Journal of diabetes and its complications最新文献

Diabetes mellitus is a metabolic disorder caused by a dysfunction in insulin action or secretion, leading to an elevation in blood glucose levels. It is a highly prevalent condition and as a result, the NHS spends 10 % of its entire budget on diabetes mellitus care, that is equivalent to £10 billion a year. Diabetes mellitus has been linked with vascular and neurological complications which may be associated with the progression of neurodegeneration and Alzheimer's disease. Chronic hyperglycaemia increases the production of the reactive oxidant species (ROS) such as methylglyoxal (MGO). MGO has been linked with vascular complications, neuropathy and cytotoxicity. The main aim of this study was to investigate the potential beneficial effect of antidiabetic agents such as metformin and dapagliflozin on human brain neuronal cells (SH-SY5Y) treated with MGO. SH-SY5Y cells were cultured in DMEM/F12 media and subjected overnight incubation with one of the following treatment conditions: Control (untreated); MGO (1 μM); MGO (100 μM); metformin (100 μM) + MGO (100 μM); and dapagliflozin (10 μM) + MGO (100 μM). Several assays were conducted to explore the effect of the treatment groups on the SH-SY5Y cells. These included: MTT assay; LDH assay, peroxynitrite fluorescence assay, and laser scanning confocal microscopy. MGO (100 μM) led to significant cell injury and damage and significantly reduced the survival of the cells by approximately 50–75 %, associated with significant increase in peroxynitrite. The addition of metformin (100 μM) or dapagliflozin (10 μM) represented significant protective effects on the cells and prevented the cell damage caused by the high MGO concentration. As a result, the findings of this research reveal that MGO-induced cell damage may partly be mediated by the generation of peroxynitrite, while the antidiabetic agents such as metformin and dapagliflozin prevent brain cell death, which potentially may play prophylactic roles against the risk of dementia in diabetic patients.

Introduction

Sodium glucose co-transporter-2 inhibitors (SGLT-2i) are increasingly being used among hospitalized patients. Our objective was to assess the risk of diabetic ketoacidosis (DKA) among hospitalized patients receiving an SGLT-2i.

Research design and methods

We conducted a multicentre cohort study of patients hospitalized at 19 hospitals. We included patients over 18 years of age who received an SGLT-2i or a dipeptidyl peptidase-4 inhibitor (DPP-4i) in hospital. The primary outcome was the risk of DKA during their hospitalization.

Results

61,517 patients received a DPP-4i and 11,061 received an SGLT-2i. The risk of inpatient DKA was 0.07 % (N = 41 events) among adults who received a DPP-4i and 0.18 % (N = 20 events) among adults who received an SGLT-2i; adjusted odds ratio of 3.30 (95 % CI: 1.85–5.72).

Conclusions

In hospitalized patients, the absolute risk of DKA was 0.2 %, which corresponded to a three-fold higher relative risk.

A type 1 diabetes (T1D) diagnosis is often followed by a period of reduced exogenous insulin requirement, with acceptable glucose control, called partial clinical remission (pCR). Various criteria exist to define pCR, which is associated with better clinical outcomes.

We aimed to develop formulae and a related online calculator to predict the probability of pCR at 3- and 12-months post-T1D diagnosis.

We analysed data from 133 adults at their T1D diagnosis (mean ± SD age: 27 ± 6 yrs., HbA1c 11.1 ± 2.0 %, 98 ± 22 mmol/mol), 3- and 12-months later. All patients were enrolled in the prospective observational InLipoDiab1 study (NCT02306005). We compared four definitions of pCR: 1) stimulated C-peptide >300 pmol/l; 2) insulin dose-adjusted HbA1c ≤9 %; 3) insulin dose <0.3 IU/kg/24 h; and HbA1c ≤6.4 % (46 mmol/mol); and 4) insulin dose <0.5 IU/kg/24 h and HbA1c <7 % (53 mmol/mol). Using readily available demographics and clinical chemistry data exhaustive search methodology was used to model pCR probability.

