Journal of Diabetes Investigation最新文献

Background: This study evaluates shifts in oral glucose-lowering drug prescription patterns and the adoption of sodium-glucose cotransporter 2 inhibitors (SGLT2is) in South Korea.

Methods: A cross-sectional and retrospective cohort analysis of the Korean National Health Insurance database (2015-2021) assessed the prescription patterns of oral glucose-lowering drugs by therapy level, SGLT2i prescriptions by cardiovascular-renal disease (CVRD) status, and the mean duration for SGLT2i therapy initiation and intensification.

Results: From 2015 to 2021, the number of individuals prescribed oral glucose-lowering drugs across all regimen levels increased. However, the proportion of individuals receiving monotherapy or dual combination therapy decreased by 9.2 percentage points, whereas the proportion prescribed triple or more combination therapy increased. SGLT2i prescriptions increased from 2.5% in 2015 to 13.9% in 2021, marking an 11.4 percentage point growth. This trend was consistent among individuals with and without CVRD, with the most significant increase observed in individuals with heart failure-from 2.2% in 2015 to 16.6%. The mean time to SGLT2i initiation post-diagnosis was shortened from 249 days in 2015 to 158 days in 2019.

Conclusions: The adoption of SGLT2i therapy was on the rise, especially among individuals with heart failure, accompanied by a notable decrease in time to treatment initiation. Despite these positive trends, the overall use of SGLT2i among individuals with CVRD remained limited.

Aim/introduction: We assess the efficacy of artificial intelligence (AI)-based, fully automated, volumetric body composition metrics in predicting the risk of diabetes.

Materials and methods: This was a cross-sectional and 10-year retrospective longitudinal study. The cross-sectional analysis included health check-up data of 15,330 subjects with abdominal computed tomography (CT) images between January 1, 2011, and September 30, 2012. Of these, 10,570 subjects with available follow-up data were included in the longitudinal analyses. The volume of each body segment included in the abdominal CT images was measured using AI-based image analysis software.

Results: Visceral fat (VF) proportion and VF/subcutaneous fat (SF) ratio increased with age, and both strongly predicted the presence and risk of developing diabetes. Optimal cut-offs for VF proportion were 24% for men and 16% for women, while VF/SF ratio values were 1.2 for men and 0.5 for women. The subjects with higher VF/SF ratio and VF proportion were associated with a greater risk of having diabetes (adjusted OR 2.0 [95% CI 1.7-2.4] in men; 2.9 [2.2-3.9] in women). In subjects with normal glucose tolerance, higher VF proportion and VF/SF ratio were associated with higher risk of developing prediabetes or diabetes (adjusted HR 1.3 [95% CI 1.1-1.4] in men; 1.4 [1.2-1.7] in women). These trends were consistently observed across each specified cut-off value.

Conclusions: AI-based volumetric analysis of abdominal CT images can be useful in obtaining body composition data and predicting the risk of diabetes.

Advancements in regenerative medicine, particularly through the use of induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs), are garnering substantial attention as potential solutions to the limited availability of donors, leading to prolonged waiting periods for people with type 1 diabetes who require transplantation of pancreatic islets from deceased donors. The promising outcomes from recent clinical trials suggest that transplantation of iPSC- or ESC-derived islet cells could pave the way for more effective and broadly accessible treatment options. This progress holds potential not only for individuals with type 1 diabetes but may also extend to type 2 diabetes treatment in the future.

Aims/introduction: Leukocyte cell-derived chemotaxin 2 (LECT2) is an obesity-associated hepatokine that causes skeletal muscle insulin resistance. Since LECT2 is up-regulated by the inactivation of the energy sensor AMPK in the liver, we hypothesized that LECT2 has potential as a biomarker for metabolic dysfunction-associated steatotic liver disease (MASLD). Therefore, we investigated whether circulating LECT2 levels are associated with insulin sensitivity, liver enzymes, and MASLD.

Materials and methods: This cross-sectional study included 138 Japanese individuals. Plasma LECT2 levels were measured using fasting blood samples. B-mode ultrasonography was used to assess hepatic steatosis.

