Journal of Diabetes Investigation最新文献

Introduction: The early detection of high-risk individuals is crucial to delay and reduce the incidence of type 2 diabetes. In this study, we aimed to explore the performance of a novel subgroup-specific biomarker strategy in the prediction of incident diabetes.

Materials and methods: In the Taiwan Lifestyle Cohort Study, adult subjects without diabetes were included and followed for the incidence of diabetes in 2006-2019. The biomarkers measured included blood secretogranin III (SCG3), vascular adhesion protein-1 (VAP-1), fibrinogen-like protein 1 (FGL1), angiopoietin-like protein 6 (ANGPTL6), and angiopoietin-like protein 4 (ANGPTL4).

Results: Among the 1,287 subjects, 12.2% developed diabetes during a 6 year follow-up. Blood VAP-1 was significantly associated with incident diabetes in the overall population (HR = 0.724, P < 0.05), participants under 65 years old (HR = 0.685, P < 0.05), those with a BMI of ≥24 kg/m² (HR = 0.673, P < 0.05), and females (HR = 0.635, P < 0.05). Blood ANGPTL6 was significantly correlated with incident diabetes in participants aged 65 and older (HR = 0.314, P < 0.05), and blood SCG3 was associated with incident diabetes in those with a BMI of <24 kg/m² (HR = 1.296, P < 0.05). Two subgroup-specific biomarker strategies were developed. The gender and BMI-specific biomarker strategy, using traditional risk factors and blood SCG3 or VAP-1 in different subgroups, could improve prediction performance, especially the specificity and positive prediction value, compared with the whole-population strategy using only traditional risk factors or traditional risk factors plus blood VAP-1.

Conclusion: Gender- and BMI-specific biomarker strategy can improve the prediction of incident diabetes. A subgroup-specific biomarker strategy is a novel approach in the prediction of incident diabetes.

Background and aims: To prevent end-stage renal disease caused by diabetic kidney disease, we created a predictive model for high-risk patients using machine learning.

Methods and results: The reference point was the time at which each patient's estimated glomerular filtration rate (eGFR) first fell below 60 mL/min/1.73 m². The input period spanned the reference point to 1 year prior. The primary endpoint was a 50% decrease in eGFR from the mean of the input period over the 3 year evaluation period. We created predictive models for patients' primary endpoints using time series data of various variables over the input period. Among 2,533 total patients, 1,409 had reference points, 31 had records for their input and evaluation periods and had reached their primary endpoints, and 317 patients had not. The area under the curve (AUC) of the predictive model peaked (0.81) when the minimum eGFR, the difference between maximum and minimum eGFR, and both maximum and minimum urinary protein values were included in the features.

Conclusion: The accuracy of prognosis prediction can be improved by considering the variable components of urinary protein and eGFR levels. This model will allow us to identify patients whose renal functions are relatively preserved with eGFR of more than 60 mL/min/1.73 m² and are likely to benefit clinically from immediate treatment intensification.

Glucagon-like peptide-1 (GLP-1) receptor agonists are antidiabetic drugs that possess a suppressive effect on the progression of atherosclerosis, and it has been thought that their anti-inflammatory effect is involved in their effect, but the detailed mechanism was unknown. Recently, Ben Nasr and colleagues have proposed easily understood mechanism for the anti-inflammatory effect of GLP-1 receptor agonists. They discovered that some normal T cells express GLP-1 receptors on their cell membranes and showed that GLP-1 has an inhibitory effect on T-cell function.

Insulin treatment should be introduced in patients with slowly progressive type 1 diabetes (SPIDDM; definite), according to the revised diagnostic criteria of SPIDDM (2023). In contrast, SPIDDM (probable) patients are in a non-insulin-dependent state; therefore, a more flexible treatment can be considered, although sulfonylurea agents should be avoided. Insulin treatment has been shown to maintain endogenous insulin secretion capacity in SPIDDM (probable); however, this does not mean that all SPIDDM (probable) patients should use insulin from the early phase. Dipeptidyl peptidase-4 inhibitors and biguanides might be the treatment of choice for SPIDDM (probable), but no evidence exists for other hypoglycemic agents. In any case, careful monitoring of the endogenous insulin secretion capacity should be carried out, and if a decrease in insulin secretion capacity is suspected, a change in treatment should be considered to prevent progression to an insulin-dependent state.

