Journal of Diabetes Investigation最新文献

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.

Introduction: Insulin icodec is a novel once-weekly basal insulin developed for the treatment of diabetes. The aim of this study was to investigate the pharmacokinetics of icodec in Chinese individuals with type 2 diabetes.

Materials and methods: In an open-label, single-group study, 24 Chinese individuals with type 2 diabetes (18-64 years, glycated hemoglobin ≤9.0%, body mass index 18.0-38.0 kg/m²) were treated with once-weekly icodec for 6 weeks. The icodec dose was constant and individualized, aimed at achieving self-measured plasma glucose of 4.4-7.0 mmol/L before breakfast. Blood samples were drawn from the first icodec dose until 35 days after last dose and were analyzed for total serum icodec concentration (i.e., the sum of albumin-bound and unbound icodec).

Results: Icodec trough concentrations measured following initiation of once-weekly icodec dosing suggested that clinical steady state for icodec was achieved after approximately 3-4 weeks of dosing. When at steady state, icodec exposure covered the full 1-week dosing interval. The geometric mean half-life was 159 h. The slopes of total icodec exposure (AUC_τ,SS) and maximum icodec concentration (C_max,SS) vs icodec dose did not differ significantly from 1, supporting dose-proportionality for both AUC_τ,SS (P = 0.40) and C_max,SS (P = 0.43). Icodec was safe and well tolerated, and no new safety issues were identified in relation to icodec in this study.

Discussion: The pharmacokinetic properties of icodec assessed at steady state in this study demonstrated well-distributed exposure across the 1-week dosing interval and a half-life that supports once-weekly administration in Chinese individuals with type 2 diabetes.

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.

Aims: To evaluate characteristics and glycemic outcomes in individuals with type 2 diabetes using injectable therapies in real-world clinical practice in Tianjin, China.

Materials and methods: Data from inpatients and outpatients receiving injectable therapies between January 2015 and December 2019 were collected from the Tianjin regional electronic medical records and retrospectively analyzed. Seven cohorts were identified, including individuals initiating injectable therapies (premixed insulin [n = 4,687], basal insulin [4,177], or glucagon-like peptide-1 receptor agonists [541]) or switching injectable therapies (premixed insulin to basal insulin [1,298], basal insulin to premixed insulin [1,457], basal insulin to basal + bolus insulin [1,772], or glucagon-like peptide-1 receptor agonists to basal insulin ± glucagon-like peptide-1 receptor agonists [82]).

Results: In participants initiating therapy, glycated hemoglobin and fasting plasma glucose were highest in the basal insulin cohort, while among participants switching therapy, the highest values were in the basal insulin ± glucagon-like peptide-1 receptor agonists cohort. Initiating therapy with premixed or basal insulin and switching from basal insulin to basal + bolus insulin improved glycemic control over 12 months. A mean delay in initiating therapy of up to 13 months after oral glucose-lowering drug failure was observed, with 60% having a delay of >6 months. This delay was associated with a lower proportion achieving glycemic control 3 months after initiation.

Conclusions: Effectiveness was not observed at all time points in all cohorts, suggesting some treatments were not used in the appropriate population. Delays in initiating injectable therapies were observed and were associated with poor glycemic control.

The change in nomenclature from nonalcoholic fatty liver disease to metabolic dysfunction associated-steatotic liver disease has emphasized the importance of metabolic abnormalities in this liver disorder. New pharmacological therapy has recently become available and resmetirom, a thyroid hormone receptor agonist, has received approval for the treatment of non-cirrhotic metabolic dysfunction-associated steatohepatitis and significant liver fibrosis.

Aims: To assess the extent to which biomedical outcomes and cardiovascular risk profile were improved in the management of Chinese patients with type 2 diabetes enrolled in the metabolic management center (MMC) program.

Materials and methods: We performed propensity score matching of diabetic patients in the MMC program for at least 12 months to those with diabetes under usual primary care, based on age, sex, fasting plasma glucose (FPG) level, and diabetes duration. Difference-in-difference analysis was conducted to compare changes in biomedical outcomes, attainment of treatment targets, and cardiovascular disease (CVD) risk reduction.

