Late Diabetic Complications Research Articles

Synthesis and pharmacological properties of novel guanidine derivatives of quinazoline-2,4(1H,3H)-dione

Introduction: Na+/H+ exchanger type 1 (NHE-1) is a validated drug target for the treatment of cardiovascular and ophthalmic diseases due to the cytoprotective, anti-ischemic and anti-inflammatory properties of NHE-1 inhibitors. This article presents data on the synthesis and pharmacological activity studies of novel guanidine derivatives of quinazoline-2,4(1H,3H)-dione 6-11 and reference drugs amiloride, rimeporide, zoniporide, dexamethasone, aminoguanidine, and acetylsalicylic acid. Materials and Methods: Pharmacological properties were assessed using pH-dependent platelets deformation assay, anti-inflammatory activity assay on LPS-stimulated peritoneal macrophages, antiglycation assay, analysis of platelet aggregation in vitro and measurement of intraocular pressure in vivo. Results: Several compounds combine NHE-1 inhibition with antiglaucomic and antiplatelet activity. Compound 11 significantly inhibits pro-inflammatory activation of murine macrophages (IC50 15.64 μM) and effectively suppresses the formation of glycated proteins (38.1±2.6% in C 1 mM). Conclusion: The investigated compounds represent a promising scaffold for development of agents for the treatment of cardiovascular pathologies, glaucoma, excessive inflammation, and late diabetic complications including retina diabetics and thrombosis.

Biomarkers of Oxidative Stress in Diabetic Microvascular Complications Review Article

Reactive oxygen species (ROS) are produced as a result of biochemical processes that are not in balance with the body's antioxidant defense mechanism. This metabolic dysfunction is referred to the oxidative stress (OS). Metabolic dysfunction-associated diseases are affected by changes in the redox balance. It is now widely recognized that oxidative stress significantly affects diabetes mellitus (DM), particularly type 2 diabetes. The biochemical changes associated with DM could disturb the oxidative milieu, leading to several microvascular complications in diabetic patients. Thus, DM is a perfect disease to explore the harmful consequences of oxidative stress and how to treat it. Oxidative stress triggered by hyperglycemia is an important contributor to the effects of diabetic microvascular diseases. Uncontrolled hyperglycemia carried by deficiencies in insulin secretion or action produces a number of problems, such as peripheral vascular disorders, nephropathy, neuropathy, retinopathy, increased morbidity and/or mortality, as well as the incidence of diabetes mellitus (DM) are rising globally. The development and progression of diabetic problems are strongly correlated with reactive oxygen species and oxidative stress, according to a wide body of research. This review aims to explore various markers of oxidative stress and the role of ROS in the pathogenesis and progression of late diabetic microvascular complications.

Association of Testosterone Level and Anti-SARS-CoV-2 Antibodies in Diabetic Patients in Babylon, Iraq

Abstract Background: The risk of developing a more aggressive disease condition is influenced by age and the presence of comorbidities such as diabetes, hypertension, obesity, and cardiovascular diseases. Diabetics may experience late diabetes complications such as diabetic renal disease and ischemic heart disease, which can make them frailer and exacerbate the severity of viral infections such as COVID-19 disease, which can result in kidney or heart failure. Objectives: To evaluate the levels of testosterone hormone in association with glucose levels in the diabetic population, choosing (50) diabetic patients with no known history of COVID-19 infection or receiving a COVID-19 vaccine were enrolled in the study. Materials and Methods: The anti-SARS-CoV-2 antibody was assessed for all patients and in 40 healthy individuals (control group). The study was carried out from January to May 2023 in Marjan Medical City and a private clinical laboratory. Testosterone levels and anti-SARS-CoV-2 antibodies were measured using manual principles and the methods of the Automated Fluorescent Immunoassay System. Fine care for the detection of HBA1C and Fuji film for RBS. Results: The results showed that reduced testosterone hormone level is associated with increased HBA1C and blood glucose levels, as well as anti-CoV-2–IgG antibodies. There is a negative (indirect) correlation between HBA1C and testosterone hormone, in contrast to a positive correlation with anti-SARS-CoV-2–IgG antibodies. Conclusion: Reduced testosterone hormone levels might indicate a more complicated prognosis of diabetes and in another way might be used as a treatment modality to regulate blood sugar levels after increasing its expression.

