Current Diabetes Reviews - Volume 20, Issue 6, 2024

In recent years, various conventional formulations have been used for the treatment and/or management of ocular medical conditions. Diabetic retinopathy, a microvascular disease of the retina, remains the leading cause of visual disability in patients with diabetes. Currently, for treating diabetic retinopathy, only intraocular, intravitreal, periocular injections, and laser photocoagulation are widely used. Frequent administration of these drugs by injections may lead to serious complications, including retinal detachment and endophthalmitis. Although conventional ophthalmic formulations like eye drops, ointments, and suspensions are available globally, these formulations fail to achieve optimum drug therapeutic profile due to immediate nasolacrimal drainage, rapid tearing, and systemic tearing toxicity of the drugs. To achieve better therapeutic outcomes with prolonged release of the therapeutic agents, nano-drug delivery materials have been investigated. These nanocarriers include nanoparticles, solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), dendrimers, nanofibers, in-situ gel, vesicular carriers, niosomes, and mucoadhesive systems, among others. The nanocarriers carry the potential benefits of site-specific delivery and controlled and sustained drug release profile. In the present article, various nanomaterials explored for treating diabetic retinopathy are reviewed.

Background: One of the largest problems for global public health is diabetes mellitus (DM) and its micro and macrovascular consequences. Although prevention, diagnosis, and treatment have generally improved, its incidence is predicted to keep rising over the coming years. Due to the intricacy of the molecular mechanisms, which include inflammation, oxidative stress, and angiogenesis, among others, discovering treatments to stop or slow the course of diabetic complications is still a current unmet need. Methods: The pathogenesis and development of diabetic neuropathies may be explained by a wide variety of molecular pathways, hexosamine pathways, such as MAPK pathway, PARP pathway, oxidative stress pathway polyol (sorbitol) pathway, cyclooxygenase pathway, and lipoxygenase pathway. Although diabetic neuropathies can be treated symptomatically, there are limited options for treating the underlying cause. Result: Various pathways and screening models involved in diabetic neuropathies are discussed, along with their possible outcomes. Moreover, both medicinal and non-medical approaches to therapy are also explored. Conclusion: This study highlights the probable involvement of several processes and pathways in the establishment of diabetic neuropathies and presents in-depth knowledge of new therapeutic approaches intended to stop, delay, or reverse different types of diabetic complications.

Cardiovascular complications and renal disease is the growing cause of mortality in patients with diabetes. The subversive complications of diabetes such as hyperglycemia, hyperlipidemia and insulin resistance lead to an increase in the risk of myocardial infarction (MI), stroke, heart failure (HF) as well as chronic kidney disease (CKD). Among the commercially available anti-hyperglycemic agents, incretin-based medications appear to be safe and effective in the treatment of type 2 diabetes mellitus (T2DM) and associated cardiovascular and renal disease. Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have been shown to be fruitful in reducing HbA1c, blood glucose, lipid profile, and body weight in diabetic patients. Several preclinical and clinical studies revealed the safety, efficacy, and preventive advantages of GLP-1RAs against diabetes- induced cardiovascular and kidney disease. Data from cardio-renal outcome trials had highlighted that GLP-1RAs protected people with established CKD from significant cardiovascular disease, lowered the likelihood of hospitalization for heart failure (HHF), and lowered all-cause mortality. They also had a positive effect on people with end-stage renal disease (ESRD) and CKD. Beside clinical outcomes, GLP-1RAs reduced oxidative stress, inflammation, fibrosis, and improved lipid profile pre-clinically in diabetic models of cardiomyopathy and nephropathy that demonstrated the cardio-protective and reno-protective effect of GLP-1RAs. In this review, we have focused on the recent clinical and preclinical outcomes of GLP-1RAs as cardio-protective and reno-protective agents as GLP-1RAs medications have been demonstrated to be more effective in treating T2DM and diabetes-induced cardiovascular and renal disease than currently available treatments in clinics, without inducing hypoglycemia or weight gain.

Background: The degenerative tendency of diabetes leads to micro- and macrovascular complications due to abnormal levels of biochemicals, particularly in patients with poor diabetic control. Diabetes is supposed to be treated by reducing blood glucose levels, scavenging free radicals, and maintaining other relevant parameters close to normal ranges. In preclinical studies, numerous in vivo trials on animals as well as in vitro tests are used to assess the antidiabetic and antioxidant effects of the test substances. Since a substance that performs poorly in vitro won't perform better in vivo, the outcomes of in vitro studies can be utilized as a direct indicator of in vivo activities. Objective: The objective of the present study is to provide research scholars with a comprehensive overview of laboratory methods and procedures for a few selected diabetic biomarkers and related parameters. Method: The search was conducted on scientific database portals such as ScienceDirect, PubMed, Google Scholar, BASE, DOAJ, etc. Conclusion: The development of new biomarkers is greatly facilitated by modern technology such as cell culture research, lipidomics study, microRNA biomarkers, machine learning techniques, and improved electron microscopies. These biomarkers do, however, have some usage restrictions. There is a critical need to find more accurate and sensitive biomarkers. With a few modifications, these biomarkers can be used with or even replace conventional markers of diabetes.