There was low concordance between pCR definitions (kappa 0.10). The combination of age, HbA1c, diastolic blood pressure, triglycerides and smoking at T1D onset predicted pCR at 12-months with an area under the curve (AUC) = 0.87. HbA1c, triglycerides and insulin dose 3-mths post-diagnosis had an AUC = 0.89. A related calculator for pCR in adult-onset T1D is available at http://www.bit.ly/T1D-partial-remission.

Aim

This study aimed to investigate the short-and long-term effect on diabetic retinopathy (DR) in individuals with type 1 diabetes treated with continuous subcutaneous insulin injections (CSII) compared to those using multiple daily injections (MDI).

Methods

We conducted a register-based matched cohort study utilizing data from the Danish Registry of Diabetic Retinopathy as well as several other national Danish health registers. Our cohort consisted of all individuals with type 1 diabetes who attended the Danish screening program for DR from 2013 to 2022. We included individuals registered with CSII treatment, and compared them to individuals using MDI, matched by age, sex, and DR level. Cox regression analysis was performed to evaluate the outcomes.

Results

The study included 674 individuals treated with CSII and 2006 matched MDI users. In our cohort 53.4 % were female and median age was 36 (IQR 27–47). Average follow-up risk-time was 4.8 years. There was no difference in the risk of DR worsening between the CSII group and MDI group (HR 1.05 [95%CI 0.91; 1.22], p = 0.49). However, an increased risk of focal photocoagulation was observed in the CSII group (HR 2.40 [95%CI 1.11; 5.19], p = 0.03).

Conclusions

Our findings indicate that CSII treatment does not confer a significant difference in the overall short- and long-term risk of DR worsening or ocular intervention compared to MDI treatment. These results provide insights into the DR outcomes of CSII treatment in individuals with type 1 diabetes.

Aims

This study assessed whether changes associated with cerebral small vessel disease (CSVD) evaluated from head computed tomography (CT) images captured for non-related clinical purposes predict overall survival (OS), leg salvage (LS), and amputation-free survival (AFS) after lower extremity amputation (LEA).

Methods

We retrospectively included a cohort of 240 patients who had undergone a lower extremity amputation in Tampere University Hospital between the years 2007 and 2020 and had a head CT scan (within one year before amputation). A neuroradiologist graded the white matter lesions (WMLs) and reported infarcts, and the latter's effects on OS, LS, and AFS were evaluated.

Results

Altogether, 162 (67.5 %) and 91 (38.1 %) patients had WMLs and infarcts, respectively. Mild/moderate (HR 1.985, CI 95 % 1.317–2.992) and severe (HR 2.259, CI 95 % 1.501–3.399) WMLs and infarcts (HR 1.413, CI 95 % 1.029–1.940) were associated with inferior OS. After a minor amputation, mild/moderate (HR 2.012, CI 95 % 1.054–3.843) and severe (HR 3.879, CI 95 % 2.096–7.180) WMLs were similarly associated with inferior AFS.

Conclusions

Overall, WML and infarcts detected on head CT scans were associated with impaired OS after LEA and AFS after minor LEA. Evaluation of CSVD could provide useful prognostic information for clinicians.

Aims

This study examined serum cytochrome P450-soluble epoxide hydrolase (CYP450-sEH) oxylipins and depressive symptoms together in relation to cognitive performance in individuals with type 2 diabetes mellitus (T2DM).

Methods

Clinically cognitively normal T2DM individuals were recruited (NCT04455867). Depressive symptom severity was assessed using the Beck Depression Inventory-II (BDI-II; total scores ≤13 indicated minimal depressive symptoms and ≥ 14 indicated significant depressive symptoms). Executive function and verbal memory were assessed. Fasting serum oxylipins were quantified by ultra-high-performance liquid chromatography tandem mass-spectrometry.

