A molecular perspective for the use of type IV tyrosine kinase inhibitors as anticancer therapeutics

Tyrosine kinases are enzymes that can transfer a phosphate group from ATP to a specific protein tyrosine, serine or threonine residue within a cell, operating as a switch that can turn ‘on’ and ‘off’ causing different physiological alterations in the body. Mutated kinases have been shown to display an equilibrium shift toward the activated state. Types I–III have been studied intensively leading to drugs like imatinib (type II), cobimetinib (type III), among others. It is the same scenario for types V–VII; however, there is a lacuna in information regarding type IV inhibitors, although recently some advances have surfaced. This review aims to accumulate the knowledge gained so far about type IV inhibitors.     

Trends of self-reported non-adherence among type 2 diabetes medication users in the United States across three years using the self-reported Medication Adherence Reasons Scale

Background & aimsTo determine the trends of self-reported non-adherence rates among adults taking Type 2 medicines (T2D) medicines between 2017 and 2019 and to identify the patterns for the frequently reported reasons for non-adherence in the United States.Methods & resultsData from the National Health and Wellness Survey, a self-administered, internet-based cross-sectional survey of US adults from 2017 to 2019 was used. Non-adherence was measured using the self-reported Medication Adherence Reasons Scale (MAR-Scale). Frequencies were used to identify the reasons for non-adherence for insulin and non-insulin therapies for T2D.Data were obtained from 2983 respondents in 2017, 5416 in 2018, and 5268 in 2019. Based on the MAR-Scale, the self-reported medication non-adherence rate was 25% in 2017, 21% in 2018, and 27% in 2019. The most common reason for non-adherence across all the three years was simple forgetfulness, yet patients reported the lowest mean number of days missing medication for that reason. Though less frequently reported, non-adherence lasted longer when patient did not know how to take their medicines, cost was a reason, or had concerns about the long term effects of the medicines.ConclusionsWith no significant improvement in adherence with T2D medicines over time, regardless of better awareness and extensive diabetes education, focus should be on individualized non-adherence reasons-based interventions.     

Effect of exercises according to the circadian rhythm in type 2 diabetes: Parallel-group,single-blind,crossover study

Background and aimTo evaluate the effectiveness of structured exercise appropriate the circadian rhythm in terms of blood sample test (BST), functionality and quality of life (QoL) in individuals with type 2 diabetes.Methods and resultsThis was a parallel-group, single-blind, crossover study. Thirty individuals with type 2 diabetes aged 35–65 years were enrolled in the study and allocated into 2 groups as the Morning Chronotype (MC) Group (n = 15) and the Evening Chronotype (EC) Group (n = 15) using Morningness-Eveningness Questionnaire which was used to determine the chronotypes. Participants were evaluated in terms of BST, functionality and QoL at the beginning of the study (T0), at 6 (T1), 12 (T2), and 18 (T3) weeks after the study started. A structured exercise program for 3 days a week over 6 weeks was applied in accordance with the chronotypes (T1-T2) and cross-controlled for the chronotypes (T2-T3). Significant differences were found in favor of the exercise given at the appropriate time for the chronotype in all parameters in both groups within groups (T0-T1-T2-T3) (p < 0.05). In the time1group interactions, exercise in accordance with the appropriate chronotype in both groups provided the highest statistical improvement in all parameters (p < 0.05).ConclusionIt was concluded that structured exercise performed at the appropriate time for chronotype improves HbA_1c, fasting blood glucose, HDL-LDL cholesterol, triglyceride, total cholesterol, functionality and quality of life in type 2 diabetes. This variation in blood values was observed to reflect the quantitative effects of exercise administered according to the circadian rhythm in individuals with type 2 diabetes.Trial registrationClinicalTrials.gov (NCT04427488). The protocol of the study was registered at ClinicalTrials.gov (NCT04427488).     

Contraception use and knowledge related to pregnancy in diabetic women

BackgroundDiabetes mellitus prevalence is increasing among women of child-bearing age. Diabetic pregnancy is associated with major maternal and fetal risks, and these can be reduced by preconception care. Pregnancy can be planned using appropriate effective contraception. The objective of this study was to assess diabetic patients’ knowledge about pregnancy and to describe their contraceptive use.Study designAn observational study was conducted from February to July 2020 at Reims University Hospital, France. Inclusion criteria were: women aged 18 to 40 years, with type 1 (T1D) or type 2 diabetes (T2D). Patients filled out a survey about contraceptive use and knowledge regarding diabetic pregnancy and data were completed from medical records.ResultsEighty-nine T1D and 33 T2D patients were included, with mean ages of 27.9 ± 6.3 and 32.6 ± 4.6 years, respectively. Seventy-five percent reported that they had been informed about pregnancy-related risks and 67% about the need to plan pregnancy. The preconception HbA1c target was known by 33% of patients. Appropriate knowledge about pregnancy was greater in T1D patients (65.9%, versus 36.4% in T2D patients; P = 0.003). The rate of patients using an effective contraceptive method was 66.4%. Fifteen percent patients for whom contraception was recommended reported having no contraceptive method; 12.5% of contraception users were using a contraindicated method.ConclusionA large majority of diabetic women were aware of pregnancy-related risks and the importance of pregnancy planning, but there are still gaps, especially in T2D patients. We need to improve our practices by providing more information and better access to appropriate effective contraception.ClinicalTrials.gov numberNCT04350879.     

PHLPPs: Emerging players in metabolic disorders

1. Download : Download high-res image (137KB)
2. Download : Download full-size image

     

Risk of acute pancreatitis with incretin-based therapy: a systematic review and updated meta-analysis of cardiovascular outcomes trials

ABSTRACT

Background

The link of acute pancreatitis (AP) with Incretin based therapies (IBTs) in type 2 diabetes has existed since United States Food and Drug Administration alert in 2010. This issue still remains unresolved due to conflicting results among studies.     

