In Vitro Anti-Diabetic Activities and UHPLC-ESI-MS/MS Profile of Muntingia calabura Leaves Extract

Anti-diabetic compounds from natural sources are now being preferred to prevent or treat diabetes due to adverse effects of synthetic drugs. The decoction of Muntingia calabura leaves was traditionally consumed for diabetes treatment. However, there has not been any published data currently available on the processing effects on this plant’s biological activity and phytochemical profile. Therefore, this study aims to evaluate the effect of three drying methods (freeze-drying (FD), air-drying (AD), and oven-drying (OD)) and ethanol:water ratios (0, 50, and 100%) on in vitro anti-diabetic activities of M. calabura leaves. In addition, an ultrahigh-performance-liquid chromatography–electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS) method was used to characterize the metabolites in the active extract. The FD M. calabura leaves, extracted with 50% ethanol, is the most active extract that exhibits a high α-glucosidase and α-amylase inhibitory activities with IC50 values of 0.46 ± 0.05 and 26.39 ± 3.93 µg/mL, respectively. Sixty-one compounds were tentatively identified by using UHPLC-ESI-MS/MS from the most active extract. Quantitative analysis, by using UHPLC, revealed that geniposide, daidzein, quercitrin, 6-hydroxyflavanone, kaempferol, and formononetin were predominant compounds identified from the active extract. The results have laid down preliminary steps toward developing M. calabura leaves extract as a potential source of bioactive compounds for diabetic treatment.

Structural Bases for Hesperetin Derivatives: Inhibition of Protein Tyrosine Phosphatase 1B, Kinetics Mechanism and Molecular Docking Study

In the present study, we investigated the structure-activity relationship of naturally occurring hesperetin derivatives, as well as the effects of their glycosylation on the inhibition of diabetes-related enzyme systems, protein tyrosine phosphatase 1B (PTP1B) and α-glycosidase. Among the tested hesperetin derivatives, hesperetin 5-O-glucoside, a single-glucose-containing flavanone glycoside, significantly inhibited PTP1B with an IC50 value of 37.14 ± 0.07 µM. Hesperetin, which lacks a sugar molecule, was the weakest inhibitor compared to the reference compound, ursolic acid (IC50 = 9.65 ± 0.01 µM). The most active flavanone hesperetin 5-O-glucoside suggested that the position of a sugar moiety at the C-5-position influences the PTP1B inhibition. It was observed that the ability to inhibit PTP1B is dependent on the nature, position, and number of sugar moieties in the flavonoid structure, as well as conjugation. In the kinetic study of PTP1B enzyme inhibition, hesperetin 5-O-glucoside led to mixed-type inhibition. Molecular docking studies revealed that hesperetin 5-O-glucoside had a higher binding affinity with key amino residues, suggesting that this molecule best fits the PTP1B allosteric site cavity. The data reported here support hesperetin 5-O-glucoside as a hit for the design of more potent and selective inhibitors against PTP1B in the search for a new anti-diabetic treatment.

Prevalence of vaginal candidiasis and associated factors in pregnant women with diabetes

Background/aims Vaginal candidiasis is commonly experienced by women with diabetes, but its prevalence is not well documented in Zimbabwe. This study aimed to assess the prevalence of vaginal candidiasis and factors associated with diabetic treatment adherence in pregnant women with diabetes. Methods This cross-sectional study was conducted on a consecutive sample of 157 participants from a central hospital in Harare, Zimbabwe. A structured questionnaire and physical examination of the perineum were used to collect data. All procedures were conducted in privacy. Diagnosis of vaginal candidiasis was made clinically. Data were analysed using the Chi-squared test, with P<0.05 being significant. Results The prevalence of vaginal candidiasis was 19.7%. There was a significant association between monthly family income (P=0.041), parity (P=0.029) and number of living children (P=0.049) and the presence of vaginal candidiasis. Women with poor adherence to diabetic therapy were 3.95 times more likely to have vaginal candidiasis (P=0.002). Conclusions Individualised health education on glycaemic control and good perineal hygiene remains key in the prevention of vaginal candidiasis among diabetic pregnant women.

Characteristics of the type 2 diabetic patients with hypoglycemia in a tertiary referral hospital

Background. Hypoglycemia is an important complication of the treatment of type 2 diabetes mellitus, which constitutes a barrier in stringent diabetic control. Beside it constitutes nearly 10 % of emergency department admissions that caused by adverse drug events, it may also increase morbidities and mortality by inducing, cardiac arrhythmias, neurological impairment and ischemic events. Hypoglycemia is the most common side effect of insulin treatment, however, oral antidiabetic agents may also induce hypoglycemic complications. In present retrospective study, we purposed to observe general characteristics and laboratory data of the type 2 diabetic patients whom presented with mild or moderate/severe hypoglycemia. Materials and methods. Patients with type 2 diabetes mellitus whom presented to our institution with hypoglycemia between January 2019 and January 2020 were retrospectively analyzed. General characteristics and laboratory data of the subjects recorded. Patients grouped into two groups, group I consisted of subjects with mild hypoglycemia and group II consisted of patients with moderate/severe hypoglycemia. Data of the subjects in groups I and II were compared. Results. There were 15 subjects in group I and 23 in group II. HbA1c and other laboratory markers were not significantly different in study groups. Similarly diabetes duration and anti-diabetic treatment were not significantly different in study groups. The rate of geriatric patients was significantly higher in group II compared to group I (p = 0.04). Conclusions. Subjects with moderate/severe hypoglycemia tend to be more frequently in geriatric age and HbA1c not correlates with the degree of the hypoglycemia. Since neither duration of diabetes, nor anti-diabetic treatment were associated with the severity of the hypoglycemia, each case should be evaluated individually to prevent further episodes which could increase morbidity and mortality in diabetic population.

