Frontiers in Clinical Drug Research-Diabetes and Obesity

Diabetes and heart failure are emerging as twin epidemics with huge socioeconomic implications in patients across the globe. The situation is even abysmal considering the unique challenges faced by the health care sector in the lower-income countries with the growing size of the diabetes population (12.34% as reported by IDF 2019). Heart failure (HF) represents one of the most common yet less-recognized comorbidities of type 2 diabetes mellitus (T2DM). Besides, limited understanding of this multifactorial disease, together with a lack of effective therapeutics, has led to an underestimation of the risk in this population. However, until recently, the emerging classes have started to rekindle our efforts to understand this cardiometabolic conundrum once again due to the latest reports of their distinct therapeutic effects in the prevention of hospitalization of concomitant heart failure. Prevention of HF in patients with diabetes needs to be a priority for all caregivers as it is not only possible now to treat effectively but often rewarding from the patient's quality of life perspective in the long run. The present review is an attempt to summarize the current base of knowledge on the epidemiology, interrelationships of HF and T2DM and their shared pathophysiology, clinical correlates, and the current status of emerging novel therapies.

Diabetic mellitus (DM) is one of the major progressive metabolic syndromes and it is estimated that currently 390 million people are suffering from diabetes and more than 592 million people would be affected by the end of 2025 worldwide. In general, DM can be broadly classified into two types: DM type-I can be caused by the lack of insulin levels due to the destruction of pancreatic β-cells in the body, and the other DM type-II can be triggered by insulin resistance. However, this impairment of glucose homeostasis leads to several complications, such as cardiovascular risks, renal disorders, risk of blindness, poor blood drift, and dermatological complications. So far, various types of therapeutic drug agents are available for the treatment of DM, for instance, α-Glucosidase inhibitors, Biguanides, Dipeptidyl peptidase-4 inhibitors, Insulin analogs, GLP-1 agonists, SGLT2 inhibitors, Sulfonyl urease inhibitors and Thiazolidinedione’s, respectively. However, the long-term usage of these drugs was reported to show adverse effects. Therefore, significant attention is required to treat diabetic problems. Moreover, potential drug agents are desirable to treat DM with myriad therapeutic complications. At present, natural products are the prominent alternative and safer medications for the development of modern drug discovery. Although Western medicine is substituted for 80% of traditional medicine, in some countries, people rely on natural herbs as a remedy for the treatment of certain chronic diseases. In this concern, flavonoids are the prevalent group of natural bioactive molecules that have shown interesting biological activities, including antidiabetic properties. Hence, in the stated book chapter, we are intended to emphasize the importance and therapeutic potential of flavonoids as templates for future diabetic therapeutic drugs. Further, in silico studies of few reported flavonoids (rich in the edible source) have been accomplished to establish their molecular interactions with diverse diabetic targets. Therefore, the current chapter serves as a bird’s eye view of anti-diabetic flavonoids for further experimental studies and to develop potent markers of therapeutic agents.

Owing to the incidence of diabetes, glucose sensing in diabetes diagnosis and therapy is of great significance. In addition, in the drug and food sectors, glucose sensing is also important. Via different techniques, such as electrochemical or optical approaches, glucose sensing has been achieved. Sensors play an important role in the identification of chemical and biological samples and have attracted a great deal of interest in recent decades. Signals are produced by the binding of the analytical sensor. Varieties of chemical sensor, including cationic and anionic sensors, are used. In chemical sensing, molecular recognition and molecular transduction exist. There are three pieces of a chemo sensor, the binding site receptor, the device whose properties change with the binding and the spacer. The advanced glucose sensors development with high sensitivity and suitability has been facilitated by novel transducers made with nanomaterials that combine fluorescent methods. Glucose detection by a chemo sensor is discussed in this chapter. In addition, techniques for combining biological sensing and fluorescent nanomaterials components are explored, and the applicability of the chemosensor is also illustrated, making it suitable for glucose sensing. It is concluded that the extensive use of chemosensors in the health care sector makes them convenient instruments for real-time identification and long-term tracking of the environmental, biological and physical state of the human body.

