Synergistic Effect of β-Carotene and Metformin on Antihyperglycemic and Antidyslipidemic Activities in Streptozotocin-Induced Diabetic Rats

Purpose: Worldwide prevalence of diabetes mellitus (DM) has become an issue of great concern in current decades. To date, a large number of biological properties have been reported from carotenoids, particularly protective effects against cancer, cardiovascular diseases, and DM, including enhancement of insulin sensitivity.In this study, we aimed to evaluate the efficacy of β-carotene as an additive agent with metformin in ameliorating Type2 (T2)DM. Methods: In this experiment, fasting blood glucose level (BGL), low density lipoprotein (LDL), high density lipoprotein (HDL), total cholesterol (TC) and triglycerides (TG) were measured in serum of Wister albino rats with streptozotocin (STZ)-induced diabetes and after treatment with metformin (850mg/70kg b.w.) and β-carotene (10 mg/70kg b.w.) administered orally once daily for three weeks. Results: Metformin and β-carotene treatments individually resulted in significant (p<0.001) reversal of the diabetes induced increase in BGL, LDL, TC and TG, whereas significantly increased the STZ-induced decrease in HDL, compared to diabetic control. As compared to the monotherapy, the combination therapy with metformin and β-carotene showed a significant (p<0.001) attenuation of BGL and serum level of LDL, TC, and TG and a slight increase (p<0.05) in serum HDL level, as compared to the treatment with β-carotene, but not with metformin. Conclusion: The combination therapy of β-carotene and metformin produced a significant antidiabetic and antihyperlipidemic effect than the monotherapy alone and provides a scientific rationale for their use in antidiabetic therapy as a potential antioxidant.

Oral Antidiabetics and Sleep Among Type 2 Diabetes Patients: Data From the UK Biobank

Previous small-scale studies have found that oral antidiabetic therapy is associated with sleep difficulties among patients with type 2 diabetes (T2D). Here, we used data from 11 806 T2D patients from the UK Biobank baseline investigation to examine the association of oral antidiabetic therapy with self-reported difficulty falling and staying asleep and daily sleep duration. As shown by logistic regression adjusted for, e.g., age, T2D duration, and HbA1c, patients on non-metformin therapy (N=815; 86% were treated with sulphonylureas) had a 1.24-fold higher odds ratio of reporting regular difficulty falling and staying asleep at night compared to those without antidiabetic medication use (N=5 366, P&lt;0.05) or those on metformin monotherapy (N=5 625, P&lt;0.05). Non-metformin patients reported about 8 to 10 minutes longer daily sleep duration than the other groups (P&lt;0.05). We did not find significant differences in sleep outcomes between untreated and metformin patients. Our findings suggest that non-metformin therapy may result in sleep initiation and maintenance difficulties, accompanied by a small but significant sleep extension. The results of the present study must be replicated in future studies using objective measures of sleep duration and validated questionnaires for insomnia. Considering that most T2D patients utilize multiple therapies to manage their glycemic control in the long term, it may also be worth investigating possible interactions of antidiabetic drugs on sleep.

Behavioral Sciences in the Optimization of Pharmacological and Non-Pharmacological Therapy for Type 2 Diabetes

Type 2 diabetes mellitus is one of the main chronic diseases worldwide, with a significant impact on public health. Behavioral changes are an important step in disease prevention and management, so the way in which individuals adapt their lifestyle to new circumstances will undoubtedly be a predictor of the success of the treatments instituted, contributing to a reduction in the morbidity and mortality that may be associated with them. It is essential to prepare and educate all diabetic patients on the importance of changing behavioral patterns in relation to the disease, with health professionals assuming an extremely important role in this area, both from a pharmacological and non-pharmacological point of view, and also ensuring the monitoring of the progress of these measures. Diabetes is a chronic disease that requires a high self-management capacity on the part of patients in order to achieve success in treating the disease, and non-adherence to therapy or non-compliance with the previously defined plan, together with an erratic lifestyle, will contribute to failure in controlling the disease. The lower adherence to pharmacological and non-pharmacological treatment in diabetes is mainly correlated to socio-economic aspects, lower health literacy, the side effects associated with the use of antidiabetic therapy or even the concomitant use of several drugs. This article consists of a narrative review that aims to synthesize the findings published in the literature, retrieved by searching databases, manuals, previously published scientific articles and official texts, following the methodology of the Scale for Assessment of Narrative Review Articles (SANRA). We aim to address the importance of behavioral sciences in the treatment of diabetes, in order to assess behavior factors and barriers for behavior changes that have an impact on the therapeutic and non-therapeutic optimization in patients with type 2 diabetes mellitus control.

