Circulating miRNA as potential biomarkers for diabetes mellitus type 2: should we focus on searching for sex differences?

microRNAs are non-coding molecules, approximately 22 nucleotides in length, that regulate various cellular processes. A growing body of evidence has suggested that their dysregulated expression is involved in the pathogenesis of diverse diseases, including diabetes mellitus type 2 (DM2). Early onset of this chronic and complex metabolic disorder is frequently undiagnosed, leading to the development of severe diabetic complications. Notably, DM2 prevalence is rising globally and an increasing number of articles demonstrate that DM2 susceptibility, development, and progression differ between males and females. Therefore, this paper discusses the role of microRNAs as a source of novel diagnostic biomarkers for DM2 and aims to underline the importance of sex disparity in biomarkers research. Taking into account an urgent need for the development of sex-specific diagnostic strategies in DM2, recent results have shown that circulating miRNAs are promising candidates for sex-biased biomarkers.

New genetically determined risk factors of diabetic retinopathy in type 2 diabetes mellitus: final report

Background. According to the International Diabetes Federation, the number of people with diabetes mellitus is going to increase from 366 to 552 million by 2030. More than 1.5 million patients with diabetes are registered in Ukraine, of which 84–95 % have type 2 diabetes. Diabetic retinopathy (DR) is one of the common diabetes complications, being one of the leading causes of blindness and low vision, in particular in people of occupational age. Metabolic disorders, including activation of the polyol pathway of glucose utilization, play an important role in the pathogenesis of DR, with aldose reductase playing a key role, the activity of which is associated with the polymorphism of its gene, AKR1B1. The study of new meta­bolic and genetic mechanisms for the development and progression of DR in type 2 diabetes mellitus in patients from the Ukrainian population is an actual task of modern ophthalmology. Purpose: to investigate and generalize new genetically determined risk factors for diabetic retinopathy in type 2 diabetes mellitus. Materials and methods. The study involved 409 participants, who were divided into four groups: 1 — comparison cohort (98 people without diabetes mellitus type 2); 2 — 76 patients (stage I DR, without fundus chan­ges); 3 — 64 individuals with non-proliferative DR; 4 — 64 patients with proliferative DR; control group for genetic researches included 107 ophthalmologically healthy individuals. All patients underwent blood sampling for molecular genetic research by puncture of the ulnar vein and aspiration of 2.5 ml of blood through a 23G 5.0 ml disposable syringe (Hemoplast, Etalon+, Ukraine), followed by a release into a 3.0 ml container (Vacuette K3E K3EDTA, Greiner Bio-One, Austria). Distribution of polymorphic alleles and genotypes of rs759853 and rs9640883 aldose reductase gene (AKR1B1) in patients with non-proliferative DR, proliferative DR and in the control group and their association with disease and effects on the occurrence, mechanisms of development and progression of DR were studied. Based on the conducted researches, a model of DR development prognosis was developed by construction of multiple regression with sufficient reliability of degree of influence of independent variables on a calculated indicator. Results. As a result of our research, we identified new genetically determined risk factors for the development and progression of the different stages of DR in patients with diabetes mellitus type 2, namely the role of polymorphic alleles and genotypes rs759853 and rs9640883 of the AKR1B1 gene. The deve­loped logistic regression models found that the risk of DR incidence is five times lower in carriers of the G/G and G/A genotypes compared to carriers of the A/A genotype rs759853 polymorphism (p < 0.001). It was found that the risk is twice as high (p = 0.01) for carriers of the G/G genotype rs9640883 compared to the A/A + G/A genotypes. The risk of developing proliferative DR is 3.3 times lower in carriers of the G/G genotype and 2.5 times lower in carriers of the G/A genotype compared to carriers of the A/A genotype rs759853. Conclusions. Therefore, on the basis of our clinical, ophthalmological, molecular genetic and statistical studies we have identified new risk factors for the development and progression of different stages of DR in patients with diabetes mellitus type 2. Mathematical models of development and progression of different stages of DR in patients with diabetes type 2 were built.

Association of CDKAL1 RS10946398 Gene Polymorphism with Susceptibility to Diabetes Mellitus Type 2: A Meta-Analysis

Background. Diabetes is one of the common chronic diseases in which susceptibility is determined by a combination of genetic and environmental factors, and more than 90% of diabetic patients are diabetes mellitus type 2 (T2DM). The existing studies on the association between CDKAL1 rs10946398 gene polymorphism and susceptibility to type 2 diabetes are inconsistent across populations. Aim. We aim to explore the association between CDKAL1 rs10946398 gene polymorphism and susceptibility to type 2 diabetes in different populations. Methods. We examined all studies before June 12, 2021, that associated CDKAL1 rs10946398 with T2DM. Heterogeneity was assessed by meta-analysis of allelic inheritance models (A vs. C), dominant inheritance models (AA vs. AC+CC), and recessive inheritance model (AA+AC vs. CC); I 2 was used to assess the heterogeneity (if I 2 < 50 %, the fixed-effects model was used; if I 2 ≥ 50 %, the random-effects model was used for data consolidation); correlation was judged by a forest map; potential publication bias was tested by the Egger test ( p > 0.05 indicates that there is no publication bias). Results. Fourteen data totaling 30288 subjects, including 19272 controls and 11016 patients with T2DM, met our inclusion criteria. In the Asian population, the differences were statistically significant ( p < 0.01 ) for dominant genetic model ( OR = 0.75 , 95 % CI = 0.64 -0.88, p = 0.0003 ). But the allelic effect model ( OR = 0.87 , 95 % CI = 0.75 -1.02, p = 0.08 ) and the recessive genetic model ( OR = 0.85 , 95 % CI = 0.66 -1.10, p = 0.23 ) were not statistically significant ( p > 0.01 ). In the non-Asian population, the differences were statistically significant ( p < 0.01 ) for the allelic effect model ( OR = 0.83 , 95 % CI = 0.77 -0.88, p < 0.00001 ), the dominant model ( OR = 0.79 , 95 % CI = 0.72 -0.87, p < 0.00001 ), and the recessive model ( OR = 0.78 , 95 % CI = 0.70 -0.87, p < 0.0001 ). Conclusion. In this study, CDKAL1 RS10946398 was positively associated with T2DM, but the association was different in Asian populations.

