Temporal response characterization across individual multiomics profiles of prediabetic and diabetic subjects

Longitudinal deep multi-omics profiling, which combines biomolecular, physiological, environmental and clinical measures data, shows great promise for precision health. However, integrating and understanding the complexity of such data remains a big challenge. Here we propose a bottom-up framework starting from assessing single individuals' multi-omics time series, and using individual responses to assess multi-individual grouping based directly on similarity of their longitudinal deep multi-omics profiles. We applied our method to individual profiles from a study profiling longitudinal responses in type 2 diabetes mellitus. After generating periodograms for individual subject omics signals, we constructed within-person omics networks and analyzed personal-level immune changes. The results showed that our method identified both individual-level responses to immune perturbation, and the clusters of individuals that have similar behaviors in immune response and which was associated to measures of their diabetic status.

High Fasting Blood Glucose Level With Unknown Prior History of Diabetes Is Associated With High Risk of Severe Adverse COVID-19 Outcome

BackgroundWe aimed to understand how glycaemic levels among COVID-19 patients impact their disease progression and clinical complications.MethodsWe enrolled 2,366 COVID-19 patients from Huoshenshan hospital in Wuhan. We stratified the COVID-19 patients into four subgroups by current fasting blood glucose (FBG) levels and their awareness of prior diabetic status, including patients with FBG<6.1mmol/L with no history of diabetes (group 1), patients with FBG<6.1mmol/L with a history of diabetes diagnosed (group 2), patients with FBG≥6.1mmol/L with no history of diabetes (group 3) and patients with FBG≥6.1mmol/L with a history of diabetes diagnosed (group 4). A multivariate cause-specific Cox proportional hazard model was used to assess the associations between FBG levels or prior diabetic status and clinical adversities in COVID-19 patients.ResultsCOVID-19 patients with higher FBG and unknown diabetes in the past (group 3) are more likely to progress to the severe or critical stage than patients in other groups (severe: 38.46% vs 23.46%-30.70%; critical 7.69% vs 0.61%-3.96%). These patients also have the highest abnormal level of inflammatory parameters, complications, and clinical adversities among all four groups (all p<0.05). On day 21 of hospitalisation, group 3 had a significantly higher risk of ICU admission [14.1% (9.6%-18.6%)] than group 4 [7.0% (3.7%-10.3%)], group 2 [4.0% (0.2%-7.8%)] and group 1 [2.1% (1.4%-2.8%)], (P<0.001). Compared with group 1 who had low FBG, group 3 demonstrated 5 times higher risk of ICU admission events during hospitalisation (HR=5.38, 3.46-8.35, P<0.001), while group 4, where the patients had high FBG and prior diabetes diagnosed, also showed a significantly higher risk (HR=1.99, 1.12-3.52, P=0.019), but to a much lesser extent than in group 3.ConclusionOur study shows that COVID-19 patients with current high FBG levels but unaware of pre-existing diabetes, or possibly new onset diabetes as a result of COVID-19 infection, have a higher risk of more severe adverse outcomes than those aware of prior diagnosis of diabetes and those with low current FBG levels.

Factors Related to Early Marginal Bone Loss in Dental Implants—A Multicentre Observational Clinical Study

This study evaluated the effect of clinical and patient-related factors on marginal bone loss. The sample was composed of individuals who were treated at two dental schools in southern Brazil. The variables evaluated were divided into individual (age, sex, diabetes, hypertension and antihypertensive use), and implant levels (arch, position, brand, protection, torque, time). After implant installation and following the second stage, periapical radiographs were obtained to measure the distance between the peri-implant bone crest and implant platform. Measurements were performed using ImageJ software. Data were analyzed using linear and Poisson multilevel regression. Fifty-eight patients with 113 implants were evaluated. The mean marginal bone loss was 0.45 ± 0.48 mm. Considering the linear multivariate model, age, diabetes, torque and time between surgery and reopening were found to be significant (p < 0.05). In the dichotomous model (bone loss <0.2 mm and ≥0.2 mm), only high torques resulted in higher marginal bone loss (p = 0.033). Marginal bone loss occurred before the second surgical stage and was greater in implants with high torque. Torque below 20 N, reopening performed after six months, diabetic status and young age all resulted in higher marginal bone loss, but these values are probably not clinically significant. These variables must be better explored in future studies.

