Zi Zeng，Ting Shui，Li-Jun Yi，Yn Wng，Guo-Min Song

aGraduate College，Tianjin University of Traditional Chinese Medicine，Tianjin 300193，China

bSchool of Nursing，Tianjin University of Traditional Chinese Medicine，Tianjin 300193，China

cDepartment of Nursing，Tianjin Hospital，Tianjin 300211，China

Original article

Effect of case management on patients with type 2 diabetes mellitus：a meta-analysis

Zi Zenga，Ting Shuaia，Li-Juan Yia，Yan Wangb，Guo-Min Songc，*

aGraduate College，Tianjin University of Traditional Chinese Medicine，Tianjin 300193，China

bSchool of Nursing，Tianjin University of Traditional Chinese Medicine，Tianjin 300193，China

cDepartment of Nursing，Tianjin Hospital，Tianjin 300211，China

A R T I C L E I N F O

Article history：

Received 21 January 2016

Received in revised form

12 February 2016

Accepted 11 March 2016

Available online 18 June 2016

Case management

Type 2 diabetes mellitus

Meta-analysis

Systematic review

Background：Case management is a term used to describe the activities performed by a physician or other health care professional to ensure the coordination of medical services required by a patient. Managed care requires the incorporation of information pertaining to patient evaluation，treatment planning，referrals，and follow-up care to ensure that payment for services is received and that care is ongoing and comprehensive.The objective of this review was to assess the efficacy of case management in patients with type 2 diabetes mellitus with respect to outcomes such as glycosylated hemoglobin（HbA1c），systolic blood pressure（SBP），diastolic blood pressure（DBP），and low-density lipoprotein（LDL）.

Methods：Databases including PubMed，Embase，Web of Science，the Cochrane Library，the China National Knowledge Infrastructure（CNKI），VIP，Wan Fang and the Chinese Biomedical Literature Database（CBM）were searched for randomized controlled trials（RCTs）dating as late as Jan，2015.Reference sections of the included studies were also searched.

Results：Twelve studies，involving 11 RCTs that evaluated a total of 4000 patients，were included in this analysis.Two of the 12 studies evaluated the same RCT.Seven of the 12 studies reported HbA1cas an outcome，and three trials reported changes in SBP，DBP and LDL levels as outcomes.The pooled results indicated that statistically significant improvements in HbA1c（MD=-0.35，95%CI（-0.68，-0.02），P=0.04）and LDL levels（MD=-2.49，95%CI（-4.04，-0.93），P=0.002）were associated with the case management group compared with control group；however，no statistically significant differences in DBP（MD=-0.08，95%CI（-0.68，0.52），P=0.8）and SBP（MD=-0.96，95%CI（-5.77，3.84），P=0.69）were observed.

Conclusions：Case management was effective in improving HbA1cand LDL levels in patients with type 2 diabetes mellitus.Although no statistically significant differences in DBP and SBP between the case management group and the control group were observed，further research is required to draw a conclusion about the effect of managed care on these outcomes.Based on this meta-analysis of clinical trials，we conclude that case management offers an effective clinical method for the treatment of type 2 diabetes.

©2016 Shanxi Medical Periodical Press.Publishing services by Elsevier B.V.This is an open access article under the CC BY-NC-ND license（http：//creativecommons.org/licenses/by-nc-nd/4.0/）.

1.Introduction

Diabetes imposes a heavy burden on health-care systems and on patients and their families.The World Health Organization（WHO）reports that the worldwide prevalence of diabetes will reach 366 million by 2030，with many new cases of diabetes occurring in developing countries，especially in Southeast Asiaand among the working class.1Thus，the implementation of diabetes prevention programs and intervention programs to improve glycemic control in people with diagnosed diabetes is a public health problem worth prioritizing.The condition of impaired glucose tolerance also represents a serious public health problem that requires more attention.This is exemplified by the fact that approximately 70%of people with impaired glucose tolerance have the potential to develop diabetes，and diabetes is associated with an increased risk of cardiovascular disease.Many ethnic minorities are at an increased risk of developing type 2 diabetesand of developing the disease at an earlier age.Furthermore，higher morbidity and mortality rates are associated with diabetes in these populations.2，3Therefore，it is imperative to identify measures that address these serious problems.Case management has been considered an effective approach for improving the condition of diabetic patients.An earlier study4reported the results of a meta-analysis evaluating the effect of case management on HbA1cin patients with diabetes.The results demonstrated that case management intervention was associated with substantial improvements in HbA1cfrom baseline compared with control groups4that were not involved in a case management intervention program.Many studies evaluating the effect of case management programs on HbA1c，however，are controversial.5-7Furthermore，a systematic review of the effect of case management specifically for patients with type 2 diabetes mellitus has not been performed.Therefore，the aim of this meta-analysis was to evaluate the effect of case management，as assessed by multiple treatment outcomes，in patients with type 2 diabetes.The main objective of this review was to summarize the evidence associated with the effect of case management on clinical outcomes，such as HbA1c，SBP，DBP and LDL levels，in patients with type 2 diabetes mellitus.