Fungal Invasive Co-Infection Due to Aspergillus fumigatus and Rhizopus arrhizus: A Rhino-Orbital Presentation

Aspergillosis and mucormycosis are filamentous fungal infections occurring predominantly in immunocompromised patients. Fulminant process with rapid infiltration of the contiguous tissue is distinctive for both type of fungi. The rhinocerebral co-infection by Aspergillus and Mucorales is very rare and is usually associated in immunocompromised patients with a high mortality rate. This rare co-infection leads to difficulties in diagnosis, and therapeutic delays can result in a poor prognosis. Overall, the treatment of choice is surgical debridement and liposomal amphotericin B. This paper describes a combined aspergillosis and mucormycosis case in a diabetes mellitus type 2 patient with chronic ulcerations of the palatal and cheek. To our knowledge, this is the first report of an uncommon co-infection of Aspergillus fumigatus and Rhizopus arrhizus in a rhino-orbital presentation.

Different patterns of cutaneous manifestation of diabetes mellitus type-2 observed in tertiary care centre of South West Rajasthan

Diabetes mellitus (DM) is a common endocrinal disorder caused by complex interaction of genetics and environmental factors. Various dermatological features are known to be cutaneous markers of diabetes mellitus like diabetic dermatopathy, acrochordons, acanthosis nigricans and bullous diabeticorum, etc. An observational cross-sectional study on a total of 400 patients of Diabetes Mellitus Type-2. A complete cutaneous examination was done in all cases to observe for the presence of any specific or nonspecific dermatosis. All the statistical tests were two sided and P-value &#60;0.05 was considered as significant level. This study showed that in specific cutaneous disorders, Acrochordon 138(34.5%) was the most common manifestation which was followed by, Bacterial Infections 93(23.5%), Dermatophytosis 77(19.2%), Candidiasis 76(19%), Acanthosis nigricans 50(12.5%) and Onychomycosis 33(8.25%) in decreasing order. Xerosis 259(64.7%) was the commonest manifestation in non-specific cutaneous disorders followed by, Generalized pruritus 200(50%), Seborrheic keratosis 35(8.75%) in decreasing order. Cutaneous manifestations are quite common in uncontrolled (HbA1c&#62;7gm) type 2 diabetes mellitus as compare to controlled group. Uncontrolled group is more prone to develop diabetic complication like hypertension, diabetic retinopathy and peripheral neuropathy etc. It is concluded that, Diabetes mellitus Type-2 involves the skin quite often and whenever patients present with multiple skin manifestation and then diabetic statusshould be checked and controlled.

Current Challenges and Future Trends of Enzymatic Paper-Based Point-of-Care Testing for Diabetes Mellitus Type 2

A point-of-care (POC) can be defined as an in vitro diagnostic test that can provide results within minutes. It has gained enormous attention as a promising tool for biomarkers detection and diagnosis, as well as for screening of chronic noncommunicable diseases such as diabetes mellitus. Diabetes mellitus type 2 is one of the metabolic disorders that has grown exponentially in recent years, becoming one of the greatest challenges to health systems. Early detection and accurate diagnosis of this disorder are essential to provide adequate treatments. However, efforts to reduce incidence should remain not only in these stages but in developing continuous monitoring strategies. Diabetes-monitoring tools must be accessible and affordable; thus, POC platforms are attractive, especially paper-based ones. Paper-based POCs are simple and portable, can use different matrixes, do not require highly trained staff, and are less expensive than other platforms. These advantages enhance the viability of its application in low-income countries and hard-to-reach zones. This review aims to present a critical summary of the main components required to create a sensitive and affordable enzymatic paper-based POC, as well as an oriented analysis to highlight the main limitations and challenges of current POC devices for diabetes type 2 monitoring and future research opportunities in the field.

Host Defence Peptides in Diabetes Mellitus Type 2 Patients with Periodontal Disease. A Systematic Review

The aim of the study was to critically assess and review the latest evidence relating the associations between host defence peptides (HDPs), periodontal diseases (PD) and diabetes mellitus type 2 (DM2). To explore studies on HDPs, periodontal disease, and DM2, researchers utilised specific key phrases to search the electronic databases PubMed (National Library of Medicine), Embase (Ovid), Medline (EBSCO), and Dentistry and Oral Sciences (EBSCO). Quality assessment was conducted by means of the Newcastle Ottawa scale and the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool. Following a thorough screening process, a total of 12 papers (4 case-control, 6 cross-sectional, 1 animal, and 1 in vitro) fulfilled the selection criteria and were included. The majority of research found that HDPs were upregulated in DM2 patients with PD. Three investigations, however, found that HDPs were downregulated in DM2 patients with PD. HDPs play a part in the pathophysiology of PD and DM2. Nonetheless, more human, animal and laboratory investigations are needed to fully understand validation of the link, as the evidence is limited. Understanding HDPs as common moderators is critical, aimed at unlocking their potential as therapeutic and diagnostic agents.