A Serum Marker for Early Pancreatic Cancer with a Possible Link to Diabetes

Background Pancreatic cancer (PC) has a grim prognosis, and an early diagnostic biomarker has been highly desired. The molecular link between diabetes and PC has not been well-established. Methods Bioinformatics screening was performed for a serum PC marker. Experiments in cell lines (5 PC and 1 normal cell lines), mouse models, and human tissue staining (37 PC and 10 normal cases) were performed to test asprosin production from PC. Asprosin’s diagnostic performance was tested with serums from multi-center cohorts (347 PC, 209 normal, and 55 additional diabetic subjects) and evaluated according to PC status, stages, and diabetic status, which was compared with that of CA19-9. Results Asprosin, a diabetes-related hormone, was found from the bioinformatics screening, and its production from PC was confirmed. Serum asprosin levels from multi-center cohorts yielded an age-adjusted diagnostic AUC of 0.987 (95% confidence interval [CI] = 0.961 to 0.997), superior to that of CA19-9 (AUC = 0.876, 95% CI = 0.847 to 0.905), and a cut-off of 7.18 ng/mL, at which the validation set exhibited a sensitivity of 0.957 and a specificity of 0.924. Importantly, the performance was maintained in early-stage and non-metastatic PC, consistent with the tissue staining. A slightly lower performance against additional diabetic patients (n = 55) was restored by combining asprosin and CA19-9 (AUC = 0.985, 95% CI = 0.975 to 0.995). Conclusion Asprosin is presented as an early-stage PC serum marker that may provide clues for PC-induced diabetes. Larger prospective clinical studies are warranted to solidify its utility.

Eight-Year Longitudinal Associations of the Onset of Prediabetes and Diabetes with Cognitive Function Decline Among Chinese Adults Aged 45 Years or Older

Background With the population aging, diabetes and cognitive function decline are increasingly common among older adults worldwide. However, the evidence about the effects and mechanism of prediabetes and diabetes on cognitive function is still limited. The purposes of this longitudinal study were to estimate the longitudinal associations of the onset of prediabetes and diabetes status with cognitive function among Chinese adults aged 45 years or older during an 8-year period; to estimate the clinical risk factors associated with cognitive function among patients with prediabetes and diabetes. Methods Participants were enrolled between 2011 and 2012, and followed up between 2018 and 2019 in the China Health and Retirement Longitudinal Study. In this study, we focused on newly diagnosed diabetic status, and those diagnosed with diabetes before or not providing fasting blood samples were excluded. Diabetic status was assessed according to the 2010 American Diabetes Association (ADA) guidelines. The general cognitive function, demographic characteristics, and clinical and biochemical factors were also measured. Results At baseline, 849 (21.3%) participants were first diagnosed with prediabetes, and 444 (11.1%) were diabetes patients. After adjusting for age, gender, marital status, education level, ever smoking, ever drinking, self-comment about health, hypertension, dyslipidemia, depressive symptoms, cognitive function, and clinical and biochemical measurements at baseline, diabetes status was a significant risk factor for subsequent cognitive decline (unstandardized β estimate=-0.47, 95% CI=-0.91~-0.04). Further stratification analyses found that only triglyceride concentrations were negatively associated with cognitive function among prediabetes patients (unstandardized β estimate=-0.004, 95% CI=-0.007~-0.001), and only creatine reactive protein was significantly associated with cognitive decline among diabetes patients (unstandardized β estimate=-0.065, 95% CI=-0.122~-0.009). Conclusions There is a positive longitudinal association between the onset of diabetes and cognitive decline among middle-aged and elderly Chinese. The management of triglycerides through lifestyle modification for prediabetes and specific adjunctive anti-inflammatory therapy for diabetes could benefit cognitive performance.

The Aneugenicity of Ketone Bodies in Colon Epithelial Cells Is Mediated by Microtubule Hyperacetylation and Is Blocked by Resveratrol

Diabetes mellitus (DM) is considered to be associated with an increased risk of colorectal cancer. Recent studies have also revealed that tubulin hyperacetylation is caused by a diabetic status and we have reported previously that, under microtubule hyperacetylation, a microtubule severing protein, katanin-like (KL) 1, is upregulated and contributes to tumorigenesis. To further explore this phenomenon, we tested the effects of the ketone bodies, acetoacetate and β-hydroxybutyrate, in colon and fibroblast cells. Both induced microtubule hyperacetylation that responded differently to a histone deacetylase 3 knockdown. These two ketone bodies also generated intracellular reactive oxygen species (ROS) and hyperacetylation was commonly inhibited by ROS inhibitors. In a human fibroblast-based microtubule sensitivity test, only the KL1 human katanin family member showed activation by both ketone bodies. In primary cultured colon epithelial cells, these ketone bodies reduced the tau protein level and induced KL1- and α-tubulin acetyltransferase 1 (ATAT1)-dependent micronucleation. Resveratrol, known for its tumor preventive and tubulin deacetylation effects, inhibited this micronucleation. Our current data thus suggest that the microtubule hyperacetylation induced by ketone bodies may be a causal factor linking DM to colorectal carcinogenesis and may also represent an adverse effect of them that needs to be controlled if they are used as therapeutics.