World Journal of Diabetes最新文献

Patients with type 1 diabetes mellitus (T1DM) experience multiple episodes of hypoglycemia, resulting in dysfunctional counter-regulatory responses with time. The recent experimental study by Jin et al explored the role of intestinal glucagon-like peptide-1 (GLP-1) in impaired counter-regulatory responses to hypoglycemia. They identified intestinal GLP-1 along with GLP-1 receptor (GLP-1R) as the new key players linked with impaired counter-regulatory responses to hypoglycemia in type 1 diabetic mice. They also demonstrated that excessive expression of GLP-1 and GLP-1R was associated with attenuated sympathoadrenal responses and decreased glucagon secretion. The study has enormous clinical relevance as defective counter regulation and hypoglycemia unawareness negatively impacts the intensive glycemic management approach in this group of patients. However, the physiological processes must be validated in dedicated human studies to comprehensively understand the pathophysiology of this complex relationship, and to clarify the true extent of impaired hypoglycemia counter regulation by intestinal GLP-1. For now, following the results of the index study and other similar studies, GLP-1 analogues usage in T1DM must be carefully monitored, as there is an inherent risk of worsening the already impaired counter-regulatory responses in these patients. Further studies in the future could identify other key players involved in this clinically relevant interaction.

Diabetic osteoporosis (DOP) is a serious complication of diabetes mellitus. It is urgent to explore efficient clinical treatment strategies for DOP. It has been found that mesenchymal stem cell-derived extracellular vesicles (MSC-EVs), as an emerging cell-free therapy, show great potential in DOP treatment. MSC-EVs can effectively promote bone formation, inhibit bone resorption, and modulate the inflammatory microenvironment by delivering cargoes of microRNAs, long non-coding RNAs, and proteins to target cells, thereby ameliorating bone loss in DOP. However, there are limited reports on the treatment of DOP with MSC-EVs. To evoke more attention to this potential strategy, this article summarised the extant literature on MSC-EVs for DOP to provide new directions for further research and to promote the application of MSC-EVs in the clinical management of DOP.

Diabetes is one of the most devastating medical dilemmas impacting every region of the world severely. The study by Tian et al investigates glymphatic system dysfunction in the context of glucose metabolism and diabetes, using diffusion tensor imaging along the perivascular space. The study evaluated individuals with type 2 diabetes mellitus (T2DM), prediabetes, and normal glucose metabolism. It found that prediabetic and T2DM groups had significantly impaired glymphatic function. Glymphatic dysfunction may serve as an early indicator of cognitive deterioration in diabetes due to the correlations shown between these abnormalities and clinical factors as well as cognitive performance. The study has some positives, such as thorough evaluations and novel imaging methods, but its cross-sectional design and limited sample size restrict its applicability. More extensive, long-term research is required to verify these results. Furthermore, there are significant clinical implications. Patients with diabetes may benefit from immediate therapies to prevent microvascular and macrovascular damage if glymphatic dysfunction is identified early. The study promotes comprehensive diabetes care with a focus on maintaining cognitive function. In conclusion, the work of Tian et al is crucial because it opens the door to better treatment and diagnostic strategies for diabetes-related cognitive deterioration.

Diabetes is one of the most catastrophic diseases ruling every corner of the world, and this has led to elevated incidents of end-stage kidney disease (ESKD). The standard treatment for ESKD is kidney transplantation/replacement, which is limited due to a deficiency of donors. Hence, dialysis has become the second-best option for treating patients with ESKD. Patients with ESKD with underlying diabetes have an additional risk of complications and infections over non-diabetic ESKD patients. Furthermore, these patients also experience variations in blood glucose levels and are more liable to develop malnutrition. This article elaborates on the different dialysis methods for ESKD patients. This editorial highlights the evidence-based studies that include randomized clinical trials, cohort studies, retrospective studies and case-control studies and suggests the most suitable type of dialysis under the following components.

