Complications In Diabetic Patients Research Articles

Circadian rhythm of plasminogen activator inhibitor-1 and cardiovascular complications in type 2 diabetes.

Cardiovascular complications are a common death cause in type 2 diabetes patients, as they are often combined. Plasminogen-activator Inhibitor 1 (PAI-1) participates in the development and progression of cardiovascular complications in diabetes. Insulin resistance increases PAI-1 production, and high PAI-1 levels lead to an environment conducive to thrombosis and earlier and more severe vascular disease. Current evidence also suggests that PAI-1 has a rhythmic profile of circadian fluctuations and acrophase in the morning within a single day, which might explain the high morning incidence of cardiovascular events. Thus, PAI-1 is a possible drug target. Although several PAI-1 inhibitors have been developed, none have yet been allowed for clinical use. Research on rhythm has also led to the concept of "chronotherapy", a rhythm-based drug regimen expected to improve the treatment of cardiovascular complications in diabetic patients. Herein, we searched several databases and reviewed relevant articles to describe the circadian rhythm characteristics and endogenous molecular mechanisms of PAI-1, its relationship with insulin resistance, the causes of cardiovascular complications caused by PAI-1, and the current development of PAI-1 inhibitors. We also summarized the possibility of using the circadian rhythm of PAI-1 to treat cardiovascular complications in diabetic patients.

Prevalence, management and complications of diabetic patients in Pabna city

Prevalence, management and complications of diabetic patients in Pabna city

Synthesis, in-Silico studies and biological evaluation of pyrimidine based thiazolidinedione derivatives as potential anti-diabetic agent

Despite the advancements in the management of Diabetes mellitus, the design and synthesis of drug molecule which ameliorates the hyperglycemia and associated secondary complications in diabetic patients, still remains a challenge. Herein, we report the synthesis, characterization and anti-diabetic evaluation of pyrimidine-thiazolidinedione derivatives. The synthesized compounds were characterized by 1H NMR, 13C NMR, FTIR and Mass Spectroscopic analytical techniques. The in-silico ADME studies depicted that the compounds were within the permissible limits of the Lipinski’s rule of five. The compounds 6e and 6m showing the best results in OGTT were evaluated for in-vivo anti-diabetic evaluation in STZ induced diabetic rats. Administration of 6e and 6m for four weeks decreased the blood glucose levels significantly. Compound 6e (4.5 mg/kg p.o.) was the most potent compound of the series. It reduced the level of blood glucose to 145.2 ± 1.35 compared to the standard Pioglitazone (150.2 ± 1.06). Moreover, the 6e and 6m treated group did not show increase in bodyweight. The biochemical estimations showed that the levels of ALT, ASP, ALP, urea, creatinine, blood urea nitrogen, total protein and LDH restored to normal in 6e and 6m treated groups as compared to STZ control group. The histopathological studies supported the results obtained in biochemical estimations. Both the compounds did not show any toxicity. Moreover, the histopathological studies of pancreas, liver, heart and kidney revealed that the structural integrity of these tissues restored to almost normal in 6e and 6m treated groups as compared to STZ control group. Based upon these findings it can be concluded that the pyrimidine-based thiazolidinedione derivatives represent novel anti-diabetic agents with least side effects.

Healing mechanism of diabetic foot ulcers using single-cell RNA-sequencing.

Diabetic foot ulcer (DFU) is one of the common and severe complications in diabetic patients, mainly caused by the interaction of various factors such as peripheral neuropathy, peripheral vascular disease, and infection. Moreover, vascular damage, disorder of tissue cells, decreased expression level of neurotrophic factor, and decreased growth factor caused by long-term exposure to a high glucose environment can also lead to prolonged or incomplete wound healing. This imposes a tremendous financial burden on the patients' family and society. Although various innovative techniques and drugs have been developed to treat DFU, the therapeutic effect is still unsatisfactory. We filtered and downloaded the single-cell dataset of diabetic patients from the Gene Expression Omnibus (GEO) website and used the Seurat package in R for creation of single-cell objects, integration, control of quality, clustering, cell type identification, differential gene analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and intercellular communication analysis. Diabetic healing-related differentially expressed gene (DEG) analysis showed that there were 1,948 differential genes between tissue stem cells in healing and non-healing wounds, of which 1,198 genes were up-regulated and 685 genes were down-regulated. The results of GO functional enrichment analysis in tissue stem cells showed that they were closely related to wound healing. The CCL2-ACKR1 signaling pathway activity in tissue stem cells influenced the biological activity of endothelial cell subpopulation, which ultimately promoted the healing of DFU wounds. The CCL2-ACKR1 axis is closely associated with DFU healing.