Obesity is a multifactorial disease that is characterised by excess body fat and enlarged adipose tissue. Obesity is closely associated with several noncommunicable diseases, including type 2 diabetes, pulmonary arterial hypertension, dyslipidemia, non-alcoholic fatty liver diseases, hypoventilation syndrome, different types of cancers, inflammation, and cardiovascular diseases. The best preventive strategies for obesity are physical exercise, diet, and weight loss. Since this is not possible for all people, pharmacotherapy is required. The current therapy for obesity includes synthetic drugs and surgical procedures, which has high cost and many adverse effects. Hence the development of novel and natural drugs is necessary for the management of obesity. Numerous in vivo and in vitro investigations have proved that herbal medicine can ameliorate obesity, and those research findings include not only the individual plants but also different phytochemicals, extracts and polyhedral formulations. The inhibitory effects of different phytochemicals on the lipase enzyme activity, adipocyte differentiation, and promoting effects on energy expenditures and lipid metabolism are the different mechanisms that account for the management of obesity. So based on the previous research findings, researchers conclude that a synergistic drug which is formulated by combining potential medicinal herbs with a typical anti-obesity drug along with lifestyle modifications could ameliorate obesity and associated complications. This chapter summarises the current status and prospects of synergistic drugs and polyherbal formulations in the development of a safe and functional drug for the management of obesity.

Diabetes is a deep-seated and persistent ailment that has a comprehensive and long term effect on carbohydrate, fat, and protein metabolism. This malady is usually associated with hyperglycemia over an extended time which may be due to either flaw in the production of pancreatic insulin or implausible insulin target tissue.

Current pharmacological treatment strategies aim to promote pancreatic insulin release, reduce glucose output from the liver, or increase insulin sensitivity of adipocytes. But none of these current strategies have an appreciable curative effect on diabetes. Continuous exercise and workouts accompanied by lifestyle modifications have been found to improve glycemic control in diabetic patients which have not been well adapted with all patients. This emphasizes the role and urges herbal anti-diabetic drugs as they have a remarkably wide array of primary and secondary metabolites that have noted anti-diabetic actions accompanied by anti-oxidant action. But an herbal antidiabetic drug has got some limitations like a difference in constituents due to different geographical locations, scientific misidentification, product contamination, inappropriate time and method of harvesting, adulteration, etc. So, drug standardization is an indispensable tool to ensure the safety and efficacy of herbal anti-diabetic drugs. Regulatory agencies worldwide have set up stringent regulatory frameworks that have led to the development of herbal anti-diabetic drugs positively. When two or more drugs (either herbal or synthetic) are administered together, there may be either chemical or pharmacological interaction that may alter the effect of either both or sometimes one agent which cannot be easily predicted and understandable. These interactions may affect clinical safety and efficacy via additive/synergistic or antagonistic interactions. While antagonistic interactions tend to receive more attention due to safety concerns, additive/synergistic interactions increase the desired pharmacological response which is a boon to us in treatment, for which special attention has to be paid. In this chapter, a detailed and in-depth analysis of herbal antidiabetic drugs and various commonly used anti-diabetic plants are discussed. Also, problems associated with herbal anti-diabetic drugs and methods to overcome along with special emphasis on their clinical and therapeutic implications including reported herb-drug interactions, are examined.

Curcuma longa, due to its broad scope of remedial possibilities, is still utilized as a diet-based remedy against diabetes mellitus and diabetic intricacies by legitimately connecting with various cellular pathways that incite diabetes mellitus pathogenesis. This chapter investigates the general valuable impacts of Curcuma longa on diabetes mellitus and its related complications based on experimental studies. Alongside clarifying the useful facts of Curcuma longa, it might be helpful to consider those cellular pathways which directly relate to diabetes. The possible mechanism of action of Curcuma longa as anti-hyperglycemic considered inhibition of lipid peroxidation, starch using compounds, transcriptional compounds, and activation of antioxidant enzyme capacity. Subsequently, Curcuma longa shows its antidiabetic restorative impacts by expanding insulin affectability, securing β-cells of pancreatic islets, diminishing fat accumulation, reducing oxidative stress, or enhancing glucose take-up by the tissues. Other than this, Curcuma longa, likewise, shows defensive impacts against a few diabetic-linked complications, prominently diabetic cataracts, and kidney function, along with the antioxidant agents. Taking everything into account, this work recommends that Curcuma longa help in treating diabetes and complications that occur due to diabetes; however, tolerant advising is also necessary as directing power to achieve diet-based treatment if there should be an occurrence of diabetes. In this chapter, we discuss basic and clinical proof of Curcuma longa's potential for diabetes mellitus treatment mainly due to its hypoglycemic, antioxidant, and antiinflammatory qualities.