METHODS: In the current study, we performed quantitative real-time PCR to measure salivary levels of C-reactive protein (CRP) and interleukin-6 (IL-6) in saliva obtained from patients diagnosed with mild COVID-19, in a diabetic group (DG; n = 10) and a non-diabetic group (NDG; n = 13). All participants were diagnosed with periodontitis, while six participants with periodontitis but not diagnosed with COVID-19 were included as controls.
RESULTS: We found increases in salivary total protein levels in both the DG and NDG compared to control patients. In both groups, salivary CRP and IL-6 levels were comparable. Additionally, the levels of salivary CRP were significantly correlated with total proteins, in which a strong and moderate positive correlation was found between DG and NDG, respectively. A linear positive correlation was also noted in the relationship between salivary IL-6 level and total proteins, but the correlation was not significant. Interestingly, the association between salivary CRP and IL-6 levels was positive. However, a moderately significant correlation was only found in COVID-19 patients with diabetes, through which the association was validated by a receiver operating curve.
CONCLUSIONS: These finding suggest that salivary CRP and IL-6 are particularly relevant as potential non-invasive biomarker for predicting diabetes risk in mild cases of COVID-19 accompanied with periodontitis.
DESIGN: Systematic umbrella review of existing meta-analyses.
DATA SOURCES: MEDLINE, PsycINFO, Embase, and the Cochrane Database of Systematic Reviews, as well as manual searches of reference lists from 2009 to June 2023.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Systematic reviews and meta-analyses of cohort, case-control, and/or cross sectional study designs. To evaluate the credibility of evidence, pre-specified evidence classification criteria were applied, graded as convincing ("class I"), highly suggestive ("class II"), suggestive ("class III"), weak ("class IV"), or no evidence ("class V"). The quality of evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) framework, categorised as "high," "moderate," "low," or "very low" quality.
RESULTS: The search identified 45 unique pooled analyses, including 13 dose-response associations and 32 non-dose-response associations (n=9 888 373). Overall, direct associations were found between exposure to ultra-processed foods and 32 (71%) health parameters spanning mortality, cancer, and mental, respiratory, cardiovascular, gastrointestinal, and metabolic health outcomes. Based on the pre-specified evidence classification criteria, convincing evidence (class I) supported direct associations between greater ultra-processed food exposure and higher risks of incident cardiovascular disease related mortality (risk ratio 1.50, 95% confidence interval 1.37 to 1.63; GRADE=very low) and type 2 diabetes (dose-response risk ratio 1.12, 1.11 to 1.13; moderate), as well as higher risks of prevalent anxiety outcomes (odds ratio 1.48, 1.37 to 1.59; low) and combined common mental disorder outcomes (odds ratio 1.53, 1.43 to 1.63; low). Highly suggestive (class II) evidence indicated that greater exposure to ultra-processed foods was directly associated with higher risks of incident all cause mortality (risk ratio 1.21, 1.15 to 1.27; low), heart disease related mortality (hazard ratio 1.66, 1.51 to 1.84; low), type 2 diabetes (odds ratio 1.40, 1.23 to 1.59; very low), and depressive outcomes (hazard ratio 1.22, 1.16 to 1.28; low), together with higher risks of prevalent adverse sleep related outcomes (odds ratio 1.41, 1.24 to 1.61; low), wheezing (risk ratio 1.40, 1.27 to 1.55; low), and obesity (odds ratio 1.55, 1.36 to 1.77; low). Of the remaining 34 pooled analyses, 21 were graded as suggestive or weak strength (class III-IV) and 13 were graded as no evidence (class V). Overall, using the GRADE framework, 22 pooled analyses were rated as low quality, with 19 rated as very low quality and four rated as moderate quality.
CONCLUSIONS: Greater exposure to ultra-processed food was associated with a higher risk of adverse health outcomes, especially cardiometabolic, common mental disorder, and mortality outcomes. These findings provide a rationale to develop and evaluate the effectiveness of using population based and public health measures to target and reduce dietary exposure to ultra-processed foods for improved human health. They also inform and provide support for urgent mechanistic research.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023412732.