Journal of Diabetes Investigation最新文献

Aims: This study aimed to delineate the effect of hyperglycemia on the Alu/LINE-1 hypomethylation and in ERK1/2 genes expression in type 2 diabetes with and without cataract.

Methods: This study included 58 diabetic patients without cataracts, 50 diabetic patients with cataracts, and 36 healthy controls. After DNA extraction and bisulfite treatment, LINE-1 and Alu methylation levels were assessed using Real-time MSP. ERK1/2 gene expression was analyzed through real-time PCR. Total antioxidant capacity (TAC), and fasting plasma glucose (FPG) were measured using colorimetric methods. Statistical analysis was performed with SPSS23, setting the significance level at P < 0.05.

Results: The TAC levels were significantly lower for cataract and diabetic groups than controls (259.31 ± 122.99, 312.43 ± 145.46, 372.58 ± 132.95 nanomole of Trolox equivalent) with a significant correlation between FPG and TAC levels in both the cataract and diabetic groups (P < 0.05). Alu and LINE-1 sequences were found to be statistically hypomethylated in diabetic and cataract patients compared to controls. In these groups, TAC levels were directly correlated with Alu methylation (P < 0.05) but not LINE-1. ERK1/2 gene expression was significantly higher in diabetic and cataract patients, showing increases of 2.41-fold and 1.43-fold for ERK1, and 1.27-fold and 1.5 for ERK2, respectively. ERK1 expression correlated significantly with FPG levels. A reverse correlation was observed between TAC levels and ERK1/2 expression.

Conclusions: Our findings indicate that hyperglycemia-induced oxidative stress may alter ERK1/2 gene expression patterns and induce aberrant hypomethylation in Alu and LINE-1 sequences. These aberrant changes may play a contributing role in diabetic complications such as cataracts.

Aims: This study investigated the association between maternal age and early and late gestational diabetes mellitus (GDM).

Methods: In total, 72,270 pregnant women were included in this prospective birth cohort study. Associations between maternal age and early GDM (diagnosed at <24 gestational weeks) and late GDM (diagnosed at ≥24 gestational weeks) were evaluated using a multinomial logistic regression model with possible confounding factors. The reference category was maternal age of 30-34.9 years.

Results: Higher maternal age was associated with higher odds of early and late GDM (P-value for trend <0.0001 and <0.0001, respectively). The adjusted odds ratios (aORs) for early GDM with maternal age of 35-39.9 years and ≥40 were 1.399 (95% confidence interval [CI]: 1.134-1.725) and 2.494 (95% CI: 1.828-3.402), respectively. The aORs for late GDM with maternal age of 35-39 years and ≥40 were 1.603 (95% CI: 1.384-1.857) and 2.276 (95% CI: 1.798-2.881), respectively.

Conclusions: Higher maternal age was associated with an increased risk of GDM regardless of when GDM was diagnosed. The association between maternal age and early GDM was similar to that between maternal age and late GDM.

Aims/introduction: This study examined the effects of high-intensity interval walking training (IWT) compared to moderate-intensity continuous walking training (CWT) on muscle strength, walking ability, and health-related quality of life (QOL) in people with diabetes accompanied by lower extremity weakness.

Materials and methods: People with diabetes accompanied by low isometric knee extensor strength using a simple manual dynamometer (n = 50) were screened and randomly divided into 2 groups: CWT (n = 25) and IWT (n = 25). Both groups were instructed by a physical therapist to perform walking training with the goal of 120 min/week over a 5-month period. The primary outcome, mean change of isometric knee extensor strength, and secondary outcomes, such as gait speed and health-related QOL, were measured at baseline and the end of the intervention.

Results: At the end of the intervention, there was no significant difference in the degree of change in isometric knee extension strength between the two groups. However, there was a significant increase in changes in gait speed and physical QOL in the IWT group (gait speed, P < 0.01; physical QOL, P < 0.05).

Conclusions: The present study showed that IWT for people with diabetes accompanied by lower extremity weakness did not improve knee extension muscle strength compared to CWT but did improve walking ability and physical QOL.

Low-density lipoprotein cholesterol (LDL-C) is known to be a causal substance of atherosclerosis, but its usefulness as a predictive biomarker for atherosclerotic cardiovascular disease (ASCVD) is limited. In patients with type 2 diabetes (T2D), LDL-C concentrations do not markedly increase, while triglycerides (TG) concentrations are usually elevated. Although TG is associated with ASCVD risk, they do not play a direct role in the formation of atheromatous plaques. TG changes the risk of ASCVD in a way that is dependent on LDL-C, and TG is the primary factor in reducing LDL particle size. Small dense (sd)LDL, a potent atherogenic LDL subfraction, best explains the "Atherogenic Duo" of TG and LDL-C. Although hypertriglyceridemia is associated with small-sized LDL, patients with severe hypertriglyceridemia and low LDL-C rarely develop ASCVD. This suggests that quantifying sdLDL is more clinically relevant than measuring LDL size. We developed a full-automated direct sdLDL-C assay, and it was proven that sdLDL-C is a better predictor of ASCVD than LDL-C. The sdLDL-C level is specifically elevated in patients with metabolic syndrome and T2D who have insulin resistance. Due to its clear link to metabolic dysfunction, sdLDL-C could be named "metabolic LDL-C." Insulin resistance/hyperinsulinemia promotes TG production in the liver, causing steatosis and overproduction of VLDL1, a precursor of sdLDL. sdLDL-C is closely associated with steatotic liver disease and chronic kidney disease, which are common complications in T2D. This review focuses on T2D and discusses the clinical significance of sdLDL-C including its composition, pathophysiology, measurements, association with ASCVD, and treatments.

