Diabetes Distress Among the Roma Population From a Tertiary Care Center in Romania.

Background Distress in patients with diabetes is a condition that has received significant attention in recent years; however, data regarding the psychological assessment and the impact of the emotional burden of diabetes among the Roma population are still scarce in the medical literature. Material and methods We conducted an observational, transversal study that included 310 adult patients with diabetes mellitus, aged between 18 and 85 years old, of which the majority (61%) were women; patients were selected from a tertiary hospital providing diabetes care; diabetes distress was evaluated using a standardized questionnaire, the diabetes distress scale (DDS), validated on Romanian patients. Results In the study population, a great proportion of patients showed diabetes distress, with 24.8% (N=82) having moderate distress and 29.7% (N=121) having severe distress. In the Caucasian group, there were significantly more patients without distress than in the Roma patients,while on the contrary, more Roma patients experienced severe distress compared to the opposite group (64.5%, N=78 versus 35.5%, N=43). In the Caucasian group, a statistical significance was observed regarding interpersonal distress, with Caucasian women having a higher score than men. Concerning the Roma patients, total DDS and all subscales´ scores were statistically significant, with Roma women having higher scores than men. A statistical significance was observed between ethnicity and diabetes distress scores, with the Roma population having higher median values than Caucasian patients. It was also demonstrated that the lack of education, a higher diabetes evolution, and a higher glycated hemoglobin (HbA1c) level (above 8%) have influenced the risk of severe DDS in the Caucasian group, while in the Roma patients, employment status (being unemployed) represents a risk factor for severe DDS. Conclusion The Roma patients included in our study experienced higher distress scores compared to Caucasians. These results are substantial as they emphasize the need to include the evaluation of diabetes distress in clinical practice to facilitate the early initiation of intervention measures. There is nevertheless limited data regarding this particular ethnic group; therefore, further research is still needed.

A Systematic Review of Semaglutide's Influence on Cognitive Function in Preclinical Animal Models and Cell-Line Studies.

Since we aim to test new options to find medication for cognitive disorders, we have begun to assess the effect of semaglutide and to conduct a review gathering studies that have attempted this purpose. This systematic review focuses on the cognitive effects of semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1 RA), in the context of neurological and cognitive impairment. Semaglutide, a synthetic GLP-1 analog, showcased neuroprotective effects beyond metabolic regulation. It mitigated apoptosis and improved cognitive dysfunction in cerebrovascular disease, suggesting broader implications for neurological well-being. Also, studies highlighted GLP-1 RAs' positive impact on olfactory function in obese individuals with type 2 diabetes, on neurodegenerative disorders, multiple sclerosis, and endotoxemia. In order to analyze current studies that assess the impact of semaglutide on cognitive function, a literature search was conducted up to February 2024 on two online databases, MEDLINE (via PubMed) and Web of Science Core Collection, as well as various websites. Fifteen studies on mice populations and two studies on cell lines were included, analyzed, and assessed with bias-specific tools. The neuroprotective and anti-apoptotic properties of GLP-1 and its analogs were emphasized, with animal models and cell line studies demonstrating enhanced cognitive function. While promising, limitations include fewer studies, highlighting the need for extensive research, particularly in the human population. Even though this medication seems promising, there are significant limitations, one of which is the lack of studies on human subjects. Therefore, this review aims to gather current evidence.

Changes in C-Peptide Values in Children with Type 1 Diabetes - a Three-Year Study.

Background: C-peptide is used as an important indicator of residual insulin secretion in patients diagnosed with type 1 diabetes mellitus (T1DM) and treated with insulin. Aim:We have aimed to monitor the serum C-peptide (CP) levels during the first three years after diagnosis of T1DM in a cohort of children admitted to the Diabetes Department of "M. S. Curie" Emergency Clinical Hospital for Children, Bucharest, Romania, and to investigate the factors that could influence the rate of decline in its secretion. Method:We conducted a longitudinal, retrospective cohort study on a group of 215 children and adolescents who met the inclusion criteria and were monitored in our clinic over the course of a long period of time. We analyzed several parameters, including fasting serum CP values at diagnosis and yearly throughout T1DM evolution, the severity of diabetic ketoacidosis (DKA) at onset, HbA1c at diagnosis, family history of T1DM/T2DM, patient gender and presence of concurrent acute infectious disease at diagnosis, with the purpose of evaluating their influence on the preservation of endogenous insulin secretion. Based on serum CP value measured three years after T1DM onset, patients were divided into two groups: group 1, with low insulin residual secretion (CP < 0.6 ng/mL), and group 2, with preserved insulin residual secretion (CP ≥0.6 ng/mL) Results:At the moment of diagnosis, patients in group 1 were younger than those in group 2 (6.03 ± 3.54 years and 9.76 ± 2.75 years, respectively). The proportion of children with diabetic ketoacidosis (DKA) at onset was greater in group 1 (68% of patients) than group 2, in which the majority of subjects (60%) did not have DKA. The C-peptide value at diagnosis was significantly lower (0.55 ± 0.36 ng/mL) among patients in group 1 than those in group 2 (1.11 ± 0.59 ng/mL). In group 1 there was a higher proportion of patients (65%) with acute infectious disease at onset. Family history of T1DM/T2DM was associated with a more rapid decline in CP values. Our data showed no correlation between CP levels monitored for three years and HbA1c at diagnosis and no association with the gender of each patient. Conclusion:Patients with higher CP concentrations at diagnosis maintained increased values (> 0.6 ng/mL) three years after disease onset. Younger children had a faster decline of CP secretion during the first three years following diabetes diagnosis. In patients with severe symptoms (DKA) and associated infectious disease at onset, a risk of rapid CP decline was found.

