Plasma thromboxane B2 and 6-keto-prostaglandin-F1α in patients with type 2 diabetes mellitus

Objective To investigate the changes of plasma thrombexane B2 (TXB2) and 6-keto-prostaglan-din-F1α (6-keto-PGF1α) in patients with type 2 diabetic mellitus and their roles in the pathogenesis of diabetic macroangiopathy. Methods Plasma levels of TXB2 and 6-keto-PGF1α were measured with RIA in 60 cases of type 2 diabetic patients(43 patients with and 17 without diabetic macroangiopathy), with 31 cases of controls. Results Plasma levels of TXB2 in type 2 diabetic patients were significantly higher than those in controls. However, plasma levels of 6-keto-PGF1α in type 2 diabetic patients were significantly lower than those in controls. Changes of both indexes were more significant in type 2 diabetic patients with macroangiopathy than those without macroangiopathy. Plasma levels of TXB2 showed negative correlation with 6-keto-PGF 1α. Conclusion TXB2 and 6-keto-PGF 1 α may play important roles in the pathogenesis of diabetic macroangiopathy. Determination of TXB2 and 6-keto-PGF1α levels in type 2 diabetic patients may be useful for early detection of diabetic macroangiopathy.     

Plasma thromboxane B2 and 6-keto-prostaglandin-F1α in patients with type 2 diabetes mellitus

Objective To investigate the changes of plasma thrombexane B2 (TXB2) and 6-keto-prostaglan-din-F1α (6-keto-PGF1α) in patients with type 2 diabetic mellitus and their roles in the pathogenesis of diabetic macroangiopathy. Methods Plasma levels of TXB2 and 6-keto-PGF1α were measured with RIA in 60 cases of type 2 diabetic patients(43 patients with and 17 without diabetic macroangiopathy), with 31 cases of controls. Results Plasma levels of TXB2 in type 2 diabetic patients were significantly higher than those in controls. However, plasma levels of 6-keto-PGF1α in type 2 diabetic patients were significantly lower than those in controls. Changes of both indexes were more significant in type 2 diabetic patients with macroangiopathy than those without macroangiopathy. Plasma levels of TXB2 showed negative correlation with 6-keto-PGF 1α. Conclusion TXB2 and 6-keto-PGF 1 α may play important roles in the pathogenesis of diabetic macroangiopathy. Determination of TXB2 and 6-keto-PGF1α levels in type 2 diabetic patients may be useful for early detection of diabetic macroangiopathy.     

Plasma thromboxane B2 and 6-keto-prostaglandin-F1α in patients with type 2 diabetes mellitus

Objective To investigate the changes of plasma thrombexane B2 (TXB2) and 6-keto-prostaglan-din-F1α (6-keto-PGF1α) in patients with type 2 diabetic mellitus and their roles in the pathogenesis of diabetic macroangiopathy. Methods Plasma levels of TXB2 and 6-keto-PGF1α were measured with RIA in 60 cases of type 2 diabetic patients(43 patients with and 17 without diabetic macroangiopathy), with 31 cases of controls. Results Plasma levels of TXB2 in type 2 diabetic patients were significantly higher than those in controls. However, plasma levels of 6-keto-PGF1α in type 2 diabetic patients were significantly lower than those in controls. Changes of both indexes were more significant in type 2 diabetic patients with macroangiopathy than those without macroangiopathy. Plasma levels of TXB2 showed negative correlation with 6-keto-PGF 1α. Conclusion TXB2 and 6-keto-PGF 1 α may play important roles in the pathogenesis of diabetic macroangiopathy. Determination of TXB2 and 6-keto-PGF1α levels in type 2 diabetic patients may be useful for early detection of diabetic macroangiopathy.     

Plasma thromboxane B2 and 6-keto-prostaglandin-F1α in patients with type 2 diabetes mellitus

Objective To investigate the changes of plasma thrombexane B2 (TXB2) and 6-keto-prostaglan-din-F1α (6-keto-PGF1α) in patients with type 2 diabetic mellitus and their roles in the pathogenesis of diabetic macroangiopathy. Methods Plasma levels of TXB2 and 6-keto-PGF1α were measured with RIA in 60 cases of type 2 diabetic patients(43 patients with and 17 without diabetic macroangiopathy), with 31 cases of controls. Results Plasma levels of TXB2 in type 2 diabetic patients were significantly higher than those in controls. However, plasma levels of 6-keto-PGF1α in type 2 diabetic patients were significantly lower than those in controls. Changes of both indexes were more significant in type 2 diabetic patients with macroangiopathy than those without macroangiopathy. Plasma levels of TXB2 showed negative correlation with 6-keto-PGF 1α. Conclusion TXB2 and 6-keto-PGF 1 α may play important roles in the pathogenesis of diabetic macroangiopathy. Determination of TXB2 and 6-keto-PGF1α levels in type 2 diabetic patients may be useful for early detection of diabetic macroangiopathy.     

