Journal of Diabetes Investigation最新文献

Aims/introduction: Ginsenoside Rg1 is an active ingredient found mainly in ginseng that has a variety of pharmacological effects, such as hypoglycemic, antioxidant, and anti-inflammatory effects, and it inhibits vascular formation. In this study, we explored the effect of ginsenoside Rg1 on angiogenesis in diabetic retinopathy (DR) on the basis of its ability to inhibit angiogenesis and the specific molecular mechanism involved.

Materials and methods: We induced an in vivo model of diabetes by injection of 55 mg/kg streptozotocin (STZ) into the abdominal cavity of SD rats daily for 3 days. Moreover, human retinal microvascular endothelial cells (HRMECs) were treated with 30 mmol/L glucose for 24 h to construct a high-glucose (HG) cell model in vitro. The expression of related genes and proteins was detected by RT-qPCR and Western blotting. HRMECs and retinal damage were evaluated by CCK-8, scratch, tube formation assays, and HE staining.

Results: In this study, Rg1 inhibited HG-induced angiogenesis of HRMECs and inhibited STZ-induced vascular leakage and capillary degeneration in vivo, alleviating the progression of DR. Mechanistically, Rg1 upregulated the expression of FBXW7 by inhibiting miR-100-3p, thereby promoting the ubiquitination and degradation of c-MYC, inhibiting HG-induced HRMECs proliferation, migration, invasion, and angiogenesis, and improving the development of DR.

Conclusions: Overall, our study demonstrates that ginsenoside Rg1 can inhibit DR angiogenesis via the miR-100-3p/FBXW7/c-MYC molecular axis. These findings provide a novel idea for the treatment of DR and provide an experimental basis for further research on the application of Rg1 in the treatment of DR.

Aims/introduction: To investigate the predictive value of the biliverdin reductase-A (BVR-A) and the homeostasis model assessment for insulin resistance (HOMA-IR) on mild cognitive impairment (MCI) in patients with type 2 diabetes mellitus, and to establish a nomogram model.

Materials and methods: This study included 140 patients with type 2 diabetes mellitus. Based on Montreal Cognitive Assessment (MoCA) scores, participants were categorized into the normal cognitive function (T2DM-NCF) group (65 cases) and the mild cognitive impairment (T2DM-MCI) group (75 cases). Multivariate logistic regression analysis was performed to identify the factors associated with MCI in patients with type 2 diabetes mellitus. A nomogram prediction model was developed using R software for the selected factors, and its predictability and accuracy were verified.

Results: Compared with the T2DM-NCF group, subjects with MCI were older, had a longer duration of diabetes, higher HOMA-IR, lower BVR-A, lower cognitive scores, and lower education levels (all P < 0.05). Multivariate logistic regression analysis showed that duration of diabetes (OR = 1.407, 95% CI: 1.163-1.701), HOMA-IR (OR = 1.741, 95% CI: 1.197-2.53), and BVR-A (OR = 0.528, 95% CI: 0.392-0.712) were significantly associated with the development of MCI in patients with type 2 diabetes mellitus. The C-index of the nomogram was 0.863 (95% CI: 0.752-0.937).

Conclusions: Our findings suggest that BVR-A and HOMA-IR are significantly associated with the development of MCI in patients with type 2 diabetes mellitus. The nomogram incorporating BVR-A and HOMA-IR aids in predicting the risk of developing MCI in these patients.

Aim: Subclinical diabetic peripheral neuropathy (sDPN) in patients with type 2 diabetes mellitus is insidious, but has been complicated with neurological damage. The aim of this study was to investigate the association between brachial-ankle pulse wave velocity (baPWV) and sDPN in patients with type 2 diabetes mellitus, and to provide reference for clinical prevention and treatment of sDPN.

Materials and methods: From November 2021 to May 2024, a total of 711 type 2 diabetes mellitus patients without symptoms and signs of peripheral nerve damage were recruited. According to whether the nerve conduction velocity (NCV) was abnormal or not, they were divided into the sDPN group and the non-diabetic peripheral neuropathy (non-DPN) group. Logistic regression model, restricted cubic spline (RCS) analysis and subgroup analysis were used to evaluate the correlation between baPWV and sDPN.

Results: A total of 204 (28.69%) of the 711 participants were diagnosed with sDPN. Both amplitude and conduction velocity were negatively correlated with baPWV. In the fully adjusted model, elevated baPWV levels were significantly associated with an increased sDPN risk, with odds ratio (OR) = 1.084, 95% confidence interval (CI): (1.023, 1.148), P = 0.006. RCS showed a linear association between baPWV and sDPN. Subgroup analysis further confirmed that the positive association between baPWV and sDPN was consistent and robust across groups.

Conclusions: Our study indicates a pronounced link between higher baPWV and increased risk of sDPN among type 2 diabetes mellitus patients without symptoms and signs of peripheral nerve damage. These findings underscore the importance of baPWV for early identification of sDPN.