2.Methods

2.1.Inclusion criteria

2.1.1.Participants

Patients over the age of 18 years who were diagnosed with type 2 diabetes mellitus were included in this review.Ethnicity and comorbidities were not parameters of the inclusion criteria.

2.1.2.Interventions

This analysis included studies employing multiple types of case management intervention programs，such as telephone-based intervention and face-to-face instruction.

2.2.Outcomes

2.2.1.Primary outcome

Glycated hemoglobin（HbA1c）measured after the intervention phase was the primary outcome of this study.

2.2.2.Secondary outcomes

SBP，DBP，LDL，HDL，total cholesterol，and some additional variables were analyzed quantitatively or qualitatively，depending on the variable being evaluated.

2.3.Study design

Randomized controlled studies meeting the inclusion criteria were considered for analysis，regardless of the outcomes they evaluated in the study.

2.4.Search strategy

We searched eight electronic databases，namely，PubMed，Embase，Web of Science，CENTRAL，CNKI（China National Knowledge Infrastructure），VIP，Wan Fang and CBM，using combinations of Mesh and the following entry terms：“NIDDM”，“Maturity-Onset Diabetes”，“Diabetes Mellitus，Noninsulin-Dependent”，“Diabetes Mellitus，Adult-Onset”，“Adult-Onset Diabetes Mellitus”，“Diabetes Mellitus，Adult Onset”，“Diabetes Mellitus，Ketosis-Resistant”，“Diabetes Mellitus，Ketosis Resistant”，“Ketosis-Resistant Diabetes Mellitus”，“Diabetes Mellitus，Maturity-Onset”，Diabetes Mellitus，“Non Insulin Dependent”，“Diabetes Mellitus，Non-Insulin-Dependent”， “Non-Insulin-Dependent Diabetes Mellitus”，“Diabetes Mellitus，Noninsulin Dependent”，“Diabetes Mellitus，Slow-Onset”，“Diabetes Mellitus，Slow Onset”，“Slow-Onset Diabetes Mellitus”，“Diabetes Mellitus，Stable”，“Stable Diabetes Mellitus”，“Diabetes Mellitus，Type II”，“Maturity-Onset Diabetes Mellitus”，“Maturity Onset Diabetes Mellitus”，“MODY”，“Type 2 Diabetes Mellitus”，“Noninsulin-Dependent Diabetes Mellitus”，“type 2 Diabetes Mellitus”，“case management”and random.We manually searched the references of included articles to identify any additional relevant literature.

2.5.Review methods

The systematic review and meta-analysis was designed according to guidelines described in the Cochrane Handbook for Systematic Reviews of Interventions.8Searches and data extraction were performed by two individual investigators（ZZ and ST）. Each trial identified in the search was evaluated for relevant domains，including author，number of participants，year published，allocation method，age of included patients，disease duration，intervention and control measures，length of treatments，patient inclusion and exclusion criteria，baseline values and outcome measures.Any disagreement between investigators was resolved through discussion with a third investigator（SGM）.All remaining articles were viewed as full text.A quality assessment of the trials included in this study was performed independently by two reviewers according to the criteria described in the Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0.8Evaluation domains for the quality assessment included randomization sequence generation，allocation concealment，blinding of participants and study personnel，blinding of outcome assessment，incomplete outcome data，selective reporting and other biases.Based on the information extracted from the primary studies，each parameter was rated as“high risk”，“unclear risk”or“low risk”.All studies included in this meta-analysis were reviewed for heterogeneity in clinical factors and methodology.If clinical heterogeneity existed，data could not be combined.All extracted data were entered into RevMan 5.3（Copenhagen：The Nordic Cochrane Centre，The Cochrane Collaboration，2013）for statistical analysis.All extracted data pertained to continuous outcomes.If more than two treatment groups were evaluated，data associated with the most intensive or effective intervention group and with the control group were used for analysis.Standard mean differences（SMDs）with 95%confidence intervals（Cis）for continuous outcomes were selected for calculating the pooled effects.The I2test was used to calculate the percentage of total variation across studies due to heterogeneity.Values greater than 50%indicate a substantial level of heterogeneity.In the absence of clinical heterogeneity and the presence of statistical heterogeneity（I2greater than 60%），we used a random effects model.If studies were similar enough to consider for pooled analysis，we used a fixed effect model for low to moderate levels of heterogeneity（I2values were 0-60%）.9

Endpoint data were used to calculate the summarized results. Subgroup analysis was performed if any sources of heterogeneity were identified.

