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Medicina (Kaunas, Lithuania) Jun 2024The complement cascade is a vital system in the human body's defense against pathogens. During the natural aging process, it has been observed that this system is... (Review)
Review
The complement cascade is a vital system in the human body's defense against pathogens. During the natural aging process, it has been observed that this system is imperative for ensuring the integrity and homeostasis of the retina. While this system is critical for proper host defense and retinal integrity, it has also been found that dysregulation of this system may lead to certain retinal pathologies, including geographic atrophy and diabetic retinopathy. Targeting components of the complement system for retinal diseases has been an area of interest, and in vivo, ex vivo, and clinical trials have been conducted in this area. Following clinical trials, medications targeting the complement system for retinal disease have also become available. In this manuscript, we discuss the pathophysiology of complement dysfunction in the retina and specific pathologies. We then describe the results of cellular, animal, and clinical studies targeting the complement system for retinal diseases. We then provide an overview of complement inhibitors that have been approved by the Food and Drug Administration (FDA) for geographic atrophy. The complement system in retinal diseases continues to serve as an emerging therapeutic target, and further research in this field will provide additional insights into the mechanisms and considerations for treatment of retinal pathologies.
Topics: Humans; Retinal Diseases; Complement System Proteins; Animals; Complement Inactivating Agents; Diabetic Retinopathy; Retina
PubMed: 38929562
DOI: 10.3390/medicina60060945 -
Medicina (Kaunas, Lithuania) May 2024Over the last few years, given the increase in the incidence and prevalence of both type 2 diabetes mellitus (T2DM) and heart failure (HF), it became crucial to develop... (Review)
Review
Over the last few years, given the increase in the incidence and prevalence of both type 2 diabetes mellitus (T2DM) and heart failure (HF), it became crucial to develop guidelines for the optimal preventive and treatment strategies for individuals facing these coexisting conditions. In patients aged over 65, HF hospitalization stands out as the predominant reason for hospital admissions, with their prognosis being associated with the presence or absence of T2DM. Historically, certain classes of glucose-lowering drugs, such as thiazolidinediones (rosiglitazone), raised concerns due to an observed increased risk of myocardial infarction (MI) and cardiovascular (CV)-related mortality. In response to these concerns, regulatory agencies started requiring CV outcome trials for all novel antidiabetic agents [i.e., dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and sodium-glucose cotransporter-2 inhibitors (SGLT2is)] with the aim to assess the CV safety of these drugs beyond glycemic control. This narrative review aims to address the current knowledge about the impact of glucose-lowering agents used in T2DM on HF prevention, prognosis, and outcome.
Topics: Humans; Diabetes Mellitus, Type 2; Heart Failure; Hypoglycemic Agents; Dipeptidyl-Peptidase IV Inhibitors; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 38929529
DOI: 10.3390/medicina60060912 -
Medicina (Kaunas, Lithuania) May 2024: Dementia is increasing worldwide. This study aimed to examine the impact of comorbidity burden and frailty on dementia prognosis in patients with dementia. : This...
: Dementia is increasing worldwide. This study aimed to examine the impact of comorbidity burden and frailty on dementia prognosis in patients with dementia. : This retrospective cohort study was conducted with 47 patients with dementia who were followed for up to two years. The Modified Charlson Comorbidity Index (MCCI), Mini-Mental State Examination (MMSE-E), and Edmonton Fragility Scale were used besides laboratory and clinical findings. : The mean age of the 47 patients was 78.77 ± 12.44 years. During the follow-up period, MMSE-E scores were observed to improve in 50% of the patients. Initial MMSE-E scores were found to be lowest in men and patients with coronary artery disease or depression, while final MMSE-E scores were observed to be lowest in patients with depression and low vitamin B12 or vitamin D levels. The rates of decrease in MMSE-E scores in non-, moderately and severely frail patients were 21.4%, 55.6%, and 70.6%, respectively. There was a moderate negative correlation between MMSE-E scores and both comorbidity burden and frailty scores. The mediation analysis revealed that frailty was a complete mediator, and that comorbidity burden led to an increase in frailty and a decrease in MMSE-E scores. During the follow-up period, patients with moderate frailty, hypertension, diabetes mellitus, alcohol and tobacco use, low B12 levels, or hypothyroidism showed an increased risk of decrease in cognitive functions. : There was a significant association between dementia prognosis and both frailty and biological deficits. We recommend the adoption of a syndemic approach in the follow-up of dementia, as we believe that the prevention of frailty and associated biological deficits will contribute to slowing dementia's clinical course.
