Association of KLF14 rs4731702 gene polymorphism with metabolic phenotype in young patients with type 1 diabetes.

AIM: To explore the potential association between the KLF14 rs4731702 polymorphism and metabolic syndrome traits among patients diagnosed with type 1 diabetes (T1D). METHODS: The study group included 350 patients with T1D and 250 healthy control subjects. The analysis focused on the genotyping of KLF14 rs4731702 single nucleotide polymorphism (SNP), as well as evaluating serum concentrations of inflammatory markers, blood pressure, lipid profiles, and the quantitative status of CD4 + CD25highFOXP3+ T cells. RESULTS: Patients with T1D carrying the T allele of KLF14 rs4731702 SNP had higher high-density lipoprotein cholesterol, lower low-density lipoprotein cholesterol, as well as lower glycated haemoglobin and serum concentration of proinflammatory markers than C allele carriers. They also developed hypertension less often than carriers of the C allele. The analysis of CD4 + CD25highFOXP3+ regulatory T-cell status based on KLF14 genotype showed that, in T1D patients, those with the TT genotype had the highest frequency of these cells compared to carriers of the CC and CT genotypes. CONCLUSION: Our study suggests that the T allele of the KLF14 rs4731702 SNP might confer a protective effect against the development of obesity, hypertension, dyslipidaemia, and chronic inflammatory state in patients diagnosed with T1D.

Adherence and Retention Rates to Home-Based Video Exercise Programs in Older Adults-Systematic Review and Meta-Analysis.

Introduction: This systematic review and meta-analysis aimed to investigate adherence and retention rates to home-based video exercise programs and identify key factors associated with these rates in older adults to understand the effectiveness of home-based video exercise interventions. Methods: We searched PubMed, Web of Science, and Scopus for articles addressing adherence to and retention of home-based video exercise programs. The study was conducted following PRISMA recommendations. Results: A total of 26 articles, including 1,292 participants older than 65, were included in the final qualitative and quantitative syntheses. The weighted mean of the retention rate was 91.1, and of the attendance rate was 85.0, with low I2 = 3.5, not significant p = 0.409 heterogeneity. The generalized regression models showed a positive effect of session duration on the attendance rate (%), where the possible change from <20 min to >60 min duration could decrease the attendance rate (%) B = -24.390 (p <0.001). The delivery method had a significant effect, where the absence of live contact with the coach in web-based or DVD-delivered interventions could decrease the attendance rate (%) compared to the online sessions B = -11.482 (p = 0.010). The lockdown during the COVID-19 pandemic had a positive effect on both the attendance rate (%) B = 10.321 (p = 0.019) and retention rate (%) B = 9.577 (p = 0.032). Conclusions: This systematic review and meta-analysis indicate that supervised home-based video exercise programs lasting less than 60 min might be a suitable and sustainable exercise mode to keep older adults active, especially in times resembling feelings of confinement.

The Impact of Metabolic Memory on Immune Profile in Young Patients with Uncomplicated Type 1 Diabetes.

Metabolic memory refers to the long-term effects of achieving early glycemic control and the adverse implications of high blood glucose levels, including the development and progression of diabetes complications. Our study aimed to investigate whether the phenomenon of metabolic memory plays a role in the immune profile of young patients with uncomplicated type 1 diabetes (T1D). The study group included 67 patients with uncomplicated type 1 diabetes with a mean age of 15.1 ± 2.3 years and a minimum disease duration of 1.2 years. The control group consisted of 27 healthy children and adolescents with a mean age of 15.1 ± 2.3 years. Patients were divided into three groups according to their HbA1c levels at the onset of T1D, and the average HbA1c levels after one and two years of disease duration. The subgroup A1 had the lowest initial HbA1c values, while the subgroup C had the highest initial HbA1c values. Cytokine levels (including TNF-α, IL-35, IL-4, IL-10, IL-18, and IL-12) were measured in all study participants. Our data analysis showed that subgroup A1 was characterized by significantly higher levels of IL-35 and IL-10 compared to all other groups, and significantly higher levels of IL-4 compared to group B. Additionally, a comparative analysis of cytokine levels between the groups of diabetic patients and healthy controls demonstrated that subgroup A1 had significantly higher levels of anti-inflammatory cytokines. The lipid profile was also significantly better in subgroup A1 compared to all other patient groups. Based on our findings, it appears that an inflammatory process, characterized by an imbalance between the pro- and anti-inflammatory cytokines, is associated with poor glycemic control at the onset of diabetes and during the first year of disease duration. These findings also suggest that both metabolic memory and inflammation contribute to the abnormal lipid profile in patients with type 1 diabetes.

