Diabetology International最新文献

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) coexists with type 2 diabetes and is rising in Japan. Liver fibrosis progression in MASLD causes adverse outcomes, highlighting the need for early risk stratification. The utility of the Metabolic Dysfunction-Associated Fibrosis 5 (MAF-5) score has not been assessed in Japanese populations, especially among individuals with type 2 diabetes. Herein, the clinical relevance of the MAF-5 score was assessed in Japanese patients with MASLD.

Methods: This prespecified secondary analysis used data from a study titled "A Study to Estimate the Severity of MAFLD Using Continuous Glucose Monitoring." Sixty-six patients diagnosed with metabolic dysfunction-associated fatty liver disease (MAFLD) underwent vibration-controlled transient elastography. All participants were subsequently confirmed to meet the revised diagnostic criteria for MASLD. The MAF-5 score and FIB-4 index were calculated for each participant. Correlations between these scores and liver stiffness measurement (LSM) were assessed using Spearman's rank correlation coefficient. Significant fibrosis was defined as LSM ≥ 8.0 kPa. The predictive performance of each score was evaluated using the area under the receiver operating characteristic curve (AUROC).

Results: The final analysis included 57 participants (28 with type 2 diabetes). The MAF-5 score significantly correlated with LSM, whereas the FIB-4 index did not. These associations were consistent regardless of diabetes status. The AUROC for the MAF-5 score was higher than that for the FIB-4 index.

Conclusion: The MAF-5 score may serve as a useful noninvasive marker for predicting liver fibrosis in Japanese patients with MASLD, regardless of diabetes status.

It is well known in clinical practice that when pancreatic β-cells are chronically exposed to hyperglycemia, β-cell function is gradually deteriorated. It has been revealed that under diabetic conditions oxidative stress is provoked and expression levels of insulin gene transcription factors and incretin receptors are down-regulated which are closely associated with β-cell glucose toxicity. We showed that expression levels of these factors were preserved by reducing glucose toxicity with SGLT2 inhibitor. In addition, we showed that it was more beneficial to use incretin-based drugs at an early stage of diabetes when incretin receptor expression was preserved in β-cells. Similarly, we showed that expression levels of incretin receptors in arterial cells were down-regulated which seemed to be associated with the progression of atherosclerosis. Imeglimin is a relatively new anti-diabetic drug and has been used in clinical practice. Recently we have reported that imeglimin exerts beneficial effects on mitochondria morphology in β-cells and/or number and quality of insulin granules. In addition, we have reported that imeglimin shows favorable effects against the development of atherosclerosis independently of glycemic and lipid control. Taken together, it is likely that augmentation of oxidative stress and decreased expression levels of insulin gene transcription factors and incretin receptors are closely associated with pancreatic β-cell glucose toxicity. In addition, incretin-based drugs and imeglimin are expected to exert favorable effects against β-cell glucose toxicity and the development of atherosclerosis when they are appropriately introduced.

Background: Cardiovascular autonomic neuropathy (CAN) is a common but underrecognized diabetic complication. Although heart rate variability (HRV) analysis is a less invasive alternative to cardiovascular autonomic reflex tests, it is not routinely performed due to time and equipment constraints. This study aimed to assess whether HRV analysis using electrocardiograms (ECG) recorded during cardio-ankle vascular index (CAVI) measurement can serve as a practical substitute for conventional resting ECG-based HRV assessment.

Methods and results: This cross-sectional study enrolled 48 patients with diabetes and 20 healthy controls. HRV spectral indices were calculated from ECG recorded during both resting (3-min HRV) and CAVI measurement (CAVI-HRV). Agreement between HRV indices obtained under different conditions was evaluated by intraclass correlation coefficients and Bland-Altman analyses. Correlations between HRV parameters and clinical indices were examined. Participants with diabetes showed significantly lower HRV (especially high-frequency power), and reduced coefficient of variation of RR intervals. HF power of CAVI-HRV showed good agreement with 3-min HRV, whereas LF power showed only moderate concordance. HRV spectral parameters did not significantly correlate with severity of sensorimotor polyneuropathy.

Conclusions: HRV analysis performed during CAVI measurement reliably assesses parasympathetic function in diabetes. This approach may provide a convenient, accessible strategy for early CAN screening.

Early diagnosis and treatment of immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs) are essential because they directly impact patient quality of life. This report describes the case of an 85-year-old woman with type 2 diabetes on insulin therapy, whose glycemic fluctuations became highly unstable following irAE development. During treatment for refractory hepatocellular carcinoma with tremelimumab and durvalumab, she developed hyperglycemia and was hospitalized. Endogenous insulin secretion remained intact, and hyperglycemia improved after admission. Continuous glucose monitoring (CGM) revealed nocturnal and early-morning hypoglycemia from the fourth day of admission. Insulin requirements were tapered off; however, persistent anorexia and dyspnea led to the diagnosis of hypopituitarism through endocrine testing. For patients with diabetes who experience abnormal blood glucose fluctuations after ICI therapy, clinicians should monitor changes in endogenous insulin secretion and consider the possibility of hypoadrenocorticism. CGM may be valuable for detecting these endocrine abnormalities.