MiR-223-3p mediates the diabetic kidney disease progression by targeting IL6ST/STAT3 pathway.

Diabetic kidney disease (DKD), the most pervasive complication in diabetic patients, has become a major health threat to the aging population. Our previous miRNA profiling identified hsa-miR-223-3p as a dysregulated miRNA in the DKD samples, which may serve as a biomarker for DKD diagnosis. However, the specific mechanism of miR-223-3p in the pathogenesis of DKD remains to be elucidated. In this study, we first verified that miR-223-3p level was significantly decreased in the invitro cell model and invivo db/db DKD model, accompanied with endothelial cell damage. Importantly, inhibiting the expression of miR-223-3p exacerbated high-glucose induced damages in Human Umbilical Vein Endothelial Cells (HUVECs) and Human Renal Glomerular Endothelial Cells (HRGECs), while miR-223-3p overexpression showed the opposite effect. We further demonstrated that miR-223-3p associated with IL6T mRNA and attenuated the progression of DKD by suppressing the downstream STAT3 activation, indicative of the implication of miR-223-3p/IL6T/STAT3 axis in the pathogenesis of DKD.

Matrix Metalloproteinase-2 (MMP-2) and-9 (MMP-9) Gene Variants and Microvascular Complications in Type 2 Diabetes Patients.

Vascular complications are the leading cause of increased morbidity and mortality of diabetic patients. It has been postulated that matrix metalloproteinases MMP-2 and MMP-9, zinc-dependent endopeptidases through remodeling of the extracellular matrix, can contribute to the onset and progression of diabetic vascular complications. The aim of our study was to assess whether there is a major difference in single nucleotide polymorphisms in the MMP-2 (at position -1306C˃T) and MMP-9 (at position -1562C˃T) gene in type 2 diabetic patients and healthy controls and to determine whether there is an association of these gene variants with the presence of microvascular complications in diabetic patients. Our study included 102 type 2 diabetes patients and a control group which was comprised of 56 healthy controls. All diabetic patients were screened for microvascular diabetes complications. Genotypes were detected by polymerase chain reactions followed by restriction analyses with specific endonucleases and their frequencies were determined. The MMP-2 variant -1306C>T showed a negative correlation with type 2 diabetes (p=0.028). It was also shown that the presence of the -1306C allele increases the probability of developing type 2 diabetes. This was a 2.2 fold increase and that the -1306 T allele has a protective role in regards to type 2 diabetes. The MMP-2 variant -1306T showed a negative correlation with diabetic polyneuropathy (p=0.017), meaning that allele-1306T has a protective role in regards to diabetic polyneuropathy while the presence of allele -1306C increases the probability of developing diabetic polyneuropathy by 3.4 fold. Our study showed that the MMP-2 gene variant (-1306C) doubles the risk of developing type 2 diabetes, and for the first time an association of this gene variant and the presence of diabetic polyneuropathy was shown.

Association between low‐carbohydrate diets and continuous glucose monitoring‐derived time in ranges

ABSTRACTAimsLow‐carbohydrate diets have become popular in the general community. The mutual relationship between the percentage of total energy intake from carbohydrates (CHO/E), glycemic control indices, and diabetes complications remains unclear.Materials and MethodsThis cross‐sectional study included 177 patients with type 2 diabetes mellitus who regularly visited outpatient clinics. In this study, dietary questionnaires were used to assess the intake ratio of the three macronutrients, and the low‐carbohydrate‐diet score was calculated. We investigated the association between the low‐carbohydrate‐diet score, continuous glucose monitoring (CGM)‐derived short‐term glycemic control indices, and diabetes complications in patients with type 2 diabetes mellitus.ResultsThe results are presented as medians (interquartile ranges) unless otherwise stated. Hemoglobin A1c was 7.1% (6.6–7.7%), CGM‐derived time in range (TIR) was 75.3% (62.8–87.0%), body mass index (BMI) was 24.0 (22.1–26.3) kg/m2, and CHO/E was 49.8% (44.8–55.6%). BMI, triglycerides, and CGM‐derived time above range decreased significantly with increasing low‐carbohydrate‐diet scores. However, no significant association was found between the low‐carbohydrate‐diet score and glycemic control indices, including TIR, mean amplitude of glycemic excursions, and vascular complications of type 2 diabetes mellitus.ConclusionModerate‐carbohydrate diets positively impact weight control and lipid metabolism but may have a limited effect on short‐term glycemic variability in Japanese patients with type 2 diabetes mellitus.

