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BMJ Open Diabetes Research & Care May 2024ACE cleaves angiotensin I (Ang I) to angiotensin II (Ang II) inducing vasoconstriction via Ang II type 1 (AT1) receptor, while ACE2 cleaves Ang II to Ang (1-7) causing...
INTRODUCTION
ACE cleaves angiotensin I (Ang I) to angiotensin II (Ang II) inducing vasoconstriction via Ang II type 1 (AT1) receptor, while ACE2 cleaves Ang II to Ang (1-7) causing vasodilatation by acting on the Mas receptor. In diabetic kidney disease (DKD), it is still unclear whether plasma or urine ACE2 levels predict renal outcomes or not.
RESEARCH DESIGN AND METHODS
Among 777 participants with diabetes enrolled in the Urinary biomarker for Continuous And Rapid progression of diabetic nEphropathy study, the 296 patients followed up for 9 years were investigated. Plasma and urinary ACE2 levels were measured by the ELISA. The primary end point was a composite of a decrease of estimated glomerular filtration rate (eGFR) by at least 30% from baseline or initiation of hemodialysis or peritoneal dialysis. The secondary end points were a 30% increase or a 30% decrease in albumin-to-creatinine ratio from baseline to 1 year.
RESULTS
The cumulative incidence of the renal composite outcome was significantly higher in group 1 with lowest tertile of plasma ACE2 (p=0.040). Group 2 with middle and highest tertile was associated with better renal outcomes in the crude Cox regression model adjusted by age and sex (HR 0.56, 95% CI 0.31 to 0.99, p=0.047). Plasma ACE2 levels demonstrated a significant association with 30% decrease in ACR (OR 1.46, 95% CI 1.044 to 2.035, p=0.027) after adjusting for age, sex, systolic blood pressure, hemoglobin A1c, and eGFR.
CONCLUSIONS
Higher baseline plasma ACE2 levels in DKD were protective for development and progression of albuminuria and associated with fewer renal end points, suggesting plasma ACE2 may be used as a prognosis marker of DKD.
TRIAL REGISTRATION NUMBER
UMIN000011525.
Topics: Humans; Male; Female; Diabetic Nephropathies; Angiotensin-Converting Enzyme 2; Biomarkers; Middle Aged; Glomerular Filtration Rate; Peptidyl-Dipeptidase A; Aged; Prognosis; Disease Progression; Follow-Up Studies
PubMed: 38816205
DOI: 10.1136/bmjdrc-2024-004237 -
BMJ Open Diabetes Research & Care May 2024We compared the kidney outcomes between patients with diabetic kidney disease (DKD) aged ≥75 years initiating sodium-glucose cotransporter 2 (SGLT2) inhibitors versus...
INTRODUCTION
We compared the kidney outcomes between patients with diabetic kidney disease (DKD) aged ≥75 years initiating sodium-glucose cotransporter 2 (SGLT2) inhibitors versus other glucose-lowering drugs, additionally presenting with or without proteinuria.
RESEARCH DESIGN AND METHODS
Using the Japan Chronic Kidney Disease Database, we developed propensity scores, implementing a 1:1 matching protocol. The primary outcome included the decline rate in estimated glomerular filtration rate (eGFR), and secondary outcomes incorporated a composite of a 40% reduction in eGFR or progression to end-stage kidney disease.
RESULTS
At baseline, the mean age at initiation of SGLT2 inhibitors (n=348) or other glucose-lowering medications (n=348) was 77.7 years. The mean eGFR was 59.3 mL/min/1.73m and proteinuria was 230 (33.0%) patients. Throughout the follow-up period, the mean annual rate of eGFR change was -0.80 mL/min/1.73 m/year (95% CI -1.05 to -0.54) among SGLT2 inhibitors group and -1.78 mL/min/1.73 m/year (95% CI -2.08 to -1.49) in other glucose-lowering drugs group (difference in the rate of eGFR decline between the groups was 0.99 mL/min/1.73 m/year (95% CI 0.5 to 1.38)), favoring SGLT2 inhibitors (p<0.001). Composite renal outcomes were observed 38 in the SGLT2 inhibitors group and 57 in the other glucose-lowering medications group (HR 0.64, 95% CI 0.42 to 0.97). There was no evidence of an interaction between SGLT2 inhibitors initiation and proteinuria.