The global prevalence of diabetes continues to rise, necessitating advancements in treatment, such as glucagon-like peptide-1 receptor agonists. While oral semaglutide has demonstrated comparable efficacy to injectable formulations, gastrointestinal symptoms remain a barrier to continued use. This study analyzed factors associated with discontinuation of oral semaglutide due to gastrointestinal symptoms in individuals newly prescribed the drug at Jikei University Hospital between 2022 and 2023. A total of 358 individuals were categorized into discontinuation (n =  65) and continuation (n  = 293) groups based on continuation of treatment for at least 180 days. Logistic regression analyses identified higher HbA1c levels and metformin use as significant predictive factors for discontinuation at 3 mg. Furthermore, individuals taking metformin  ≥  1000 mg/day (high-dose metformin) exhibited a significantly higher risk of discontinuation due to gastrointestinal symptoms. In the supplementary analyses that included individuals who escalated from 3 mg to higher doses, metformin use-regardless of dose-was associated with early gastrointestinal-related discontinuation at 3 mg. No significant predictive factors were identified at 7 mg or 14 mg. These findings suggest that careful consideration should be given when initiating oral semaglutide, particularly in individuals with high HbA1c levels or those receiving metformin therapy.

Supplementary information: The online version contains supplementary material available at 10.1007/s13340-025-00868-0.

Aims: Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) are the foundation of renoprotective therapy in chronic kidney disease (CKD). However, some patients cannot tolerate these agents. This study aimed to evaluate the efficacy and safety of finerenone in patients with or without ACEi/ARB therapy.

Methods: We retrospectively analyzed 83 patients with CKD and diabetes who received finerenone for ≥ 3 months at our hospital (June 2022 to March 2025). The patients were divided into ACEi/ARB users (n = 52) and non-users (n = 31). Changes in the estimated glomerular filtration rate, urinary albumin-to-creatinine ratio, and serum potassium concentrations were compared.

Results: The urinary albumin-to-creatinine ratio significantly decreased after finerenone treatment in both groups (ACEi/ARB: 478 to 143 mg/gCr, p < 0.001; non-ACEi/ARB: 548 to 433 mg/gCr, p = 0.049). The degree of this reduction was greater in the ACEi/ARB group than in the non-ACEi/ARB group (0.376 vs. 0.846, p = 0.006). The estimated glomerular filtration rate significantly declined after finerenone treatment in the ACEi/ARB group (40 to 36.5 mL/min/1.73 m², p = 0.004) but not in the non-ACEi/ARB group. Serum potassium concentrations slightly increased after finerenone treatment in the ACEi/ARB group (p = 0.014) but not in the non-ACEi/ARB group. Adverse events included hyperkalemia (n = 7), renal failure (n = 1), and discontinuation in 11 patients.

Conclusions: Finerenone reduces albuminuria even without ACEis/ARBs, but the effect is more pronounced with co-administration, albeit with higher risks of a decline in the estimated glomerular filtration rate and hyperkalemia. Finerenone monotherapy may be beneficial when ACEis/ARBs cannot be used, whereas combined therapy remains more effective but requires careful monitoring.

Supplementary information: The online version contains supplementary material available at 10.1007/s13340-025-00866-2.

Insulin edema is an uncommon complication that typically arises soon after initiating insulin therapy, most often in individuals with newly diagnosed diabetes or poorly controlled hyperglycemia. An old report from a single hospital in Africa showed an incidence of 3.5% among 491 insulin-treated individuals. Although the precise pathophysiology remains uncertain, proposed mechanisms include insulin-induced sodium retention, increased vascular permeability, and dysregulation of the renin-angiotensin-aldosterone system. Insulin edema has been described in both type 1 and type 2 diabetes; however, occurrence in slowly progressive type 1 diabetes mellitus (SPIDDM) is exceptionally rare. We report a woman with SPIDDM who developed bilateral lower-leg edema shortly after starting basal-bolus insulin therapy with insulin aspart and insulin degludec. She exhibited no signs of heart failure, liver disease, renal impairment, or allergic reaction to insulin. Cardiac function was normal on echocardiography, and B-type natriuretic peptide levels were within the reference range. She experienced marked edema and an approximately 7-kg weight gain after insulin initiation. Following modification of the insulin regimen and dietary sodium restriction (8 g/day of salt), the edema resolved rapidly within nine days without the use of diuretics. This case illustrates that insulin edema can occur even in individuals with SPIDDM. The observed improvement after insulin regimen adjustment likely reflects the combined influence of glycemic stabilization, fluid-electrolyte balance, and potential formulation-related factors, rather than a direct causal difference between insulin types. Clinicians should recognize this rare yet clinically important complication and adopt an individualized management approach that includes careful glycemic correction and, when appropriate, adjustment of the insulin regimen.

