To explore whether non-high-density-lipoprotein cholesterol (non-HDL-c) is associated with depression, a total of 26 819 Canadians aged 45–85 from the Canadian Longitudinal Study on Aging (CLSA) were included in analysis. Non-HDL-c, the difference between total-c and HDL-c, was categorized into five levels, i.e., <2.6, 2.6 to <3.7, 3.7 to <4.8, 4.8 to 5.7, and ≥5.7 mmol/L. History of clinical depression was collected by questionnaire at an in-home interview, and current potential depression status was determined by CES-D10 (Center for Epidemiological Studies Depression Scale 10 questions version) score, i.e., ≥10 vs. <10. Logistic continuation ratio model for ordinal data was used to estimate the odds of being at or above a higher non-HDL-c category for depression status. Compared with those without clinical depression history and currently undepressed, the adjusted odds ratios (95% CI) were 1.09 (1.02, 1.17) for those without clinical depression history but currently depressed, 1.05 (0.98, 1.12) for those had clinical depression history but currently undepressed, and 1.21 (1.10, 1.32) for those had clinical depression history and currently depressed. The average of non-HDL-c for four depression groups were 3.64, 3.71, 3.69, and 3.82 mmol/L, respectively, and group 4 was statistically higher than others ( p < 0.001). In conclusion, people with both current depression and a history clinical depression are at an increased risk of having high level of non-HDL-c.

Background: Cancer is a growing public health challenge. Innovative approaches to prevent the future burden of cancer are needed. Diabetes medications may help to decrease the risk of cancers, however, a better understanding of relationships by cancer site and diabetes medication class are essential to guide future clinical trials. However, there is not adequate knowledge synthesis on different types of diabetes medications and cancer types. We aim to provide an integrated view of diabetes medications’ role and site-specific cancers.Methods: This systematic review will include observational studies (cohort, nested case-control, case-cohort, and case-control) and randomized controlled trials in human adults in which the effect of diabetes medication use on breast, lung, colorectal, prostate, liver, and pancreatic cancers was evaluated. The former four are among the most common cancer types, while liver and pancreatic cancer are of interest due to the biological roles of the liver and pancreas in blood glucose regulation. MEDLINE, Embase, Web of Science Core Collection, and Cochrane CENTRAL will be searched using a comprehensive and sensitive search strategy. The reference list of identified studies and relevant systematic reviews will be manually screened. Two reviewers will independently screen studies, extract data, and assess quality. Random-effect models will be employed to obtain overall pooled estimates of associations and corresponding 95% confidence intervals (CIs). This systematic review and meta-analyses will be reported following the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Results will be reported as specified by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.Discussion: Findings of this review will help to clarify relationships between diabetes medication and cancer, which is critical for future efforts to improve cancer prevention. Further, challenges and limitations identified in this review will foster opportunities to refine design and analysis procedures in future studies. Systematic review registration: The systematic review protocol was registered on Open Science Framework (https://osf.io/frg5z) and on PROSPERO (registration number CRD42021239348).