CONCLUSIONS
The benefits of SGLT2 inhibitors on renal outcomes are also applicable to older patients with DKD aged≥75 years.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Female; Male; Aged; Japan; Glomerular Filtration Rate; Diabetic Nephropathies; Databases, Factual; Renal Insufficiency, Chronic; Aged, 80 and over; Diabetes Mellitus, Type 2; Follow-Up Studies; Disease Progression; Hypoglycemic Agents; Prognosis; Treatment Outcome
PubMed: 38816204
DOI: 10.1136/bmjdrc-2024-004115 -
BMJ Open Diabetes Research & Care May 2024The Look AHEAD randomized clinical trial reported that an 8-year intensive lifestyle intervention (ILI) compared with diabetes support and education (DSE) in adults aged... (Randomized Controlled Trial)
Randomized Controlled Trial
Within and post-trial effects of an intensive lifestyle intervention on kidney disease in adults with overweight or obesity and type 2 diabetes mellitus: a secondary analysis of the Look AHEAD clinical trial.
INTRODUCTION
The Look AHEAD randomized clinical trial reported that an 8-year intensive lifestyle intervention (ILI) compared with diabetes support and education (DSE) in adults aged 45-76 years with type 2 diabetes and overweight/obesity delayed kidney disease progression. Here, we report long-term post-intervention follow-up for the trial's secondary outcome of kidney disease.
RESEARCH DESIGN AND METHODS
We examined effects of ILI (n=2570) versus DSE (n=2575) on decline in estimated glomerular filtration rate (eGFR) to <45 mL/min/1.73 m or need for kidney replacement therapy (KRT: dialysis or kidney transplant) during intervention and post-intervention follow-up (median 15.6 years overall).
RESULTS
Incidence of eGFR <45 mL/min/1.73 m was lower in ILI during the intervention (HR=0.80, 95% CI=0.66 to 0.98) but not post-intervention (HR=1.03, 0.86 to 1.23) or overall (HR=0.92, 0.80 to 1.04). There were no significant treatment group differences in KRT. In prespecified subgroup analyses, age×treatment interactions were significant over total follow-up: p=0.001 for eGFR <45 mL/min/1.73 m and p=0.01 for KRT. The 2205 participants aged >60 years at baseline had benefit in both kidney outcomes during intervention and overall (HR=0.75, 0.62 to 0.90 for eGFR <45 mL/min/1.73 m; HR=0.62, 0.43 to 0.91 for KRT). The absolute treatment effects were greater post-intervention: ILI reduced the rate of eGFR <45 mL/min/1.73 m by 0.46 and 0.76 cases/100 person-years during and post-intervention, respectively; and reduced KRT by 0.15 and 0.21 cases/100 person-years. The younger participants experienced no such post-intervention benefits.
CONCLUSIONS
ILI reduced kidney disease progression during and following the active intervention in persons aged ≥60 years. ILI should be considered for reducing kidney disease incidence in older persons with type 2 diabetes.