Aims/introduction: We investigated the association between the ankle reflex and the estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes.

Materials and methods: This was a single-center, retrospective, observational cohort study. A total of 1,387 patients who underwent an ankle reflex examination between January 2005 and December 2015 were included in the analysis for the primary outcome. The findings of the ankle reflex examination were classified into three groups: normal, decreased, or absent. The primary outcome was defined as the incidence of a 40% loss of eGFR from baseline. A survival time analysis using the Kaplan-Meier method and a regression analysis using a Cox proportional hazards model were conducted to evaluate the association between the ankle reflex test results and loss of eGFR.

Results: The ankle reflex test results were as follows: normal, n = 678 (48.9%); decreased, n = 270 (19.5%); and absent, n = 439 (31.6%) patients. The median follow-up period was 5.6 years in the observational period. In the univariate regression analysis, decreased and absent ankle reflexes were significantly associated with loss of eGFR. Moreover, decreased ankle reflex (hazard ratio: 1.83, 95% confidence interval: 1.16-2.87) and absent ankle reflex (hazard ratio: 2.57, 95% confidence interval: 1.76-3.76) were independently associated with loss of eGFR after adjusting for prognostic risk factors.

Conclusions: Decreased and absent ankle reflexes are closely and independently associated with loss of eGFR in patients with type 2 diabetes.

Aims/introduction: We evaluated the effect of the MiniMed™ 770G, an insulin pump using hybrid closed-loop technology, on blood glucose management and quality of life in Japanese people with type 1 diabetes.

Materials and methods: This was a 52-week, prospective, observational study. Fifty Japanese people with type 1 diabetes switched from the MiniMed™ 640G to 770G, and we analyzed the continuous glucose monitoring data of 24 subjects who used auto mode throughout the study. We also analyzed the scores of the Diabetes Therapy-Related Quality of Life questionnaire completed by 26 auto-mode users before and after the treatment change.

Results: The baseline time in range 70-180 mg/dL was 67.3 (54.8-78.4)%, with a significant improvement beginning 8 weeks after the switch and lasting until 52 weeks. The baseline time below range <70 mg/dL was 1.9 (0.6-3.6)%, with a significant increase at week 8; however, the mean value was less than 4% throughout the study period. On the other hand, the number of blood glucose measurements significantly increased. While there was no significant difference in the overall change in the total Diabetes Therapy-Related Quality of Life score, there was a significant decrease in the treatment satisfaction score.

Conclusions: Use of the MiniMed™ 770G improved continuous glucose monitoring metrics. However, treatment satisfaction decreased, probably due to the increased frequency of blood glucose monitoring necessary to maintain auto mode.

Objective: This study aimed to assess the correlation between hip circumference (HC) and the risk of cardiovascular disease (CVD) and type 2 diabetes mellitus using Mendelian randomization (MR) to overcome observational study limitations.

Design: MR analysis utilized genetic variation from the MR Base in a two-sample analysis. Three methods were employed: MR-Egger regression, weighted median estimator, and inverse variance weighting (IVW).

Setting: Data was acquired from MR Base, a platform summarizing genome-wide association study (GWAS) data for MR research.

Main outcome measures: Publicly available summary statistics datasets from GWAS meta-analyses were used, with HC and HC adjusted for body mass index (BMI) as exposures. Data for CVD and type 2 diabetes mellitus were obtained as outcomes.

Results: Results indicated a positive causal relationship between HC and CVD (IVW: P = 1.84e-07, OR: 1.37, 95% CI: 1.22-1.54) as well as type 2 diabetes mellitus (IVW: P = 0.04, OR: 1.62, 95% CI: 1.02-2.56), independent of BMI. However, HC after BMI adjustment showed no significant causal relationship with CVD (IVW: P = 0.05, OR: 1.09, 95% CI: 1.00-1.19) and exhibited a negative association with type 2 diabetes mellitus (IVW: P = 0.00, OR: 0.76, 95% CI: 0.66-0.88), suggesting a protective effect against type 2 diabetes mellitus.

