concluded that their findings supported the clinical recommendations suggested by the ADA.

Another insightful evaluation compiled previous studies of SMBG in non-insulin-using patients with T2DM.13 The authors identified 97 studies on the topic. Of these, only six trials met their strict inclusion criteria and were included in the analysis. Their analysis concluded that the six randomized,  controlled trials, when combined, demonstrated a statistically significant reduction (0.39%) in patients who monitored versus patients who did not. They further commented that this was a clinically significant reduction because previous trials had demonstrated that an A1C reduction of 0.39% correlated with an approximate 14% reduction in microvascular complications.

Structured Testing

It seems clear from the discussion above that SMBG is useful in patients with T2DM regardless of whether they are treated with insulin, oral medications, or no medications. This leads us to a very interesting area of investigation. Is the pattern of testing important? Is a structured testing method more efficacious and cost-effective than the SMBG utilized in usual care situations? This would on its face seem a much more difficult proposition to prove since nonstructured monitoring in this population is associated with an A1C reduction of 0.39%, and it seems unlikely that a significant further drop in A1C would occur simply by structuring the testing. This, however, was recently proven to be so in a well-controlled trial that compared structured testing to usual testing patterns.14

This study was a 12-month, prospective, cluster-randomized trial of several hundred patients. Subjects were patients with T2DM who were insulin-naïve and were recruited and studied in 34 primary care practices across the U.S. Patients were randomized to an active control group (ACG) with enhanced usual care or to structured testing (STG) with enhanced usual care. The patients in the ACG were managed with visits at baseline, then at 1, 3, 6, 9, and 12 months that focused directly on their diabetes. They received free blood glucose meters and strips and office point-of-care A1C testing. They were instructed to use their meter following their physicians' recommendations but did not receive any additional SMBG instruction or prompting. Patients in the STG received the same level of care but had specific direction regarding their SMBG. They were asked to use the ACCU-CHEK 360° View Blood Glucose Analysis System of testing (FIGURE 1). The patients were asked to use this pattern of testing for 3 days prior to each visit. This entailed intensive monitoring for 3 days (7 points per day) and plotting of these data along with information regarding meal size and energy level. Physicians in the STG arm were trained to use the SMBG tool and were contacted during the study to ensure consistent intervention.

At the end of the 12-month study, the STG patients who completed the trial had A1C values that were reduced by a mean of 1.3% compared to a 0.8% mean reduction in the ACG. This difference of 0.5% in the STG is clinically and statistically significant. All of the patients in the study experienced an improvement in general well-being during the trial (measured by the standardized World Health Organization [WHO]-15 assessment tool).

The reason for this significant drop in A1C levels in the STG is probably multifaceted. First, the use of this tool provided prescribers with useful metabolic information. They could detect patterns and causes for those patterns based on diet, medication, and activity level. This allowed the prescribers to make informed decisions regarding medications. In fact, patients who completed the trial in the STG had treatment changes at more clinic visits (threefold greater) than did those in the ACG. Additionally, the information from the tool was probably used by the patients to help them understand the impact of diet, exercise, and medication on their blood glucose levels as well as the relationship between energy levels and glycemic control. To put it succinctly, this tool provides and presents blood glucose data in a meaningful format as opposed to the inscrutable results in the usual paroxysmal pattern of blood glucose testing.

Finally, one concern of doing such periodic intensive testing is the cost and frequency of testing. This study revealed that there were no significant differences in SMBG frequency between the two groups. Overall, those in the ACG measured their glucose as frequently as those in the STG; however, the data from the STG were probably more clinically meaningful and allowed for adjustments in therapy. In fact, one of our greatest problems with SMBG data in patients with T2DM is that the gathered data do not demonstrate significant patterns and are often clinically meaningless.

Based on this study, the use of this system of testing would therefore not increase cost compared to routine testing. The structured pattern of testing seems to offer a very useful and effective manner of glucose testing that is cost-effective and lowers glycemic indices significantly more than conventional testing patterns.

Conclusion

SMGB is an important tool in the management of patients with T2DM. While some studies have questioned its use, particularly in non-insulin-treated patients, SMBG has been shown to be effective overall in all patients with T2DM. The question of how monitoring should be structured is probably more germane to the question of whether it should be used. A recent prospective, controlled study suggests that the use of structured testing is cost-effective and is associated with significantly greater glycemic lowering than the use of conventional testing patterns.

REFERENCES

1. Wild S, Roglic G, Green A, et al. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004;27:2569.
2. Centers for Disease Control and Prevention. National Diabetes Fact Sheet. 2007. www.cdc.gov/diabetes/pubs/pdf/ ndfs_2007.pdf. Accessed February 7, 2011.
3. Gahagan S, Silverstein J. Prevention and treatment of type 2 diabetes mellitus in children, with special emphasis on American Indian and Alaska Native children. American Academy of Pediatrics Committee on Native American Child Health. Pediatrics. 2003;112(4):328-347.
4. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). National Diabetes Statistics. 2007. http://diabetes.niddk.nih.gov/ dm/pubs/statistics. Accessed February 7, 2011.
5. AACE/ACE. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Endoc Pract. 2007;13(suppl 1):1-68. www.aace.com/pub/pdf/ guidelines/DMGuidelines2007. pdf. Accessed January 11, 2011.
6. American Diabetes Association. Clinical practice recommendations. Diabetes Care. 2011;34(1):S1-S98.
7. Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2009;32(1):193-203.
8. Rodbard HW, Jellinger PS, Davidson JA, et al. Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control. Endocr Pract. 2009;15(6):540-559.
9. Farmer A, Wade A, Goyder E, et al. Impact of self monitoring of blood glucose in the management of patients with non-insulin treated diabetes: open parallel group randomized trial. BMJ. 2007;335:132-139.
10. Simon J, Gray A, Clarke P, et al. Cost effectiveness of self monitoring of blood glucose in patients with non-insulin treated type 2 diabetes: economic evaluation of data from the DiGEM trial. BMJ. 2008;336:1177-1183.
11. O'Kane MJ, Bunting B, Copeland M, et al, on behalf of the ESMON study group. Efficacy of self monitoring of blood glucose in patients with newly diagnosed type 2 diabetes (ESMON study): randomised controlled trial. BMJ. 2008;336:1174-1176.
12. Karter AJ, Ackerson LM, Darbinian JA, et al. Self-monitoring of blood glucose levels and glycemic control: the Northern California Kaiser Permanente Diabetes Registry. Am J Med. 2001;111:1-9.
13. Welschen LM, Bloemendal E, Nijpels G. Self-monitoring of blood glucose in patients with type 2 diabetes who are not using insulin: a systematic review. Diabetes Care. 2005;28(2):1510-1517.
14. Polonsky WH, Fisher L, Schikman CH, et al. Structured self-monitoring of blood glucose significantly reduces A1C levels in poorly controlled non-insulin treated type 2 diabetes. Diabetes Care. 2011;34:262-267.

To comment on this article, contact rdavidson@uspharmacist.com.