Diabetology International最新文献

Maturity-onset diabetes of the young type 5 (MODY5), causally associated with loss-of-function of the HNF1B gene, is a rare form of monogenic diabetes that has been underdiagnosed in part because microdeletions of chromosome 17q12 encompassing the HNF1B gene cannot be detected by sequencing-based approaches, which accounts for about 50% of MODY5 cases. We herein describe a 37-year-old Japanese woman who manifested diabetic ketosis at the onset. The coexistence of features associated with MODY5, including abnormal renal function, impaired insulin secretion, pancreatic hypoplasia and hypomagnesemia, prompted us to decode her genomic information using whole-exome sequencing, where we were not able to identify any pathogenic HNF1B gene mutations. We further examined her genomic integrity using multiplex ligation probe amplification (MLPA) analysis, leading to identification of the 17q12 microdeletion which was further supported by array comparative genomic hybridization (array-CGH). Her insulin secretory capacity was insufficient, whereas her total daily dose of insulin was 11 U/day (0.25 U/Kg/day), indicating that she was relatively sensitive to insulin. As a possible explanation, we found that her plasma glucagon level was below the detection limit. Since inactivation of acetyl-CoA carboxylase 1 (ACACA), encoded in close proximity to the HNF1B gene, was reported to blunt glucagon secretion, the concurrent deletion of the ACACA gene may be in part responsible for this manifestation. In conclusion, the genetic analyses of MODY5 cases require the judicious use of appropriate genetic technologies. In addition, alpha-cell dysfunction may at least in part account for the variable clinical manifestations of MODY5.

Supplementary information: The online version contains supplementary material available at 10.1007/s13340-025-00804-2.

Heart failure (HF) is characterized by impairments in cardiac function and heart structural changes. Type-2 diabetes mellitus (T2DM) is a chronic metabolic disorder affecting millions worldwide. It is a risk factor for cardiovascular disease. Patients with T2DM are at an increased risk of developing HF. Multifactorial pathophysiology underlies HF in T2DM patients. Inflammation, oxidative stress, insulin resistance, and endothelial dysfunction are some of the mechanisms involved. Dipeptidyl peptidase-4 (DPP-IV) inhibitors may affect cardiac function by modulating inflammation and oxidative stress, affecting endothelial function, and modifying myocardial fibrosis. An antidiabetic drug class known as DPP-IV inhibitors improves patients' glycemic control in T2DM patients. However, DPP-IV inhibitors have been shown to lower glucose levels and alter HF risk in addition to their glucose-lowering effects. Sitagliptin is an oral medication used to treat T2DM. Sitagliptin is often used in combination with other diabetes medications. A preclinical study showed that sitagliptin improved cardiac function in models of heart failure. The precise mechanisms responsible for this improvement are not yet fully understood, but it could be related to inflammation and oxidative stress. Patients with T2DM are more prone to HF, which highlights the necessity of effective therapies to improve both blood glucose control and cardiovascular health. Sitagliptin offers potential cardioprotective and glucose-lowering benefits for these patients. However, further research is required to fully comprehend the role of sitagliptin in the treatment of HF in individuals with T2DM.

Immune checkpoint inhibitor (ICI)-related type 1 diabetes mellitus (T1DM) is a severe immune-related adverse event (irAE), occurring in < 1% of cases. ICI-related T1DM typically progresses more rapidly than conventional acute-onset T1DM, but is slower than conventional fulminant T1DM, suggesting different processes of onset and progression. Positivity rates for glutamic acid decarboxylase (GAD) antibodies differ, with ICI-related T1DM showing a lower positivity rate than conventional acute-onset T1DM. However, no detailed follow-up studies have examined the GAD antibody levels before and after the onset of ICI-related T1DM. We report the case of a 58-year-old Japanese man with type 2 diabetes mellitus diagnosed with renal carcinoma and multiple lung metastases. Chemotherapy with pembrolizumab (an anti-programmed death-1 antibody) was initiated. On the first day of treatment, the patient's insulin secretion capacity was preserved, and GAD antibodies were negative. Thirty-four days after chemotherapy initiation, the patient developed diabetic ketoacidosis and was diagnosed with ICI-related T1DM. Interestingly, GAD antibodies became positive (17.7 U/mL) approximately one month after the initial ICI administration. Subsequently, GAD antibody levels declined rapidly, with negative conversion occurring in only 205 days (approximately 6.5 months). To the best of our knowledge, this is the first reported case of closely monitoring GAD antibody dynamics before and after the onset of ICI-related T1DM. Here, the dynamics of the GAD antibodies were clearly distinct from those in conventional acute-onset T1DM. This case report may provide valuable insights into the differences between the autoimmune responses of ICI-related and conventional T1DM in their disease onset and progression.

Background: Metformin treatment has a risk factor of reduced serum concentrations of vitamin B12 and zinc, indicating its association with homocysteine metabolism. However, this association remains to be clarified in patients with type 2 diabetes (T2DM) accompanied by kidney dysfunction.