Results: The mean age and body mass index (BMI) of participants were 63.5 ± 10.2 years and 23.0 ± 3.1 kg/m², respectively. Higher LECT2 levels positively correlated with homeostatic model assessment for insulin resistance (HOMA-IR) values and negatively correlated with the quantitative insulin sensitivity check index (QUICKI) among all participants (HOMA-IR; non-standardized β (B) = 6.38, P < 0.01: QUICKI; B = -161, P < 0.01). These correlations were stronger in the low BMI group (HOMA-IR; B = 13.85, P < 0.01: QUICKI; B = -180, P < 0.01). LECT2 levels also positively correlated with gamma-glutamyl transferase levels (B = 0.01, P = 0.01) and alanine aminotransferase levels (B = 0.33, P = 0.02). Higher LECT2 levels correlated with the prevalence of MASLD (odds ratio = 1.14, P = 0.02).

Conclusions: The present results suggest the potential of plasma LECT2 levels as a biomarker for insulin resistance in individuals who are not overweight and the prevalence of MASLD in the general population.

Aim/introduction: Although immune checkpoint inhibitor-related type 1 diabetes mellitus (ICI-T1DM) is a rare condition, it is of significant concern globally. We aimed to elucidate the precise incidence, risk factors, and impact of ICI-T1DM on survival outcomes.

Materials and methods: The study is a large retrospective cohort study, performed using the DeSC Japanese administrative claims database comprising 11 million patients. The database population is reportedly similar to the entire population of Japan. Patients administered ICI between 2014 and 2022 were enrolled in the study, including 21,121 patients. The risk factors for ICI-T1DM development and their characteristics were evaluated by logistic regression analysis. Development of a new irAE after the day following the first administration of ICI was set as the study outcome.

Results: ICI-T1DM was observed in 102 (0.48%) of the 21,121 patients after ICI initiation. PD-(L)1 and CTLA-4 combination therapy was associated with an increased risk of ICI-T1DM compared with PD-1 monotherapy (odds ratio [OR], 2.36; 95% confidence interval [CI], 1.21-4.58; P = 0.01). Patients with a prior diagnosis of diabetes mellitus (OR, 1.59; 95% CI, 1.03-2.46; P = 0.04) or hypothyroidism (OR, 2.48; 95% CI, 1.39-4.43; P < 0.01) also exhibited an increased risk of ICI-T1DM. The Kaplan-Meier analysis revealed that patients with ICI-T1DM showed higher survival rates than those without (log-lank test, P < 0.01). Multivariable Cox regression analysis demonstrated that ICI-T1DM development was associated with lower mortality (hazard ratio, 0.60; 95% CI, 0.37-0.99; P = 0.04).

Conclusions: Collectively, the results of this study demonstrate the precise incidence and risk factors of ICI-T1DM. The development of ICI-T1DM, like other irAEs, is associated with higher survival rates.

Background: Gold standard methods of type 2 diabetes mellitus are expensive and therefore not practical for large scale studies in low-income countries. We have investigated the total cholesterol, high density lipoprotein (HDL), and glucose (CHG) index for diagnosis of type 2 diabetes mellitus index which is derived from fasting state. In this study we aimed to compare the accuracy of with CHG index and triglycerides (TG) and glucose levels (TyG) as surrogates of type 2 diabetes mellitus.

Methods: A total of 9,704 individuals between 35 and 65 years of age were recruited as part of the Mashhad stroke and heart atherosclerotic disorder (MASHAD) study. They were categorized into two groups, those with and without type 2 diabetes mellitus. The cut-off in groups to detection of type 2 diabetes mellitus was fasting blood glucose ≥126 mg/dL in blood sample. Receiver operating characteristic (ROC) curve analysis was used to establish the cut-off of indices to evaluate the sensitivity and specificity of them.

Results: The best cut-off of CHG index for diagnosis of type 2 diabetes mellitus was 5.57 which was associated with a sensitivity of 70.38% and specificity of 89.82% values. This was in comparison to the TyG index. LR+ CHG index was 6.91 compared to 3.47 for the TyG index and the AUC of CHG index was 0.864 (0.857, 0.871) compared with 0.825 (0.818, 0.833) for the TyG index. This indicates that the CHG index has a higher efficiency value to diagnose of type 2 diabetes mellitus.

Conclusions: The CHG index could be useful for the detection of type 2 diabetes mellitus.

Aims/introduction: This study aims to investigate the association between cross-sectional area (CSA) imaging findings of nerve ultrasound and conventional nerve conduction studies (NCS) for patients with distal symmetric sensorimotor polyneuropathy (DSPN) due to type 2 diabetes mellitus.