The Complex Network of Cytokines and Chemokines in Pediatric Patients with Long-Standing Type 1 Diabetes.

Type 1 diabetes (T1D) is a progressive disorder leading to the development of microangiopathies and macroangiopathies. Numerous cytokines and chemokines are involved in the pathogenesis of T1D complications. The study aimed to assess the presence of complications in patients with long-standing T1D and its relationship with serum biomarker concentrations. We examined 52 T1D subjects, with a disease duration ≥4 years and 39 healthy controls. The group of T1D patients was further divided into subgroups based on the duration of the disease (<7 years and ≥7 years) and the metabolic control assessed by the HbAlc level (<8% and ≥8%). We used Luminex Technology to assess a wide range of biomarker concentrations. A 24 h urine test was done to evaluate the rate of albuminuria. Optical coherence tomography (OCT) was conducted to detect early retinopathic changes. Subclinical atherosclerosis was assessed by measuring the carotid intima-media thickness (IMT). T1D patients showed remarkably higher concentrations of EGF, eotaxin/CCL11, MDC/CCL22, sCD40L, TGF-α, and TNF-α. Moreover, we reported statistically significant correlations between cytokines and IMT. Biomarker concentrations depend on numerous factors such as disease duration, metabolic control, and the presence of complications. Although the majority of pediatric T1D patients do not present signs of overt complications, it is indispensable to conduct the screening for angiopathies already in childhood, as its early recognition may attenuate the further progression of complications.

Associations of the obesity gene FTO variant with complications and comorbidities in patients with type 1 diabetes.

BACKGROUND AND AIMS: Because FTO gene is connected with the risk of obesity, cardiovascular disease and hypertension, as well as type 2 diabetes, we hypothesize that the rs9939609 FTO polymorphism may affect type 1 diabetes (T1D) complications and comorbidities. METHODS: We have investigated the associations of the FTO gene variant with the T1D and its complications and comorbidities, as well as the serum levels of pro- and anti-inflammatory markers and lipid profiles. RESULTS: The key results of our study are as follows: (1) the rs9939609 FTO polymorphism does not predispose individuals to T1D; (2) AA genotype is associated with an increased risk of overweight and obesity, retinopathy, hypertension, dyslipidemia and celiac disease; (3) AT genotype is associated with a decreased risk of retinopathy and celiac disease, whereas TT genotype is connected with decreased risk of dyslipidemia; (4) the FTO rs9939609 polymorphism affects the inflammatory status as well as lipid profile in T1D patients. CONCLUSIONS: Our results, for the first time, comprehensively indicate that the rs9939609 FTO polymorphism could be considered a genetic marker for increased susceptibility to T1D complications and comorbidities as well as suggests importance of FTO-mediated pathways in their etiology.

Gender-Related Difference in Skin Oxygenation in Young Patients with Uncomplicated Type 1 Diabetes.

Gender, through genetic, epigenetic and hormonal regulation, is an important modifier of the physiological mechanisms and clinical course of diseases. In diabetes mellitus, there are gender differences in incidence, prevalence, morbidity, and mortality. This disease also has an impact on the microvascular function. Therefore, this cross-sectional study was designed to investigate how gender affects the cutaneous microcirculation. We hypothesized that gender should be an important factor in the interpretation of capillaroscopy and transcutaneous oxygen saturation results. The study group consisted of 42 boys and 55 girls, uncomplicated diabetic pediatric patients. Females (F) and males (M) did not differ in terms of age, age at onset of diabetes, or diabetes duration. Furthermore, they did not differ in metabolic parameters. The comparison showed that group F had lower BP, higher pulse, and higher HR than group M. Group F had significantly lower creatinine and hemoglobin levels than group M. In children and adolescents with type 1 diabetes without complications, there was a gender difference in microcirculatory parameters. The resting transcutaneous partial pressure of oxygen was significantly higher in females than in males. However, there were no gender-related differences in basal capillaroscopic parameters or vascular reactivity during the PORH test. Our results indicate that studies investigating the structure and function of the microcirculation should consider the role of gender in addition to known cofactors such as puberty, body mass index, physical activity, and cigarette smoking.

The Impact of Disease Duration on Microcirculatory Dysfunction in Young Patients with Uncomplicated Type 1 Diabetes.