Diabetic retinopathy is a well-recognised microvascular complication of diabetes and is among the leading cause of blindness all over the world. Over the last decade, there have been advances in the diagnosis of diabetic retinopathy and diabetic macular edema. At the same time, newer therapies for the management of diabetic retinopathy have evolved. As a result of these advances, a decline in severe vision loss due to diabetes has been witnessed in some developing countries. However, there is a steady increase in the number of people affected with diabetes, and is expected to rise further in the coming years. Therefore, it is prudent to identify diabetic retinopathy, and timely intervention is needed to decrease the burden of severe vision loss. An effort has been made to review all the existing knowledge regarding diabetic retinopathy in this article and summarize the present treatment options for diabetic retinopathy.

Background: Thiazolidinediones, also known as glitazones, are considered as biologically active scaffold and a well-established class of anti-diabetic agents for the treatment of type 2 diabetes mellitus. Thiazolidinediones act by reducing insulin resistance through elevated peripheral glucose disposal and glucose production. These molecules activate peroxisome proliferated activated receptor (PPARγ), one of the sub-types of PPARs, and a diverse group of its hybrid have also shown numerous therapeutic activities along with antidiabetic activity. Objective: The objective of this review was to collect and summarize the research related to the medicinal potential, structure-activity relationship and safety aspects of thiazolidinedione analogues designed and investigated in type 2 diabetes during the last two decades. Methods: The mentioned objective was achieved by collecting and reviewing the research manuscripts, review articles, and patents from PubMed, Science Direct, Embase, google scholar and journals related to the topic from different publishers like Wiley, Springer, Elsevier, Taylor and Francis, Indian and International government patent sites etc. Results: The thiazolidinedione scaffold has been a focus of research in the design and synthesis of novel derivatives for the management of type 2 diabetes, specifically in the case of insulin resistance. The complications like fluid retention, idiosyncratic hepatotoxicity, weight gain and congestive heart failure in the case of trosiglitazone, and pioglitazone have restricted their use. The newer analogues have been synthesized by different research groups to attain better efficacy and less side effects. Conclusion: Thus, the potential of thiazolidinediones in terms of their chemical evolution, action on nuclear receptors, aldose reductase and free fatty acid receptor 1 is well established. The newer TZD analogues with better safety profiles and tolerability will soon be available in the market for common use without further delay.

Background: Type 2 diabetes mellitus (T2DM) is frequently referred to as a "lifestyle illness". In 2000, India (31.7 million) had the greatest global prevalence of diabetes mellitus, followed by China (20.8 million), the United States (17.7 million), and other countries. In recent years, the treatment of gene therapy (T2DM) has attracted intensive interest. Objective: We aimed to critically review the literature on the various techniques and methods, which may be a possible novel approach through the gene therapy CRISPR Cas9 and some other gene editing techniques for T2DM. Interventional and pharmacological approaches for the treatment of T2DM were also included to identify novel therapies for its treatment. Method: An extensive literature survey was done on databases like PubMed, Elsevier, Science Direct and Springer. Conclusion: It can be concluded from the study that recent advancements in gene-editing technologies, such as CRISPR Cas9, have opened new avenues for the development of novel therapeutic approaches for T2DM. CRISPR Cas9 is a powerful tool that enables precise and targeted modifications of the genome.

Background: Vitamin D deficiency is becoming a widely recognized global health issue. Serum values of 25-(OH) vitamin D (<20 ng/ml) are used to identify vitamin D deficiency. By prompting vascular endothelial cells to activate their nuclear receptor in cardio-myocytes, Vitamin D regulates obesity, Renin-angiotensin system (RAS), energy consumption, and pancreatic cell function. Vitamin D deficiency has been associated with diabetes, asthma, hyperlipidaemia, and pulmonary hypertension in humans. Methods: PubMed and Google Scholar databases were utilised to search the literature on vitamin D and related diseases. Result: It is also linked to an elevated risk of death and heart disease. On the other hand, metaanalyses of vitamin D intervention and trials have found no substantial changes in insulin sensitivity, lipid markers, or blood pressure, which result in the association between deficiency of vitamin D and cardiovascular disease. Conclusion: In this review, we present the most recent research on the effects of Vitamin D therapy on various cardiovascular diseases and diabetes, and explain the underlying mechanisms.