Topics: Humans; Male; Female; Retrospective Studies; Aged; Dementia; Prognosis; Aged, 80 and over; Frailty; Cohort Studies; Comorbidity; Frail Elderly; Middle Aged
PubMed: 38929527
DOI: 10.3390/medicina60060910 -
Medicina (Kaunas, Lithuania) May 2024: The rise in global diabetes cases, reaching a staggering 529 million in 2021 from 108 million in 1980, underscores the urgency of addressing its complications, notably...
: The rise in global diabetes cases, reaching a staggering 529 million in 2021 from 108 million in 1980, underscores the urgency of addressing its complications, notably macrovascular ones like coronary artery, cerebrovascular, and peripheral artery diseases, which contribute to over 50% of diabetes mortality. Atherosclerosis, linked to hyperglycemia-induced endothelial dysfunction, is pivotal in cardiovascular disease development. Cytokines, including pentraxin 3 (PTX3), copeptin, lipoprotein(a) [Lp(a)], and matrix metalloproteinase-9 (MMP-9), influence atherosclerosis progression and plaque vulnerability. Inhibiting atherosclerosis progression is crucial, especially in diabetic individuals. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs), increasingly used for type 2 diabetes, show promise in reducing the cardiovascular risk, sparking interest in their effects on atherogenesis. This study sought to examine the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on biomarkers that indicate the instability of atherosclerotic plaques. These biomarkers include pentraxin 3 (PTX3), copeptin (CPC), matrix metalloproteinase-9 (MMP-9), and lipoprotein(a) [Lp(a)]. : A total of 34 participants, ranging in age from 41 to 81 years (with an average age of 61), who had been diagnosed with type 2 diabetes mellitus (with a median HbA1c level of 8.8%), dyslipidemia, and verified atherosclerosis using B-mode ultrasonography, were included in the study. All subjects were eligible to initiate treatment with a GLP-1 RA-dulaglutide. : Significant reductions in anthropometric parameters, blood pressure, fasting glucose levels, and HbA1c levels were observed posttreatment. Moreover, a notable decrease in biochemical markers associated with atherosclerotic plaque instability, particularly PTX3 and MMP-9 ( < 0.001), as well as Lp(a) ( < 0.05), was evident following the GLP-1 RA intervention. These findings underscore the potential of GLP-1 RAs in mitigating atherosclerosis progression and plaque vulnerability, thus enhancing cardiovascular outcomes in individuals with type 2 diabetes mellitus.
Topics: Humans; Pilot Projects; Biomarkers; Middle Aged; Male; Diabetes Mellitus, Type 2; Female; Plaque, Atherosclerotic; C-Reactive Protein; Serum Amyloid P-Component; Glucagon-Like Peptides; Matrix Metalloproteinase 9; Aged; Cytokines; Hypoglycemic Agents; Recombinant Fusion Proteins; Atherosclerosis; Lipoprotein(a); Glycopeptides; Immunoglobulin Fc Fragments
PubMed: 38929525
DOI: 10.3390/medicina60060908 -
Medicina (Kaunas, Lithuania) May 2024: Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and...
: Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. Accumulating evidence in animal models suggests that loss of interleukin-10 (IL-10) anti-inflammatory actions might contribute to lobular inflammation, considered one of the first steps toward NASH development. However, the role of IL-10 in lobular inflammation remains poorly explored in humans. We examined mRNA and protein levels of IL-10 in liver biopsies and serum samples from morbidly obese patients, investigating the relationship between IL-10 and lobular inflammation degree. : We prospectively enrolled morbidly obese patients of both sexes, assessing the lobular inflammation grade by the Brunt scoring system to categorize participants into mild ( = 7), moderate ( = 19), or severe ( = 13) lobular inflammation groups. We quantified the hepatic mRNA expression of IL-10 by quantitative polymerase chain reaction and protein IL-10 levels in liver and serum samples by Luminex Assay. We estimated statistical differences by one-way analysis of variance (ANOVA) and Tukey's multiple comparison test. : The hepatic expression of IL-10 significantly diminished in patients with severe lobular inflammation compared with the moderate lobular inflammation group ( = 0.01). The hepatic IL-10 protein levels decreased in patients with moderate or severe lobular inflammation compared with the mild lobular inflammation group ( = 0.008 and = 0.0008, respectively). In circulation, IL-10 also significantly decreased in subjects with moderate or severe lobular inflammation compared with the mild lobular inflammation group ( = 0.005 and < 0.0001, respectively). : In liver biopsies and serum samples of morbidly obese patients, the protein levels of IL-10 progressively decrease as lobular inflammation increases, supporting the hypothesis that lobular inflammation develops because of the loss of the IL-10-mediated anti-inflammatory counterbalance.
