Effects of caloric restriction, fasting and circadian alignment on longevity in mice and potential risks and benefits of extrapolation to humans.
Effects of caloric restriction, fasting and circadian alignment on longevity in mice and potential risks and benefits of extrapolation to humans.
Fibrosis is the principle reason for heart failure in diabetes. Regarding the involvement of long non-coding ribonucleic acid zinc finger E-box binding homeobox 1 antisense 1 (ZEB1-AS1) in diabetic myocardial fibrosis, we explored its specific mechanism.
Human cardiac fibroblasts (HCF) were treated with high glucose (HG) and manipulated with plasmid cloning deoxyribonucleic acid 3.1-ZEB1-AS1/microribonucleic acid (miR)-181c-5p mimic/short hairpin RNA specific to sirtuin 1 (sh-SIRT1). ZEB1-AS1, miR-181c-5p expression patterns, cell viability, collagen I and III, α-smooth muscle actin (α-SMA), fibronectin levels and cell migration were assessed by reverse transcription quantitative polymerase chain reaction, cell counting kit-8, western blot and scratch tests. Nuclear/cytosol fractionation assay verified ZEB1-AS1 subcellular localization. The binding sites between ZEB1-AS1 and miR-181c-5p, and between miR-181c-5p and SIRT1 were predicted and verified by Starbase and dual-luciferase assays. The binding of SIRT1 to Yes-associated protein (YAP) and YAP acetylation levels were detected by co-immunoprecipitation. Diabetic mouse models were established. SIRT1, collagen I, collagen III, α-SMA and fibronectin levels, mouse myocardium morphology and collagen deposition were determined by western blot, and hematoxylin–eosin and Masson trichrome staining.
Zinc finger E-box binding homeobox 1 antisense 1 was repressed in HG-induced HCFs. ZEB1-AS1 overexpression inhibited HG-induced HCF excessive proliferation, migration and fibrosis, and diminished collagen I, collagen III, α-SMA and fibronectin protein levels in cells. miR-181c-5p had targeted binding sites with ZEB1-AS1 and SIRT1. SIRT1 silencing/miR-181c-5p overexpression abrogated ZEB1-AS1-inhibited HG-induced HCF proliferation, migration and fibrosis. ZEB1-AS1 suppressed HG-induced HCF fibrosis through SIRT1-mediated YAP deacetylation. ZEB1-AS1 and SIRT1 were repressed in diabetic mice, and miR-181c-5p was promoted. ZEB1-AS1 overexpression improved myocardial fibrosis in diabetic mice, and reduced collagen I, collagen III, α-SMA and fibronectin protein levels in myocardial tissues.
Long non-coding ribonucleic acid ZEB1-AS1 alleviated myocardial fibrosis through the miR-181c-5p–SIRT1–YAP axis in diabetic mice.
Psoriasis is a chronic inflammatory skin disease that is associated with obesity and myocardial infarction. Obesity-induced changes in lipid metabolism promote T helper 17 (Th17) cell differentiation, which in turn promotes chronic inflammation. Th17 cells have central roles in many inflammatory diseases, including psoriasis and atherosclerosis; however, whether treatment of obesity attenuates Th17 cells and chronic inflammatory diseases has been unknown. In this study, we found an increase in Th17 cells in a patient with obesity, type 2 diabetes and psoriasis. Furthermore, weight loss with diet and exercise resulted in a decrease in Th17 cells and improvement of psoriasis. This case supports the hypothesis that obesity leads to an increase in Th17 cells and chronic inflammation of the skin and blood vessel walls, thereby promoting psoriasis and atherosclerosis.
This study aimed to investigate the clinical utility of 3 Screen ICA ELISA in identifying immune-mediated type 1 diabetes in Japanese subjects.
We compared the positivity of 3 Screen ICA were compared with autoantibodies against GAD, IA-2, and ZnT8 in 638 patients with type 1 diabetes and 159 healthy control subjects.
With a cut-off value of 20.0 index, 67.4% of acute-onset type 1 diabetic patients, 71.8% of slowly progressive type 1 diabetic (SPIDDM) patients, and none of the fulminant type 1 diabetic patients showed 3 Screen ICA levels above this threshold. The prevalence of 3 Screen ICA was 14.2% higher in acute-onset type 1 diabetes and 1.6% higher in SPIDDM than in GADA. 3 Screen ICA-positive cases were found in 4.8% of cases of individual autoantibody-negative acute-onset type 1 diabetes and 3.8% of SPIDDM, indicating improved diagnostic sensitivity with the 3 Screen ICA. Among individual autoantibody-negative patients, the sum of each autoantibody level was significantly lower in fulminant type 1 diabetes than in acute onset type 1 diabetes and in SPIDDM (P < 0.0001). Additionally, 84.2% of patients negative for individual autoantibodies but positive for 3 Screen ICA had a sum of individual autoantibody levels of ≥4.7 U/mL. Furthermore, 3 Screen ICA levels were significantly higher in patients with type 1 diabetes with other autoimmune diseases than in those without (P < 0.0001).