Predicting the dynamics of heart rate variability in patients with type 1 diabetes against improving glycemic control

The aim of the study: to analyze the effect of improvement of glycemic control on heart rate variability changes in patients with type 1 diabetes against the background of insulin therapy correction and to predict this dynamics based on the parameters of continuous glucose monitoring. We examined 49 patients with the level of glycosylated hemoglobin ≥7% and <10% without late diabetic complications. The average age – 32.0 (21.5; 38.0) years, the average disease duration – 9.5 (5.0; 17.5) years. The study was based on the simultaneous registration of heart rate variability and continuous glucose monitoring before and 3 months after correction of insulin therapy. Logistic regression analysis and ROC-analysis were used to predict the changes. After 3 months, the patients had significant decrease in the level of glycosylated hemoglobin, glycose variability, and a decrease in the frequency of hypoglycemic episodes. Heart rate variability increased in 73.5% of persons. The presence of hypoglycemia, standard deviation of blood glucose levels and glomerular filtration rate after treatment turned out to be prognostic factors for the predicting improvement in heart rate variability (the proportion of correct prediction of the patient's actual belonging to one or another prognostic group was 76.39%). Based on the calculation of the theoretical values of the positive result probability using the logistic equation, a detailed scale for predicting changes in heart rhythm variability for type 1 diabetes patients was proposed: up to 0.07 – a low probability of a positive result; 0.07-0.29 – the probability of a positive result is below average; 0.29-0.51 – a moderate probability of a positive result; 0.51-0.90 – high probability of a positive result; more than 0.90 – a very high probability of a positive result. We found that improvement of glycemic control leads to an increase in both frequency and time characteristics of heart rate variability. The increase in the likelihood of improvement of heart rate variability in patients with type 1 diabetes was more likely to be associated with reduced glycose variability and fewer hypoglycemic episodes. We developed a predictive mathematical model of heart rate variability based on the continuous glucose monitoring parameters for type 1 diabetes with sensitivity of 88.0% and specificity 68.18%, AUC 0.739 (p=0.001).

Evaluating usability of and satisfaction with mHealth app in rural and remote areas-Germany GIZ collaboration in Bosnia-Herzegovina to optimize type 1 diabetes care.

Type 1 diabetes mellitus (T1DM) management in children and adolescents requires intensive supervision and monitoring to prevent acute and late diabetes complications and to improve quality of life. Digital health interventions, in particular diabetes mobile health apps (mHealth apps) can facilitate specialized T1DM care in this population. This study evaluated the initial usability of and satisfaction with the m-Health intervention Diabetes: M app, and the ease of use of various app features in supporting T1DM care in rural and remote areas of Bosnia-Herzegovina with limited access to specialized diabetes care. This cross-sectional study, performed in February-March 2023, evaluated T1DM pediatric patients who used the Diabetes: M app in a 3-month mHealth-based T1DM management program, along with their parents and healthcare providers (HCPs). All participants completed self-administered online questionnaires at the end of the 3-month period. Data were analyzed by descriptive statistics. The study population included 50 T1DM patients (children/parents and adolescents) and nine HCPs. The mean ± SD age of the T1DM patients was 14 ± 4.54 years, with 26 (52%) being female. The mean ± SD age of the HCPs was 43.4 ± 7.76 years; all (100%) were women, with a mean ± SD professional experience of 17.8 ± 8.81 years. The app was reported usable in the domains of ease-of-use and satisfaction by the T1DM children/parents (5.82/7.0), T1DM adolescents/young adults (5.68/7.0), and HCPs (5.22/7.0). Various app features, as well as the overall app experience, were rated positively by the participants. The results strongly support the usability of mHealth-based interventions in T1DM care, especially in overcoming care shortage and improving diabetes management and communications between HCPs and patients. Further studies are needed to compare the effectiveness of apps used to support T1DM management with routine care.

Association between Glucose-lowering Treatments and Risk of Diabetic Retinopathy in People with Type 2 Diabetes: A Nationwide Cohort Study.