Topics: Humans; Interleukin-10; Obesity, Morbid; Female; Male; Adult; Middle Aged; Liver; Prospective Studies; Inflammation; Non-alcoholic Fatty Liver Disease
PubMed: 38929479
DOI: 10.3390/medicina60060862 -
Medicina (Kaunas, Lithuania) May 2024: The risk of developing glycemic dysregulation up to overt diabetes mellitus (DM) after an episode of acute pancreatitis (AP) is increasingly being analyzed. We aimed...
: The risk of developing glycemic dysregulation up to overt diabetes mellitus (DM) after an episode of acute pancreatitis (AP) is increasingly being analyzed. We aimed to assess the changes in serum glucose levels associated with the first episode of AP, as well as the impact of dysglycemia on outcomes such as the severity of inflammation, the length of hospitalization, mortality, and the persistence of hyperglycemia at follow-up. : All patients experiencing their first episode of AP, who presented to the Emergency Room (ER) between 1 January 2020 and 31 December 2023, were retrospectively included. On-admission serum glucose and peak serum glucose during hospitalization were the biological markers used to assess glucose metabolism impairment, and they were correlated with outcomes of AP. : Our study included 240 patients, 46.67% (112 patients) having a biliary etiology for an AP flare. Patients with COVID-19-associated AP exhibited the highest on-admission and peak serum glucose levels (244.25 mg/dL and 305.5 mg/dL, respectively). A longer hospital stay was noted in patients with peak serum glucose levels of ≥100 mg/dL (9.49 days) compared to normoglycemic patients (6.53 days). Both on-admission and peak glucose levels were associated with elevated CRP levels during hospitalization. A total of 83.78% of patients who received antibiotics exhibited on-admission hyperglycemia, and 72.07% had peak serum glucose levels of ≥100 mg/dL. The presence of hyperglycemia at follow-up was associated with both on-admission and peak serum glucose levels of ≥100 mg/dL, as well as with a longer stay, higher CRP levels, and antibiotic use during index admission. : On-admission hyperglycemia predicts a higher inflammatory response in patients at the first episode of AP, while the presence of hyperglycemia during hospitalization is associated with imaging and biological severity and longer hospitalizations, indicating a more severe disease course. Both on-admission and peak in-hospital hyperglycemia were identified as risk factors for sustained hyperglycemia at follow-up.
Topics: Humans; Retrospective Studies; Male; Female; Middle Aged; Pancreatitis; Blood Glucose; Adult; Length of Stay; Hyperglycemia; COVID-19; Aged; Hospitalization; Severity of Illness Index; Biomarkers
PubMed: 38929473
DOI: 10.3390/medicina60060856 -
Medicina (Kaunas, Lithuania) May 2024: This study aimed to investigate the relationship between the systemic immune inflammation (SII) index and the development of micro and macro complications and...
Investigation of the Systemic Immune Inflammation (SII) Index as an Indicator of Morbidity and Mortality in Type 2 Diabetic Retinopathy Patients in a 4-Year Follow-Up Period.
: This study aimed to investigate the relationship between the systemic immune inflammation (SII) index and the development of micro and macro complications and mortality within the first year and the following three years in type 2 diabetic retinopathy patients. : The retrospective study included 523 type 2 diabetic retinopathy patients seen in the endocrinology outpatient clinic of our hospital between January and December 2019. Their demographic and clinical characteristics were analyzed using descriptive statistics. The normal distribution of quantitative data was assessed by the Shapiro-Wilk test. Mann-Whitney U, McNemar-Chi-square, and Cochran's Q tests were used to analyze the SII values and complication rates over time. An ROC analysis determined the sensitivity and specificity of SII. A multiple linear regression analysis examined the relationship between variables and SII, while Spearman's test assessed the correlation between CRP and SII. < 0.05 was accepted as significant. : The mean age of patients was 63.5 ± 9.3 years, with mean SII values of 821.4 ± 1010.8. Higher SII values were significantly associated with acute-chronic renal failure, peripheral arterial disease, and hospitalization rates in both the first year and the following three years ( < 0.05 for all). Significant cut-off values for SII were found for micro- and macrovascular complications and death within the first year ( < 0.05 for all). The ROC curve analysis identified an optimal SII cut-off value of >594.0 for predicting near-term (1-year) complications and mortality, with a sensitivity of 73.8% and specificity of 49.4% (area under the ROC curve: 0.629, = 0.001). Multiple linear regression indicated that smoking of at least 20 pack-years had a significant positive effect on SII. The Spearman test showed a weak positive correlation between SII and CRP. : High SII values predict both early and late acute-chronic renal failure, peripheral arterial disease, and hospitalizations in patients with type 2 diabetic retinopathy. The study also shows that high SII values may predict microvascular and macrovascular complications of type 2 DM and mortality risk in the early period in patients with type 2 diabetic retinopathy. In addition, comorbidities and inflammatory habits, such as long-term smoking, should be considered in the clinical use of SII.