3.Results

Atotal of 212 trials wereidentified in the initial literature search，and an additional two studies were identified from other sources. Twelve studies10-21that included data from 11 clinical trials with a total of 4000 participants were selected for further analysis according to inclusion and exclusion criteria.The duration of thesestudies was approximately 2 years，but it varied slightly among the different studies.Among the selected studies，seven trials analyzed quantitatively.The flow diagram of the literature retrieval and selection process is presented in Fig.1.

Methodologies used in the included trials are presented in Fig.2.

3.1.Quantitative analysis

3.1.1.The effect of case management versus usual care on HbA1c

A total of 929 patients participated in the seven trials that reported changes inas a study outcome.There was substantial heterogeneity among the seven trials（P＜0.00001，I2=86%）；therefore，the random effects model of analysis was used.The pooled results demonstrated that there was a statistically significant difference in HbA1cassociated with the case management study group compared with the control group（MD=-0.35，95%CI（-0.68，-0.02），P=0.04）（Fig.3）.No obvious heterogeneity sources were identified，and therefore，subgroup analysis cannot be performed.

3.1.2.The effect of case management versus usual care on LDL

Three trials evaluating a total of 893 patients with type 2 diabetes reported change in LDL as an outcome of the study.12，13，16No substantial heterogeneity was detected in these studies（P=0.09，I2=59%）；therefore，a fixed-effects model of analysis was performed to calculate the mean effect size.The analysis demonstrated that a statistically significant difference in LDL was associated with the case management group compared with the usual care group（MD=-2.49，95%CI（-4.04，-0.93），P=0.002）（Fig.4）.

3.1.3.The effect of case management versus usual care on SBP

Three trials evaluating a total of 893 patients reported changes in SBP as an outcome of the study.12，13，16Substantial heterogeneity was detected among the studies（P=0.0006，I2=87%）；therefore，the random effects model was employed.The results demonstrated that no statistically significant difference in SBP was associated with the case management group compared with the control group（MD=-0.96，95%CI（-5.77，3.84），P=0.69）（Fig.5）.However，the case management group was associated with a numerically greater decrease in SBP，indicating that this parameter might warrant future investigation.Obvious heterogeneity sources were not identified，and therefore，subgroup analysis cannot be performed.

3.1.4.The effect of case management versus usual care on DBP

Three trials evaluating a total of 893 patients with type 2 diabetes reported changes in DBP as an outcome of the study.12，13，16No substantialheterogeneity wasdetected among the studies（P=0.18，I2=41%）；therefore，a random effects model of analysis was performed to calculate mean difference.The results demonstrated that no statistically significant difference in DBP was associated with the case management group compared with the control group（MD=-0.08，95%CI（-0.68，0.52），P=0.80）（Fig.6）.However，the case management group was associated with a numerically greater decrease in DBP，indicating that this parameter might warrant future investigation.

3.2.Qualitative analysis

Outcomes reported in only one of the studies included in this analysis could not be used for comparative analyses.These outcomes included total cholesterol，HDL，triglycerides，BMI，blood glucose levels，quality of life，and compliance behaviors.The use of case management for patients with type 2 diabetes demonstrated promising effects on many of these outcomes.One study11demonstrated that a relatively short period of case management for patients with type 2 diabetes without clinically identifiable retinopathy significantly diminished the risk of these patients developing retinopathy during the follow-up period.One study10found that case management provided an advantage over standard provider care（SPC）with respect to patient compliance in eating two or more servings of fresh fruit and vegetables per day. One study14found that improved diabetes control in the elderly following a telemedicine case management intervention program that followed existing guidelines was associated with less global cognitive decline.This effect seemed to be mediated primarily by improvements in HbA1c；however，more comprehensive evidence is required to confirm this finding.