Aims/introduction: As the prevalence of diabetes increases with age, the number of elderly patients with diabetes in Japan, a super-aged society, continues to increase. We conducted a survey to investigate the extent to which outpatients with diabetes recognize dementia as a complication of diabetes.

Materials and methods: A questionnaire was distributed among 777 patients with diabetes to investigate their awareness of dementia and its risk factors. Among these, the Mini-Mental State Examination was also administered to patients over 65 years of age who wished to undergo a cognitive function test among those who participated in the questionnaire survey to examine the factors leading to a decline in cognitive function.

Results: 458 patients selected poor blood glucose control and 176 selected hypoglycemia as the condition that rendered patients susceptible to dementia. Regarding the risk factors for suspected cognitive decline, the risk increased in the following order: old age; lack of knowledge about dementia; and treatment with diet/exercise, oral hypoglycemic agents/Glucagon-like peptide-1, and insulin. Regarding the relationship between cognitive decline and blood glucose control, the risk of suspected cognitive decline increased in the following order: within the standard value, above and below the standard values, in terms of the level of glycated hemoglobin set in "Blood Glucose Control Target for Elderly Diabetes" defined by the Japan Geriatrics Society and the Japan Diabetes Society.

Conclusions: When examining and treating diabetes, it may be pertinent to instruct older adults on target HbA1c levels based on their condition.

Aims/introduction: The mechanisms of the renoprotective effects of sodium-glucose cotransporter 2 inhibitors are unknown. This study aimed to explore the effect and mechanism of tofogliflozin on urinary albumin by administration, withdrawal, and re-administration.

Materials and methods: Individuals with type 2 diabetes mellitus and stage 2 or 3 diabetic nephropathy were enrolled. Tofogliflozin was administered for 24 weeks, withdrawn for 12 weeks (withdrawal period), and re-administered for 24 weeks. The primary endpoint was the change in urinary albumin/creatinine ratio (UACR). The secondary endpoints included hemoglobin A1c (HbA1c), hepatic biomarkers, lipid profiles, physical examinations, and blood counts.

Results: A total of 47 individuals were enrolled. UACR significantly decreased throughout the observation period. It also significantly decreased, increased, and again decreased during the period of the 1st administration, withdrawal, and re-administration, respectively. HbA1c, body weight, waist circumference, and systolic blood pressure also showed the same tendency. Aspartate aminotransferase and alanine aminotransferase significantly decreased throughout the observation period, but did not increase during the withdrawal period.

Conclusions: Urinary albumin improved during the administration of tofogliflozin and worsened during its withdrawal, suggesting the reversibility of its renoprotective effect. The administration of tofogliflozin should be continued to avoid the reversal of glycemic control, renoprotective effects, and other beneficial effects.

Background: Executive functions (EFs) are important for the Type 1 diabetes mellitus (T1DM) self-care perspective. This study aimed to investigate whether patients with T1DM have poorer EFs than healthy controls (HCs) and whether there are differences in EFs between childhood-onset and adult-onset T1DM.

Methods: This study included 94, 110, and 100 participants with childhood-onset and adult-onset T1DM and HCs, respectively. All participants completed the Wisconsin Card Sorting Test to assess EFs. The Chinese version of the WAIS and BDI-II were performed to determine IQ and emotion in all participants.

Results: The childhood-onset group made lower scores of WCST total errors (P = 0.015), perseverative errors (P = 0.038) than the HC group, and the adult-onset group made lower scores of WCST total errors (P = 0.025) than the HC group. In the diabetes group, after controlling diabetes duration, the childhood-onset group made significantly higher scores of WCST total errors (P = 0.040), perseverative errors (P = 0.038), and non-perseverative errors (P = 0.013). In the childhood-onset group, perseverative errors were significantly associated with duration of T1DM (β = -0.24, t = -2.34, P = 0.021), and the history of severe hypoglycemia affects the non-perseverative errors(β = -0.26, t = -2.55, P = 0.013).

Conclusions: T1DM is associated with EF decrements, and there are differences in EFs between childhood-onset and adult-onset T1DM. These findings indicate that we should consider detecting and intervening in EF deficits in the T1DM population according to the age of onset.

Aims/introduction: Phosphoglycerate dehydrogenase (PHGDH), which controls serine synthesis, has been linked to retinal disease. However, there are no clues about its involvement in the diabetic retinopathy (DR) progression. Therefore, we aimed to investigate the relationship between PHGDH, serine synthesis, and DR and their underlying molecular mechanisms.