Materials and methods: We enrolled 103 patients with type 2 diabetes mellitus and collected their demographic data, modified Michigan Neuropathy Screening Instrument (mMNSI) score, NCS, and ultrasonography images of peripheral nerves. The relationship of ultrasound variables for individual nerves and the ultrasound pattern sum score (UPSS) to conventional NCS findings was investigated.

Results: A higher grade of DSPN was associated with a notably higher CSA. Multivariate step-wise regression analysis revealed that the number of abnormal nerves was a positive independent variable for UPSS (β coefficient = 0.4205; P < 0.0001). Of the five nerves studied, abnormalities of the tibial nerve (P ≤ 0.0100) and ulnar nerve (P = 0.052) were the most significant variables.

Conclusions: The tibial nerve exhibited the most substantial association with elevated UPSS. In addition, a strong correlation was observed between abnormal NCS findings and UPSS in patients with DSPN.

Introduction: Developing a more effective treatment for the global impact of diabetic kidney disease is crucial. This study examined the renoprotective effects of combining glucagon-like peptide-1 receptor agonists (GLP-1 RA) with sodium-glucose cotransporter 2 inhibitors (SGLT2i) compared to SGLT2is alone in type 2 diabetes (DM).

Materials and methods: This retrospective cohort study used data from the TriNetX Global Collaborative Network. Type 2 DM patients with estimated glomerular filtration rates ≥60 mL/min/1.73 m² who used GLP-1 RA or SGLT2i between January 1, 2013, and December 31, 2023. Propensity score matching balanced baseline characteristics, resulting in 71,186 patients in each group (combined GLP-1 RA and SGLT2i therapy vs SGLT2i alone). Cox regression model was adopted to compare outcomes over a 5-year period, including major adverse kidney events (MAKE), acute kidney injury (AKI), end-stage kidney disease (ESKD), and all-cause mortality.

Results: After matching, the average age was 57.1 ± 10.8 years for the GLP-1 RA plus SGLT2i group and 57.2 ± 11.7 years for the SGLT2i-only group. The GLP-1 RA plus SGLT2i group had significantly lower risk of MAKE (hazard ratio [HR]: 0.73, 95% confidence interval [CI]: 0.69-0.77), AKI (HR: 0.82, 95% C0I: 0.77-0.87), ESKD (HR: 0.61, 95% CI: 0.47-0.78), and all-cause mortality (HR: 0.54, 95% CI: 0.50-0.58) compared to the SGLT2i-only group. Moreover, subgroup analyses showed consistent benefits across different subgroups.

Conclusions: Dual therapy with GLP-1 RA and SGLT2i is supported to enhance renal outcomes and address the growing burden of diabetic kidney disease.

Aims/introduction: Diabetic kidney disease (DKD) is a major cause of kidney failure. FOS-like antigen 2 (FOSL2) has been revealed to be increased in kidney biopsies of patients with lupus nephritis, while its association with DKD remains unsolved. This study aimed to characterize the role of FOSL2 in DKD and its mechanism.

Method: The kidney tissues of DKD mice induced by STZ and a high-fat diet were subjected to PAS and Masson's staining. Glomerular mesangial cells (MCs) were treated with high glucose (HG) or normal glucose (NG). CCK-8 and EdU assays were performed to detect cell proliferation, and immunoblotting was conducted to analyze ECM deposition. ChIP-qPCR was performed on MCs to detect the binding of FOSL2 on the TGF-β1 promoter and a dual-luciferase assay to detect the impact of FOSL2 on the transcription of the TGF-β1 promoter.

Results: FOSL2 was elevated in the kidney tissues of DKD mice. Knockdown of FOSL2 reduced the mRNA expression of TGF-β1 to decrease the protein expression of GLUT1 and mTOR in the kidney tissues of DKD mice, and TGF-β1 reversed the effects caused by knockdown of FOSL2. The mTOR inhibitor Rapamycin alleviated kidney injury in the presence of FOSL2. Knockdown of FOSL2 inhibited the proliferation and improved ECM deposition of MCs, which were reversed by TGF-β1. Rapamycin and GLUT1 inhibitor BAY-876 reversed the promotion effect of FOSL2 on the proliferation of NG-MCs/HG-MCs and improved ECM deposition of MCs.

Conclusions: Our data demonstrated that FOSL2 accentuates DKD in mice by increasing TGF-β1-induced GLUT1/mTOR signaling.