Stability Study of Super Saturable Catechin-Self Nano Emulsifying Drug Delivery System as Antidiabetic Therapy

Diabetes mellitus is a metabolic syndrome characterized by hyperglycemic and increased ROS production, which causes oxidative stress. Catechin isolated from the tea plant has oxidative stress inhibitor activity and anti-diabetic activity with low absorption in circulation systemic. Therefore, it is formulated in a super saturable catechin-self nano emulsifying drug delivery system (SSC-SNEDDS). Stability is one of the factors that affect the safety, quality, and efficacy of SSC-SNEDDS. This study aims to evaluate the stability of the formulated oil phase using oleic acid, croduret as a surfactant, and propylene glycol as a co-surfactant. Stability studies were carried out by several tests, namely heating-cooling cycle assay, freeze-thaw cycle assay, centrifugation, and endurance assay. Droplet characterization in the form of changes in diameter, zeta potential, and mobility in evaluating stability tests using dynamic light scattering-particle size analyzer (DLS-PSA). Real-time stability was also evaluated by observing changes in the infrared spectrum pattern using FTIR-ATR. After the stability test, the emulsion droplet size of SSC-SNEDDS was still below 100 nm and showed good stability. It can be concluded that the formula has a good stability profile.

The management of type 2 diabetes before, during and after Covid-19 infection: what is the evidence?

Patients with Covid-19 place new challenges on the management of type 2 diabetes, including the questions of whether glucose-lowering therapy should be adjusted during infection and how to manage a return to normal care after resolution of Covid-19 symptoms. Due to the sudden onset of the pandemic, physicians have by necessity made such important clinical decisions in the absence of robust evidence or consistent guidelines. The risk to patients is compounded by the prevalence of cardiovascular disease in this population, which alongside diabetes is a major risk factor for severe disease and mortality in Covid-19. We convened as experts from the Central and Eastern European region to consider what advice we can provide in the setting of type 2 diabetes and Covid-19, considering the evidence before, during and after infection. We review recommendations that have been published to date, and consider the best available—but currently limited—evidence from large observational studies and the DARE-19 randomized control trial. Notably, we find a lack of guidance on restarting patients on optimal antidiabetic therapy after recovering from Covid-19, and suggest that this may provide an opportunity to optimize treatment and counter clinical inertia that predates the pandemic. Furthermore, we emphasize that optimization applies not only to glycaemic control, but other factors such as cardiorenal protection. While we look forward to the emergence of new evidence that we hope will address these gaps, in the interim we provide a perspective, based on our collective clinical experience, on how best to manage glucose-lowering therapy as patients with Covid-19 recover from their disease and return to normal care.

Initiation of insulin therapy in patients with type 2 diabetes: An observational study

The aim of the study was to assess the initiation of insulin therapy in patients with type 2 diabetes using health claims data on prescription medicines. The study evaluated time to insulin initiation and prescribing patterns of other anti-diabetic medicines before and after insulin initiation. Five years after starting non-insulin antidiabetic therapy, 6.4 % of patients were prescribed insulin, which is substantially lower compared to other similar studies. Among all patients who initiated insulin therapy in 2013, 30 % did not continue any other antidiabetic therapy. However, this proportion was lowered to 20 % in 2018. Before insulin initiation in 2018, metformin was prescribed in only 67 % of patients and sulfonylureas in 78 % of patients. Moreover, metformin and sulfonylureas were discontinued after insulin initiation in 26 and 37 % of patients, resp. More attention should be paid to the continuation of oral anti-diabetics, particularly metformin, after insulin initiation.