Results: Of 557 pairs of diabetic patients matched 1:1 (n = 1,114), the MMC cohort exhibited greater improvements in FPG (-0.84 mmol/L, 95% confidence interval [CI] -1.22 to -0.46, P < 0.001), diastolic blood pressure [BP] (-2.08 mmHg, 95%CI -3.21 to -0.94, P < 0.001), body mass index [BMI] (-0.29 kg/m², 95%CI -0.51 to -0.07, P = 0.009), low-density lipoprotein cholesterol (0.13 mmol/L, 95%CI 0.04-0.23, P = 0.008), high-density lipoprotein cholesterol (0.05 mmol/L, 95%CI 0.01-0.08, P = 0.017), and 10-year CVD risk (Framingham CVD risk, -0.94%, 95%CI -1.71 to -0.17, P = 0.017; atherosclerotic CVD risk, -0.77%, 95%CI -1.34 to -0.20, P = 0.009) when compared to the usual primary care cohort after adjustment for confounders. More patients in the MMC cohort achieved treatment targets with lifestyle modifications than their counterparts under primary care.

Conclusions: Enrolment in the MMC program appears promising in the management of FPG, BP, BMI, lifestyle, and CVD risk in diabetic patients, suggesting the necessity of incorporating the MMC program into routine primary care.

Advanced glycation end-products (AGEs) have been extensively studied because of their close association with the onset and progression of diabetic complications. However, owing to their formation through diverse metabolic pathways, AGEs often reflect a wide range of pathological conditions rather than being specific to diabetic complications. Consequently, identifying an AGE that directly correlates only with diabetic complications remains a challenge. Chronic hyperglycemia not only saturates the glycolytic pathway but also upregulates the polyol pathway, leading to the excessive production of fructose, a highly reactive reducing sugar. Although it has long been understood that fructose-derived AGEs contribute to diabetic complications, their chemical structures remain unidentified. Recent breakthroughs have revealed that glucoselysine (GL) is a primary fructose-specific AGE. Unlike other AGEs, GL is exclusively formed from fructose and not from other reducing sugars, such as glucose or galactose. This specificity provides GL with a distinct advantage in that its production pathway can be traced, making it a reliable indicator of polyol pathway activity. Furthermore, emerging evidence suggests that GL levels correlate with the progression of diabetic complications, including both micro- and macrovascular complications, making it a promising biomarker. GL's potential extends beyond diagnostics, as it may serve as a therapeutic target for managing complications associated with prolonged hyperglycemia and enhanced of polyol pathway. This review focuses on the enhanced polyol pathway and the formation of GL and discusses its biochemical characteristics, clinical significance, and potential as a novel diagnostic marker and therapeutic target in diabetic care.

Objective: To exam the role of miR-92a/KLF2/miR-483 in the pathogenesis of metabolic syndrome.

Methods: In this study, the serum of healthy controls and patients with metabolic syndrome were collected to detect the circulating level of miR-92a and miR-483. In vitro cultured HUVECs, overexpression or suppression of miR-92a, miR-483 or KLF2 to determine the relationship among miR-92a, KLF2 and miR-483. Ang II, ox-LDL, or high glucose treatment were used to mimic the metabolic syndrome. HUVECs or HepG2 cells were treated with Telmisartan, Atorvastatin, or metformin, the miR-483 and its target gene expression was detected. In animal experiment, ob/ob mice were chose to confirm the changes of miR-92a, KLF2, and miR-483.

Results: Compared with the healthy controls, the level of miR-92a was significantly increased, while miR-483 level was remarkably decreased in the patients with metabolic syndrome. In vitro cultured HUVECS, overexpression of miR-92a significantly reduced the expression of miR-483, but overexpression of miR-483 had no effect on miR-92a. Overexpression of KLF2 could downregulate miR-483 level, while inhibition of KLF2 had the opposite effect. When HUVECs and HepG2 were stimulated with Ang II, ox-LDL and high glucose, the expression of miR-483 was significantly decreased and its target genes was increased. Anti-miR-92a could reverse the effect. Furthermore, Telmisartan, Atorvastatin, and Metformin significantly increased miR-483 expression and decreased its target gene expression, which could be reversed by miR-92a mimic. The level of miR-92a was significantly increased in HepG2 cells, which were treated with exosomes derived from endothelial cells with miR-92a overexpression. ob/ob mice showed the similar effects.

Conclusions: Endothelial dysfunction and fatty liver are critically involved in the pathogenesis of metabolic syndrome. MicroRNAs can mediate the cellular communication between vascular endothelial cells (ECs) and distal cell. Serum miR-92a level was higher in metabolic syndrome patients than controls. KLF2 is the target gene of miR-92a, which can increase the production of miR-483, miR-483 acts on its target genes CTGF, ET-1, and β-catenin to protect cell function. EC miR-92a is secreted out of cells into the blood, circulates through the blood to the liver, and continues to exert its biological effects after being absorbed by hepatocytes. LNA-miR-92a administration reversed endothelial cell damage and fatty liver caused by metabolic syndrome by affecting the KLF2/miR-483 pathway.