Glycaemic variability is possibly linked to the development of diabetic retinopathy, and newer second-line glucose-lowering treatments in type 2 diabetes might reduce glycaemic variability. This study aimed to investigate whether newer second-line glucose-lowering treatments are associated with an alternative risk of developing diabetic retinopathy in people with type 2 diabetes. A nationwide cohort of people with type 2 diabetes on second-line glucose-lowering treatment regimens in 2008-2018 was extracted from the Danish National Patient Registry. Adjusted time to diabetic retinopathy was estimated with a Cox Proportional Hazards model. The model was adjusted for age, sex, diabetes duration, alcohol abuse, treatment start year, education, income, history of late-diabetic complications, history of non-fatal major adverse cardiovascular events, history of chronic kidney disease, and history of hypoglycaemic episodes. Treatment regimens of metformin + basal insulin (HR: 3.15, 95% CI: 2.42-4.10) and metformin + glucagon-like peptide-1 receptor agonist (GLP-1-RA, HR: 1.46, 95% CI: 1.09-1.96) were associated with an increased risk of diabetic retinopathy compared with metformin + dipeptidyl peptidase-4 inhibitors (DPP-4i). Treatment with metformin + sodium-glucose cotransporter-2 inhibitor (SGLT2i, HR: 0.77, 95% CI: 0.28-2.11) was associated with the numerically lowest risk of diabetic retinopathy compared with all regimens investigated. Findings from this study indicate that basal insulin and GLP-1-RA are suboptimal second- line choices for people with type 2 diabetes at risk of developing diabetic retinopathy. However, many other considerations concerning the choice of second-line glucose-lowering treatment for type 2 diabetes patients should be taken into account.

Traditional and emerging strategies using hepatocytes for pancreatic regenerative medicine.

Although pancreas and islet cell transplantation are the only ways to prevent the late complications of insulin-dependent diabetes, a shortage of donors is a major obstacle to tissue and organ transplantation. Stem cell therapy is an effective treatment for diabetes and other pancreatic-related diseases, which can be achieved by inducing their differentiation into insulin-secreting cells. The liver is considered an ideal source of pancreatic cells due to its similar developmental origin and strong regenerative ability as the pancreas. This article reviews the traditional and emerging strategies using hepatocytes for pancreatic regenerative medicine and evaluates their advantages and challenges. Gene reprogramming and chemical reprogramming technologies are traditional strategies with potential to improve the efficiency and specificity of cell reprogramming and promote the transformation of hepatocytes into islet cells. At the same time, organoid technology, as an emerging strategy, has received extensive attention. Biomaterials provide a three-dimensional culture microenvironment for cells, which helps improve cell survival and differentiation efficiency. In addition, clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing technology has brought new opportunities and challenges to the development of organoid technology.

"Hyperglycemic Memory": Observational Evidence to Experimental Inference.

Several epidemiological studies have appreciated the impact of "duration" and "level" of hyperglycemia on the initiation and development of chronic complications of diabetes. However, glycemic profiles could not fully explain the presence/absence and severity of diabetic complications. Genetic issues and concepts of "hyperglycemic memory" have been introduced as additional influential factors involved in the pathobiology of late complications of diabetes. In the extended phase of significant diabetes randomized, controlled clinical trials, including DCCT/EDIC and UKPDS, studies have concluded that the quality of glycemic or metabolic control at the early time around the diabetes onset could maintain its protective or detrimental impact throughout the following diabetes course. There is no reliable indication of the mechanism by which the transient exposure to a given glucose concentration level could evoke a consistent cellular response at target tissues at the molecular levels. Some biological phenomena, such as the production and the concentration of advanced glycation end products (AGEs), reactive oxygen species (ROS) and protein kinase C (PKC) pathway activations, epigenetic changes, and finally, the miRNAs-mediated pathways, may be accountable for the development of hyperglycemic memory. This work summarizes evidence from previous experiments that may substantiate the hyperglycemic memory soundness by its justification in molecular terms.

Mangiferin alleviates diabetic pulmonary fibrosis in mice via inhibiting endothelial-mesenchymal transition through AMPK/FoxO3/SIRT3 axis.