Our findings suggest that the 3 Screen ICA ELISA may be a valuable screening tool for Japanese patients with type 1 diabetes, potentially increasing the diagnostic sensitivity and accuracy beyond the existing GADA, IA-2A, and ZnT8A tests.
Substantial variability in demographic and clinical characteristics exists among patients with type 2 diabetes mellitus, which may impact treatment. This post-hoc analysis evaluated the efficacy and safety of imeglimin 1,000 mg twice daily (BID) monotherapy in type 2 diabetes mellitus patients according to demographic and clinical characteristics.
Data were pooled from two placebo-controlled, 24 week, randomized, double-blind studies in adults with type 2 diabetes mellitus. Outcomes (least squares mean [LSM] change in HbA1c from baseline to week 24, and safety) were analyzed according to subgroups based on demographics, clinical characteristics, and comorbidities.
The difference in LSM change in HbA1c from baseline to week 24 was statistically significant for imeglimin vs placebo in all patient subgroups analyzed (P < 0.05 each), including demographics (age, body mass index), clinical characteristics (duration of type 2 diabetes mellitus, chronic kidney disease [CKD] stage, and prior medication use) and comorbidities (hypertension, dyslipidemia, risk of hepatic fibrosis and liver function parameter status). A statistically significant separation from placebo in HbA1c was observed at week 4 and maintained through week 24. No new safety concerns were identified with imeglimin in any patient subpopulations.
The efficacy and safety of imeglimin was demonstrated across patient subgroups, irrespective of baseline demographic and clinical characteristics. Our findings confirm the efficacy and safety of imeglimin across a broad spectrum of patients with type 2 diabetes mellitus.
To investigate whether the COVID-19 pandemic affected behavioral changes and glycemic control in patients with diabetes and to conduct a survey of telemedicine during the pandemic.
In this retrospective study, a total of 2,348 patients were included from 15 medical facilities. Patients were surveyed about their lifestyle changes and attitudes toward telemedicine. Hemoglobin A1c (HbA1c) levels were compared among before (from June 1 to August 31, 2019) and in the first (from June 1 to August 31, 2020) and in the second (from June 1 to August 31, 2021) year of the pandemic. A survey of physician attitudes toward telemedicine was also conducted.
The HbA1c levels were comparable between 2019 (7.27 ± 0.97%), 2020 (7.28 ± 0.92%), and 2021 (7.25 ± 0.94%) without statistical difference between each of those 3 years. Prescriptions for diabetes medications increased during the period. The frequency of eating out was drastically reduced (51.7% in 2019; 30.1% in 2020), and physical activity decreased during the pandemic (48.1% in 2019; 41.4% in 2020; 43.3% in 2021). Both patients and physicians cited increased convenience and reduced risk of infection as their expectations for telemedicine, while the lack of physician–patient interaction and the impossibility of consultation and examination were cited as sources of concern.
Our data suggest that glycemic control did not deteriorate during the COVID-19 pandemic with appropriate intensification of diabetes treatment in patients with diabetes who continued to attend specialized diabetes care facilities, and that patients and physicians shared the same expectations and concerns about telemedicine.
The triglyceride-glucose (TyG) index is a simple and reliable indicator of insulin resistance, and is associated with the development and poor outcomes of cardiovascular disease. Subclinical left ventricular dysfunction (SLVD) is frequently detected in approximately one-third of diabetes patients, but it has not been established whether the TyG index correlates with SLVD. We carried out this research to evaluate the relationship between the TyG index and SLVD in type 2 diabetes mellitus patients.
This was a cross-sectional and observational study of 183 type 2 diabetes mellitus inpatients at Nanjing Drum Tower Hospital, Nanjing, China. The TyG index and homeostasis model assessment 2 estimates for insulin resistance (HOMA2-IR) were calculated from biochemical measurements, and speckle-tracking echocardiography was carried out. According to global longitudinal strain (GLS) by echocardiography, participants were categorized into the SLVD (GLS <18%) group or the non-SLVD (GLS ≥18%) group.
