Contribution of Diabetes to the Incidence and Prevalence of Comorbid Conditions (Cancer, Periodontal Disease, Fracture, Impaired Cognitive Function, and Depression): A Systematic Review of Epidemiological Studies in Japanese Populations

Background Several epidemiological studies have determined the relationship between diabetes and the incidence and/or prevalence of recently identified comorbid conditions (cancer, periodontal disease, fracture, cognitive impairment, and depression). These relationships may vary by country or race/ethnicity. We aimed to systematically review studies in this field conducted with the Japanese population because such a review in the Japanese population has never been undertaken. Methods We conducted systematic literature searches in PubMed and Ichushi-Web databases for studies published until December 2016. Studies comparing the incidence and/or prevalence of the comorbidities among the Japanese population were included. The studies were classified as integrated analyses, cohort studies, case-control studies, or cross-sectional studies. Results We identified 33 studies (cancer: 17, periodontal disease: 5, fracture: 5, cognitive impairment: 4, and depression: 2). Although several cohort studies and meta-analyses had assessed the development of cancer in diabetes, there was scant epidemiological evidence for the other conditions. Indeed, only one cohort study each had been conducted for periodontal disease, fracture, and cognitive impairment, whereas other evidence was cross-sectional, some of which was induced from baseline characteristic tables of studies designed for other purposes. Conclusion In Japan, there is insufficient evidence about the relationship between diabetes and the incidence/prevalence of periodontal disease, fracture, cognitive impairment, and depression. By contrast, several cohort studies and integrated analyses have been conducted for the relationship with cancer. Further studies should be undertaken to estimate the contribution of diabetes on the incidence/prevalence of comorbidities that may be specific to the Japanese population.


Rationale
3 Describe the rationale for the review in the context of what is already known.

5-11
Objectives 4 Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, outcomes, and study design (PICOS).

METHODS
Protocol and registration 5 Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide registration information including registration number.
None Eligibility criteria 6 Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered, language, publication status) used as criteria for eligibility, giving rationale.

11-12
Information sources 7 Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched.

11-12
Search 8 Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated.

11-12
Study selection 9 State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis).

12-14
Data collection process 10 Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators.

12-14
Data items 11 List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and simplifications made.

12-14
Risk of bias in individual studies 12 Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis.

12-13
Synthesis of results 14 Describe the methods of handling data and combining results of studies, if done, including measures of consistency (e.g., I 2 ) for each meta-analysis.

None
Additional analyses 16 Describe methods of additional analyses (e.g., sensitivity or subgroup analyses, meta-regression), if done, indicating which were pre-specified.

Study selection
17 Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram.

14-21
Study characteristics 18 For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and provide the citations.

14-21
Risk of bias within studies 19 Present data on risk of bias of each study and, if available, any outcome level assessment (see item 12).

14-21
Results of individual studies 20 For all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each intervention group (b) effect estimates and confidence intervals, ideally with a forest plot. 14-21

DISCUSSION
Summary of evidence 24 Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users, and policy makers).

21-22
Limitations 25 Discuss limitations at study and outcome level (e.g., risk of bias), and at review-level (e.g., incomplete retrieval of identified research, reporting bias). 1) Representativeness of the exposed cohort 2) Selection of the non exposed cohort 3) Ascertainment of exposure 4) Demonstration that outcome of interest was not present at start of study 1) Assessment of outcome 2) Was follow-up long enough for outcomes to occur

Reference (Publication year)
1) Comparability of cohorts on the basis of the design or analysis