Diabetes mellitus results in numerous complications. Diabetic pulmonary fibrosis (DPF), a late pulmonary complication of diabetes, has not attracted as much attention as diabetic nephropathy and cardiomyopathy. Mangiferin (MF) is a natural small molecular compound that exhibits a variety of pharmacological effects including anti-inflammatory, anti-cancer, anti-diabetes, and anti-fibrosis effects. In this study, we investigated whether long-term diabetes shock induces DPF, and explored whether MF had a protective effect against DPF. We first examined the lung tissues and sections of 20 diabetic patients obtained from discarded lung surgical resection specimens and found that pulmonary fibrosis mainly accumulated around the pulmonary vessels, accompanied by significantly enhanced endothelial-mesenchymal transition (EndMT). We established a mouse model of DPF by STZ injections. Ten days after the final STZ injection, the mice were administered MF (20, 60 mg/kg, i.g.) every 3 days for 4 weeks, and kept feeding until 16 weeks and euthanized. We showed that pulmonary fibrotic lesions were developed in the diabetic mice, which began around the pulmonary vessels, while MF administration did not affect long-term blood glucose levels, but dose-dependently alleviated diabetes-induced pulmonary fibrosis. In human umbilical vein endothelial cells (HUVECs), exposure to high glucose (33.3 mM) induced EndMT, which was dose-dependently inhibited by treatment with MF (10, 50 μM). Furthermore, MF treatment promoted SIRT3 expression in high glucose-exposed HUVECs by directly binding to AMPK to enhance the activity of FoxO3, which finally reversed diabetes-induced EndMT. We conclude that MF attenuates DPF by inhibiting EndMT through the AMPK/FoxO3/SIRT3 axis. MF could be a potential candidate for the early prevention and treatment of DPF.

Vascular complications of diabetes mellitus worldwide and in Russia: The path of 100 years. A review

With the discovery and introduction of insulin, the "palette" of life-threatening conditions for patients with diabetes mellitus has changed dramatically: from diabetic coma of the "pre-insulin era" to severe vascular complications in the modern period. The key risk factors for diabetic angiopathies in diabetes mellitus are poor glycemic control in combination with a long course of the disease. Over the past 30 years, there has been a downward trend in the incidence of late vascular complications of diabetes both worldwide and in Russia. In particular, the frequency of cardiovascular events (myocardial infarctions, strokes, amputations) decreased, and the incidence of several other complications, such as diabetic retinopathy and neuropathy, stabilized. However, the incidence of chronic kidney disease and chronic heart failure is still increasing. The Joslin Medal, awarded to patients over 50, 75 and even 80 years of life with diabetes, reflects success in the fight against this disease.

Gut microbiota in relationship to diabetes mellitus and its late complications with a focus on diabetic foot syndrome: A review.

Diabetes mellitus is a chronic disease affecting glucose metabolism. The pathophysiological reactions underpinning the disease can lead to the development of late diabetes complications. The gut microbiota plays important roles in weight regulation and the maintenance of a healthy digestive system. Obesity, diabetes mellitus, diabetic retinopathy, diabetic nephropathy and diabetic neuropathy are all associated with a microbial imbalance in the gut. Modern technical equipment and advanced diagnostic procedures, including xmolecular methods, are commonly used to detect both quantitative and qualitative changes in the gut microbiota. This review summarises collective knowledge on the role of the gut microbiota in both types of diabetes mellitus and their late complications, with a particular focus on diabetic foot syndrome.

A Mitochondrial Nanoguard Modulates Redox Homeostasis and Bioenergy Metabolism in Diabetic Peripheral Neuropathy.

As a major late complication of diabetes, diabetic peripheral neuropathy (DPN) is the primary reason for amputation. Nevertheless, there are no wonder drugs available. Regulating dysfunctional mitochondria is a key therapeutic target for DPN. Resveratrol (RSV) is widely proven to guard mitochondria, yet the unsatisfactory bioavailability restricts its clinical application. Tetrahedral framework nucleic acids (tFNAs) are promising carriers due to their excellent cell entrance efficiency, biological safety, and structure editability. Here, RSV was intercalated into tFNAs to form the tFNAs-RSV complexes. tFNAs-RSV achieved enhanced stability, bioavailability, and biocompatibility compared with tFNAs and RSV alone. With its treatment, reactive oxygen species (ROS) production was minimized and reductases were activated in an in vitro model of DPN. Besides, respiratory function and adenosine triphosphate (ATP) production were enhanced. tFNAs-RSV also exhibited favorable therapeutic effects on sensory dysfunction, neurovascular deterioration, demyelination, and neuroapoptosis in DPN mice. Metabolomics analysis revealed that redox regulation and energy metabolism were two principal mechanisms that were impacted during the process. Comprehensive inspections indicated that tFNAs-RSV inhibited nitrosation and oxidation and activated reductase and respiratory chain. In sum, tFNAs-RSV served as a mitochondrial nanoguard (mito-guard), representing a viable drilling target for clinical drug development of DPN.