Topics: Humans; Diabetes Mellitus, Type 2; Middle Aged; Male; Female; Aged; Obesity; Glomerular Filtration Rate; Overweight; Life Style; Follow-Up Studies; Disease Progression; Diabetic Nephropathies; Risk Reduction Behavior; Prognosis
PubMed: 38816203
DOI: 10.1136/bmjdrc-2024-004079 -
Acta Dermato-venereologica May 2024Martorell hypertensive ischaemic leg ulcer (Martorell HYTILU) is a rare but significant cause of distal leg ulcers. Although hypertension and diabetes are known factors... (Comparative Study)
Comparative Study
Martorell hypertensive ischaemic leg ulcer (Martorell HYTILU) is a rare but significant cause of distal leg ulcers. Although hypertension and diabetes are known factors in its development, the precise pathogenesis of Martorell HYTILU remains elusive. To reach a better understanding of Martorell HYTILU, transcriptomic analysis was conducted through RNA sequencing and immunohistochemical comparison of Martorell HYTILU (n = 17) with chronic venous ulcers (n = 4) and healthy skin (n = 4). Gene expression analysis showed a marked activation of immune-related pathways in both Martorell HYTILU and chronic venous ulcers compared with healthy skin. Notably, neutrophil activity was substantially higher in Martorell HYTILU. While pathway analysis revealed a mild downregulation of several immune pathways in Martorell HYTILU compared with chronic venous ulcers, keratinization, cornification, and epidermis development were significantly upregulated in Martorell HYTILU. Additionally, STAC2, a gene encoding for a protein promoting the expression of the calcium channel Cav1.1, was significantly upregulated in Martorell HYTILU and was detected perivascularly in situ (Martorell HYTILU n = 24; chronic venous ulcers n = 9, healthy skin n = 11). The high expression of STAC2 in Martorell HYTILU suggests that increased calcium influx plays an important role in the pathogenesis of the disease. Consequently, calcium channel antagonists could be a promising treatment avenue for Martorell HYTILU.
Topics: Humans; Male; Female; Varicose Ulcer; Aged; Chronic Disease; Hypertension; Middle Aged; Skin; Ischemia; Gene Expression Profiling; Transcriptome; Case-Control Studies; Leg Ulcer; Aged, 80 and over
PubMed: 38813744
DOI: 10.2340/actadv.v104.40090 -
Turkish Journal of Medical Sciences 2023Community-acquired pneumonia (CAP) is one of the leading infectious causes of mortality, and diabetes mellitus is a globally prevalent disease. Consequently, the... (Comparative Study)
Comparative Study
BACKGROUND/AIM
Community-acquired pneumonia (CAP) is one of the leading infectious causes of mortality, and diabetes mellitus is a globally prevalent disease. Consequently, the cooccurrence of these two disorders can be common and create challenging medical conditions. Therefore, it was aimed to compare the various aspects of CAP in diabetic and nondiabetic patients, in order to have a comprehensive and comparative picture of the differences.
MATERIALS AND METHODS
In this cross-sectional study, CAP patients with and without diabetes were assessed for clinicoradiological signs, laboratory features, disease severity, and pneumonia outcomes.
RESULTS
Analyzed herein were 172 CAP patients (77 had diabetes and 95 were nondiabetic). Clinical and radiological signs of pneumonia were mostly similar between the groups, except for purulent sputum, which was more prevalent among the nondiabetic patients. The laboratory results were also mostly similar. However, analysis of the outcomes and prognosis showed different results. The diabetic patients had a longer mean duration of hospital stay (8.52 days vs. 7.93 days, p = 0.015), higher median pneumonia severity based on the CURB-65 criteria (3 vs. 2, p = 0.016), and higher intensive care unit (ICU) admission requirement (22.1% vs. 7.3%, p = 0.004). Moreover, the mortality rate for the diabetic patients was nonsignificantly higher (16.8% vs. 15.7%, p = 0.453). Furthermore, the results of the logistic regression analysis showed that the diabetic patients had significantly higher odds of experiencing more severe forms of pneumonia (adjusted odds ratio (AOR): 5.77, 95% CI: 2.52-13.20), requiring ICU hospitalization (AOR: 3.56, 95% CI: 1.39-9.11), and having a longer hospital stay (AOR: 2.01, 95% CI: 1.09-3.71). In addition, although there was no significant relationship between the severity of pneumonia and the amount of glycated hemoglobin (HbA1c) in the diabetic patients (p = 0.940), the higher level of HbA1c in the nondiabetic patients was significantly correlated with a higher severity of pneumonia (p = 0.002).