Treat-to-target comparison between once daily biphasic insulin aspart 30 and insulin glargine in Chinese and Japanese insulin-naïve subjects with type 2 diabetes

Abstract

Objective:

To investigate whether once daily biphasic insulin aspart 30 (BIAsp 30) is noninferior to once daily insulin glargine (IGlar) among Chinese and Japanese insulin-naïve subjects with type 2 diabetes mellitus (T2DM).     

A multicenter,epidemiological study of the treatment patterns,comorbidities and hypoglycemia events of patients with type 2 diabetes and moderate or severe chronic kidney disease – the ‘LEARN’ study

Objective Management of patients with type 2 diabetes (T2DM) and stage 3 to 5 chronic kidney disease (CKD) is challenging. The aim of the ‘LEARN’ study was to describe treatment patterns employed in this population and to record comorbidities, glycemic control and hypoglycemia episodes in routine clinical practice in Greece.

Research design and methods ‘LEARN’ was a non-interventional, multicenter, cross-sectional study conducted in Greece between 15 February 2013 and 4 July 2013. A total of 120 adult patients were enrolled from four hospital sites in different geographic regions of Greece.

Results Participants had a mean age of 69.1?±?10.3 years and a male:female ratio of 2:1. Nearly all patients (99.2%) suffered from at least one comorbidity, with hypertension (95.8%) and hyperlipidemia/dyslipidemia (78.3%) being the most prevalent. Of the overall study population, 57.5% was managed with insulin therapy only, 30.8% with oral antidiabetics only and 11.7% with a combination of insulin and oral antidiabetics. The overall rate of glycemic control, defined as glycated hemoglobin (HbA_1c)?≤?7.0% during the most recent assessment, was 55.0%. This rate was significantly higher among those receiving oral antidiabetics only (73.0%) compared to insulin only (47.8%) or a combination of both types of treatment (42.9%) (p?=?0.03). Moreover, patients receiving oral antidiabetics only had experienced fewer hypoglycemia episodes over the last 7 days prior to the study visit (0.1?±?0.4) compared to patients receiving insulin only (0.9?±?1.7) (p?=?0.03).

Conclusions Although this is an observational study, it seems that oral antidiabetic therapy might be advantageous for heavily burdened T2DM patients with moderate or severe CKD in terms of glycemic control and hypoglycemia episodes. More data preferably from randomized trials is needed in order to validate this hypothesis.     

Adverse drug reactions associated with the use of liraglutide in patients with type 2 diabetes – focus on pancreatitis and pancreas cancer

Introduction: The glucagon-like peptide-1 (GLP-1) receptor agonist, liraglutide, is a widely used drug for the treatment of type 2 diabetes. Liraglutide is one of several incretin-based agents that have been suggested to be associated with pancreatitis and pancreas cancer. The suspicion accelerated after publication of an autopsy study claiming increased incidences of several pathological changes in pancreata from patients with diabetes treated with incretin-based drugs.

Areas covered: The aim of the present review is to give an overview of the pharmacology of liraglutide and provide a review of adverse reactions associated with liraglutide with a focus on the risk of pancreatitis and pancreas cancer.

Expert opinion: When comprehensively reviewing the available literature, no clear and significant associations between liraglutide and pancreatitis and/or pancreas cancer seem evident. However, a recently published analysis suggests a trend toward a slightly elevated risk of pancreatitis with GLP-1 receptor agonists (including liraglutide), which may become statistical significant as more data become available. Well-established side effects are of gastrointestinal origin, typical mild-to-moderate and of transient character. The risk of hypoglycemia associated with liraglutide treatment is low.     