Results

The study included 85 participants with minimal depressive symptoms and 27 with significant symptoms (mean age: 63.3 ± 9.8 years, 49 % women). In all participants, higher concentrations of linoleic acid derived sEH (12,13-dihydroxyoctadecamonoenoic acid; DiHOME) and CYP450 (12(13)-epoxyoctadecamonoenoic acid; EpOME) metabolites were associated with poorer executive function (F_1,101 = 6.094, p = 0.015 and F_1,101 = 5.598, p = 0.020, respectively). Concentrations of multiple sEH substrates interacted with depressive symptoms to predict 1) poorer executive function, including 9(10)-EpOME (F_1,100 = 12.137, p < 0.001), 5(6)-epoxyeicosatrienoic acid (5(6)-EpETrE; F_1,100 = 6.481, p = 0.012) and 11(12)-EpETrE (F_1,100 = 4.409, p = 0.038), and 2) verbal memory, including 9(10)-EpOME (F_1,100 = 4.286, p = 0.041), 5(6)-EpETrE (F_1,100 = 6.845, p = 0.010), 11(12)-EpETrE (F_1,100 = 3.981, p = 0.049) and 14(15)-EpETrE (F_1,100 = 5.019, p = 0.027).

Conclusions

Associations of CYP450-sEH metabolites and depressive symptoms with cognition highlight the biomarker and therapeutic potential of the CYP450-sEH pathway in T2DM.

Aim

To determine the association between atherogenic markers, such as total cholesterol/high density lipoprotein cholesterol ratio (TC/HDL-C), triglycerides/HDL-C ratio (TG/HDL-C), and triglycerides-glucose index (TyG), and the risk of 1-year amputation in adults with diabetic foot in a tertiary level hospital.

Methods

Retrospective cohort study conducted in 162 adult patients with diabetic foot. The outcome was amputation, defined as “primary amputation in patients' clinical history after their first hospitalization due to foot ulcer.”. The cutoff point was determined using Youden's J statistic. The relative risk (RR) was presented as an association measure.

Results

A TyG index of >9.4 [RR: 1.64 (1.10–2.45)] was associated with a high risk of amputation after 1-year in adults with diabetic foot. However, while a TC/HDL ratio of >4.69 [RR: 1.38 (0.94–2.03)] and a TG/HDL-C ratio > 3.57 [RR: 1.35 (0.89–2.06)] did not show associations with risk of amputation after 1-year.

Conclusions

Only a TyG index of >9.4 was associated with an increased risk of 1-year amputation in adults with diabetic foot. Future studies with larger samples and a longitudinal design may provide more robust evidence and a better understanding of clinical implications.

Objective

Diabetic foot ulcers (DFU) are a major sequela of uncontrolled diabetes with a high risk of adverse outcomes. Poor DFU outcomes disproportionately impact patients living in rural and economically distressed communities with lack of access to consistent, quality care. This study aimed to analyze the risk of geographic and economic disparities, including rural status and county economic distress, on the disease burden of DFU at presentation utilizing the SVS WIfI classification system.

Methods

We conducted a retrospective review of 454 patients diagnosed with a DFU from 2011 to 2020 at a single institution's inpatient and outpatient wound care service. Patients >18 years old, with type II diabetes mellitus, and diabetic foot ulcer were included.

Results

ANCOVA analyses showed rural patients had significantly higher WIfI composite scores (F(1,451) = 9.61, p = .002), grades of wound (F(1,439) = 11.03, p = .001), and ischemia (F(1,380) = 12.574, p = .001) compared to the urban patients. Patients that resided in at-risk economic counties had significantly higher overall WIfI composite scores (F(2,448) = 3.31, p = .037) than patients who lived in transitional economic counties, and higher foot infection grading (F(2,440) = 3.02, p = .05) compared to patients who lived in distressed economic counties. DFU patients who resided in distressed economic counties presented with higher individual grades of ischemia (F(2, 377) = 3.14, p = .04) than patients in transitional economic counties. Chi-Square analyses demonstrated patients who resided in urban counties were significantly more likely to present with grade 1 wounds (χ2(3) = 9.86, p = .02) and grade 0 ischemia (χ2(3) = 16.18, p = .001) compared to patients in rural areas. Economically distressed patients presented with significantly less grade 0 ischemia compared to patients in transitional economic counties (χ2(6) = 17.48, p = .008).

Conclusions

Our findings are the first to demonstrate the impact of geographic and economic disparities on the disease burden of DFU at presentation utilizing the SVS WIfI classification system. This may indicate need for improved multidisciplinary primary care prevention strategies with vascular specialists in these communities to mitigate worsening DFU and promote early intervention.