Background: Glomerular endothelial cell (GENC) injury is a characteristic of early-stage diabetic nephropathy (DN), and the investigation of potential therapeutic targets for preventing GENC injury is of clinical importance.

Aim: To investigate the role of β-arrestin-2 in GENCs under DN conditions.

Methods: Eight-week-old C57BL/6J mice were intraperitoneally injected with streptozotocin to induce DN. GENCs were transfected with plasmids containing siRNA-β-arrestin-2, shRNA-activating transcription factor 6 (ATF6), pCDNA-β-arrestin-2, or pCDNA-ATF6. Additionally, adeno-associated virus (AAV) containing shRNA-β-arrestin-2 was administered via a tail vein injection in DN mice.

Results: The upregulation of β-arrestin-2 was observed in patients with DN as well as in GENCs from DN mice. Knockdown of β-arrestin-2 reduced apoptosis in high glucose-treated GENCs, which was reversed by the overexpression of ATF6. Moreover, overexpression of β-arrestin-2 Led to the activation of endoplasmic reticulum (ER) stress and the apoptosis of GENCs which could be mitigated by silencing of ATF6. Furthermore, knockdown of β-arrestin-2 by the administration of AAV-shRNA-β-arrestin-2 alleviated renal injury in DN mice.

Conclusion: Knockdown of β-arrestin-2 prevents GENC apoptosis by inhibiting ATF6-mediated ER stress in vivo and in vitro. Consequently, β-arrestin-2 may represent a promising therapeutic target for the clinical management of patients with DN.

Background: Limited joint mobility is the proven risk factor for diabetic foot ulceration when present in the subtalar and first metatarsophalangeal joints. Evidence shows that a foot-related exercise program, combined with a health-promoting program, can improve the signs and symptoms of diabetic polyneuropathy, enhance gait, restore mobility in the foot and ankle joints, redistribute pressure while walking, and increase foot strength and function. As a result, these exercise programs can help mitigate the risk factors for diabetic foot ulceration.

Aim: To determine the effect of supervised stretching, strengthening, functional and walking exercises on joint mobility and muscle strength in patients with diabetic polyneuropathy.

Methods: This was a randomized controlled trial conducted in a tertiary hospital. The study included 82 participants allocated into the intervention group (alpha-lipoic acid and exercise on 15 consecutive therapeutic days, n = 42) and control group (alpha lipoic acid only, n = 40). Muscle strength included dorsal and plantar flexors dynamometry and strength score, while range of motion included ankle, subtalar and first metatarsophalangeal joint goniometry.

Results: Change of motion range was significantly higher in the intervention group compared to the control group regarding ankle joint on day 15 (9.9 ± 7.2 vs 0.1 ± 3.3; P = 0.006) and month 6 (2.8 ± 7.3 vs -0.9 ± 4.1; P < 0.001), subtalar joint on day 15 (7.5 ± 5.1 vs -0.25 ± 2.25; P < 0.001) and month 6 (3.9 ± 6.4 vs -0.13 ± 3.49; P < 0.001). Change in dorsal flexors was significantly higher in the intervention group compared to the control group on day 15 (2.62 ± 1.69 vs 0.10 ± 1.35; P < 0.001) and month 6 (0.66 ± 2.38 vs -0.75 ± 1.94; P = 0.004) as well as plantar flexors on day 15 (3.3 ± 1.6 vs 0.3 ± 1.5; P < 0.001) and month 6 (1.8 ± 2.2 vs -0.9 ± 2.1; P < 0.001). Muscle strength score change was significantly lower in the intervention group compared to the control group on day 15 (-1.45 ± 1.42 vs -0.03 ± 0.16; P < 0.001) and month 6 (-1.17 ± 1.53 vs 0.20 ± 0.56; P < 0.001).

Conclusion: Exercise in combination with alpha-lipoic acid can improve joint mobility, as well as strength of the foot and lower leg muscles in patients with diabetic polyneuropathy.