Consistency of 1-day and 3-day average dietary intake and the relationship of dietary intake with blood glucose, hbA1c, BMI, and lipids in patients with type 2 diabetes

Purpose: This study aimed to determine the consistency of 1-day and 3-day average dietary intake using the 24-hour diet recall method and to investigate the relationship of diet intake with physiological indicators potentially associated with diabetic complications in patients with diabetes.Methods: This study conducted a secondary data analysis using pretest data of a nursing intervention study entitled “Development of deep learning based AI coaching program for diabetic patients with high risk and examination of its effects (PNUH, IRB No. 05-2021-030).” Data were analyzed through descriptive analysis, one-way repeated-measures analysis of variance, and Pearson correlation coefficients using SPSS 26.0.Results: The average total daily calorie intake over 3 days was 1,494.48±436.47 kcal/day: 1,510.90±547.76 kcal/day on the first day, 1,414.22±527.58 kcal/day on the second day, 1,558.34±645.83 kcal/day on the third day, showing significant differences (F=3.59, p=.031). The correlation coefficient between the 1-day and 3-day average dietary intake was 0.41–0.77 for each nutrient and 0.62–0.80 for each food group. Vegetable intake showed negative correlations with body mass index (BMI; r=-.19, p=.023) and triglycerides (r=-.18, p=.036), whereas dairy intake was positively associated with low-density lipoprotein-cholesterol (LDL; r=-0.18, p=.034) and triglycerides (r=.40, p<.001).Conclusion: This study demonstrated that 1-day dietary intake was highly correlated with 3-day average dietary intake using the 24-hour diet recall method. Food groups showed significant associations with physiological indicators of potential diabetic complications such as BMI, triglycerides, and LDL levels. Further studies are needed to improve the knowledge base on the relationships between physiological indicators and food groups.

Post-Load Insulin Secretion Patterns are Associated with Glycemic Status and Diabetic Complications in Patients with Type 2 Diabetes Mellitus.

To examine whether the different patterns of post-load insulin secretion can identify the heterogeneity of type 2 diabetes mellitus (T2DM). Six hundred twenty-five inpatients with T2DM at Jining No. 1 People's Hospital were recruited from January 2019 to October 2021. The 140 g steamed bread meal test (SBMT) was conducted on patients with T2DM, and glucose, insulin, and C-peptide levels were recorded at 0, 60, 120, and 180 min. To avoid the effect of exogenous insulin, patients were categorized into three different classes by latent class trajectory analysis based on the post-load secretion patterns of C-peptide. The difference in short- and long-term glycemic status and prevalence of complications distributed among the three classes were compared by multiple linear regression and multiple logistic regression, respectively. There were significant differences in long-term glycemic status (e. g., HbA1c) and short-term glycemic status (e. g., mean blood glucose, time in range) among the three classes. The difference in short-term glycemic status was similar in terms of the whole day, daytime, and nighttime. The prevalence of severe diabetic retinopathy and atherosclerosis showed a decreasing trend among the three classes. The post-load insulin secretion patterns could well identify the heterogeneity of patients with T2DM in short- and long-term glycemic status and prevalence of complications, providing recommendations for the timely adjustment in treatment regimes of patients with T2DM and promotion of personalized treatment.

The relationship between physical activity and diabetes in middle-aged and elderly people.