This study aimed to evaluate the earliest changes in the structure and function of the peripheral microcirculation using capillaroscopy and transcutaneous oxygen pressure measurement in children and adolescents with type 1 diabetes mellitus at baseline and during post-occlusive reactive hyperemia (PORH) in the function of diabetes duration. Sixty-seven patients with type 1 diabetes mellitus (T1D), aged 8 to 18 years, and twenty-eight age- and sex-matched healthy subjects were included in the analysis. Diabetic patients were divided into subgroups based on median disease duration. The subgroups differed in chronological age, lipid levels, and thyroid hormones. Capillaroscopy was performed twice: at baseline and then again after the PORH test. Transcutaneous oxygen pressure also was recorded under baseline conditions during and after the PORH test. Comparison of capillaroscopy and transcutaneous oxygen pressure parameters at rest and after the PORH showed no statistically significant difference between the subgroups. This remained true after adjusting for variables that differentiated the two subgroups. However, in the group of patients with long-standing diabetes, significant negative correlations were observed between the Coverage value after the PORH test and capillary reactivity with TcPO2_zero (biological zero). Significant positive correlations were also found between distance after the PORH test and TcPO2_zero. The results of our study indicate that in patients with a shorter duration of diabetes, the use of multiple tests provides a better characterization of the structure and function of microcirculation because the onset of dysfunction does not occur at the same time in all the tests.

Comparison of Metabolic Control in Children and Adolescents Treated with Insulin Pumps.

BACKGROUND: While insulin pumps remain the most common form of therapy for youths with type 1 diabetes (T1DM), they differ in the extent to which they utilize data from continuous glucose monitoring (CGM) and automate insulin delivery. METHODS: The aim of the study was to compare metabolic control in patients using different models of insulin pumps. This retrospective single-center study randomly sampled 30 patients for each of the following treatments: Medtronic 720G without PLGS (predictive low glucose suspend), Medtronic 640G or 740G with PLGS and Medtronic 780G. In the whole study group, we used CGM systems to assess patients' metabolic control, and we collected lipid profiles. In three groups of patients, we utilized CGM sensors (Guardian 3, Guardian 4, Libre 2 and Dexcom G6) to measure the following glycemic variability proxy values: time in range (TIR), time below 70 mg/dL (TBR), time above 180 mg/dL (TAR), coefficient of variation (CV) and mean sensor glucose. RESULTS: Medtronic 640G or 740G and 780G users were more likely to achieve a target time in the target range 70-180 mg/dL (≥80%) [Medtronic 720G = 4 users (13.3%) vs. Medtronic 640G/740G = 10 users (33.3%) vs. Medtronic 780G = 13 users (43.3%); p = 0.0357)] or low glucose variability [Medtronic 720G = 9 users (30%) vs. Medtronic 640G/740G = 18 users (60%) vs. Medtronic 780G = 19 users (63.3%); p = 0.0175)]. CONCLUSIONS: Any integration between the insulin pump and CGM was associated with better glycemic control. More advanced technologies and artificial intelligence in diabetes help patients maintain better glycemia by eliminating various factors affecting postprandial glycemia.

Prevalence of malaria in Arusha Region in the northern Tanzania.

BACKGROUND: The World Health Organization (WHO) reported an estimated 249 million malaria cases globally in 2023, of which 94% were reported from Africa. Tanzania, a Sub-Saharan African country, has an exceptionally high malaria prevalence (3.6 million in 2023). The aim of the present study was to assess malaria prevalence rates in the Arusha Region, northern Tanzania. This region is famous for its national parks and wildlife reserves, and it is visited by thousands of tourists from all over the world each year. The assessment of malaria prevalence in the region is important in the context of the necessity to administer antimalarial chemoprophylaxis to international travellers. MATERIAL AND METHODS: The study group consisted of 101 people, residents of the Karatu District in the Arusha Region, aged between 1 and 73 years, who volunteered to participate in the screening. Phase I of the study was conducted in July 2022 in the Karatu Lutheran Hospital in Karatu Town (located close to the Ngorongoro Conservation Area and the Serengeti National Park). During this phase a venous blood sample was collected from each patient. The samples were tested for malaria using a rapid diagnostic test (mRDT); the same samples were also used to measure haemoglobin concentration and next they were applied onto the Whatman FTA micro cards for further molecular diagnostics in Poland (phase II). RESULTS: mRDT detected two (2.0%) infections caused by Plasmodium (the etiological factor of malaria), the molecular tests (RT-PCR) confirmed the two positive results by mRDT but also detected infections in six other samples (7.9% in total). The study found that six patients were infected with the Plasmodium falciparum species, while two other subjects had co-infections (P. falciparum + P. ovale, P. falciparum + P. vivax + P. malariae). CONCLUSIONS: The study findings confirm the prevalence of malaria in areas located close to national parks in northern Tanzania and support the use of antimalarial chemoprophylaxis in international travellers visiting the area. The present study found co-infections caused by four different species of Plasmodium species which supports the prevalence of different parasitic species in Sub-Saharan Africa and is in line with CDC reports but contrary to WHO reports which estimate that 100% of malaria cases in Sub-Saharan Africa are caused by P. falciparum.