Conclusions: After adjusting for BMI, adipose tissue concentrated in the hip region showed a protective effect against type 2 diabetes mellitus but not against CVD. These findings offer insights into diabetes prevention and treatment strategies, and may inform plastic surgery procedures. Further research is needed to validate these findings and explore underlying mechanisms.

Objective: Diabetic foot ulcers (DFU) are one of the most destructive complications of diabetes mellitus. The aim of this study was to link miR-155 and SOX2 with DFU to explore the regulation of wound healing by DFU and its potential mechanism.

Methods: Human keratinocytes (HaCaT) were induced with advanced glycation end products (AGEs) to construct DFU models in vitro. AGE-induced HaCaT cells were subjected to CCK-8 assays, flow cytometry, and wound healing assays to evaluate cell proliferation, apoptosis, and migration capacity, respectively. RT-qPCR and Western blotting were used to determine gene and protein expression levels, respectively. N6-methyladenosine (M6A) levels in total RNA were assessed using an M6A methylation quantification kit.

Results: Our results suggested that the inhibition of miR-155 promoted wound healing in an in vitro DFU model, while the knockdown of HIF-1α reversed this process, and that HIF-1α was a target protein of miR-155. In addition, knockdown of HIF-1α promoted the m6A level of SOX2 mRNA, inhibited the expression of SOX2, and inhibited the activation of the EGFR/MEK/ERK signaling pathway, thus inhibiting the proliferation and migration of HaCaT cells and promoting the apoptosis of HaCaT cells, while overexpression of SOX2 reversed this effect. We also found that METTL3 knockdown had the opposite effect of HIF-1α knockdown.

Conclusions: Inhibition of miR-155 promoted the expression of HIF-1α and attenuated the m6A modification of SOX2 mRNA, thereby promoting the expression of SOX2 and activating the downstream EGFR/MEK/ERK signaling pathway to promote wound healing in an in vitro DFU model.

In a multicenter trial, LX9211 significantly reduced pain in diabetic peripheral neuropathy (DPN) patients, with the 10 mg dose showing notable relief by the first week. Although the higher dose was less effective, side effects like dizziness and nausea were generally mild. These findings highlight the importance of exploring both pharmaceutical and natural treatments, such as flavonoids, for managing DPN.

Purpose: Previous studies have shown higher cardiovascular mortality risk with higher monocyte-lymphocyte ratio levels in general population. However, the levels of oxidative stress in individuals with type 2 diabetes are higher than those in the general population, which may affect the link between monocyte-to-lymphocyte ratio and cardiovascular disease deaths. And the association between the monocyte-to-lymphocyte ratio and mortality risk in people with type 2 diabetes still be unknown. This study aimed to investigate the prognostic significance of monocyte-to-lymphocyte ratio in type 2 diabetes.

Methods: This analysis involved 2,954 individuals with type 2 diabetes from the National Health and Nutrition Examination Survey 1999-2010. The National Death Index records through December 31, 2019, was used to determine all-cause and cardiovascular mortality. The prognostic roles were determined using Cox regression models, restricted cubic spline analysis, and time-dependent receiver operating characteristic curve analysis.

Results: During an average follow-up period of 12.4 years, a total of 1,007 deaths occurred, while 252 were due to cardiovascular disease. An elevated monocyte-to-lymphocyte ratio level exhibited a significant dose-response relationship with an increased risk of all-cause mortality (1.34 [95% CI 1.12, 1.60] for all-cause mortality [P trend = 0.001]). The multivariable-adjusted HR was 1.81 (95% CI 1.25, 2.63) (P trend = 0.001) for cardiovascular mortality indicating a U-shaped relationship (P nonlinear = 0.013).

Conclusions: The results of this study indicate a U-shaped relationship between the monocyte-to-lymphocyte ratio and cardiovascular mortality in individuals with diabetes. Both very low and high monocyte-to-lymphocyte ratio monocyte-to-lymphocyte ratio values were found to be associated with increased cardiovascular mortality risk.