Background: Shikonin is a natural remedy that is effective at treating diabetic wounds. NFAT5 is a potential therapeutic target for diabetes, and mitochondrial function is essential for wound healing. However, the relationship among Shikonin, NFAT5, and mitochondrial function has not been thoroughly studied. Here, we offer new perspectives on the advantages of shikonin for managing diabetes.

Aim: To assess the therapeutic mechanism of shikonin in diabetic wounds, its relationship with NFAT5, and its protection of mitochondrial function.

Methods: Hypertonic cell and diabetic wound mouse models were established. NFAT5 expression was measured through western blotting and immunofluorescence, in vivo and in vitro. Mitochondrial function was evaluated using reactive oxygen species (ROS) detection and JC-1 and Calcein AM dyes. Mitochondrial structures were observed using transmission electron microscopy. The NFAT5/AMPK pathway was analyzed using a transfection vector and an inhibitor. The effect of shikonin on cells under hypertonic conditions via the NFAT5/AMPK pathway was assessed using western blotting.

Results: Shikonin treatment preserved HaCaT cell viability, while significantly reducing cyclooxygenase-2 expression levels in a high-glucose environment (P < 0.05). Additionally, shikonin maintained mitochondrial morphology, enhanced membrane potential, reduced membrane permeability, and decreased ROS levels in HaCaT cells under hyperosmolar stress. Furthermore, shikonin promoted wound healing in diabetic mice (P < 0.05). Shikonin also inhibited NFAT5, in vivo and in vitro (P < 0.05). Shikonin treatment reduced NFAT5 expression levels, subsequently inhibiting AMPK expression in vitro (P < 0.05). Finally, shikonin inhibited several key downstream molecules of the NFAT5/AMPK pathway, including mammalian target of rapamycin, protein kinase B, nuclear factor kappa-light-chain-enhancer of activated B cells, and inducible nitric oxide synthase (P < 0.05).

Conclusion: Shikonin protects mitochondria via the NFAT5/AMPK-related pathway and enhances wound healing in diabetes.

Background: Familial partial lipodystrophy disease (FPLD) is a collection of rare genetic diseases featuring partial loss of adipose tissue. However, metabolic difficulties, such as severe insulin resistance, diabetes, hypertriglyceridemia, and hypertension frequently occur alongside adipose tissue loss, making it susceptible to misdiagnosis and delaying effective treatment. Numerous genes are implicated in the occurrence of FPLD, and genetic testing has been for conditions linked to single gene mutation related to FPLD. Reviewing recent reports, treatment of the disease is limited to preventing and improving complications in patients.

Case summary: In 2017, a 31-year-old woman with diabetes, hypertension and hypertriglyceridemia was hospitalized. We identified a mutation in her peroxisome proliferator-activated receptor gamma (PPARG) gene, Y151C (p.Tyr151Cys), which results in a nucleotide substitution residue 452 in the DNA-binding domain (DBD) of PPARG. The unaffected family member did not carry this mutation. Pioglitazone, a PPARG agonist, improved the patient's responsiveness to hypoglycemic and antihypertensive therapy. After one year of treatment in our hospital, the fasting blood glucose and glycosylated hemoglobin of the patient were close to normal.

Conclusion: We report a rare PPARG mutation, Y151C, which is located in the DBD of PPARG and leads to FPLD, and the preferred agent is PPARG agonists. We then summarized clinical phenotypic characteristics of FPLD3 caused by PPARG gene mutations, and clarified the relationship between different mutations of PPARG gene and the clinical manifestations of this type of FPLD. Additionally, current treatments for FPLD caused by PPARG mutations are reviewed.

Background: Chronic hyperglycemia can damage the microcirculation, which impairs the function of various organs and tissues and predisposes individuals to chronic complications. Sarcopenia (SP) is the age-related decline in muscle mass and function that contributes to the sequelae of type 2 diabetes. In particular, diabetic patients are at higher risk of SP because of insulin resistance, chronic inflammation, and decreased physical activity.