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.

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.

Aims/introduction: This analysis seeks to evaluate the cost-effectiveness of urine albumin-to-creatinine ratio testing compared with urine protein-creatinine ratio testing and no urine testing for the identification of kidney damage in individuals with type 2 diabetes who have, or are at risk of, chronic kidney disease in Japan.

Materials and methods: A health-economic model estimated the clinical and economic consequences of different tests to evaluate kidney damage in line with Japanese guidelines, taking a Japanese healthcare perspective. Differences in the diagnostic performance of tests were considered by the integration of real-world Japanese data. Outcomes were considered over a lifetime horizon, and included costs, prevented dialyses, life years gained, quality-adjusted life years, and incremental cost-effectiveness ratios.

Results: Repeated urine albumin-to-creatinine ratio testing was found to be cost-effective compared with both urine protein-creatinine ratio testing and no urine testing, yielding incremental cost-effectiveness ratios of ¥2,652,693 and ¥2,460,453, respectively.

Conclusions: Repeated urine albumin-to-creatinine ratio testing is cost-effective compared with urine protein-creatinine ratio testing and no urine testing in Japanese individuals with type 2 diabetes, supporting existing clinical evidence that albumin-to-creatinine ratio testing should be used more widely, particularly compared with other urine tests such as urine protein-creatinine ratio testing.

Atypical diabetes with overlapping clinical features of type 1 (T1D) and type 2 (T2D) is common and challenging diagnostically and for implementing effective treatment. Here, we validate a recently reported genetic probability of type 1 diabetes (GenProb-T1D) from the UK Biobank (UKB) for differentiating type 1 diabetes and type 2 diabetes in a diabetes patient cohort from a healthcare system-based biobank in the USA. Among 3,363 diabetes patients, we confirmed the performance of GenProb-T1D in differentiating typical type 1 diabetes vs type 2 diabetes. Furthermore, for 359 atypical diabetes patients, those with GenProb-T1D higher than the pre-defined cutoff derived from the UKB had clinical presentations more consistent with that of typical type 1 diabetes. Similar findings were found in participants of European and non-European ancestries. This study provides necessary validation to translate GenProb-T1D into genetic testing in a multi-ancestry cohort. Measuring underlying genetic susceptibility of type 1 diabetes and type 2 diabetes can supplement current clinical tools for earlier and more accurate diagnoses of diabetes.

Aims/introduction: This study evaluated the usability, satisfaction, and accuracy of a real-time continuous glucose monitoring (rt-CGM) in children and adolescents with type 1 diabetes (T1D) attending a summer camp.

Materials and methods: Seven children and adolescents with T1D (camper) and 31 of healthcare providers (HCPs) participating in a 2-day summer camp in Kumamoto, Japan were enrolled. The usability and satisfaction were evaluated by tailored questionnaire. The accuracy of rt-CGM was evaluated using self-monitoring of blood glucose (BG) and sensor glucose (SG) values before or after (off camp) and during (on camp) the camp.

Results: The score of the usefulness of rt-CGM showed 3.29 ± 0.90 in campers and 4.23 ± 0.87 in HCPs (P = 0.017). The degree of recommendation score for rt-CGM was 3.29 ± 1.11 in campers and 4.23 ± 0.79 in HCPs (P = 0.013). Time in range (TIR) off camp was 45.9% and that on camp was 57.0%. Time above range (TAR) off camp was 53.4% and that on camp was 42.4%. The mean absolute relative difference (MARD) off camp was 19.7% ± 25.2%, whereas that on camp was 16.0% ± 14.8% (P = 0.367). Clinically acceptable zones of the error grid analyses were approximately 96% in total.

Conclusions: Rt-CGM exhibited higher usability and recommendation scores in HCPs than those in campers. This may be related to relatively lower accuracy in rt-CGM. Overall usability and recommendation are clinically satisfactory, but due to relatively low accuracy, no decision should be made based on a single, non-verified SG value alone.

Aims/introduction: This study aimed to identify low- and high-risk diabetes groups within prediabetes populations using data from the Taiwan Biobank (TWB) and UK Biobank (UKB) through a clustering-based Unsupervised Learning (UL) approach, to inform targeted type 2 diabetes (T2D) interventions.

Materials and methods: Data from TWB and UKB, comprising clinical and genetic information, were analyzed. Prediabetes was defined by glucose thresholds, and incident T2D was identified through follow-up data. K-means clustering was performed on prediabetes participants using significant features determined through logistic regression and LASSO. Cluster stability was assessed using mean Jaccard similarity, silhouette score, and the elbow method.

Results: We identified two stable clusters representing high- and low-risk diabetes groups in both biobanks. The high-risk clusters showed higher diabetes incidence, with 15.7% in TWB and 13.0% in UKB, compared to 7.3% and 9.1% in the low-risk clusters, respectively. Notably, males were predominant in the high-risk groups, constituting 76.6% in TWB and 52.7% in UKB. In TWB, the high-risk group also exhibited significantly higher BMI, fasting glucose, and triglycerides, while UKB showed marginal significance in BMI and other metabolic indicators. Current smoking was significantly associated with increased diabetes risk in the TWB high-risk group (P < 0.001). Kaplan-Meier curves indicated significant differences in diabetes complication incidences between clusters.

Conclusions: UL effectively identified risk-specific groups within prediabetes populations, with high-risk groups strongly associated male gender, higher BMI, smoking, and metabolic markers. Tailored preventive strategies, particularly for young males in Taiwan, are crucial to reducing T2D risk.