Diabetes is a group of diseases marked by poor control of blood glucose levels. Diabetes mellitus (DM) occurs when pancreatic cells fail to make insulin, which is required to keep blood glucose levels stable, disorders, and so on. High glucose levels in the blood induce diabetic effects, which can cause catastrophic damage to bodily organs such as the eyes and lower extremities. Diabetes is classified into many forms, one of which is controlled by hyperglycemia or Diabetic Kidney Disease (DKD), and another that is not controlled by hyperglycemia (nondiabetic kidney disease or NDKD) and is caused by other factors such as hypertension, hereditary. DKD is associated with diabetic nephropathy (DN), a leading cause of chronic kidney disease (CKD) and end-stage renal failure. The disease is characterized by glomerular basement membrane thickening, glomerular sclerosis, and mesangial expansion, resulting in a progressive decrease in glomerular filtration rate, glomerular hypertension, and renal failure or nephrotic syndrome. It is also represented by some microvascular complications such as nerve ischemia produced by intracellular metabolic changes, microvascular illness, and the direct impact of excessive blood glucose on neuronal activity. Therefore, DKD-induced nephrotic failure is worse than NDKD. MicroRNAs (miRNAs) are important in the development and progression of several diseases, including diabetic kidney disease (DKD). These dysregulated miRNAs can impact various cellular processes, including inflammation, fibrosis, oxidative stress, and apoptosis, all of which are implicated during DKD. MiRNAs can alter the course of DKD by targeting several essential mechanisms. Understanding the miRNAs implicated in DKD and their involvement in disease development might lead to identifying possible therapeutic targets for DKD prevention and therapy. Therefore, this review focuses specifically on DKD-associated DN, as well as how in-silico approaches may aid in improving the management of the disease.

Hypoglycemia is a limiting adverse effect of glucose-lowering medications and particularly insulin replacement therapy. This review provides insights into the burden of hypoglycemia in the management of diabetes and outlines strategies available to reduce the risk of hypoglycemia and improve patients’ well-being. People with type 1 diabetes are primarily affected by hypoglycemic episodes which are associated with direct physical harms like injuries and cardiac events as well as indirect psychosocial consequences including constant anxiety, absenteeism, increased healthcare costs and overall poorer quality of life. These complications are more prominent amongst individuals with hypoglycemia unawareness or overnight hypoglycemia and could even extend to caregivers such as parents of children with diabetes. Patients experiencing frequent or severe hypoglycemic events might also develop a pathological fear of hypoglycemia and adopt aberrant behaviors intending to maintain higher blood glucose levels. Modern pharmaceutical options with a safer profile in terms of hypoglycemia are available including novel basal insulins with lower rates of nocturnal hypoglycemia along with ultra-rapid-acting insulin analogs with a shorter duration of action that might avert late post-meal hypoglycemia. Continuous glucose monitoring and sensor-augmented insulin pump therapy with low glucose suspend technology can also prevent hypoglycemia, although concerns about cost and patient satisfaction remain. Advancements in insulin therapy and technological modalities should be coupled with ongoing education and support for patients to become co-managers of their disease and reduce the risk of hypoglycemia.

Background: Prediabetes is a reversible condition before the onset of Type 2 Diabetes Mellitus. Untreated condition of prediabetes will develop into diabetes and its complications. The prevalence of prediabetes has been emerging worldwide and has a considerable socioeconomic impact. The current study reviews the roles of early detection, educational models, life modification, and prophylaxis of individuals with prediabetes in preventing the progression of prediabetes into Type 2 Diabetes Mellitus and complications in the future. Methods: This study included published articles from several electronic databases. The obtained articles were limited to March 2023. Articles that were not open access and not in Indonesian or English were excluded. The protocol for this study used the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020. Results: Of 39627 articles, 39601 were excluded due to duplication and did not meet the eligibility criteria. At the final, there were 26 articles that were eligible for systematic review. Conclusion: Prevention of the development of prediabetes into diabetes is essential. A comprehensive understanding and training on intensive lifestyle modification protocols from local and national experts in diabetes prevention through digital-based education models and linguistically and culturally approach can be considered. Intensive lifestyle modification and pharmacological approaches may improve the outcome. Regular monitoring of glycemic control is also important for early diagnosis of diabetes, especially in patients with special conditions.