Methods: This cross-sectional study was conducted in 149 patients with T2DM (96 men, 53 women), including diabetic kidney disease. Serum concentrations of homocysteine, as well as vitamin B12, folic acid, and zinc, were measured in outpatient T2DM patients. The study subjects were divided into two groups: patients with and without metformin administration (Met [ +], n = 62; Met [ -], n = 87). To explore the effect of kidney function, we also analyzed the data after dividing all the patients according to kidney function (chronic kidney disease [CKD] group, n = 66; non-CKD group, n = 83).

Results: The Met ( +) group exhibited significantly higher serum zinc levels and lower serum homocysteine levels than the Met ( -) group. In the non-CKD group, metformin administration was positively associated with serum zinc levels, as demonstrated by multiple linear regression analysis adjusted for confounding factors (β = 0.287, p = 0.021). However, no significant association between metformin administration and serum zinc levels was observed in the CKD group. Moreover, there were no associations between serum homocysteine levels and metformin administration.

Conclusions: The relationship between metformin treatment and serum zinc levels differed based on the presence or absence of CKD in patients with T2DM.

Purpose: The phase angle is a mathematical concept representing the time relationship between two periodic waveforms, and has gained some importance for its potential clinical applications. The purpose of this review was to investigate the role of phase angle in diabetes mellitus.Studies have investigated the relationship between the phase angle and glycemic control, insulin resistance, and diabetes-related complications. Phase angle has demonstrated its potential as a prognostic marker for diabetic complications, enabling early identification and intervention. It might be beneficial for evaluating disease severity, monitoring treatment response, and predicting long-term results in diabetics.

Results and conclusion: Although the phase angle offers significant advantages, its clinical use in managing diabetes is still in its early stages, and there are certain issues that need to be resolved. Standardization of measurement techniques and interpretation criteria is essential to ensure consistency and comparability across studies and clinical settings. Investigating the role of phase angle in the treatment of diabetes provides significant knowledge about its potential as a non-invasive and informative parameter. Identifying the importance of phase angle in diabetes might help to improve risk stratification, treatment strategies, and patient outcomes. Additional research is required to determine its therapeutic value and discover the mechanisms underlying its association with diabetes and its complications.

Aims: Underestimating hyper-/hypoglycemia or failure to perceive hyperglycemia hinders optimal glucose management in diabetes care. Our study investigated individuals who, while aware of their hyper-/hypoglycemia, may not perceive them as problematic. Also, we clarified the factors contributing to discrepancies between these individuals' perceptions and the objective measurements.

Materials and methods: This study was a prospective observational study comprising 284 Japanese individuals with type 2 diabetes who underwent ambulatory blinded professional continuous glucose monitoring (CGM) and self-administered the Diabetes Treatment Satisfaction Questionnaire (DTSQ). Individuals with a time above range (TAR; > 180 mg/dL) ≥ 25% and those who answered 0 ("never") or + 1 ("almost never") for the frequency of hyperglycemia in the DTSQ were defined as having no-perception of hyperglycemia. Individuals with a time below range (TBR; < 70 mg/dL) ≥ 4% with an answer of 0 or + 1 for the frequency of hypoglycemia were labeled as having no-perception of hypoglycemia. Multivariate logistic regression analysis was performed to analyze clinical characteristics associated with the discrepancies between failure to perceive hyper-/hypoglycemia and TAR ≥ 25% or TBR ≥ 4%.

Results: Insulin-use (odds ratio [OR] = 0.29, p < 0.05) and older age (OR = 1.05, p < 0.05) were independent determinants of no-perception of hyperglycemia. Low eGFR was an independent determinant of no-perception of hypoglycemia (OR = 0.94, p < 0.05).

Conclusions: No-insulin-use, being an older adult, and renal dysfunction are linked to the discrepancy between the perception of hyper-/hypoglycemia and actual blood glucose. These results will help create personalized diabetes care.

Introduction: COVID-19 emergency declarations and ensuing lockdowns affected lifestyle and glycemic control in individuals with diabetes mellitus, with some studies finding improvement and others deterioration of glucose management. The effects of such emergency declarations in Asian populations, including individuals with type 1 diabetes (T1D) managed with a sensor-augmented pump (SAP), have been unclear, however. We here investigated the impact of a COVID-19 emergency declaration on glycemic control in Japanese individuals with T1D treated with a SAP device.

Methods: This retrospective investigation included individuals with T1D who were managed with SAP technology and had continuous glucose monitoring including sensor glucose levels and time above range, time in range [TIR], and time below range and insulin dose data available in electronic health records from February to July 2020, corresponding to periods before, during, and after the declared emergency.

Results: The 78 enrolled individuals had a mean age of 44.6 years, diabetes duration of 15.4 years, and hemoglobin A_1c level of 7.3%. Average sensor glucose levels improved from 152.0 mg/dL before to 148.0 mg/dL during and 147.6 mg/dL after the emergency. TIR increased from 68.8% before to 71.3% during and 71.4% after the emergency. Total daily insulin dose decreased from 40.9 U before to 39.6 U after the emergency. After the emergency declaration, individuals with an initial TIR of ≤ 70% showed increased sensor adherence as well as a greater improvement in glycemic control compared with those with a TIR of > 70%.