Supplementary information: The online version contains supplementary material available at 10.1007/s13340-025-00864-4.

The global prevalence of diabetes mellitus (DM) and heart failure (HF) is rapidly increasing. Hyperglycemia, insulin resistance and hyperglycemia-induced oxidative stress in people with DM are the key etiological factors of HF. The factors disrupt systemic, myocardial and cellular mechanisms, leading to lipotoxicity, mitochondrial dysfunction, altered calcium signaling and inflammation, ultimately resulting in HF. Heart failure on the other hand induces new-onset diabetes by modulating insulin signaling. Despite the availability of novel treatment approaches, these comorbid conditions continue to increase hospitalization, treatment expenditure and mortality. Therefore, a thorough understanding of the complex bidirectional relationship between DM and HF might be helpful in managing the associated complications of both conditions. This review aims to provide an overview of cellular and pathophysiological interplay of the glucovascular continuum from DM to HF, and vice versa. Additionally, updated estimates on prevalence and outcomes of incident HF in people with DM and new-onset DM after HF are discussed. Guidelines from the United States, Europe and Korea recommended sodium glucose cotransporter-2 inhibitors (SGLT-2is) for primary prevention of DM and HF, and for reduction of HF hospitalization. Evidences from large-scale clinical trials and meta-analyses have shown that SGLT2i (empagliflozin, canagliflozin and dapagliflozin), semaglutide (glucagon-like peptide-1 receptor agonist) and finerenone (mineralcorticoid receptor antagonist) act as effective anti-diabetic agents and provide cardiovascular protection. Future research should prioritize diabetic control to manage and prevent lipotoxicity, oxidative stress, inflammation and advanced glycation end-product formation in order to diminish the disease burden.

Type 2 diabetes (T2D) is a chronic metabolic disorder characterized by hyperglycemia, insulin resistance, and β-cell dysfunction. It is a complex disease involving the interaction of genetic, environmental, and lifestyle factors. Three-dimensional (3D) in vitro models provide substantial advantages over conventional 2D models for the study of biology, disease, and medicine. Current 3D models include spheroids, organoids, and organ-on-chip systems. The use of 3D models has become increasingly popular in T2D research. These models allow for the visualization and manipulation of complex biological systems, providing insight into the underlying mechanisms of the disease. They have been employed to study various aspects of T2D, including β-cell function, insulin secretion, and glucose metabolism. This review aims to summarize the current state of 3D models for T2D research, highlighting their advantages, limitations, and future directions.

Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors can effectively improve blood glucose levels in patients with type 2 diabetes, reduce the risk of cardiovascular disease and heart failure, and prevent chronic kidney disease. Although they reduce uric acid (UA) levels, few studies have investigated the relationship between UA reduction and renal function. We evaluated the degree of reduction in UA levels, various metabolic parameters, and renal function in patients with type 2 diabetes mellitus treated with luseogliflozin in order to develop a better renal protection strategy.

Methods: This retrospective study analyzed 353 patients with type 2 diabetes who were newly treated with luseogliflozin. Patients were divided into two groups based on baseline UA levels, namely, the low group (< 6.0 mg/dL) and high group (≥ 6.0 mg/dL), with 74 patients in each group. Changes in metabolic parameters including glycated hemoglobin (HbA1c), UA levels, and estimated glomerular filtration rate (eGFR) were monitored over 12 months.

Results: Both groups showed significant reductions in UA and HbA1c at 12 months. eGFR decreased significantly in the low group (- 3.1 ± 0.9 mL/min/1.73 m², p = 0.002), whereas no significant change was observed in the high group (- 0.8 ± 1.3 mL/min/1.73 m², p = 0.667). UA reduction was greater in the high group (- 1.0 ± 0.2 mg/dL vs. - 0.3 ± 0.1 mg/dL, p < 0.001). UA changes were significantly correlated with eGFR changes (p = 0.008) but not with HbA1c changes.

Conclusion: Changes in eGFR after luseogliflozin administration were significantly correlated with baseline eGFR, uACR, and changes in uric acid levels (Δ uric acid). The change in uric acid levels following SGLT2 inhibitor treatment was associated with metabolic parameters such as blood pressure and albuminuria, suggesting that it may function as a surrogate marker reflecting renal metabolic processes.