Incidence of Lower Extremity Amputation in Romania: A Nationwide 5-Year Cohort Study, 2015-2019.

Background and Objectives: The primary objective of this study was to investigate the incidence of lower extremity amputations (LEAs) in a representative population from Romania, in both diabetic and non-diabetic adults, including trauma-related amputations. The secondary objective was to evaluate the trends in LEAs and the overall ratio of major-to-minor amputations. Material and Methods: The study was retrospective and included data from the Romanian National Hospital Discharge Records, conducted between 1 January 2015 and 31 December 2019. Results: The overall number of cases with LEAs was 88,102, out of which 38,590 were aterosclerosis-related LEAs, 40,499 were diabetes-related LEAs, and 9013 were trauma-related LEAs, with an ascending trend observed annually for each of these categories. Of the total non-traumatic amputations, 51.2% were in patients with diabetes. Most LEAs were in men. The total incidence increased from 80.61/100,000 in 2015 to 98.15/100,000 in 2019. Conclusions: Our study reported a 21% increase in total LEAs, 22.01% in non-traumatic LEAs, and 19.65% in trauma-related amputation. The minor-to-major amputation ratio increased over the study period in patients with diabetes. According to these findings, it is estimated that currently, in Romania, there is one diabetes-related amputation every hour and one non-traumatic amputation every 30 min.

PI3K/AKT/mTOR Dysregulation and Reprogramming Metabolic Pathways in Renal Cancer: Crosstalk with the VHL/HIF Axis.

Renal cell carcinoma (RCC) represents 85-95% of kidney cancers and is the most frequent type of renal cancer in adult patients. It accounts for 3% of all cancer cases and is in 7th place among the most frequent histological types of cancer. Clear cell renal cell carcinoma (ccRCC), accounts for 75% of RCCs and has the most kidney cancer-related deaths. One-third of the patients with ccRCC develop metastases. Renal cancer presents cellular alterations in sugars, lipids, amino acids, and nucleic acid metabolism. RCC is characterized by several metabolic dysregulations including oxygen sensing (VHL/HIF pathway), glucose transporters (GLUT 1 and GLUT 4) energy sensing, and energy nutrient sensing cascade. Metabolic reprogramming represents an important characteristic of the cancer cells to survive in nutrient and oxygen-deprived environments, to proliferate and metastasize in different body sites. The phosphoinositide 3-kinase-AKT-mammalian target of the rapamycin (PI3K/AKT/mTOR) signaling pathway is usually dysregulated in various cancer types including renal cancer. This molecular pathway is frequently correlated with tumor growth and survival. The main aim of this review is to present renal cancer types, dysregulation of PI3K/AKT/mTOR signaling pathway members, crosstalk with VHL/HIF axis, and carbohydrates, lipids, and amino acid alterations.

The Safety Profile of Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-like Peptide 1 Receptor Agonists in the Standard of Care Treatment of Type 2 Diabetes Mellitus.

AIM: We evaluated the safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) for their use with other glucose-lowering drugs and drugs for the treatment of type 2 diabetes mellitus (T2DM), in a standard-of-care regimen with maximum tolerated doses, and, respectively, when compared with metformin. METHODS: We conducted a retrospective, observational study on 405 patients that were seen in the outpatient clinic of the N Paulescu National Institute for Diabetes Mellitus, Bucharest, Romania, in 2019. Their demographics, metabolic parameters, and medication safety were evaluated at three follow-up visits, from baseline, six months, and twelve months. RESULTS: Both SGLT-2is and GLP-1 RAs are safe regarding creatinine, eGFR, urea, GOT, and GPT upon the comparison of the data from the six- and twelve-month visits with the initial visit, and also the twelve-month visit with the six-month visit. Moreover, when comparing SGLT-2is and GLP-1 RAs with metformin, there are safety data only for urea. CONCLUSIONS: In this retrospective analysis, both SGLT-2is and GLP-1 RAs, when used in conjunction with other glucose-lowering, blood-pressure-lowering, and lipid-lowering medications, appeared to be safe for the management of T2DM.