Conclusion: Individuals with T1D treated with a SAP device showed improved glycemic management after the COVID-19 emergency declaration.

Supplementary information: The online version contains supplementary material available at 10.1007/s13340-025-00802-4.

Aims: We examined if there has been improvements in the lifespan of people who died from diabetes in Japan between 2000 and 2020 using the novel average lifespan shortened (ALSS) measure.

Methods: The number of deaths due to diabetes in Japan were obtained from the World Health Organization mortality database. We calculated age standardized rates (ASR) using direct method adjusted to the World Standard Population. Years of life lost (YLL) due to diabetes was calculated using Japanese life tables. ALSS measure was calculated as a ratio of YLL to the expected lifespan. We used the bootstrap method to calculate 95% confidence interval (95% CI) for the ALSS measure.

Results: The ASR of deaths due to diabetes decreased from 5.5 to 3.7 deaths per 100,000 people in men, and from 2.9 to 1.5 deaths in women over the study period. The ALSS results show that men with diabetes lost 18.0% (95% CI 17.7-18.3) of their lifespan at the beginning of the study period, but only 14.3% (95% CI 14.1-14.6) of their lifespan at the end of the study period. Similarly, the ALSS values for women decreased from 15.0% (95% CI 14.7-15.2) of their lifespan to 12.1% (95% CI 11.9-12.3) at the end of the study period.

Conclusion: Results from the new ALSS measure show lifespan of people who died from diabetes prolonged by about 4 and 3 percentage points in men and women over the study.

Objectives: High remnant-like lipoprotein (RLP) cholesterolemia has been reported as a risk factor for cardiovascular events in stable angina patients receiving statin therapy. However, there are no established treatments for lowering RLP cholesterol in patients on statins. Glucagon-Like Peptide-1 (GLP-1) receptor agonists are known to reduce cardiovascular events, but the underlying mechanism is not fully understood. We hypothesized that the lipid profile-improving effects of GLP-1 receptor agonists may also contribute to lowering RLP cholesterol.The purpose of this study was to investigate whether oral semaglutide, a GLP-1 receptor agonist, exerts a cholesterol-lowering effect on RLP cholesterol.

Methods: This study was designed as a single-center, single-group, before-and-after comparison trial. The study population consisted of patients with ischemic heart disease who were receiving statin therapy, had initiated oral semaglutide for diabetes, and had an RLP cholesterol level of 3.9 mg/dL or higher before starting semaglutide (N = 41). RLP cholesterol levels were measured in all patients 3 months after initiating semaglutide therapy. RLP cholesterol levels before and after semaglutide treatment were compared.

Results: After initiating semaglutide, RLP cholesterol levels were significantly lower compared to baseline levels (before 8.52 ± 3.96 mg/dL After 5.46 ± 2.88 mg/dL, P < 0.001). In 21 patients who switched from DPP-4 inhibitors to semaglutide, RLP cholesterol levels also significantly decreased (7.33 ± 1.03 mg/dL → 6.75 ± 0.95 mg/dL, P < 0.001). Additionally, among 30 patients who were already on SGLT-2 inhibitors, RLP cholesterol levels significantly decreased after starting semaglutide (8.01 ± 3.37 mg/dL → 5.42 ± 2.37 mg/dL, P < 0.001). No correlation was observed between the reduction in RLP cholesterol and weight loss.

Conclusions: Oral semaglutide significantly reduced RLP cholesterol levels in patients with ischemic heart disease who were receiving statin therapy.

Background: While there is an urgent need worldwide to establish methods that prevent diabetic foot ulcers, the effectiveness of a prevention protocol using thermography has been reported. As the number of diabetic patients in Indonesia is increasing, an online program for wound care specialists was developed to disseminate this protocol. The present study evaluated the impact of an online program on wound care specialists' knowledge of diabetic foot ulcer prevention using thermography.

Methods: This single-group quasi-experimental study was conducted in cooperation with the Indonesian Wound Enterostomal Continence Nurses Association with regard to curriculum and content design, and the evaluation methods of online education for thermography-based diabetic foot ulcer prevention using the learning management system. A questionnaire with 50 multiple-choice questions previously validated for content and readability on the knowledge of diabetic foot ulcer prevention using thermography was used for training evaluations.

Results: Of 106 Indonesian wound care specialists evaluated, the paired t-test revealed a significant difference between the before and after training questionnaire scores on knowledge (52.0 ± 10.3, 85.2 ± 10.6, respectively, p < 0.001). Repeated measures analysis of variance revealed interactions between time (before and after training) and gender, and between time and type of certificate (p = 0.046, p = 0.014, respectively).

Conclusions: An asynchronous e-learning program is an effective method to increase wound care specialists' knowledge of diabetic foot ulcer prevention. These findings suggest that online educational interventions are effective and can be tailored to meet the needs of healthcare professionals, thereby ultimately contributing to better patient care outcomes in preventing DFUs.