Machine learning methods in the differential diagnosis of difficult-to-classify types of diabetes mellitus

The course of difficult-to-classify types of diabetes mellitus (DM) (slowly developing immune-mediated DM of adults (LADA), monogenic forms of DM (MODY)) has common features with both type 1 DM (T1DM) and type 2 DM (T2DM), so often remain misdiagnosed. Errors in determining the type of diabetes lead to incorrect treatment tactics, which leads to poor glycemic control, the development of complications, a decrease in the patient's quality of life, and increased mortality.The key method for diagnosing MODY is sequencing of genes associated with this disease, and LADA is an immunological blood test in combination with the features of the clinical picture. However, the exact criteria for referring patients to these studies have not yet been determined. Performing these studies on all patients without exception with risk factors can lead to unjustified economic costs, and access to them is often difficult. In this regard, various automated algorithms have been developed based on statistical methods and machine learning (deep neural networks, “decision trees”, etc.) to identify patients for whom an in-depth examination is most justified. Among them are algorithms for the differential diagnosis of T1DM and T2DM, algorithms specializing in the diagnosis of only LADA or only MODY, only one algorithm is aimed at multiclass classification of patients with diabetes. One of the algorithms is widely used, aimed at diagnosing MODY in patients under the age of 35 years. However, existing algorithms have a number of disadvantages, such as: small sample size, exclusion of patients with MODY or older patients from the study, lack of verification of the diagnosis using appropriate studies, and the use of late complications of diabetes as parameters for diagnosis. Often the research team did not include practicing physicians. In addition, none of the algorithms are publicly available and have not been tested for patients in Russia. This manuscript presents an analysis of the main automated algorithms for the differential diagnosis of diabetes, developed in recent years.

Lichen Simplex Chronic Skin Problems in Diabetes Mellitus Patient: A Case Report

Diabetes mellitus is an endocrine, metabolic disease that can occur in all ages and socioeconomic groups. Uncontrolled diabetes mellitus can cause various complications. One of them is the manifestation of the skin. Chronic lichen simplex in diabetes mellitus patients was reported in cases with uncontrolled blood sugar levels greatly affecting chronic skin lesions in patients. Controlled sugar levels and appropriate topical therapy and psychological management in patients are expected to provide better output and prognosis. The patient came with complaints of itchy, red and painful wounds on both legs, accompanied by a fever for 7 days, Previously the patient often had numbness and tingling in the upper and lower extremities. Patients often scratch their skin, resulting in wounds that then dry out and thicken. The patient also has the comorbid disease of Diabetes mellitus. Complaints have been recurring frequently and have been felt for more than the last 2 years. Itching often recurs, especially when you think about something a lot and when you are resting. Based on the dermatological examination, the results showed that on both lower limbs, there were non-layered smooth white scaly lesions, lichenification accompanied by hyperpigmentation, the size of the plaques had indistinct boundaries, there was slight edema and erythema, multiple erosions with black crusts on the surface of the lesion were not easily removed. Diabetes mellitus is associated with dermatologist disorders. Early recognition of initial cutaneous changes such as xerosis, hyperkeratosis, or skin infections by appropriate management could help reduce late or severe complications of diabetes. Although most dermatological conditions require specific treatment, the most important rule is to improve blood glucose levels control in patients. Education in treatment, hygiene, emotional stress and lifestyle changes are important for improving the quality of life for patients with diabetes mellitus.

Frontline Worker Safety in the Age of COVID-19: A Global Perspective.