4.Conclusions

4.1.Reporting quality

With respect to the domain of random sequence generation，one study was judged to present a high risk of bias due tothe use of incorrect randomization methods.19Regarding the domain of allocation concealment，two trials were rated as presenting a low risk of bias due to the use of sealed envelopes.13，16，17However，with respect to the domains of blinding for participants and personnel and blinding outcome assessment，11 studies were judged as presenting an unclear risk of bias，1-11and one was rated as presenting a high risk.21Therefore，allocation concealment may have been influenced，which could have led to performance and measurement bias.With respect to the domain of incomplete outcome data，five studies were judged as presenting a high risk of bias due to a lack of detailed descriptions pertaining to dropouts.10，11，13，14，16，17Regarding selective reporting，two RCTs were judged to present a high risk of bias due to a failure to report all required results.11，16，17Finally，two studieswere judged as presenting a high risk of bias for using a pre-protocol（PP）principle to analyze the results with exclusion bias，potentially leading to overestimated results.10，16，17

4.2.Necessities

Recent data from the National Health and Nutrition Examination Survey（NHANES）2003-2006 suggest that only 12.2%of diabetes patients have simultaneous control of blood pressure（BP），glycemia，and lipids.Case management using physician extenders（nurses，pharmacists，etc.）is a method that has previously been used to improve risk factor control.22Once considered a disease of western society，type 2 diabetes mellitus（T2DM）has now spread globally，and Asia accounts for approximately 60%of the world's diabetic patients.23Obesity and T2DM have become a serious public health problem.24Effective interventions must integrate coordination of care and discharge planning into today's best practice models.25However，the effect of case management for diabetic patients has demonstrated conflicting results.An earlier study3reported results of a meta-analysis evaluating theeffect of case management for HbA1con patients with diabetes. These results demonstrated a large effect size favoring case managementintervention overcontrolgroupswith respectto improving HbA1cvalues from baseline.3However，no systematic review evaluating the efficacy of case management in patients with T2DM has been performed.This meta-analysis was conducted to determine if case management provides advantages over usual care for type 2 diabetic patients.

4.3.Limitations

4.3.1.Limitations for included literature

Questions regarding the effect of case management on type 2 diabetes mellitus still remain.Limitations of this study include differences in the methods of case management and variations in duration time，factors which might affect the robustness of the pooled results.In addition，the relatively small sample size of the pooled dataset may lack the power to detect meaningful results. The most effective case management program with respect to method and duration of time should be explored further.Case management for type 2 diabetic patients could benefit from standardization and systematization efforts.Among the studies included in this analysis，some case management programs were employed in combination with additional methods such as community health work16and motivational interviewing.12A combination of approaches might produce different results compared with case management alone.From this perspective，it could be worth investigating whether or not a combination of interventionmethods provides advantages in the use of one intervention method alone.While meaningful results for some outcomes were obtained in this study，some outcomes could not be used for pooled analysis due to a lack of sufficient information.However，some of these outcomes might be valuable for assessing the effects of case management on factors such as the quality of life and compliance behaviors.Furthermore，the studies included in this analysis did not assess cost-effectiveness，which is considered as an important factor in the real-world clinical setting.

4.3.2.Limitations of this review

Springer Link，ScienceDirect，and some other databases，were not included in our search；therefore，there is a risk of partial selection bias.In addition，the inclusion of only English and Chinese literature may have resulted in selection bias for language limitations，which potentiallyaffected the credibility of the pooled results of this study.

In conclusion，case management was proven to be effective in improving HbA1cand LDL in patients with type 2 diabetes mellitus，although no significant differences in DBP and SBP were demonstrated.We conclude that case management provides an effective clinical strategy for patients with type 2 diabetes.

Conflicts of interest

All contributing authors declare no conflicts of interest.

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How to cite this article：Zeng Z，Shuai T，Yi L-J，et al.Effect of case management on patients with type 2 diabetes mellitus：a metaanalysis.Chin Nurs Res.2016；3：71-76.http：//dx.doi.org/10.1016/ j.cnre.2016.06.008

*Corresponding author.

E-mail address：tjyysgm@163.com（G.-M.Song）.

Peer review under responsibility of Shanxi Medical Periodical Press.

http：//dx.doi.org/10.1016/j.cnre.2016.06.008

2095-7718/©2016 Shanxi Medical Periodical Press.Publishing services by Elsevier B.V.This is an open access article under the CC BY-NC-ND license（http：//creativecommons. org/licenses/by-nc-nd/4.0/）.