Diabetology International最新文献

Atherosclerotic peripheral artery disease (PAD), that is, arteriosclerosis obliterans, is pathologically rooted in atherosclerosis, similar to other cardiovascular diseases. In addition to smoking, hypertension, and dyslipidemia, diabetes mellitus is a major risk factor. People with diabetes mellitus have an elevated risk of developing PAD. PAD in turn increases the risk of diabetic foot ulcers and gangrene in the population. Rest pain, nonhealing ulcers, and gangrene associated with chronic ischemia are known as chronic limb-threatening ischemia (CLTI). This article gives an overview of the link between atherosclerotic PAD, particularly CLTI, and diabetes mellitus. First, the clinical impact of CLTI among patients with diabetes mellitus is presented. Second, its clinical features, including prognosis, comorbidity, occurrence, and seasonality, are mentioned. The clinical management of CLTI is also discussed. Diabetes mellitus has notable clinical impact on CLTI and vice versa. CLTI has different clinical features from those of other atherosclerotic cardiovascular diseases. Its clinical profile also differs between individuals with both diabetes mellitus and CLTI and general people with diabetes mellitus. There is considerable room for improvement in CLTI treatment and management. Clinical measures taken before revascularization, including CLTI risk assessment, prompt diagnosis, and expedited referral to vascular specialists, may enhance CLTI outcomes. Further research is warranted to obtain more evidence.

The mechanistic complexity in type 2 diabetes (T2DM) is primarily responsible for the degrees of heterogeneity and development of complications. A complex mode of interactions between different pathophysiological events and diabetogenic environmental factors support for the genesis of diabetes heterogeneity both in phenotypic and clinical contexts. The currently used diabetes classification strategies suffer from several inconsistencies that cannot fully capture the inherent heterogeneity among the diabetes patients. To effectively address this pathobiological and heterogeneity-related issue in diabetes research, the current review proposes nine pathophysiological hallmarks of T2DM that aims to mechanistically explain complexities of diabetes associated pathophysiological events and their underlying features. These pathophysiological hallmarks are pancreatic beta cell dysfunction, insulin sensitivity, insulin resistance, obesity, aging, subclinical inflammation, metabolic dysregulation, prothrombotic state induction and hypertension. Detail knowledge of these pathophysiological hallmarks with their key molecular mediators, influencing factors, clinical biomarkers and clinical assessment methodologies will greatly support precision medicine approaches in diabetes including patient stratification, subtype diagnosis and treatment.

Supplementary information: The online version contains supplementary material available at 10.1007/s13340-024-00783-w.

Objectives: This clinical study assessed the three-year, long-term effects of esaxerenone, a non-steroidal aldosterone receptor blocker, on Japanese patients with type 2 diabetes, diabetic kidney disease, and hypertension who were receiving renin-angiotensin system inhibitors.

Materials and methods: Data from a computerized diabetic care database were used to retrospectively compare esaxerenone users (Group A) with non-esaxerenone users (Group B). Propensity score weighting was applied to Group B. The study primarily focused on percent changes in the Urine Albumin-Creatinine Ratio (UACR) from baseline and also examined the estimated Glomerular Filtration Rate (eGFR), blood pressure, serum potassium levels, and HbA1c.

Results: There were 199 patients in Group A and 199 in Group B, matched 1:1 using propensity scores. UACR and blood pressure were significantly lower in Group A than in Group B. Geometric mean percent changes in UACR from baseline between the two groups were as follows: - 62.7% at 1 year (95% Confidence Interval (CI): - 91.0 to - 34.1%), - 48.9% at 2 years (95% CI: - 79.4 to - 19.3%), and - 63.8% at 3 years (95% CI: - 107.4 to - 20.2%). Additionally, the present study examined the impact of combining esaxerenone with SGLT2 inhibitors and GLP-1 receptor agonists and showed consistent effects on UACR irrespective of these medications. Esaxerenone slightly lowered eGFR with a low risk of hyperkalemia but did not adversely impact glucose metabolism.