The third annual Health Watch USAsm webinar conference assembled 16 speakers from 4 continents who shared information regarding frontline worker safety in the age of COVID-19. The U.S. Bureau of Labor Statistics reported a nearly 4000% increase in workplace illness in 2020 compared with 2019. It is estimated that 2% of the U.S. workforce is not working because of long COVID. In addition, the impact is growing with each surge. After the acute illness, patients are often described as recovered, when in fact many have only survived and are coping with the multisystem impacts of long COVID. Long COVID, including its late cognitive, cardiovascular, embolic, and diabetic complications, disproportionately impacts frontline workers, many of whom are of lower socioeconomic status and represented by ethnic minorities. Natural infection and current vaccines do not provide durable protection for reinfection. Herd immunity is not possible at this time. Although SARS-CoV-2 is unlikely to be eliminated, decreasing spread is imperative to slow the rate of mutations, decrease the number of reinfections, and lower the chances of developing long COVID. The primary mode of spread is through aerosolization. Both routine breathing and talking aerosolizes the virus. With the extremely high infectivity of SARS-CoV-2, it is unlikely that central building ventilation alone will be enough to satisfactorily mitigate spread. Additional safe active air cleaning technology, such as upper-room germicidal UV-C lighting, needs to be deployed. Misinformation and disinformation have inhibited response effectiveness. Examples include downplaying the benefit of well-fitted masks and the risks that COVID-19 and long COVID pose to children, along with believing children cannot spread the disease. The engagement of local community leaders is essential to educate the community and drive social change to accept vaccinations and other public health interventions. Vaccinations and natural immunity alone are unlikely to adequately prevent community spread and do not provide durable protection against the risk of long COVID. Frontline workers must keep their immunity as high as possible and work in settings with clean air, along with wearing N95 masks when they are in contact with the public. Finally, there needs to be a financial safety net for frontline workers and their families in the event of incapacitation or death from COVID-19.

Methods for evaluation of corneal nerve fibres in diabetes mellitus by in vivo confocal microscopy: a scoping review protocol

IntroductionGlobally, 422 million people have diabetes. Late complications of diabetes are blindness, kidney failure, heart attack, stroke and lower limb amputation. The prevalence of diabetic peripheral neuropathy and diabetic retinopathy...

Exercise and nutrition in type 1 diabetes: Insights from the FinnDiane cohort.

Type 1 diabetes is a challenging disease, characterized by dynamic changes in the insulin need during life periods, seasons of the year, but also by everyday situations. In particular, changes in insulin need are evident before, during and after exercise and having meals. In the midst of different life demands, it can be very burdensome to achieve tight glycemic control to prevent late diabetes complications, and at the same time, to avoid hypoglycemia. Consequently, many individuals with type 1 diabetes are faced with diabetes distress, decreasing profoundly their quality of life. Today, the nationwide Finnish Diabetic Nephropathy (FinnDiane) Study, launched in 1997, has gathered data from more than 8,000 well-characterized individuals with type 1 diabetes, recruited from 93 centers all over Finland and has established its position as the world's leading project on studying complications in individuals with type 1 diabetes. Studying risk factors and mechanisms of diabetes complications is inconceivable without trying to understand the effects of exercise and nutrition on glycemic control and the development of diabetes complications. Therefore, in this paper we provide findings regarding food and exercise, accumulated during the 25 years of studying lives of Finnish people with type 1 diabetes.

Role of natural mTOR inhibitors in treatment of diabetes mellitus.

Diabetes mellitus is one of the most common and complex problems in today's society and is responsible for many socio-economic problems. Type 1 diabetes is due to a defect in insulin secretion caused by a destruction of pancreatic β cells. In contrast, the pathogenesis of type 2 diabetes is associated with the development of insulin resistance in the liver and peripheral tissues, a decrease in β-cell mass, and a defect in insulin secretion. Various factors such as inflammation, stress, obesity, and lifestyle are involved in diabetes. Long-term or chronic increase in glucose in these patients is the leading causes of secondary disorders such as micro- and macro-angiopathy, weakness of the antioxidant defense system, and metabolic disorders and altered lipid profile. The above conditions lead to short-term and long-term complications. These complications cause damage to the physical and physiological function of diverse organs of the body and threaten human health. Late complications of diabetes, including nephropathy, retinopathy, cardiovascular complications, neuropathy, hypertension, and weight gain, are common, and more research has been done on them. Numerous drugs such as meglitinides, biguanides, and thiazolidinedione have been proposed to reduce high blood sugar, but due to the lack of complete cure of this disease with the use of existing drugs, the tendency to use alternative and traditional therapies has increased. In the meantime, the role of herbs with hypoglycemic properties in the treatment of diabetic patients cannot be ignored. The consumption of herbs by people with diabetes has become widespread even in Western countries. The use of herbs could be considered when conventional therapies cannot control the disease, and the patient needs to be prescribed insulin. The mammalian target of rapamycin, mTOR, plays a significant role in regulating cell growth, cellular metabolic status in response to nutrients, many extracellular cues, and growth factors. Impaired insulin secretion can lead to altered mTOR signaling. The mTOR pathway has shown different behaviors depending on the situation. It has been shown that mTOR can regulate the adaptation of β cells to blood sugar, and chronic inhibition of the mTOR pathway can also induce diabetes. Here, we have reviewed recent findings on the role of mTOR in major metabolic organs, such as the liver, pancreas, brain, and adipose tissue and muscle, and discussed its potential as a diabetes-related drug target.

