Frontiers in Clinical Drug Research-Diabetes and Obesity

In diabetes mellitus (DM), non-enzymatic glycation of proteins, lipids, and fatty acids is accelerated due to persistent hyperglycemia and plays an important role in diabetes and its associated secondary complications. Glycation has the potential to alter the biological, structural, and functional properties of macromolecules. Glycated products (early and late) are both involved in provoking the immune-regulatory cells and generating autoantibodies in diabetic patients. More precisely, human serum albumin is the most abundant protein in circulation involved in glycation. Glycated albumin may accumulate in the body tissues of diabetic patients and participate in its secondary complications. This chapter compiles the studies focused on changes in the secondary and tertiary structure of proteins upon glucosylation. Various in-vitro and in-vivo approaches involved in investigating such changes are systematically reviewed. Besides, the potential role of glycated albumin in the pathogenesis of diabetes mellitus, as well as its applicability as a diagnostic marker in the progression of the disease, is also highlighted.

Several aspects need to be explored in drug therapy for diabetes patients. Some specific glucose-reducing medicines are present, while other medicines are associated with unintentional changes in hyperglycemia. Diabetes is a developing epidemic that has caused significant socioeconomic problems in several countries throughout the world. Despite scientific discoveries, greater healthcare services, and higher literacy rates, the disease continues to plague many industries, particularly developing countries. The current trends show an increase in premature mortality, which threatens world prosperity. Experimental and technical improvements have been made in sulphonylureas, alpha-glucosidase inhibitors, biguanides, and thiazolidinediones, all of which are beneficial in lowering glucose levels. The latest drug research techniques have led to the development of novel therapeutic groups such as amylin analogs, incretin mimetics, GIP analogs, active peroxisome proliferator receptors, and dipeptidyl peptidase-4 inhibitors as targets for future diabetes therapy medications. Furthermore, drug development and detection for diabetes treatment have been revolutionized by identifying and investigating bioactive compounds from herbs. This chapter discusses vital fields of clinical diabetology regarding opportunities for stem cells and nanotechnology as next-generation therapies, with an emphasis on evolving developments and reviews why plant-derived products are reliably common for treating and managing diabetes. 

Blood sugar levels have to be controlled by individuals with type II diabetes (T2D) to preserve health and longevity. For such people, artificial sweeteners (including aspartame) are proposed sugar substitutes. In particular, the protection of aspartame has long been the point of discussion. Although it is such a problematic product, T2D patients are advised by many physicians to use it during a managed diet and as part of a treatment modality. Aspartame is 200 times sweeter than sugar and has a marginal effect on blood glucose levels. It is recommended for use so that T2D can regulate carbohydrate consumption and blood sugar levels. Previous studies, however, indicate that aspartame consumption may increase a person's risk of gaining weight instead of losing weight, resulting in intolerance to blood glucose in T2D. By increasing the levels of cortisol, aspartame can act as a biochemical stressor. It may cause systemic oxidative stress by creating excess free radicals, altering the gut's microbial activity, and interacting with the receptor N-methyl D-aspartate (NMDA), resulting in insulin deficiency or tolerance. Due to the lack of reliable evidence, aspartame and its derivatives are safe for T2D yet are still debatable. In the already stressful physiology of T2D, more research is needed to provide indications and raise concerns that aspartame may worsen the prevalence of pathological physiology.

Nowadays, the investigation of mental health is a popular and important topic. Several national and international researchers have been trying to discover the different mechanisms, effects and efficacy among healthy people and patients diagnosed with chronic diseases. It is particularly important to monitor this phenomenon in childhood and adolescence regularly. The developmental processes are further hampered by the physical, mental, social and spiritual development due to the different illnesses. Therefore, it is clear that mapping mental health and various therapeutic procedures, as well as their positive and negative effects, are of paramount importance in diabetes and obesity.

In this research, after analysing the scales of ten international questionnaires, a complex Diabetes Adherence Questionnaire with 58 statements was created, the characteristics and subscales of which (1. Self-management; 2. Emotional feedback - emotional reactions associated with blood sugar level measurement; 3. Social support - parents and family; 4. Social support - peer relationships; 5. Denial of the disease; 6. Positive consequences of adherence; 7. Negative consequences of adherence, pain, discomfort, burden; 8. Relationship with the medical team; 9. Concern about the future) are described in the present book chapter. We also introduce our latest research findings on the relationship between adherence and mental health, covering selfevaluated health and quality of life, satisfaction with life, subjective well-being, vision and depression, stating that positive variables show a positive while negative variables correlate negatively with adherence. 

Diabetes and hyperlipidemia are global epidemics that significantly increase the morbidity and mortality of the affected population. Several medications have been utilized to mitigate the risk of diabetes and hyperlipidemia. Insulin, alpha-glucosidase inhibitors, thiazolidinediones have been used for decades as antidiabetic medications. Statins are a cornerstone in hyperlipidemia management. Omega‐3 fatty acid supplementation has been used to treat hypertriglyceridemia with debatable effects on cardiovascular outcomes.

In the past decade, multiple new discoveries have revolutionized the management of these disorders. Sodium–glucose cotransporter 2 (SGLT2) inhibitors are a class of oral anti-diabetic drugs with a unique mechanism of action. SGLT2 was proven to reduce cardiovascular events, including hospitalization for heart failure, with this benefit extending to patients without diabetes. PCSK9 inhibitors are a new class of antihyperlipidemic that significantly lowers plasma LDL-C on top of the conventional treatment.

In this book chapter, we review the history of diabetes and hyperlipidemia medications and discuss the new classes of lipid-lowering and anti-diabetic medications and their associated cardioprotective benefits.

Diabetes Mellitus and obesity, now coined as “Diabesity”, is a worldwide epidemic that imposes a huge burden on healthcare and society. Diabesity has been associated with poor outcomes and increased morbidity and mortality. The kidneys are a vulnerable target of diabesity. In this chapter, we discuss the epidemiology, pathophysiology, and treatment of diabesity–induced kidney disease. We specifically focus on the therapeutic targets and pharmacological management of diabesity-related kidney diseases.