CONCLUSION
While diabetic patients with CAP have the same clinicoradiological and laboratory features as nondiabetic patients, the presence of diabetes can significantly worsen the outcomes and prognosis of pneumonia.
Topics: Humans; Community-Acquired Infections; Male; Female; Middle Aged; Cross-Sectional Studies; Prognosis; Pneumonia; Aged; Length of Stay; Hospitalization; Severity of Illness Index; Diabetes Complications; Diabetes Mellitus; Adult
PubMed: 38813518
DOI: 10.55730/1300-0144.5747 -
Turkish Journal of Medical Sciences 2023The aim herein was to investigate epileptiform discharges on electroencephalogram (EEG), their correlation with glutamic acid decarboxylase 65 autoantibody (GAD-ab) in...
BACKGROUND/AIM
The aim herein was to investigate epileptiform discharges on electroencephalogram (EEG), their correlation with glutamic acid decarboxylase 65 autoantibody (GAD-ab) in newly diagnosed pediatric type 1 diabetes mellitus (T1DM) patients and interpret their medium-term utility in predicting epilepsy.
MATERIALS AND METHODS
Children presenting with T1DM between July 2018 and December 2019 were included in this prospective longitudinal study. Patients with a history of head injury, chronic illness, neurological disorder, seizure, autism, or encephalopathy were excluded. EEGs were obtained within the first 7 days of diagnosis and later reviewed by a pediatric neurologist. All of the children were clinically followed-up in pediatric endocrinology and neurology clinics for 2 years after their diagnosis.
RESULTS
A total of 105 children (46 male, 43.8%) were included. The mean age at the time of diagnosis was 9.6 ± 4.1 years (range: 11 months-17.5 years). At the time of admission, 24 (22.9%), 29 (27.6%), and 52 (49.5%) patients had hyperglycemia, ketosis, and diabetic ketoacidosis, respectively. GAD-ab was positive in 55 children (52.4%). No background or sleep architecture abnormalities or focal slowing were present on the EEGs. Of the patients, 3 (2.9%) had focal epileptiform discharges. The mean GAD-ab levels of the remaining 102 patients were 7.48 ± 11.97 U/mL (range: 0.01-50.54) (p = 0.2). All 3 children with EEG abnormality had higher levels of GAD-ab (3.59 U/mL, 31.3 U/mL, and 7.09 U/mL, respectively). None of the patients developed epilepsy during the follow-up, although 1 patient experienced Guillain-Barré syndrome (GBS).
CONCLUSION
The prevalence of epileptiform discharges in the patients was similar to those of previous studies, in which healthy children were also included. No relationship was found between the epileptiform discharges and GAD-ab, and none of the patients manifested seizures during the first 2 years of follow-up of T1DM. These data support the findings of previous studies reporting that T1DM patients with confirmed electroencephalographic abnormalities do not have an increased risk of epilepsy. On the other hand, GBS might be considered as another autoimmune disease that may be associated with T1DM in children.
Topics: Humans; Diabetes Mellitus, Type 1; Male; Child; Female; Electroencephalography; Prospective Studies; Adolescent; Child, Preschool; Infant; Epilepsy; Autoantibodies; Longitudinal Studies; Glutamate Decarboxylase
PubMed: 38813513
DOI: 10.55730/1300-0144.5749 -
Turkish Journal of Medical Sciences 2023Due to the increasing mortality and morbidity rates in diabetes mellitus (DM), which is one of the biggest health problems of our age, many treatment modalities are...
Protective effects of swimming exercises and metformin on cardiac and aortic damage caused by a high-fat diet in obese rats with type 2 diabetes, by regulating the Bcl2/Bax signaling pathway.
BACKGROUND/AIM
Due to the increasing mortality and morbidity rates in diabetes mellitus (DM), which is one of the biggest health problems of our age, many treatment modalities are still being tried. The positive effects of metformin (MET) and physical exercise (EXE) on the pathophysiology of diabetes are well known. In this study, it was aimed to detail these positive effects of MET and EXE in combination on the basis of inflammation, apoptosis mechanisms, and endogen nesfatin-1 (NES-1) synthesis.