Conclusions: Esaxerenone exerted antihypertensive and antialbuminuric effects in patients with type 2 diabetes, diabetic kidney disease, and hypertension.

Gastrointestinal hormones that potentiate insulin secretion from pancreatic β-cells are called incretins. Glucose-dependent insulinotropic polypeptide/gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the major incretins. Incretin-mediated stimulation of insulin secretion (incretin effect) plays an important role in lowering postprandial blood-glucose levels. Incretin effect is reduced under diabetic condition. Several mechanisms have been reported for the reduction of incretin effect. Incretin-related drugs are used worldwide for the treatment of type 2 diabetes. In addition, several new incretin-related drugs have been developed and are expected to be available in clinical practice.

Aim: Oral health is important in patients with diabetes. While health literacy may promote preventive dental visits, the evidence is sparse among them. Additionally, because education is indicated as a determinant of health literacy, none clarified whether health literacy can mitigate educational inequalities in healthcare-seeking behaviors. We examined combined associations of education and health literacy with preventive dental visits in patients with diabetes.

Methods: We used cross-sectional data from the Japan COVID-19 and Society Internet Survey (JACSIS) in 2020. We included 1441 patients reporting to have diabetes currently. Educational level was self-reported. Health literacy was measured using the validated scale. Preventive dental visits in the past 12 months were self-reported. We estimated multivariable-adjusted prevalence ratio (PR) for preventive dental visits.

Results: 54% of the participants had preventive dental visits; 35% had high health literacy. Overall, high health literacy was significantly associated with preventive dental visits. Being more educated and/or having high health literacy were associated with an increased prevalence of preventive dental visits (P for trend < 0.001). Compared with less education and low health literacy group, adjusted PRs (95% confidence intervals) of preventive dental visits were 1.10 (0.93, 1.31) for less education and high health literacy group, 1.14 (1.00, 1.30) for more education and low health literacy group, and 1.29 (1.13, 1.48) for more education and high health literacy group.

Conclusions: The present data suggest that health literacy may help promote preventive dental visits and do not deny the possibility that health literacy can mitigate educational inequalities in patients with diabetes.

Supplementary information: The online version contains supplementary material available at 10.1007/s13340-024-00780-z.

Endoplasmic reticulum (ER) stress due to obesity or systemic insulin resistance is an important pathogenic factor that could lead to pancreatic β-cell failure. We have previously reported that CCAAT/enhancer-binding protein β (C/EBPβ) is highly induced by ER stress in pancreatic β cells. Moreover, its accumulation hampers the response of these cells to ER stress by inhibiting the induction of the molecular chaperone 78 kDa glucose-regulated protein (GRP78). We also demonstrated that C/EBPβ is phosphorylated by CK2, which is reportedly associated with the ER stress signal. In the present study, we aimed to clarify the mechanisms underlying the effect of CK2 on pancreatic β cells using a CK2-specific inhibitor, CX4945, and shRNA-mediated knockdown and overexpression of CK2β, the regulatory subunit of CK2. The results indicate that CK2 was activated in MIN6 cells under ER stress and in pancreatic β cells of a diabetic mouse model. Under normal conditions, CK2 interacted with FL-ATF6α in MIN6 cells and regulated the expression of GRP78 and ERAD-associated proteins. Mechanistically, CK2 activation in MIN6 cells upon the overexpression of the CK2β subunit reduced ER stress signals and the accumulation of unfolded proteins via an increase in GRP78 and ERAD-associated protein levels. These results highlight the important role of CK2 in protecting against ER stress-induced apoptosis by regulating GRP78 and ERAD proteins. CK2 contributed to the clearance of unfolded or misfolded proteins in MIN6 cells under both normal and ER stress conditions. Therefore, CK2 activation could be a promising novel approach for preventing type 2 diabetes.

Supplementary information: The online version contains supplementary material available at 10.1007/s13340-024-00775-w.