New born macrosomia in gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is a metabolic complication of pregnancy. The pathogenesis of GDM is considered to involve ß-cell dysfunction and insulin resistance (IR). GDM is associated with a significant risk of macrosomia in addition to a high probability of metabolic complications for the offspring. The precise mechanism underlying GDM remains unclear. The aim of the present study was to analyse the factors associated with insulin resistance and ß-cell dysfunction involved in the pathophysiology of GDM complicated with macrosomia compared with GDM without macrosomia. In addition, another aim of the present study was to assess the relationship between GDM complicated with macrosomia and anthropometric, clinical and paraclinical parameters. The following group of patients were recruited as part of a case-control study: Patients with GDM without macrosomia, patients with GDM complicated with macrosomia and healthy gestational controls. Blood samples were collected at the third trimester of pregnancy and tested for adiponectin, leptin, insulin, proinsulin and C-peptide. Homeostatic model assessment-IR (HOMA-IR), steady state ß-cell function (HOMA%B), insulin sensitivity (HOMA%S) and body mass index (BMI) were also calculated. All patients diagnosed with GDM showed an impairment in HOMA%B and a decrease in C-peptide maternal serum concentration. Additionally, diabetic status leading to the birth of offspring with macrosomia did not induce changes in the maternal serum levels of insulin, proinsulin, adiponectin or leptin, which was also the case in patients with GDM but not macrosomia. HOMA%B presented a stronger positive correlation with pre-pregnancy BMI and maternal weight gain, and a stronger negative correlation with adiponectin. Furthermore, HOMA%S in this group exhibited strong positive correlations with maternal serum levels of high-density lipoprotein cholesterol (HDL) and aspartate aminotransferase, and a strong negative correlation with pre-pregnancy BMI. In the same patients, HOMA-IR was also found to have a high negative correlation with HDL levels, and highly positive correlations with gestational age and triglyceride levels. In conclusion, the present study suggests that the different correlations among the factors involved in the pathogenesis of GDM may explain the evolution of GDM pregnancy to macrosomia.

Non-Insulin Novel Antidiabetic Drugs Mechanisms in the Pathogenesis of COVID-19.

The present study aimed to analyse the published data and to realize an update about the use and pathogenesis of the novel antidiabetic drugs, respectively, dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1 Ra), and sodium-glucose co-transporter-2 inhibitors (SGLT-2i), in patients with type 2 diabetes mellitus (T2DM) and coronavirus disease (COVID-19). Literature research in the PubMed and Web of Science database was performed in order to identify relevant published clinical trials and meta-analyses that include information about the treatment with novel antidiabetic agents in patients with T2DM and COVID-19. A total of seven articles were included, and their primary and secondary outcomes were reported and analysed. DPP-4i has mixed results on mortality in T2DM patients with COVID-19 but with an overall slightly favourable or neutral effect, whereas GLP-1 Ra seems to have a rather beneficial impact, while SGLT-2i may be useful in acute illness. Even if there are limited data, they seem to have favourable efficacy and safety profiles. The available evidence is heterogenous and insufficient to evaluate if the benefits of non-insulin novel antidiabetic drugs in COVID-19 treatment are due to the improvement of glycaemic control or to their intrinsic anti-inflammatory effects but highlights their beneficial effects in the pathogenesis and evolution of the disease.

Continuous glucose monitoring devices: A brief presentation (Review).

As diabetes prevalence is continuously increasing, better management is needed to achieve blood glucose control, in order to prevent complications and lessen the burden of this disease. Since the first measurement of glycosuria at the beginning of the 1900s', huge advances were made in monitoring glycemia. Continuous glucose monitoring systems revolutionized diabetes management, especially for patients with type 1 diabetes. Avoiding glycemic variability and maintaining optimal glycemic control is crucial for the evolution of patients with type 1 diabetes. The usefulness of glycemic monitoring devices can be extended to patients with type 2 diabetes. It is also important to note that in those patients at risk of developing high glycemic variability (e.g. patients with advanced chronic kidney disease), continuous glycemic monitoring may improve their prognosis. These monitoring systems can be classified according to the analytical method, the degree of invasiveness, the data availability and the mode of usage. The technology is constantly improving in bioanalytical performance, biocompatibility, length of wearing time, safety and clinical features. The aim of this review was to briefly present the main characteristics of glucose biosensors, glucose monitoring systems and their clinically utility.

Hypocalcemia: A possible risk factor for anastomotic leak in digestive surgery.

