Research on CSII therapy began in the late 1970s, with a strong resurgence in the 1990s after technological advances in blood glucose monitoring devices and insulin delivery systems. In the current investigation, we analyzed through meta-analytic procedures all of the available data spanning this time period to provide a comprehensive quantified review of the existing literature on CSII therapy. Results of this meta-analysis provide strong evidence that CSII therapy is associated with significant improvements in glycemic control (decreased glycohemoglobin and mean blood glucose). Glycohemoglobin was lower in patients using pump therapy, with a greater benefit seen for patients using pump therapy for at least 1 year. Blood glucose levels were also lower for patients using pump therapy. Patients who began with CT showed the greatest blood glucose improvements when on pump therapy. It is likely that patients on MDI, who had already begun a more intensive therapy regimen, had fewer opportunities for improvement than patients on CT, which can be considered a floor effect. There were no differences noted between studies for which samples were composed of pediatric patients, adult patients, or mixed (both pediatric and adult), with the exception that studies of pediatric patients showed a greater improvement in blood glucose control during CSII therapy. Although these data suggest that the effects of CSII therapy are equivalent across age-groups, further examination of this issue is warranted because of the unique challenges faced in pediatric diabetes management.

Results of this meta-analysis also indicate that CSII therapy is associated with significant decreases in insulin requirements, although it does appear to result in weight gain, which has previously been reported with intensified insulin regimens^[4]. However, these data should be regarded cautiously because only 35% of the studies included in the meta-analysis reported on insulin requirements and only 21% of these studies reported on body weight.

With respect to potential complications of CSII use (e.g., hypoglycemia, DKA, pump malfunction, and site infections), 39 studies reported on at least one of these risks; however, they did not use a common metric when reporting the data. Thus, meta-analytic procedures could not be used. Based on this limited descriptive data, it appears that CSII use is associated with a decreased frequency of both mild and severe hypoglycemic episodes. CSII use was associated with an overall increased frequency of DKA. However, this increased risk of DKA was not evident in studies published after 1993, suggesting that CSII may no longer be associated with a greater risk of DKA compared with other forms of insulin administration. It may be that the earlier data on the increased risk of DKA led clinicians to emphasize DKA prevention with their patients. However, because only 11 studies reported on DKA risk, and only 4 of those were published since 1993, final conclusions about DKA risk in CSII therapy would be premature. Similarly, the majority of studies reporting on episodes of pump failure and catheter occlusions were published before 1988, suggesting that advancements in CSII technology and/or heightened patient vigilance (e.g., change of infusion set after two consecutive high blood glucose values) have lowered this risk.

Few studies (n = 16) assessed any aspect of psychosocial functioning, including the patient's perspectives on treatment options. Whereas these limited data suggest that there is no increased risk for poor psychosocial outcomes for CSII therapy relative to injection therapy, this finding needs to be regarded cautiously. There was little consistency in either the choice of psychosocial construct assessed or the assessment methodology (questionnaire, clinical interview) used. Clearly, additional research on the psychosocial impact of CSII therapy is needed before conclusions can be rendered.

In summary, the results of the current meta-analysis highlight the benefits of improved glycemic control associated with CSII therapy compared with traditional insulin therapies (CT or MDI). Furthermore, today's CSII therapy does not appear to be associated with significant adverse outcomes (e.g., DKA or severe hypoglycemia).

While the data appear promising, firm conclusions about the efficacy of CSII therapy would be premature because of several limitations of the data. First, the present meta-analysis does not include all published articles on CSII therapy in peer-reviewed journals because not all studies reported the data (i.e., means, SDs) necessary for the analyses. Second, not all studies included in the meta-analysis contributed data points for all outcomes variables. Furthermore, the majority of the studies in this meta-analysis were published before 1987, with relatively few studies published in the post-DCCT era that specifically examined the relative risks and benefits of CSII therapy. Additional research is needed that specifically focuses on the relative risks and benefits of CSII therapy in our technologically sophisticated times. Therefore, the results of the current study should not be viewed as a definitive statement about the efficacy of CSII therapy.

Recommendations for Future Research

We offer the following recommendations to guide future research in this endeavor. To further our understanding of the potential risks and benefits of CSII therapy, outcome data need to be reported in a standardized and systematic manner. We recommend that means and SDs of all outcome data be reported for both CSII and comparison control conditions. Potential risks and complications of CSII therapy (e.g., catheter occlusions, DKA, and hypoglycemia) should be routinely assessed and reported. Reporting insulin requirements as units per kilogram per day would allow for more reliable comparisons across studies because reporting only daily total insulin doses cannot capture the relationship between an individual's weight and his or her insulin needs. Because the impact of pump therapy on body weight remains inconclusive (studies with parallel designs yielded mixed results, whereas studies with paired designs suggested weight increases on CSII therapy), we also recommend that future studies document subject's body weight, both before initiation of CSII therapy and at the end of the study period.

While CSII therapy may be the most sophisticated and precise insulin delivery method currently available, the opportunity for improved glycemic control is only one of many potential factors that need to be considered when initiating pump therapy. CSII therapy may potentially affect the patient's quality of life and psychosocial functioning. For example, patients who choose CSII therapy often must reevaluate their previous strategies for diabetes management, including learning new skills, monitoring blood glucose values and urine ketones more frequently, and increasing awareness of insulin-to-carbohydrate ratios, all of which may potentially increase self-care demands. CSII therapy may also affect an individual's body image and sexual intimacy. Future studies that carefully examine the psychosocial impact of CSII therapy on patients and their families are needed. There is an extensive body of research that indicates that diabetes increases one's risk for depression^[88]; therefore, targeting depression would seem to be a vital psychosocial variable to include in such assessments. Other areas of psychosocial functioning that are important to assess include measurements of self-management^[89-91], quality of life^[92], family functioning^[93], and patient-provider relationships^[94]. Longitudinal prospective studies that assess individuals' reasons for initiating, continuing, and discontinuing CSII therapy are also needed. Collectively, this research will help guide clinical decision making regarding CSII therapy with the dual goals of optimizing glycemic control and improving quality of life.

Results The changes in glycated hemoglobin levels in the two study groups varied markedly according to age group (P=0.003), with a significant difference among patients 25 years of age or older that favored the continuous-monitoring group (mean difference in change, –0.53%; 95% confidence interval [CI], –0.71 to –0.35; P<0.001). The between-group difference was not significant among those who were 15 to 24 years of age (mean difference, 0.08; 95% CI, –0.17 to 0.33; P=0.52) or among those who were 8 to 14 years of age (mean difference, –0.13; 95% CI, –0.38 to 0.11; P=0.29). Secondary glycated hemoglobin outcomes were better in the continuous-monitoring group than in the control group among the oldest and youngest patients but not among those who were 15 to 24 years of age. The use of continuous glucose monitoring averaged 6.0 or more days per week for 83% of patients 25 years of age or older, 30% of those 15 to 24 years of age, and 50% of those 8 to 14 years of age. The rate of severe hypoglycemia was low and did not differ between the two study groups; however, the trial was not powered to detect such a difference.

Conclusions Continuous glucose monitoring can be associated with improved glycemic control in adults with type 1 diabetes. Further work is needed to identify barriers to effectiveness of continuous monitoring in children and adolescents.