The prevalence of diabetes has increased rapidly in recent years, and many types of therapeutic agents have been developed. However, the main purpose of these drugs is to lower blood glucose levels, and they are not fundamental solutions. In contrast, our research has been aimed at stimulating and inducing β-cell proliferation in vivo and replenishing β-cells. We demonstrated that pancreatic ductal cells are a source of β-cells both after birth and during regeneration after partial duct ligation: cell lineage tracing showed that 39% of growing islets and 50% of adult islets during tissue regeneration contained β-cells differentiated from duct cells. We also examined the factors contributing to β-cell depletion. Insulin and cyclin A genes are tightly regulated by transcriptional activators and repressors, and we found that imbalanced and excessive levels of repressors result in a drastic reduction of insulin and β-cell numbers, leading to severe diabetes. Thus, we searched for factors that induce β-cell proliferation in vivo. In our transgenic (Tg) mice, there was a sex difference in the progression of diabetes and sex steroid hormones were shown to contribute to this. Surprisingly, in diabetic male Tg mice, modulation of sex steroid hormones under certain conditions resulted in a marked increase of β-cells. We identified Greb1 as a factor inducing β-cell proliferation in response to a rapid elevation of E2 levels. This series of studies has demonstrated that islet cells exhibit plasticity and indicates that changes of islet cell mass and function are dynamic and recoverable.

The hybrid closed-loop (HCL) system, Medtronic MiniMed^™ 770G, has been available for use by Japanese individuals with type 1 diabetes mellitus since 2021. The aim of this study was to evaluate the effect of its use on glycemic variability and quality of life (QOL) in this population. This multicenter, open-label, prospective observational study included 14 Japanese individuals with type 1 diabetes mellitus treated with MiniMed^™ 640G. Participants who switched to the 770G system were evaluated for time in range (TIR) and other glycemic outcomes at baseline and at 3 and 12 months post-transition. QOL was assessed using the Diabetes Therapy-Related QOL (DTR-QOL) scale. The mean baseline glycated hemoglobin was 7.52 ± 1.05%, and body mass index (BMI) was 21.78 ± 3.07 kg/m². By study completion, individuals used the HCL system approximately 80% of the time in a day. TIR showed improvement, with an increased achievement ratio of TIR > 70% at 12 months. Hypoglycemia occurrence was minimal at 12 months. In addition, all-time sensor glucose measurements decreased after 12 months, and there were no significant changes in BMI or daily insulin dose. DTR-QOL scores did not significantly differ, possibly owing to increased total alarms and sensor calibration times. Transitioning to the Medtronic MiniMed^™ 770G system led to an improved achievement ratio of TIR > 70% and reduced hyperglycemia at 12 months. However, no significant change in QOL was observed, probably because of the increased number of total alarms.

Supplementary information: The online version contains supplementary material available at 10.1007/s13340-024-00778-7.

Background: Depression and gestational diabetes mellitus (GDM) pose significant challenges during pregnancy. Limited literature exists on depression in women with GDM, with most studies focusing on pre-pregnancy diabetes or postpartum depression. This study fills a crucial gap by specifically investigating and comparing antenatal depression among subjects with and without GDM in Bangladesh, utilizing data from the gestational period.

Methods: A cross-sectional study with a convenient, purposive sampling technique was undertaken among 111 pregnant women with (66) and without (45) GDM from September 2017 to March 2018 in the BIRDEM-2 GENERAL HOSPITAL, Dhaka. A semi-structured interview schedule was designed with items relevant to socio-demographics, obstetric history, diabetes, and depression.

Results: Different degrees of antenatal depression were identified in 61.3% of the subjects (i.e., 27% had mild, 4.5% had moderate, and 29.7% had severe depression, respectively). Out of 45 non-diabetic mothers, 11 (24.4%) had depression whereas out of 66 GDM mothers, 57 (86.4%) have depression. The exploratory analysis revealed that age group, menstruation history, and presence of GDM significantly affected depression but the multiple logistic regression model supported only GDM as a significant factor of depression. All the socio-demographic factors in this study were statistically insignificant to explain depression.

Conclusion: The risk of developing depressive symptoms increases with the presence of GDM. Therefore, it is important to screen for depression and provide treatment if necessary in women who are diagnosed with GDM.