Diabetes severity measured by treatment control status and number of anti-diabetic drugs affects presenteeism among workers with type 2 diabetes

Background The number of people with diabetes is increasing and resulting in major economic losses. Presenteeism accounts for the majority of economic losses, so measures against presenteeism are important. This study investigated the relationship between severity of type 2 diabetes and presenteeism. Methods A cross-sectional study was conducted among workers over 40 years of age. Participants were classified as normal group or diabetic treatment group using their medical examination results and health insurance claims data. Diabetic treatment groups were described by degree of treatment control: Good (HbA1c < 7%), Intermediate (7% ≤ HbA1c < 8%), and Poor (8% ≤ HbA1c). Therapy type was also divided into monotherapy and combination therapy. Logistic regression analysis was performed to predict presenteeism loss using the Quantity and Quality method. Results Data on 13,271 workers were analyzed. Presenteeism loss was significantly higher in all treatment control groups compared with the normal group, particularly for the intermediate and poor control groups. The monotherapy group did not differ from the normal group, but presenteeism loss was significantly higher in the combination therapy group than the normal group. Conclusions Presenteeism loss in workers with diabetes may be affected by diabetes severity, and even if treatment control were good, presenteeism loss could occur when the number of anti-diabetic drugs was high. Therefore, it is important to provide early intervention and continuous support as a preventive measure against not only diabetes and diabetes-related complications but also presenteeism.

Expression Profiles of Circulating microRNAs in South African Type 2 Diabetic Individuals on Treatment

Aim: The influence of disease duration and anti-diabetic treatment on epigenetic processes has been described, with limited focus on interactions with microRNAs (miRNAs). miRNAs have been found to play key roles in the regulation of pathways associated with type 2 diabetes mellitus (T2DM), and expression patterns in response to treatment may further promote their use as therapeutic targets in T2DM and its associated complications. We therefore aimed to investigate the expressions of circulating miRNAs (miR-30a-5p, miR-1299, miR-182-5p, miR-30e-3p and miR-126-3p) in newly diagnosed and known diabetics on treatment, in South Africa.Methods: A total of 1254 participants with an average age of 53.8years were included in the study and classified according to glycaemic status (974 normotolerant, 92 screen-detected diabetes and 188 known diabetes). Whole blood levels of miR-30a-5p, miR-1299, miR-182-5p, miR-30e-3p and miR-126-3p were quantitated using RT-qPCR. Expression analysis was performed and compared across groups.Results: All miRNAs were significantly overexpressed in subjects with known diabetes when compared to normotolerant individuals, as well as known diabetics vs. screen-detected (p&lt;0.001). Upon performing regression analysis, of all miRNAs, only miR-182-5p remained associated with the duration of the disease after adjustment for type of treatment (OR: 0.127, CI: 0.018–0.236, p=0.023).Conclusion: Our findings revealed important associations and altered expression patterns of miR-30a-5p, miR-1299, miR-182-5p, miR-30e-3p and miR-126-3p in known diabetics on anti-diabetic treatment compared to newly diagnosed individuals. Additionally, miR-182-5p expression decreased with increasing duration of T2DM. Further studies are, however, recommended to shed light on the involvement of the miRNA in insulin signalling and glucose homeostasis, to endorse its use as a therapeutic target in DM and its associated complications.

Comparison of rat tooth eruption in rats born from diabetic mothers

Background: Tooth eruption begins after crown and root formation and may be delayed by gestational diabetes mellitus. Metformin can control blood glucose levels through gluconeogenesis inhibition, and consuming thymoquinone for diabetic treatment will regenerate pancreatic β cells and reduce oxidative stress. Purpose: The objective of this study is to compare the tooth eruption in rats that were born with diabetes and are being treated with either metformin or thymoquinone. Methods: This study used 48 Wistar rats (Rattus norvegicus L.), and the rat sample was divided into four groups, including rats who were born from healthy mothers, rats who were born from untreated diabetic mothers, rats who were born from diabetic mothers that were treated with metformin and rats who were born from diabetic mothers that were treated with thymoquinone. Diabetes was induced by intraperitoneal injection of a single dose of streptozotocin (40 mg/kg BB). Each rat sample was taken with simple random sampling from different mothers, and body weight, blood glucose levels and levels of tooth eruption were recorded. Eruptions of the maxillary right first molar were measured from the cusp of the tooth to the alveolar epithelial lining. Results: Based on the measurements of tooth eruption, it was found that groups A, C and D were closer to mucosa on day 1, 7 and 14 than group B. Based on statistical analysis, there were significant differences (p = 0.03) between group B and groups C and D. Conclusions: Rats born from untreated diabetic mothers have more delays in tooth eruption than those born from diabetic mothers who are treated with metformin and thymoquinone. Thymoquinone has the potential to be an alternative to metformin because it has been shown to be similarly effective.