To investigate the association between diabetes symptoms and physical activity (PA) levels among middle-aged and older Chinese adults. Data for this study were obtained from 2018 Charles data. Z test, logistic regression analysis, and linear hierarchical regression analysis were performed in 5352 individuals aged ≥50 years with complete information. In terms of diabetes, 6.8% of the middle-aged and elderly people with diabetes were detected, and 93.2% of the middle-aged and elderly people without diabetes symptoms. The proportion of middle-aged and elderly people with high PA levels was 50.5%, and the proportion of middle-aged and elderly people with low PA was 49.5%. There was a significant positive correlation between low PA and diabetes (P < .05). After adjusting demographic characteristics (gender, registered permanent residence type, education level, age, widowhood) and health status characteristics (poor mood, asthma, hyperlipidemia, disability, memory disease, self-assessment of health status, hypertension, smoking, stroke, depression), there was still a statistical significance between PA level and diabetes (P < .05). The risk of diabetes of middle-aged and elderly people in China increases with age, while the risk of diabetes of middle-aged and elderly people with low level of PA is higher. The risk of diabetes is high among middle-aged and elderly people who are old, have poor self-evaluation health, suffer from hyperlipidemia, memory disease, and asthma. The middle-aged and old people should increase their PA levels to prevent and improve diabetes.

Efficacy of acupuncture on cardiovascular complications in patients with diabetes mellitus in Korea: A nationwide retrospective cohort

ObjectiveThe main aim of this study is to investigate whether acupuncture could be an effective complementary treatment for reducing the risk of macrovascular complications in diabetic patients currently taking antidiabetic medications using a nationwide population-based database. MethodsWe conducted a retrospective cohort study to assess the efficacy of acupuncture on cardiovascular complications in diabetic patients using data from patients between 40 and 79 years of age, newly diagnosed with diabetes between 2003 and 2006, found in the National Health Insurance Service-National Sample Cohort (NHIS-NSC) in Korea. From the data, we identified 21,232 diabetic patients who were taking antidiabetic medication between 2003 and 2006. The selected patients were divided into two groups—those who received acupuncture at least three times and those who received no acupuncture (non-acupuncture) in the year following their diagnosis of diabetes. After 1:1 propensity score matching (PSM), each group had 3350 patients, and the observation ceased at the occurrence of a major adverse cardiovascular event (MACE), which was defined as either myocardial infarction, stroke, or death due to cardiovascular cause. ResultsAfter PSM, the acupuncture group had a lower incidence of MACE (hazard ratio [HR]: 0.87; 95% confidence interval [CI]: 0.81–0.94; P = 0.0003) and all-cause mortality (HR: 0.77; 95% CI: 0.70–0.84; P < 0.0001) than the non-acupuncture group; the HRs for stroke-related mortality (HR: 0.75; 95% CI: 0.56–1.00; P = 0.0485), ischemic heart disease mortality (HR: 0.53; 95% CI: 0.34–0.84; P = 0.006) and circulatory system disease mortality (HR: 0.67; 95% CI: 0.55–0.82; P < 0.0001) were lower in the acupuncture group than in the non-acupuncture group in the secondary analysis. ConclusionOur results indicate that diabetic patients receiving acupuncture treatment might have a lower risk of MACE, all-cause mortality and cardiovascular mortality. This population-based retrospective study suggests beneficial effects of acupuncture in preventing macrovascular complications associated with diabetes. These findings call for further prospective cohort or experimental studies on acupuncture treatment for cardiovascular complications of diabetes.Please cite this article as: Jung H, Won T, Kim GY, Jang J, Yeo S, Lim S. Efficacy of acupuncture on cardiovascular complications in patients with diabetes mellitus in Korea: A nationwide retrospective cohort. J Integr Med. 2023; 21(2): 176–183.

Diagnostic Biomarkers of Diabetic Neuropathy

Diabetes mellitus (DM) is a chronic disease that occurs due to inadequate production of insulin or decreased effect of available insulin. Considered one of the most critical life-threatening diseases of the 21st century, the number of patients has been increasing over the past few decades. These patients suffer many problems such as neuropathy, nephropathy and rethinopathy which the first can decrease their life expectations. Diabetic peripheral neuropathy (DPN) is the most common complication in diabetic patients and more than one half of these patients develop nerve dysfunction through their life. The primary cause of diabetic foot disease is DPN which sleep disturbances, poor quality of life, depression and finally unemployment are the results of it. In this article, we are studying different biomarkers of diabetic neuropathy using related papers in order to consider them in diabetic patients and prevent further complications in them.