In comparison with non-SLVD participants, SLVD participants had higher insulin resistance, as reflected by elevated TyG and HOMA2-IR indices, as well as a higher body mass index, waist circumference and triglyceride level (P < 0.05 for each). When grouped by TyG index tertiles, an elevated TyG index was correlated with other cardiometabolic risk factors, as well as a decrease in GLS. In the multivariate logistic regression analyses, the TyG index was an independent risk factor for SLVD in type 2 diabetes mellitus patients (odds ratio 2.047, 95% confidence interval 1.07–3.914, P = 0.03), whereas HOMA2-IR was not.
The TyG index is independently associated with SLVD in type 2 diabetes mellitus patients and is a more reliable indicator of SLVD than HOMA2-IR.
Cognitive dysfunction, including mild cognitive impairment and dementia, is increasingly recognized as an important complication of type 2 diabetes mellitus. The aims of the preset study was to investigate the cognitive protection of incretin-based therapies, including glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors, in patients with type 2 diabetes mellitus.
PubMed, EMBASE, Cochrane library, Web of Science and PsycINFO were searched from the inception through 17 January 2023 for randomized controlled trials and cohort studies on the association between incretin-based therapies and cognitive function. A total of 15 studies were finally included in our systematic review, and eight of which were incorporated into our meta-analysis.
Pooled results showed that the Mini-Mental State Examination score in incretin-based therapy groups was increased by 1.20 compared with the control group (weighted mean difference 1.20, 95% confidence interval 0.39–2.01). The results of eight studies assessed by the Newcastle Ottawa Quality Assessment Scale and the Cochrane Collaboration's tool, and the quality of the eight studies were at a relatively high level. Egger's regression did not show significant publication bias.
Current evidence shows that incretin-based therapies might be more effective, when compared with the other hypoglycemic drugs, for cognitive improvement in patients with type 2 diabetes mellitus.
Although the association between uric acid levels and adverse pregnancy outcomes has been investigated, the effects of higher uric acid levels on the risk of gestational diabetes mellitus (GDM) have yet to be established. Therefore, this systematic review and meta-analysis aimed to investigate the relationship between uric acid levels during pregnancy and the risk of GDM.
PubMed/Medline, Scopus and Web of Science databases were searched up to April 2022 for relevant observational studies. A random effects model was used to estimate pooled odds ratios (OR) and 95% confidence intervals (95% CI). To assess the heterogeneity of included studies, the I2 index was used.
Among the initial 262 studies that were recognized from the databases search, 23 studies including 105,380 participants were eligible. Pooled analysis showed that higher uric acid levels significantly affected the risk of GDM (OR 2.58, 95% CI 1.89–3.52, I2 = 90.8%, P < 0.001). Subgroup analyses based on the gestational week showed that higher uric acid levels before the 20th week of gestation were significantly associated with the risk of GDM (OR 3.26, 95% CI 2.26–4.71, I2 = 89.3%, P < 0.001). Based on the meta-regression analysis, uric acid levels and odds of GDM were significantly correlated with the participants' age, and it was more significant in younger pregnant women.
This study showed a positive association between uric acid levels and the risk of GDM. Also, our results indicate that measuring uric acid levels before 20 weeks of gestation can potentially predict GDM, especially in younger women.
To investigate the relationship between the metabolic score for insulin resistance (METS-IR) index and major adverse cardiac events (MACEs) and to compare its ability to predict MACEs with other IR indices including homeostatic model assessment for IR (HOMA-IR) and triglyceride glucose (TyG) index-related parameters.
We conducted a cohort study enrolling 7,291 participants aged ≥40 years. Binary logistic regression and restricted cubic splines were performed to determine the association between METS-IR and MACEs, and the receiver operating curve (ROC) was utilized to compare the predictive abilities of IR indices and to determine the optimal cut-off points.
There were 348 (4.8%) cases of MACEs during a median follow-up of 3.8 years. Compared with participants with a METS-IR in the lowest quartile, the multivariate-adjusted RRs and 95% CIs for participants with a METS-IR in the highest quartile were 1.47 (1.05–2.77) in all participants, 1.42 (1.18–2.54) for individuals without diabetes, and 1.75 (1.11–6.46) for individuals with diabetes. Significant interactions were found between the METS-IR and the risk of MACEs by sex in all participants and by age and sex in individuals without diabetes (all P values for interaction < 0.05). In the ROC analysis, the METS-IR had a higher AUC value than other indices for predicting MACEs in individuals with diabetes and had a comparable or higher AUC than other indices for individuals without diabetes.
The METS-IR can be an effective clinical indicator for identifying MACEs, as it had superior predictive power when compared with other IR indices in individuals with diabetes.
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