Aim: To identify SP-associated factors in middle-aged and elderly male type 2 diabetes mellitus (T2DM) patients and their correlation with bone mineral density (BMD).

Methods: A retrospective analysis was conducted on 196 middle-aged and elderly male T2DM inpatients in the First Affiliated Hospital of Chongqing Medical University between June 2021 and June 2023, with 60 concurrent healthy individuals as the control group. Differences in general information, blood biochemistry, glycosylated hemoglobin, muscle strength, and detection rate of SP were compared between groups. The BMD, appendicular skeletal muscle (ASM), and fat mass, as well as grip strength and gait speed, were determined for each patient, and the ASM index (ASMI) was counted. The quantitative data were subjected to correlation and logistic regression analyses to identify risk factors for SP.

Results: Fifty-one of the 196 middle-aged and elderly male T2DM patients were diagnosed with SP, which accounted for 26.02%. The middle-aged and elderly T2DM patients with SP exhibited a longer diabetes mellitus (DM) course and a lower body mass index (BMI) and 25(OH)D₃ compared with the non-SP patients. The T2DM + SP patients exhibited lower BMI, ASM, ASMI, left- and right-hand grip strength, gait speed, and muscle and fat mass of the upper and lower limbs compared with the diabetic non-SP patients. The femoral neck, total hip, and lumbar spine L_1-4 BMD were markedly lower in T2DM + SP patients compared with those in the non-SP diabetics. Long-term DM course, low BMI, and low BMD of the femoral neck, lumbar spine L_1-4, and total hip were identified as risk factors for the development of SP.

Conclusion: T2DM patients are at risk for SP; however, measures can be taken to prevent the related risk factors.

Background: Individuals with diabetes mellitus have a higher risk of developing malignant tumors, and diagnosing these tumors can be challenging.

Aim: To confirm the benefits of using peripherally inserted central catheters (PICCs) in contrast-enhanced computerized tomography (CECT) for diagnostic imaging in diabetic patients with malignant tumors and to provide a research basis for follow-up research.

Methods: This retrospective study analyzed 204 diabetic patients with malignancies treated at The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, from January 2024 to June 2024. The patients were divided into two groups: A control group (n = 102) with indwelling peripheral intravenous catheters and a research group (n = 102) with high-pressure-resistant PICC. The study compared baseline data, the incidence of iodine contrast extravasation during CECT, the incidence of adverse events (discomfort, redness and swelling at the puncture site, and blood oozing), imaging quality, nursing time, intubation success rate, number of venipuncture attempts, and catheter maintenance cost.

Results: Male patients accounted for 51.96% in the control group and 55.88% in the research group; the average age was (59.68 ± 11.82) years in the control group and (61.41 ± 12.92) years in the research group; the proportions of lung cancer, colorectal cancer, and gastric cancer patients in the control group were 42.16%, 38.24%, and 19.61%, respectively, while those in the research group were 34.31%, 37.25%, and 28.43%, respectively. Except for the gender distribution, age, and cancer type mentioned above, other general information such as underlying diseases, puncture location, and long-term chemotherapy shows no significant differences as tested (P > 0.05). The results showed that the research group had significantly reduced incidence of iodine contrast extravasation (7 vs 1, P = 0.031), similar incidence of adverse events (11 vs 7, P = 0.324), reduced nursing time [(18.50 ± 2.68) minutes vs (13.26 ± 3.00) minutes, P = 0.000], fewer venipuncture attempts [(2.21 ± 0.78) times vs (1.49 ± 0.58) times, P = 0.000], lower catheter maintenance cost [(1251.79 ± 205.47) China yuan (CNY) vs (1019.25 ± 117.28) CNY, P = 0.000], increased intubation success rate (16.67% vs 58.82%, P = 0.000), and better imaging quality (85.29% vs 94.12%, P = 0.038).

Conclusion: High-pressure-resistant PICCs can lessen the physical burden of diabetic patients during nursing, reduce treatment costs, and improve the efficiency and quality of imaging for diagnosis malignant tumors.