Sodium alginate/gelatin hydrogels loaded with adipose-derived mesenchymal stem cells promote wound healing in diabetic rats.

Chronic refractory wounds are a common complication in diabetic patients. Adipose-derived mesenchymal stem cells (ASCs) have been shown to play an essential role in diabetic wound repair. To determine whether a composite of ASCs and sodium alginate/gelatin (Gel-Al) hydrogel can promote diabetic wound healing. Full-thickness cutaneous wounds were created in streptozotocin-induced diabetic rats prior to treatment with Gel-Al hydrogels loaded with ASCs. Hydrogel biocompatibility and wound healing were analyzed. Hematoxylin and eosin staining, Masson staining, immunofluorescence, enzyme-linked immunosorbent assays (ELISA), and quantitative real-time PCR were performed for the assessment of cellular responses. Compared to the control group or Gel-Al alone group, the combination of Gel-Al and ASCs promoted wound closure, facilitated granulation tissue regeneration and collagen deposition, and upregulated the expression of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and endothelial cell marker CD31. Moreover, the combination of Gel-Al and ASCs decreased interleukin-6 (IL-6) and interleukin-1β (IL-1β) expression, increased transforming growth factor beta1 (TGFβ1), interleukin-10 (IL-10), interleukin-4 (IL-4) and interleukin-13 (IL-13) expression, and increased M2 macrophage polarization. Gel-Al hydrogels loaded with ASCs accelerate diabetic wound healing. The Gel-Al hydrogel-based ASC system therefore represents an innovative therapeutic strategy for diabetic wound repair.

Determination of Visfatin Level in Patients with Diabetes and Peripheral Neuropathy as Early Predicted Factor

Peripheral neuropathy represents one of the common diabetic complications in patients with diabetes mellitus type 2 (DMT2). Peripheral neuropathy affects the feet, legs, hands, and arms. It was found that one-third to one-half of diabetics have peripheral neuropathy. The current study aimed to evaluate the level of visfatin in diabetic patient groups with or without peripheral neuropathy in comparison with healthy subjects to knowledge whether visfatin can be applied as a predictor factor for this type of disease complication. The study included 120 males and females ranging in age from 40 to 97 years old. (40 patients with type 2 diabetes, 40 patients with diabetic peripheral neuropathy, and 40 healthy people served as the control group.) All of the diabetes patients had a verified diagnosis (type 2). During the period from October 2021 to December 2021, the patients were assessed at the National Diabetes Center, Al-Mustansiriya University in Baghdad. Visfatin levels were tested using the ELISA technique, and HbA1c was assessed using Cobas C111. In patients, HbA1C levels are significantly higher (p≤0.05) than in controls. Males and females with DPN and DM have greater Visfatin mean values than the control group. Visfatin levels are strong indications for early diagnosis of diabetic neuropathy in both males and females, according to the current study.

Association between early glycemic management and diabetes complications in type 1 diabetes mellitus: A retrospective cohort study

AimsTo investigate the association between early HbA1c levels near diagnosis and future glycemic management, and analyzed risk factors of complications in people with T1DM. MethodsThis retrospective cohort study included 201 children and adolescents with T1DM. Patient data including sex, age at diagnosis, duration of disease, HbA1c levels, HbA1c variability during the follow-up period, and diabetes complications and comorbidities were collected. ResultsThe mean follow-up period of patients was 16.4 years. HbA1c levels in all three examined time points after diagnosis (first year, second year, and first two years) were significantly associated with recent HbA1c level, and second-year HbA1c was most closely correlated with recent HbA1c level. Elevated second-year HbA1c was a risk factor of diabetic ketoacidosis (DKA) and retinopathy, and increased variability of HbA1c was significantly related to various microvascular complications. When HbA1c is stratified into quartiles, the subjects of each quartile trend to stay within that quartile over the follow-up period. ConclusionsEarly HbA1c levels were closely associated with recent HbA1c levels and diabetes complications in patients with T1DMs. Strict glucose management after diagnosis and reducing variability of HbA1c may prevent future diabetes complications and comorbidities.

