Clinical Practice Guidelines

Definition, Classification and Diagnosis of Diabetes, Prediabetes and Metabolic Syndrome

A new range of indolyl imine system 3d-l has been successfully prepared from 4,6-dimethoxy-2,3-diphenyl-indole-7-carbaldehyde 2a and 4,6-dimethoxy-3-aryl-indole-7-carbaldehyde 2b-c via Schiff base reaction. The structure of targeted compounds was confirmed by ¹H and ¹³C NMR, FT-IR, mass spectrometry and single crystal X-ray diffraction techniques. The indolyl imine derivatives were also subjected to in vitro antidiabetic activities employing α-glucosidase and α-amylase enzymes. In terms of antidiabetic investigation, the α-glucosidase enzyme was found to be potential target due to the comparable inhibition concentrations with the standard acarbose and the compound 3e exhibited better potency than the standard. The anticholinesterase potency of the compounds was investigated towards the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. The compounds displayed moderate efficiency against the BChE enzyme with the best inhibition concentration of 30.48 μM by the compound 3h. The antioxidant properties of final compounds were determined by DPPH radical scavenging, ABTS Cation Radical Decolarization and CUPRAC Cupric Reducing Antioxidant Capacity assay methods. The ABTS cation scavenging assay provided the best responses for the compounds and the candidates 3k and 3l were determined as promising targets for the antioxidant activity. Plausible binding mode and interaction of ligands with the selected enzyme have been studied by molecular docking, supporting the experimental results. In silico ADME showed high drug likeness of the synthesized compounds.

The hypoglycemic effects of two recrystallized resistant starches, A-type (ARS) and B-type (BRS), were investigated in type 2 diabetic mice. Mice were treated with low-, medium-, or high-dose ARS, high-dose BRS, or high-dose ARS combined with BRS (ABRS). After 10 weeks of continuous intervention, the medium-dose ARS group showed a significant reduction in fasting blood glucose, area under the curve of glucose, triglyceride (P < 0.01), and low-density lipoprotein (P < 0.05) levels compared to the model group and an increase in high-density lipoprotein levels (P < 0.01). The peptide YY and glucagon-like peptide-1 levels in the high-dose ARS, BRS, and ABRS groups and the butyric acid yield in the medium-dose ARS and BRS groups were significantly increased (P < 0.01) compared to those in the model group. Medium- and high-dose ARS intervention efficiently increased the relative abundance of beneficial Bacteroidetes, Lactobacillus, Lachnospiraceae_NK4A136_group, and Faecalibaculum, and lowered the ratio of Firmicutes to Bacteroidetes. Overall, ARS exhibited greater advantages than BRS in lowering blood sugar levels.

Diabetes mellitus (DM) remains one of the pivotal diseases that have drawn the attention of researchers recently and during the last few decades. Due to its devastating symptoms, attempts to develop new drugs with mild side effects have resulted in a number of drugs that are functioning through various mechanisms. Among these, Glycogen phosphorylase (GP) inhibitors emerged as a new strategy for combating DM. GP is an enzyme that regulates blood glucose levels; it catalyses the breakdown of glycogen to glucose-1-phosphate in the liver and tissues with high and fluctuating energy demands. In the present research, we evaluate the possibility of type 2 diabetes therapy with the help of chalcones which are known to have antidiabetic activities. For this purpose, 29 chalcones were modelled, synthesised and investigated for their inhibitory activity against GP using in-vitro methods. Compounds 1, 2, and 3 were found to be the most potent compounds with IC₅₀ values 26.6, 57.1 and 75.6 µM respectively. The observed results were further validated using in-silico methods. Molecular docking simulation revealed interaction patterns that explain the structure-activity relationships of the compounds with GP. Molecular dynamic (MD) simulation demonstrated a stable complex formation between compound 1 and GP through lower value and uniformity in root mean square deviation (RMSD) of the complex and root mean square fluctuation (RMSF) of the protein Cα.

Healing of wounds is the most deteriorating diabetic experience. Felty germander (Teucrium polium) possesses antioxidant, anti-inflammatory and antimicrobial activities that could accelerate wound healing. Further, nanohydrogels help quicken healing and are ideal biomaterials for drug delivery. In the current study, the chemical profiling, and standardization of T. polium methanolic extract by LC-ESI/TOF/MS/MS and quantitative HPLC-DAD analyses were achieved. The wound healing enhancement in diabetic rats by T. polium nanopreparation (TP-NP) as chitosan nanogel (CS-NG) and investigating the potential mechanisms were investigated. The prepared hydrogel-based TP-NP were characterized with respect to particle size, zeta potential, pH, viscosity, and release of major components. LC-ESI/TOF/MS/MS metabolomic profiling of T. polium revealed the richness of the plant with phenolic compounds, particularly flavonoids. In addition, several terpenoids were detected. Kaempferol content of T. polium was estimated to be 7.85 ± 0.022 mg/ g of dry extract. The wound healing activity of TP-NP was explored in streptozotocin-induced diabetic rats. Diabetic animals were subjected to surgical wounding (1 cm diameter). Then they were divided in 5 groups (10 each). These included Group 1 (untreated control rats), Group 2 received the vehicle of CS-NG; Group 3 (0.5 g of TP prepared in hydrogel), Group 4 (0.5 g of TP-NP), Group 5 represented a positive control treated with 0.5 g of a commercial product. All treatments were applied topically for 21 days. Application of TP-NP on skin wounds of diabetic animals accelerated the healing process as evidenced by epithelium regeneration, formation of granulation tissue followed by epidermal proliferation, along with keratinization as verified by H&E. This was confirmed through enhanced collagen synthesis, as shown by raised hydroxyproline content and Col1A1 gene expression. Moreover, TP-NP significantly alleviated wound oxidative burst and diminished the expressions of inflammatory biomarkers. Meanwhile, TP-NP could enhance the expressions of transforming growth factor beta1 (TGF-β1), in addition to the angiogenic markers; vascular endothelia growth factor A (VEGFA) and platelet-derived growth factor receptor alpha (PDGFRα). Collectively, chitosan nanogel of T. polium accelerates wound healing in diabetic rats, which could be explained – at least partly – through alleviating oxidative stress and inflammation coupled with pro-angiogenic capabilities.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by persistent hyperglycaemia with significant morbidity and mortality rates. Currently, metformin is a drug used as first-line therapy during the management of T2DM patients. Despite metformin's effectiveness and potency in lowering blood sugar levels, metformin had poor bioavailability and was prescribed in high doses of 500/1000 mg daily, which subsequently led to undesirable side effects. A high-dose regimen also needs a bigger pill size, which decreases patient compliance in dysphagic patients. To address these issues, many studies have attempted to develop metformin-based orally disintegrating tablets (ODTs) that possess rapid disintegration and dissolution properties to improve patient compliance and drug bioavailability. The present review aimed to highlight the recent studies on development and critical insights into addressing the challenges pertaining to designing the optimized formulation of metformin ODTs.