MATERIALS AND METHODS
Twenty-seven type 2 DM (DM-2) male Wistar Albino rats were divided into 4 groups, as the high-fat diet (HFD), MET, EXE, and MET+EXE groups. The total duration of the study was 3 months. At the end of the experiment, blood glucose and lipid profiles were measured. Histopathological evaluation was performed on the cardiac and aortic tissues and apoptotic markers were evaluated immunohistochemically. Inflammatory markers and NES-1 levels were analyzed by enzyme-linked immunosorbent assay.
RESULTS
The plasma glucose, homeostatic model evaluation-insulin resistance (HOMA-IR), low-density lipoprotein (LDL) levels increased, and high-density lipoprotein (HDL) levels decreased significantly in the HFD group. In the treatment groups, the glucose, HOMA-IR, LDL, NES-1 levels in the plasma, as well as tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, caspase-3 (Cas-3), Bcl-2-associated X protein (Bax), and histopathological findings of inflammation in tissues were decreased. Additionally, there was an increase in plasma insulin, HDL, and tissue B-cell lymphoma-2 and levels.
CONCLUSION
It was observed that the MET and EXE treatments in the DM-2 model reduced cellular damage mechanisms such as inflammation and apoptosis. The decrease in NES-1 levels was thought to be secondary to this antiinflammatory effect. In conclusion, the results demonstrated the effectiveness of EXE in reducing DM-2 and the NES-1 levels. Further studies are needed to evaluate the effect in different EXE models and treatment durations.
Topics: Animals; Metformin; Diet, High-Fat; Diabetes Mellitus, Type 2; Rats, Wistar; Male; Rats; Signal Transduction; Proto-Oncogene Proteins c-bcl-2; Swimming; bcl-2-Associated X Protein; Obesity; Physical Conditioning, Animal; Hypoglycemic Agents; Apoptosis; Aorta; Nucleobindins; Diabetes Mellitus, Experimental
PubMed: 38813486
DOI: 10.55730/1300-0144.5727 -
Frontiers in Public Health 2024Increasing evidence supports chronic psychological stress as a risk factor for the development of type 2 diabetes. Much less is known, however, about the role of chronic...
INTRODUCTION
Increasing evidence supports chronic psychological stress as a risk factor for the development of type 2 diabetes. Much less is known, however, about the role of chronic stress in established diabetes.
METHODS
The aim of the current study was to comprehensively assess chronic stress in a sample of 73 patients with type 2 diabetes and 48 non-diabetic control participants, and to investigate associations with indicators of glycemic control (HbA1c), insulin resistance (HOMA-IR), β-cell functioning (C-peptide), illness duration, and the presence of microvascular complications. Chronic stress was measured using questionnaires [the Perceived Stress Scale (PSS), the Screening Scale of the Trier Inventory of Chronic Stress (SSCS), the Perceived Health Questionnaire (PHQ) as well as the Questionnaire on Stress in Patients with Diabetes-Revised (QSD-R)]; hair cortisol was used as a biological indicator.
RESULTS
We found that patients with type 2 diabetes had higher levels of hair cortisol in comparison to the control group ((1,112) = 5.3; = 0.023). Within the diabetic group, higher hair cortisol was associated with a longer duration of the illness ( = 0.25, = 0.04). General perceived stress did not show significant associations with metabolic outcomes in type 2 diabetes patients. In contrast, higher diabetes-related distress, as measured with the QSD-R, was associated with lower glycemic control ( = 0.28, = 0.02), higher insulin resistance ( = 0.26, = 0.03) and a longer duration of the illness ( = 0.30, = 0.01).
DISCUSSION
Our results corroborate the importance of chronic psychological stress in type 2 diabetes. It appears, however, that once type 2 diabetes has developed, diabetes-specific distress gains in importance over general subjective stress. On a biological level, increased cortisol production could be linked to the course of the illness.