Patterns of drug therapy, glycemic control, and predictors of escalation – non-escalation of treatment among diabetes outpatients at a tertiary care center

Objectives The study was conducted to assess patterns of prescribed drug therapy and clinical predictors of need for therapy escalation in outpatients with diabetes mellitus (DM). Methods This was a prospective cohort study, conducted at an apex tertiary care teaching hospital in central India for a period of 18 months. The demographic, clinical, and treatment details on the baseline and follow up visits were collected from the patients’ prescription charts. Glycemic control, adherence, pill burdens along with pattern of antidiabetic therapy escalation, and deescalations were analyzed. Results A total of 1,711 prescriptions of 925 patients of diabetes with a mean age of 53.81 ± 10.42 years and duration of disease of 9.15 ± 6.3 years were analyzed. Approximately half of the patients (n=450) came for ≥1 follow up visits. Hypertension (59.35%) was the most common comorbidity followed by dyslipidemia and hypothyroidism. The mean total daily drugs and pills per prescription were 4.03 ± 1.71 and 4.17 ± 1.38, respectively. Metformin (30.42%) followed by sulphonylureas (SUs) (21.39%) constituted majority of the AHA’s and dual and triple drug therapy regimens were most commonly prescribed. There were improvements in HbA1c, fasting/postprandial/random blood sugar (FBS/PPBS/RBS) as well as adherence to medication, diet, and exercise in the follow up visits. Among patients with follow ups, therapy escalations were found in 31.11% patients, among whom dose was increased in 12.44% and drug was added in 17.28%. Apart from Hb1Ac, FBS, and PPBS levels (p<0.001), characteristics such as age, BMI, duration of diagnosed diabetes, presence of hypertension and dyslipidemia, and daily pill burdens were found to be significantly higher in the therapy escalation group (p<0.05). Inadequate medication adherence increased the relative risk (RR) of therapy escalation by almost two times. Conclusions Disease and therapy patterns are reflective of diabetes care as expected at a tertiary care center. Higher BMI, age, pill burden, duration of diabetes, presence of comorbidities, and poor medication adherence may be the predictors of therapy escalation independent of glycemic control and such patients should be more closely monitored.

Insulin Secretion Predicts the Response to Antidiabetic Therapy in Patients With New Onset Diabetes

Aim To identify predictors for individualization of antidiabetic therapy in patients with new onset T2DM. Research Design and Methods 261 drug naïve participants in the EDICT study, with new onset diabetes, were randomized in a single-center study to receive: (1) metformin followed by glipizide and then insulin glargine upon failure to achieve HbA1c &lt;6.5%, or (2) initial triple therapy with metformin/pioglitazone/ exenatide. Each patient received 75-gram OGTT prior to start of therapy. Factors that predicted response to therapy were identified using the aROC method. Results 39 patients started and maintained the treatment goal (HbA1c &lt;6.5%) on metformin only, and did not require intensification of antihyperglycemic therapy; 54 patients required addition of glipizide to metformin; and 47 patients required insulin addition to metformin plus glipizide for glucose control. The C-Pep120/C-Pep0 ratio during the OGTT was the strongest predictor of response to therapy. Patients with ratio &lt;1.78 were more likely to require insulin for glucose control, while patients with ratio &gt;2.65 were more likely to achieve glucose control with metformin monotherapy. In patients started on initial Triple Therapy the HbA1c decreased independent of C-Pep120/C-Pep0 ratio. Conclusion The increase in plasma C-peptide concentration above fasting following glucose load predicts the response to antihyperglycemic therapy in patients with new onset diabetes. C-Pep120/C-Pep0 provides a useful tool for individualization of antihyperglycemic therapy in patients with new onset diabetes.