Insulin resistance (IR) leads to type 2 diabetes mellitus. Multiple IR causes have been identified, including inflammation. This study determines the association between IR and the inflammatory marker C-reactive protein (CRP) in a healthy Canadian population and examines potential differences by sex and age.

Participants were adults with no self-reported history of diabetes, a glycated hemoglobin (A1C) of <6.5%, and a fasting blood glucose of <7 mmol/L, and who had participated in the Canadian Health Measures Survey, cycles 1 to 4 (2007–2015). IR was calculated using the Homeostasis Model of Insulin Resistance (HOMA-IR) assessment. The crude geometric mean HOMA-IR was calculated using a one-way analysis of variance. The association between CRP levels and HOMA-IR was examined using multivariate linear regression.

A total of 4,024 eligible nondiabetic adults (1,994 [49.5%] men and 2,030 [50.4%] women) were identified. Eighty percent of the subjects were Caucasian. Among all subjects, 36% had a CRP of ≥2 mg/L. The crude geometric mean HOMA-IR was 1.33 in men and 1.24 in women. Participants with a CRP of <0.7 mg/L had a crude geometric mean HOMA-IR of 1.15 (1.13 to 1.16), compared with 1.41 (1.39 to 1.43) for those with a CRP of ≥2 mg/L. After adjusting for sex, age, race, high-density lipoprotein cholesterol, triglycerides, body mass index, smoking, and diastolic blood pressure, the HOMA-IR–CRP association remained significant. A positive trend for CRP values in men with increasing values of HOMA-IR was observed. However, this trend was not consistent with the increase in women’s CRP levels.

Elevated CPR levels are independently associated with IR in men. Prospective cohort studies can confirm the causal relationship between high CRP levels and IR and identify the underlying mechanisms.

La résistance à l’insuline (RI) mène au diabète sucré de type 2. Les multiples causes de la RI ont été déterminées, y compris l’inflammation. La présente étude permet de déterminer l’association entre la RI et le marqueur de l’inflammation, la protéine C réactive (CRP, de l’anglais C-reactive protein), au sein d’une population canadienne en bonne santé et d’examiner les différences potentielles par sexe et par âge.

Les participants étaient des adultes sans antécédents auto-déclarés de diabète, qui avaient une hémoglobine glyquée (A1c) de < 6,5 %, une glycémie à jeun de < 7 mmol/L, et ceux qui participaient à l’Enquête canadienne sur les mesures de la santé, des cycles 1 à 4 (2007–2015). La RI était calculée au moyen de l’évaluation du modèle d’homéostasie de la résistance à l’insuline (HOMA-IR, de l’anglais Homeostasis Model of Insulin Resistance). La moyenne géométrique brute de la HOMA-IR était calculée à l’aide d’une analyse de la variance à un facteur. L’association entre les concentrations de la CRP et l’HOMA-IR était examinée à l’aide de la régression linéaire multivariée.

Il y avait 4024 adultes non diabétiques admissibles, soit 1994 (49,5 %) hommes et 2030 (50,4 %) femmes. Quatre-vingts pour cent des sujets étaient des Blancs. Parmi les sujets, 36 % avaient des concentrations de CRP de ≥ 2 mg/L. La moyenne géométrique brute de la HOMA-IR était de 1,33 chez les hommes et de 1,24 chez les femmes. Les participants qui avaient des concentrations de CRP de < 0,7 mg/L avaient une moyenne géométrique brute de la HOMA-IR de 1,15 (de 1,13 à 1,16), alors que les participants qui avaient des concentrations de CRP de ≥ 2 mg/L avaient une moyenne géométrique brute de la HOMA-IR de 1,41 (de 1,39 à 1,43). Après l’ajustement selon le sexe, l’âge, la race, le cholestérol à lipoprotéines de haute densité, les triglycérides, l’indice de masse corporelle, le tabagisme et la pression artérielle diastolique, l’association entre la HOMA-IR et les concentrations de CRP restait significative. Une tendance positive des valeurs de CRP chez les hommes ayant des valeurs croissantes de la HOMA-IR était observée. Toutefois, cette tendance ne concordait pas avec l’augmentation des concentrations de CRP chez les femmes.

Les concentrations élevées de CRP sont indépendamment associées à la RI chez les hommes. Des études de cohortes prospectives permettront de confirmer la relation causale entre les concentrations élevées de CRP et la RI, et de découvrir les mécanismes sous-jacents.