New Advances in the Pathogenesis and Treatment of Dry Eye after Diabetic Cataract Surgery

Diabetic cataract is a common complication in diabetic patients. As the diabetic population continues to expand, the number of patients with diabetic cataract is also increasing. Currently, the primary treatment is cataract ultrasound emulsification hand combined with IOL implantation. However, it has been clinically found that these patients have a high incidence of postoperative dry eye, and in severe cases, corneal epithelial defects and ulcers may also occur, which affects the patient's postoperative comfort and visual function. In order to further improve the understanding of postoperative dry eye in diabetic cataract and enhance the postoperative situation, this paper reviews and analyzes the pathogenesis and new advances in the treatment of postoperative dry eye in diabetic cataract.

Retracted: High Inflammatory Factor Levels Increase Cardiovascular Complications in Diabetic Patients Undergoing Coronary Artery Bypass Grafting.

[This retracts the article DOI: 10.1155/2022/7151414.].

CMKLR1 Antagonist Alpha-NETA Protects against Diabetic Nephropathy in Mice

Introduction: Diabetic nephropathy (DN) is a common complication in diabetic patients. Chemerin, a novel adipokine, has been associated with renal damage in DN. The chemerin chemokine-like receptor 1 (CMKLR1) has been reported to participate in DN. In this study, we aimed to investigate the effect of a CMKLR1 antagonist, 2-(anaphthoyl)ethyltrimethylammonium iodide (α-NETA), on DN. Methods: To induce diabetes, 8-week-old male C57BL/6J mice were given a single intraperitoneal injection of 65 mg/kg streptozotocin (STZ). Diabetic mice were randomly assigned to receive daily doses of 0, 5, or 10 mg/kg α-NETA for 4 weeks. Results: α-NETA dose-dependently induced body weight and reduced fasting blood glucose levels in STZ-induced diabetic mice. Furthermore, α-NETA significantly reduced the expressions of renal injury markers, including serum creatinine, kidney weight/body weight, urine volume, total proteins, and albumin in the urine, and increased creatinine clearance. Periodic acid-Schiff staining also indicated that α-NETA could effectively ameliorate renal injuries in DN mice. In addition, α-NETA inhibited renal inflammation and the expressions of chemerin and CMKLR1 in mice with DN. Conclusion: In summary, our findings suggested that α-NETA has beneficial effects on the management of DN. Specifically, α-NETA effectively ameliorated renal damage and inflammation in a dose-dependent manner in mice with DN. Thus, targeting the chemerin and CMKLR1 axis with α-NETA may be a promising therapeutic strategy for the treatment of DN.

Inflammation in Diabetic Kidney Disease: Focus on New Therapeutic Considerations

Diabetic kidney disease (DKD) is the most common cause of end-stage renal disease (ESRD) in the U.S. and worldwide. A role of chronic low-grade inflammation in the microvascular complications in diabetic patients has now been widely accepted, and anti-inflammatory therapies for DKD are being actively pursued. Such therapies may be especially useful in the treatment of patients with chronic kidney disease (CKD) with normal to only moderately increased albuminuria, a DKD phenotype which is becoming more frequent. Current pharmacologic treatment for DKD includes inhibitors of the renin-angiotensin-aldosterone system (RAAS) and the sodium-glucose co-transporter 2 (SGLT2) in the proximal tubule. Both classes of agents are known to reduce blood pressure but also are thought to have anti-inflammatory, antioxidant, and anti-fibrotic effects independent of their hemodynamic actions. Large clinical trials with experimental agents such as bardoxolone and selonsertib that target inflammation and oxidative stress in DKD have been carried out or are in progress. The non-specific phosphodiesterase inhibitor pentoxifylline (PTX) is also being studied in a large US trial to see if this FDA-approved drug may be able to be repurposed to treat DKD. Other agents have also shown promising effects in small clinical trials but require further large-scale investigation.

Assessment of level of awareness of diabetes mellitus and its complications in diabetic patients- A questionnaire-based study in a tertiary care centre

Assessment of level of awareness of diabetes mellitus and its complications in diabetic patients- A questionnaire-based study in a tertiary care centre