XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

Standards of Medical Care in Diabetes

α-Glucosidase inhibitors are described as the most effective in reducing post-prandial hyperglycaemia (PPHG) from all available anti-diabetic drugs used in the management of type 2 diabetes mellitus. As flavonoids are promising modulators of this enzyme’s activity, a panel of 44 flavonoids, organised in five groups, was screened for their inhibitory activity of α-glucosidase, based on in vitro structure–activity relationship studies. Inhibitory kinetic analysis and molecular docking calculations were also applied for selected compounds. A flavonoid with two catechol groups in A- and B-rings, together with a 3-OH group at C-ring, was the most active, presenting an IC50 much lower than the one found for the most widely prescribed α-glucosidase inhibitor, acarbose. The present work suggests that several of the studied flavonoids have the potential to be used as alternatives for the regulation of PPHG.

α-Glucosidase inhibition by flavonoids: an in vitro and in silico structure-activity relationship study.

The role played by cinnamic acid derivatives in treating cancer, bacterial infections, diabetes and neurological disorders, among many, has been reported. Cinnamic acid is obtained from cinnamon bark. Its structure is composed of a benzene ring, an alkene double bond and an acrylic acid functional group making it possible to modify the aforementioned functionalities with a variety of compounds resulting in bioactive agents with enhanced efficacy. The nature of the substituents incorporated into cinnamic acid has been found to play a huge role in either enhancing or decreasing the biological efficacy of the synthesized cinnamic acid derivatives. Some of the derivatives have been reported to be more effective when compared to the standard drugs used to treat chronic or infectious diseases in vitro, thus making them very promising therapeutic agents. Compound 20 displayed potent anti-TB activity, compound 27 exhibited significant antibacterial activity on S. aureus strain of bacteria and compounds with potent antimalarial activity are 35a, 35g, 35i, 36i, and 36b. Furthermore, compounds 43d, 44o, 55g-55p, 59e, 59g displayed potent anticancer activity and compounds 86f-h were active against both hAChE and hBuChE. This review will expound on the recent advances on cinnamic acid derivatives and their biological efficacy.

Cinnamic Acid Derivatives and Their Biological Efficacy.

A comprehensive review on xanthone derivatives as α-glucosidase inhibitors.

Insulin resistance (IR), defined as an attenuated biological response to circulating insulin, is a fundamental defect in obesity and type 2 diabetes (T2D), and is also linked to a wide spectrum of pathological conditions, such as non-alcoholic fatty liver disease (NAFLD), cognitive impairment, endothelial dysfunction, chronic kidney disease (CKD), polycystic ovary syndrome (PCOS), and some endocrine tumors, including breast cancer. In obesity, the unbalanced production of pro- and anti-inflammatory adipocytokines can lead to the development of IR and its related metabolic complications, which are potentially reversible through weight-loss programs. The Mediterranean diet (MedDiet), characterized by high consumption of extra-virgin olive oil (EVOO), nuts, red wine, vegetables and other polyphenol-rich elements, has proved to be associated with greater improvement of IR in obese individuals, when compared to other nutritional interventions. Also, recent studies in either experimental animal models or in humans, have shown encouraging results for insulin-sensitizing nutritional supplements derived from MedDiet food sources in the modulation of pathognomonic traits of certain IR-related conditions, including polyunsaturated fatty acids from olive oil and seeds, anthocyanins from purple vegetables and fruits, resveratrol from grapes, and the EVOO-derived, oleacein. Although the pharmacological properties and clinical uses of these functional nutrients are still under investigation, the molecular mechanism(s) underlying the metabolic benefits appear to be compound-specific and, in some cases, point to a role in gene expression through an involvement of the nuclear high-mobility group A1 (HMGA1) protein.

Mediterranean Diet Nutrients to Turn the Tide against Insulin Resistance and Related Diseases.

α-Amylase has been considered an important therapeutic target for the management of type 2 diabetes mellitus (T2DM), decreasing postprandial hyperglycaemia (PPHG). In the present work, a panel of 40 structurally related flavonoids was tested, concerning their ability to inhibit α-amylase activity, using a microanalysis screening system, an inhibitory kinetic analysis and molecular docking calculations. From the obtained results, it was possible to observe that the flavone with a -Cl ion at 3-position of C-ring, an –OH group at 3′- and 4′- positions of B-ring and at 5- and 7- positions of A-ring and the C2 = C3 double bond, was the most active tested flavonoid, through competitive inhibition. In conclusion, some of the tested flavonoids have shown promising inhibition of α-amylase and may be considered as possible alternatives to the modulation of T2DM.

Evaluation of a flavonoids library for inhibition of pancreatic α-amylase towards a structure–activity relationship

Type 2 diabetes (T2D) is one of the most prevalent metabolic diseases worldwide and is characterized by increased postprandial hyperglycemia (PPHG). α-Amylase and α-glucosidase inhibitors have been shown to slow the release of glucose from starch and oligosaccharides, resulting in a delay of glucose absorption and a reduction in postprandial blood glucose levels. Since current α-glucosidase inhibitors used in the management of T2D, such as acarbose, have been associated to strong gastrointestinal side effects, the search for novel and safer drugs is considered a hot topic of research. Flavonoids are phenolic compounds widely distributed in the Plant Kingdom and important components of the human diet. These compounds have shown promising antidiabetic activities, including the inhibition of α-amylase and α-glucosidase. The aim of this review is to provide an overview on the scientific literature concerning the structure-activity relationship of flavonoids in inhibiting α-amylase and α-glucosidase, including their type of inhibition and experimental procedures applied. For this purpose, a total of 500 compounds is covered in this review. Available data may be considered of high value for the design and development of novel flavonoid derivatives with effective and potent inhibitory activity against those carbohydrate-hydrolyzing enzymes, to be possibly used as safer alternatives for the regulation of PPHG in T2D.

Flavonoids as potential agents in the management of type 2 diabetes through the modulation of α-amylase and α-glucosidase activity: a review

Size-dependent cytotoxicity of silver nanoparticles in human neutrophils assessed by multiple analytical approaches.

https://bibliotecadigital.ipb.pt/bitstream/10198/12943/1/2016%20Eur%20JMC%20115%2c%20381.pdf

Carina Proença

Papers

α-Glucosidase inhibition by flavonoids: an in vitro and in silico structure-activity relationship study.

Evaluation of a flavonoids library for inhibition of pancreatic α-amylase towards a structure–activity relationship

Flavonoids as potential agents in the management of type 2 diabetes through the modulation of α-amylase and α-glucosidase activity: a review

Size-dependent cytotoxicity of silver nanoparticles in human neutrophils assessed by multiple analytical approaches.

Novel chromone and xanthone derivatives: Synthesis and ROS/RNS scavenging activities.