Method: Differentially expressed genes in DR were screened using bioinformatics tools. DR mice were induced, and retinal histopathology was observed in mice. Overexpression of PHGDH was induced in the DR mice to measure l-serine, ROS, and MDA content in the retinas of DR mice. ARPE-19 cells were transfected with overexpression of PHGDH and exposed to high glucose to induce a DR in vitro model, and cell viability and apoptosis assays, serine content, and oxidative stress factor measurement were conducted. The transcriptional regulation of PHGDH by YY2 was explored by ChIP and dual-luciferase reporter assays. Finally, the combined role of YY2 and PHGDH in regulating serine synthesis, oxidative stress, and ferroptosis was investigated.

Results: PHGDH expression was reduced in DR mice, and overexpression of PHGDH alleviated DR progression by promoting serine synthesis and attenuating oxidative stress. YY2 bound to the promoter of PHGDH and mediated its transcriptional repression. YY2-mediated transcriptional repression of PHGDH caused disturbances in serine synthesis, leading to oxidative stress-triggered ferroptosis.

Conclusions: Our data prove that YY2 plays a vital role in modulating PHGDH expression, impairing serine synthesis, and expediting oxidative stress and ferroptosis.

Aims: Current metabolic syndrome (mets) criteria often lack consideration for age and gender differences. This study introduces the mets-Z score, a novel tool designed to enhance mets assessment and improve long-term outcome predictions.

Materials and methods: The mets-Z score was developed using principal component analysis (PCA) to weight five mets indicators-waist circumference, blood glucose, blood pressure, high-density lipoprotein (HDL) cholesterol, and triglycerides-by gender and age. Data from 188,739 Taiwan Biobank participants, stratified by gender and age groups (20-39, 40-54, 55-64, 65+ years), were analyzed. Predictive performance for type 2 diabetes mellitus onset was assessed over a 4- to 5-year follow-up.

Results: The mets-Z score achieved superior accuracy in predicting type 2 diabetes mellitus onset, with an AUC of 0.76 in men and 0.80 in women, significantly outperforming conventional indices (P < 0.0001).

Conclusions: By integrating age- and gender-specific variations, the mets-Z score provides a more personalized and precise tool for assessing metabolic and diabetes risk, surpassing existing methods. The tool is available for public use at http://bioinfolab.nhri.edu.tw/metsz/, supporting broader applications in precision medicine.

Aim: To estimate the efficacy and safety of the basal-bolus and premixed insulin as intensification regimens in patients with type 2 diabetes mellitus (T2DM).

Methods: A comprehensive search of online databases was performed until December 2022 to identify randomized controlled trials (RCTs) comparing premixed insulin versus basal-bolus regimen with treat-to-target intention. The Cochrane ROB-2 tool and GRADE approach were used for quality assessment and certainty of the evidence, respectively. Pooled weighted mean difference (WMD) and odds ratio (OR) were calculated using random-effects meta-analysis models.

Results: Eighteen RCTs were included in the meta-analysis, and 66% had a low risk of bias. We found no significant difference between the two regimens regarding HbA1c reduction (WMD: 0.03% [-0.05%, 0.10%]). The basal-bolus regimen improved fasting plasma glucose (FPG) more than the premixed regimen (WMD: 6.35 mg/dL [0.31, 12.39]). Both had similar effects on weight gain. The odds of developing overall, nocturnal, and severe hypoglycemia were comparable (pooled OR: 0.9, 1.02, and 1.00, respectively) with no heterogeneity. Findings of the model were robust. The certainty of the evidence was moderate to high for all outcomes except FPG.

Conclusions: Two regimens are clinically comparable. Patient preference should be considered when adopting an individualized approach in a real-world setting.

Aims/introduction: It is important to develop valid tools to evaluate hypoglycemia perception such as the Hypoglycemia Awareness Questionnaire (HypoA-Q) in patients with Type 2 Diabetes (T2D). The aim of the study is to validate the HypoA-Q in patients with T2D treated with insulin using item response theory.

Materials and methods: Individuals with T2D treated with insulin were included by non-random convenience sampling. A partial credit model was used for validation using item response theory, infit, and outfit statistics were calculated, person-item map and item characteristic curves were plotted, and differential item functioning was assessed.

Results: The study included 502 participants, the mean age at diagnosis of diabetes was 47.8 ± 13.9 years, the median time with the diagnosis was 15 years (IQR: 9-22), and the mean HbA1c 71 ± 27.3 mmol/mL (8.6 ± 2.5%), 48.6% had Glomerular Filtration Rate >60 mL/min/min². Item fit was found with items covering the full range of the construct of the participant population, although response options could be simplified. The person-item map showed that the scale covers a wide range of the construct and that the scale has items to measure these different levels. Item bias was not evident when comparing subgroups by age, sex and treatment.

Conclusions: The HypoA-Q is a valid measure for assessing hypoglycemia awareness in insulin-treated T2D patients because it has items that fit the measurement process, measures a wide range of awareness, and is free of biases related to gender, age, treatment, and duration of diabetes.