Anastomotic leaks (ALs) remain the most severe complication in digestive surgery, as well as the most consumptive in terms of human and financial resources. There is an abundance of international research which has focused on identifying and correcting risk factors, and on individualized surgical management as well. The most frequent risk factors are male sex, obesity, diabetes, advanced malignant disease, ASA score, perioperative blood loss or perioperative transfusion, long operation time, emergency operation and altered nutritional status. The aim of the present study was to measure the preoperative serum calcium level and to find a possible correlation between calcium levels and the risk of AL occurrence. A retrospective analysis of medical records for 122 patients who underwent surgical gut resection with anastomosis for different pathologies was carried out. Preoperative serum calcium level and the occurrence of AL was noted. The results revealed that the average value of total blood calcium was 8.78 mg/dl, without a significant difference in sex groups. Hypocalcemia was identified in 44 patients (36.1%). AL was identified in 8 patients (6.6%), with a statistically insignificant difference between male and female patients. The average value of blood calcium in the AL patient group was 8.07 mg/dl, while in patients without AL the average value was 8.83 mg/dl. Hypocalcemia, defined as a serum calcium level below 8.5 mg/dl, was observed in 7 of the 8 patients presenting with AL (87.5%) and 37 patients who did not present with AL (32.5%), a significant difference with which to consider and include hypocalcemia in the group of risk factors for AL (P=0.001). In conclusion, preoperative low serum calcium level can represent a risk factor for AL in digestive surgery.

Impact of adipose tissue in chronic kidney disease development (Review).

Obesity is a worldwide pandemic health issue. Obesity is associated with the pathogenesis of type 2 diabetes, hypertension, dyslipidemia, cardiovascular diseases, cancer, and kidney diseases. This systemic disease can affect the kidneys by two mechanisms: Indirectly through diabetes mellitus (DM) and hypertension and directly through adipokines secreted by adipose tissue. Obesity is a risk factor for chronic kidney disease (CKD), which is associated with an increased risk of morbidity and mortality among the adult population. Increased visceral adipose tissue leads to renal glomerular hyperfiltration and hyperperfusion, which may lead to glomerular hypertrophy, proteinuria, and CKD development. Adipokines are hormones produced by fat tissue. They are involved in energy homeostasis, sugar and fat metabolism, reproduction, immunity, and thermogenesis control. Hormones and cytokines secreted by adipose tissue contribute to the development and progression of CKD. Decreased serum or urinary adiponectin levels are specific in diabetic and non-diabetic CKD patients, while leptin presents increased levels, and both are associated with the development of glomerulopathy. Excessive adipose tissue is associated with inflammation, oxidative stress (OS), insulin resistance and activation of the renin angiotensin-aldosterone system (RAAS). Therefore, adipose tissue dysfunction plays an important role in the development of CKD.

PI3K/AKT/mTOR signalling pathway involvement in renal cell carcinoma pathogenesis (Review).

Renal cell carcinoma (RCC) accounts for over 90% of all renal malignancies, and mainly affects the male population. Obesity and smoking are involved in the pathogenesis of several systemic cancers including RCC. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signalling pathway regulates cell growth, differentiation, migration, survival, angiogenesis, and metabolism. Growth factors, hormones, cytokine and many extracellular cues activate PI3K/AKT/mTOR. Dysregulation of this molecular pathway is frequently reported in human cancers including RCC and is associated with aggressive development and poor survival rate. mTOR is the master regulator of cell metabolism and growth, and is activated in many pathological processes such as tumour formation, insulin resistance and angiogenesis. mTOR inhibitors are used at present as drug therapy for RCC to inhibit cell proliferation, growth, survival, and the cell cycle. Temsirolimus and everolimus are two mTOR inhibitors that are currently used for the treatment of RCC. Drugs targeting the PI3K/AKT/mTOR signalling pathway may be one of the best therapeutic options for RCC.

The Charcot Neuroarthropathy as Onset of Type 2 Diabetes - a Diagnostic Challenge.

Introduction: The Charcot neuro-osteoarthropathy is a devastating complication of diabetes, with negative impact on both prognosis and quality of life. Moreover, the diagnostic is often missed or delayed. Case report: A 50 years old male patient with dyslipidemia, overweight and hypertension was referred to our Diabetes Department in the context of newly diagnosed diabetes (HbA1C=11.7%), four days after left hallux trans-metatarsal amputation and debridement of the dorsal collection, for wet gangrene of the left hallux, with dorsal extension. The diagnostic of diabetic neuro-osteoarthropathy of the left foot was delayed several months. A good glycemic control was achieved with insulin glargine and metformin. We look further to introducing modern antidiabetic drugs with not only proven cardiovascular benefit but also good impact on weight. The patient needs to be managed by a multidisciplinary team, which has to include a podiatrist and a vascular surgeon. Conclusions: This case suggest the importance of rising diabetes and diabetic peripheral polyneuropathy awareness in all medical fields.