Genetic Predictors of Development of Diabetic Foot Syndrome in Patients with Diabetes Mellitus

An increase in the population of patients with diabetes mellitus affects the incidence of diabetic foot syndrome (DFS), as its chronic complication. Among the various types of growth factors that play a role in the development of late complications of diabetes, vascular endothelial growth factor, VEGF, is currently in the focus of attention. The study conducted by the authors was aimed at determining the relationship between the G634C polymorphism of the VEGFA rs2010963 gene and the predisposition to the development of diabetic foot syndrome in patients with diabetes mellitus. We examined 96 patients aged 39 to 76 years with diabetes mellitus complicated by diabetic foot syndrome. Based on the studies, it was determined that the G634C polymorphism in the VEGFA gene (rs2010963) is involved in the formation and development of diabetic foot syndrome in patients with diabetes mellitus.

LBODP037 Acute Foot Drop In An Adolescent With Type 1 Diabetes Mellitus At Onset: A Case Report

Abstract Background The incidence of type 1 diabetes (T1D) among youth is on the rise worldwide. Diabetic neuropathy is often a late manifestation of diabetes and usually results from the exposure to prolonged hyperglycemia, oxidative and inflammatory stress, and dyslipidemia. Here, we report a case of painless diabetic mononeuropathy as the presenting symptom of T1D that improved shortly after the improvement in glycemic control. Clinical case A previously healthy 15-year-old boy, presented to the emergency department (ED) with left foot weakness and dragging for 1 week. This was preceded by numbness over the left lateral leg and dorsum of the left foot. There was no history of trauma. The patient reported a history of polyuria, polydipsia, and significant weight loss for 3 months, for which he did not seek medical care. There was no family history of diabetes, hereditary neuropathy, or autoimmune diseases. Upon presentation to the ED, a general physical examination was unremarkable with a weight of 60 Kg (BMI= 20 Kg/m2), neurological examination revealed weakness in the dorsiflexion of the left foot (3/5), eversion (4/5), and normal sensation and reflexes. The remainder of the neurological examination including the right foot, upper extremities, cerebellar functions, cranial nerves and monofilament and vibration sensory testing was normal. Fundoscopic exam showed no evidence of retinopathy. The initial laboratory investigations revealed mild DKA (PH 7.28, HCO3 16mmol/L, Na 137 mEq/L, random blood glucose of 306 mg/dl, positive blood ketones) and normal kidney function. A nerve conduction study showed moderate left peroneal motor axonal neuropathy, with normal sensory nerve action potentials. Brain CT scan was unremarkable. Further tests to rule out secondary causes of neuropathy (ANA, B12 level, and thyroid function) were within normal. The diagnosis of diabetes-related mononeuropathy was confirmed by the neurology team and the patient underwent physiotherapy. After the resolution of DKA, the patient continued to use basal/bolus insulin therapy and was discharged home with close follow-up of blood glucose readings. His glycemic control has improved, and the patient reported a significant improvement in the foot drop 3 weeks later. A repeated examination by the neurology team 3 months later confirmed a complete recovery of the left foot drop. Conclusion Acute diabetic mononeuropathy can be an unusual presenting feature of T1D and may pose a diagnostic challenge. Although diabetic mononeuropathy is often a late complication of diabetes, our patient presented with acute mononeuropathy at the onset of T1D. This case highlights the importance of early diagnosis and management of diabetes to prevent and sometimes reverse diabetic neuropathy. It also shows that a complete recovery of acute diabetic mononeuropathy can be achieved by improving glycemic control in patients with newly diagnosed T1D. Presentation: No date and time listed