Topics: Humans; Middle Aged; Male; Female; Diabetic Retinopathy; Retrospective Studies; Diabetes Mellitus, Type 2; Aged; Inflammation; Follow-Up Studies; ROC Curve; Morbidity
PubMed: 38929472
DOI: 10.3390/medicina60060855 -
Children (Basel, Switzerland) Jun 2024The study aimed to estimate the prevalence of skin problems in children and adolescents with type 1 diabetes (T1D) using insulin pumps (IPs) and/or continuous glucose...
Skin Reactions in Children with Type 1 Diabetes Associated with the Use of New Diabetes Technologies-An Observational Study from a Regional Polish Pediatric Diabetes Center.
The study aimed to estimate the prevalence of skin problems in children and adolescents with type 1 diabetes (T1D) using insulin pumps (IPs) and/or continuous glucose monitoring (CGM) in our center and analyze their association with various factors. As part of the international ISPAD JENIOUS-initiated SKIN-PEDIC project, we interviewed and examined patients who visited the regional pediatric diabetes center in Opole (Poland) for four weeks regarding the use of IP and/or CGM and the presence of skin problems. Body mass index (BMI) and glycemic parameters were obtained retrospectively from medical records. Among 115 individuals (45.2% girls, 83.5% IP users, 96.5% CGM users), old scars were the most common skin problem (IP users 53.1%; CGM users 66.4%), while ≥2 types of skin problems co-occurred (IP users 40.6%; CGM users 27.3%). Longer IP use was associated with a higher prevalence of skin problems (50% for IP < 1 year, 98.1%-IP 1-3 years, 100% for IP > 3 years; < 0.001), pointing out extra attention with IP use > 1 year. No significant associations were found between skin problems and gender, age, BMI centile and glycemic parameters. Dermatological complications were common among children using IP and CGM in our center, highlighting the need for vigilant monitoring and early intervention to manage these skin-related issues effectively.
PubMed: 38929319
DOI: 10.3390/children11060740 -
Children (Basel, Switzerland) May 2024Diabetes exposure during pregnancy affects health outcomes in offspring; however, little is known about in utero exposure to preexisting parental youth-onset type 2...
Diabetes exposure during pregnancy affects health outcomes in offspring; however, little is known about in utero exposure to preexisting parental youth-onset type 2 diabetes. Offspring born to participants during the Treatment Options for Type 2 Diabetes in Adolescent and Youth (TODAY) study were administered a questionnaire at the end of the study. Of 457 participants, 37% of women and 18% of men reported 228 offspring, 80% from female participants. TODAY mothers had lower household income (<$25,000) compared to TODAY fathers (69.4% vs. 37.9%, = 0.0002). At 4.5 years of age (range 0-18 years), 16.7% of offspring were overweight according to the parental report of their primary care provider, with no sex difference. Offspring of TODAY mothers reported more daily medication use compared to TODAY fathers (50/183, 27.7% vs. 6/46, 12.2%, [ = 0.04]), a marker of overall health. TODAY mothers also reported higher rates of recidivism (13/94) than TODAY fathers (0/23). An Individualized Education Plan was reported in 20/94 (21.3%) offspring of TODAY mothers compared to 2/23 (8.7%) of TODAY fathers. This descriptive study, limited by parental self-reports, indicated offspring of participants in TODAY experience significant socioeconomic disadvantages, which, when combined with in utero diabetes exposure, may increase their risk of health and educational disparities.
PubMed: 38929210
DOI: 10.3390/children11060630 -
Antioxidants (Basel, Switzerland) Jun 2024The indolamine hormone melatonin, also known as N-acetyl-5-methoxytrypamine, is frequently associated with circadian rhythm regulation. Light can suppress melatonin... (Review)
Review
The indolamine hormone melatonin, also known as N-acetyl-5-methoxytrypamine, is frequently associated with circadian rhythm regulation. Light can suppress melatonin secretion, and photoperiod regulates melatonin levels by promoting its production and secretion at night in response to darkness. This hormone is becoming more and more understood for its functions as an immune-modulatory, anti-inflammatory, and antioxidant hormone. Melatonin may have a major effect on several diabetes-related disturbances, such as hormonal imbalances, oxidative stress, sleep disturbances, and mood disorders, according to recent research. This has raised interest in investigating the possible therapeutic advantages of melatonin in the treatment of diabetic complications. In addition, several studies have described that melatonin has been linked to the development of diabetes, cancer, Alzheimer's disease, immune system disorders, and heart diseases. In this review, we will highlight some of the functions of melatonin regarding vascular biology.
PubMed: 38929187
DOI: 10.3390/antiox13060747