Topics: Humans; Diabetes Mellitus, Type 2; Male; Female; Hydrocortisone; Middle Aged; Stress, Psychological; Cross-Sectional Studies; Hair; Aged; Surveys and Questionnaires; Insulin Resistance; Adult; Glycated Hemoglobin; Risk Factors
PubMed: 38813430
DOI: 10.3389/fpubh.2024.1289689 -
RSC Advances May 2024Diabetes mellitus, a complex metabolic disorder, presents a growing global health challenge. In 2021, there were 529 million diabetics worldwide. At the super-regional... (Review)
Review
Diabetes mellitus, a complex metabolic disorder, presents a growing global health challenge. In 2021, there were 529 million diabetics worldwide. At the super-regional level, Oceania, the Middle East, and North Africa had the highest age-standardized rates. The majority of cases of diabetes in 2021 (>90.0%) were type 2 diabetes, which is largely indicative of the prevalence of diabetes in general, particularly in older adults (K. L. Ong, , Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021, , 2023, (10397), 203-234). Nowadays, slowing the progression of diabetic complications is the only effective way to manage diabetes with the available therapeutic options. However, novel biomarkers and treatments are urgently needed to control cytokine secretion, advanced glycation end products (AGEs) production, vascular inflammatory effects, and cellular death. Emerging research has highlighted the intricate interplay between reactive oxygen species (ROS) and protein aggregation in the pathogenesis of diabetes. In this scenario, the main aim of this paper is to provide a comprehensive review of the current understanding of the molecular mechanisms underlying ROS-induced cellular damage and protein aggregation, specifically focusing on their contribution to diabetes development. The role of ROS as key mediators of oxidative stress in diabetes is discussed, emphasizing their impact on cellular components and signaling. Additionally, the involvement of protein aggregation in impairing cellular function and insulin signaling is explored. The synergistic effects of ROS and protein aggregation in promoting β-cell dysfunction and insulin resistance are examined, shedding light on potential targets for therapeutic intervention.
PubMed: 38813124
DOI: 10.1039/d4ra02349h -
Turkish Journal of Medical Sciences 2023Diabetic foot ulcers (DFUs) cause decreased quality of life due to prolonged hospital stay, loss of workforce, disabilities, psychological trauma, and increased...
BACKGROUND/AIM
Diabetic foot ulcers (DFUs) cause decreased quality of life due to prolonged hospital stay, loss of workforce, disabilities, psychological trauma, and increased healthcare costs. This study aims to assess the validity and reliability of the Diabetic Foot Scale-Short Form (DFS-SF) for Turkish-speaking individuals with DFUs.
MATERIALS AND METHODS
This was a methodological study conducted with 174 Turkish patients with DFUs from March 2020 to December 2020. Translation-back translation was performed for language equivalence and expert opinions were obtained for content validity. The scale's construct validity was tested with confirmatory factor analysis, exploratory factor analysis, and known-group validity. Cronbach's alpha was used to evaluate internal consistency. Correlation of the DFS-SF with the SF-36 was used to test criterion validity. The scale was then revised according to the TRIPOD checklist.
RESULTS
The content validity index value was 0.93 and Cronbach's alpha ranged from 0.93 to 0.97. The scale maintained its six-factor structure and the factor loadings ranged from 0.52 to 0.86. The fit indices of the model revealed good validity. The correlations (r = 0.43-0.76, p < 0.001) and known-group comparisons supported the construct validity.
CONCLUSION
The Turkish version of the DFS-SF is a reliable tool for measuring the quality of life of people suffering from DFUs.
Topics: Humans; Diabetic Foot; Turkey; Male; Female; Reproducibility of Results; Middle Aged; Quality of Life; Aged; Psychometrics; Translations; Surveys and Questionnaires; Adult; Factor Analysis, Statistical
PubMed: 38813045
DOI: 10.55730/1300-0144.5711