Title: Differentiating the effects of whey protein and guar gum preloads on postprandial glycemia in type 2 diabetes

Background and aimsWhey protein and guar gum have both been reported to reduce postprandial glycemia in health and type 2 diabetes, associated with stimulation of glucagon-like peptide-1 (GLP-1) and/or slowing of gastric emptying. Our aim was to evaluate, in type 2 diabetes, the acute effects of low dose “preloads” of whey and guar, given alone or in combination before a meal, on postprandial glycemia, insulin, GLP-1, and gastric emptying.Methods21 patients with type 2 diabetes, managed by diet or metformin alone, were each studied on 4 days. They received a preload “shake” 15min before a mashed potato meal (368.5 kcal) labeled with ¹³C-octanoic-acid. The preloads comprised either (i) 17 g whey (W), (ii) 5 g guar (G), (iii) 17 g whey + 5 g guar (WG) each sweetened with 60 mg sucralose, and (iv) 60 mg sucralose alone (control; C), all dissolved in 150 mL water. Venous blood was sampled frequently for measurements of glucose, insulin, and GLP-1 concentrations. Gastric half-emptying time (T50) was calculated from breath ¹³CO₂ excretion over 240 min.ResultsPostprandial blood glucose concentrations were lower with W and WG compared to C (each P < 0.0001, treatment × time interaction), and lower after G than C only at 30min. Insulin, GLP-1, and glucagon concentrations were higher after W than WG, G, or C (P < 0.05, treatment × time interaction), without differences between the latter three. Gastric emptying was slower with W (T50: 179.6 ± 6.1 min, P < 0.05) and WG (T50: 197.6 ± 9.7 min, P < 0.0001) when compared to C (T50: 162.9 ± 6.2 min), but did not differ between G (T50: 171.3 ± 7.0) and C (P > 0.99).ConclusionBoth whey and whey/guar preloads reduced postprandial glycemia, associated with slowing of gastric emptying. Low dose guar was less effective as a preload for glucose-lowering and did not slow gastric emptying.Clinical Trial Registry number and websiteAustralian and New Zealand Clinical Trials Registry, Trial ID ACTRN12615001272583, http://www.anzctr.org.au     

胰岛素泵强化治疗对初治2型糖尿病的疗效及预后

目的探析胰岛素泵强化治疗对初治2型糖尿病的疗效及对预后的影响。方法将2017年8月到2018年12月我院收治的120例初治2型糖尿病患者作为主要研究对象,采用数字随机表法将其分为两组,60例/组。对照组采用胰岛素皮下注射强化治疗,观察组采用胰岛素泵强化治疗,比较两组患者治疗前后的血糖变化情况和预后相关指标。结果治疗后两组患者的空腹血糖、餐后2h血糖、糖化果糖胺水平均明显低于治疗前,且观察组明显低于对照组,有显著差异;两组患者治疗后的胰岛素抵抗指数均低于治疗前,且观察组低于对照组,差异显著;观察组患者的血糖达标时间短于对照组,胰岛素用量少于对照组,组间比较存在显著差异;观察组的低血糖发生率显著低于对照组,有显著差异(P<0.05)。结论采用胰岛素泵强化治疗对初治2型糖尿病患者而言效果显著,能够降低患者的血糖值,缩短血糖达标时间,减少胰岛素的剂量,且预后佳,更值得进一步推广应用。     

Cardiovascular effects and mechanisms of sodium-glucose cotransporter-2 inhibitors

Sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors) are a new type of drug for the treatment of diabetes, and they have been proven to have a good hypoglycemic effect. Several lines of clinical evidence have shown that SGLT2 inhibitors can significantly reduce the risks of atherosclerosis, hospitalization for heart failure, cardiovascular death, and all-cause mortality and delay the progression of chronic kidney disease. Because of the protective effects of SGLT2 inhibitors on the heart and kidney, they are being studied for the treatment of heart failure and chronic kidney disease in patients without diabetes. Therefore, it is necessary for cardiologists, patients with diabetes, and nephrologists to fully understand this type of drug. In this review, we summarize the following three aspects of SGLT2 inhibitors: the recent clinical evidence of their cardiovascular benefits, their mechanisms of action, and their safety.     

The effect of education given to type 2 diabetic individuals on diabetes self-management and self-efficacy: Randomized controlled trial

AimThis study used a randomized controlled trial design and was carried out to examine the effect of education on diabetes self-management and self-efficacy in patients with type 2 diabetes.MethodsThe study was carried out between July 2016–March 2017. Data were collected using information form, Diabetes Self-Management Questionnaire (DSMQ), self-efficacy scale for patients with type 2 diabetes (DSS).The individuals in the experimental group were given education. Both groups were reminded about the control time of their metabolic values on the phone in the 3rd and 6th months.ResultsThe average age of the individuals was 59.91 ± 8.93 (n = 78), 62.8% (n = 49) were female, 92.3% (n = 72), were married, 42.3% (n = 33) were high school graduates and their diabetes duration was 7.05 ± 3.9. There was a statistically significant difference in the 6th month metabolic values in the experimental group compared to the control group. When diabetes self-management and self-efficacy were examined, a statistically significant difference was found in the experimental group compared to the control group at 3rd and 6th months (p < 0.05, p < 0.01).ConclusionIn this study, a significant increase in diabetes self-management and self-efficacy and a significant decrease in metabolic values were observed as a result of education and phone reminders given to individuals with type 2 diabetes.