Blastocystis spp. and Other Intestinal Parasites in Polish Soldiers Deployed to Lebanon and Iraq.

Intestinal parasitic infections are one of the most common infectious diseases worldwide, particularly in developing countries. A distinct group at increased risk of infection is military personnel deployed overseas for extended periods, typically six months at a time. The aim of this study was to determine the prevalence of Blastocystis spp. and other intestinal parasites in Polish military personnel returning from deployments to Lebanon (n = 206) and Iraq (n = 220). In this group of subjects, we found Blastocystis spp. (13.6%), Dientamoeba fragilis (3.3%), Entamoeba coli (0.9%), and Endolimax nana (0.5%). Entamoeba histolytica sensu lato and Chilomastix mesnili infections were detected only in one soldier returning from Lebanon and Iraq, respectively. Blastocystis subtype (ST) 3 was predominant in soldiers returning from Lebanon, followed by ST2 and ST1. ST1 infection was predominant in soldiers returning from Iraq, followed by ST3 and ST2. Our study affirms that, deployment abroad is of no influence of the prevalence of parasitic protozoa. However, it would be worth to monitor parasite infection in military personnel returning from tropical zone even if they have no actual symptoms. In addition, it is very important to determine the subtypes of Blastocystis-this may help to clearly define their pathogenicity, especially considering the scarcity of studies on Blastocystis genotypes in Iraqi and Lebanese residents.

Recommendations of the Experts of the Polish Cardiac Society (PCS) and the Polish Lipid Association (PoLA) on the diagnosis and management of elevated lipoprotein(a) levels.

Lipoprotein(a) [Lp(a)] is made up of a low-density lipoprotein (LDL) particle and a specific apolipoprotein(a). The blood concentration of Lp(a) is approximately 90% genetically determined, and the main genetic factor determining Lp(a) levels is the size of the apo(a) isoform, which is determined by the number of KIV2 domain repeats. The size of the apo(a) isoform is inversely proportional to the blood concentration of Lp(a). Lp(a) is a strong and independent cardiovascular risk factor. Elevated Lp(a) levels ≥ 50 mg/dl (≥ 125 nmol/l) are estimated to occur in more than 1.5 billion people worldwide. However, determination of Lp(a) levels is performed far too rarely, including Poland, where, in fact, it is only since the 2021 guidelines of the Polish Lipid Association (PoLA) and five other scientific societies that Lp(a) measurements have begun to be performed. Determination of Lp(a) concentrations is not easy due to, among other things, the different sizes of the apo(a) isoforms; however, the currently available certified tests make it possible to distinguish between people with low and high cardiovascular risk with a high degree of precision. In 2022, the first guidelines for the management of patients with elevated lipoprotein(a) levels were published by the European Atherosclerosis Society (EAS) and the American Heart Association (AHA). The first Polish guidelines are the result of the work of experts from the two scientific societies and their aim is to provide clear, practical recommendations for the determination and management of elevated Lp(a) levels.

PD-1 Receptor (+) T cells are associated with the efficacy of the combined treatment with regulatory t cells and rituximab in type 1 diabetes children via regulatory t cells suppressive activity amelioration.

An imbalance between exaggerated autoaggressive T cell responses, primarily CD8 + T cells, and impaired tolerogenic mechanisms underlie the development of type 1 diabetes mellitus. Disease-modifying strategies, particularly immunotherapy focusing on FoxP3 + T regulatory cells (Treg), and B cells facilitating antigen presentation for T cells, show promise. Selective depletion of B cells may be achieved with an anti-CD20 monoclonal antibody (mAb). In a 2-year-long flow cytometry follow-up, involving 32 peripheral blood T and B cell markers across three trial arms (Treg + rituximab N = 12, Treg + placebo N = 13, control N = 11), we observed significant changes. PD-1 receptor (+) CD4 + Treg, CD4 + effector T cells (Teffs), and CD8 + T cell percentages increased in the combined regimen group by the end of follow-up. Conversely, the control group exhibited a notable reduction in PD-1 receptor (+) CD4 + Teff percentages. Considering clinical endpoints, higher PD-1 receptor (+) expression on T cells correlated with positive responses, including a higher mixed meal tolerance test AUC, and reduced daily insulin dosage. PD-1 receptor (+) T cells emerged as a potential therapy outcome biomarker. In vitro validation confirmed that successful Teff suppression was associated with elevated PD-1 receptor (+) Treg levels. These findings support PD-1 receptor (+) T cells as a reliable indicator of treatment with combined immunotherapy consisting of Tregs and anti-CD20 mAb efficacy in type 1 diabetes mellitus.