Effects of intensive insulin analogues therapy on function of pancreatic β-cell, inflammatory cells factor in the sulfonylurea secondary failure patients with type 2 diabetes mellitus

目的 观察胰岛素泵强化治疗对降糖药继发性失效(SFS)的2型糖尿病患者炎性细胞因子及胰岛功能的影响.方法 50例SFS的2型糖尿病患者停用口服降糖药,改用胰岛素泵强化治疗2周,观察治疗前后的空腹血糖、餐后2-h血糖、胰岛素抵抗指数(HOMA-IR)、胰岛素分泌指数(HOMA-β)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平的变化.结果 强化治疗后,患者空腹血糖、餐后2-h血糖、HOMA-IR、TNF-α、IL-6水平均较治疗前明显下降(P＜0.05),HOMA-β较治疗前明显增高(P＜0.05).结论 胰岛素泵强化治疗可减轻SFS的2型糖尿病患者胰岛素抵抗,改善胰岛β细胞功能,降低机体炎性因子水平.     

Impact of waist/height ratio on insulin resistance and function of pancreatic β-cells in newly diagnosed Type 2 diabetes mellitus

Objective To study the impact of central obesity on insulin resistance and the function of pancreaticβcells in newly diagnosed Type 2 diabetes. Methods Eighty-six type 2 diabetes mellitus (T2DM) patients were divided into 2 groups according to their waist to hip ratio. Metabolic parameters and Insulin resistance and the function of pancreatic β-cells were compared. Insulin resistance were calculated by HOMA-IR and the function of pancreatic β-cells were detected by HOMA-βand ISF-Arg. Results HOMA-IR index, HOMA-IS and ISF-Arg in WHR ≥0.85 (male) or 0.80 (female) group were significantly higher than that of WHR ＜ 0. 85 (male) or 0. 80 (female) group ( P ＜ 0. 01 ), whereas WHR ＜ 0. 85 (male) or 0. 8 ( female ) group had significantly higher fasting sugar levels and HbA1c and favorable lipid profile (P ＜ 0.05 ). Conclusion WHR is an useful parameter in roughly judging the function of β-cell and insulin resistance.     

Long-term clinical and cost outcomes of treatment with biphasic insulin aspart 30/70 versus insulin glargine in insulin naïve type 2 diabetes patients: cost-effectiveness analysis in the UK setting

OBJECTIVES: To evaluate the long-term clinical and cost outcomes associated with biphasic insulin aspart 30/70 (BIAsp 30/70, premixed 30% soluble and 70% protaminated insulin aspart in one injection) compared to insulin glargine treatment in insulin-na?ve type 2 diabetes patients failing oral antidiabetic agents in the UK, based on findings recently reported from the INITIATE clinical trial. METHODS: The CORE Diabetes Model, a published, peer-reviewed and validated model of diabetes, was used to evaluate life expectancy, quality-adjusted life expectancy, cumulative incidence of complications and direct medical costs over patient lifetimes. The model simulates the range of diabetic complications and disease progression within a series of sub-models (cardiovascular disease, neuropathy, renal and eye disease) based on published data. Baseline cohort characteristics (54.5% male, mean age 52.45 years, mean diabetes duration 9 years, mean HbA(1c) 9.77%) and treatment effects were based on INITIATE. Costs were derived from published UK sources. The analysis was run over a 35-year time horizon (patient lifetime) from a third party payer perspective. Costs and clinical benefits were discounted at 3.5% per annum. Sensitivity analyses were performed. RESULTS: BIAsp 30/70 was associated with projected improvements in discounted life expectancy (0.19 +/- 0.20 years) and quality-adjusted life expectancy (0.19 +/- 0.14 quality-adjusted life years [QALYs]), as well as a reduced incidence of retinopathy and nephropathy complications, versus glargine. Total lifetime direct costs were 1319 pounds higher with BIAsp 30/70 than with glargine leading to an incremental cost-effectiveness ratio of 6951 pounds per QALY gained. CONCLUSIONS: This study is the first to address the long-term health economic implications of treating type 2 diabetes patients failing oral anti-diabetics with a biphasic insulin mix versus long-acting insulin. Our projections indicate that improved HbA1c levels with BIAsp 30/70 treatment are associated with improvements in life expectancy and quality-adjusted life expectancy, and that BIAsp 30/70 represents excellent value for money compared to insulin glargine in the UK.     

Impact of waist/height ratio on insulin resistance and function of pancreatic β-cells in newly diagnosed Type 2 diabetes mellitus

Objective To study the impact of central obesity on insulin resistance and the function of pancreaticβcells in newly diagnosed Type 2 diabetes. Methods Eighty-six type 2 diabetes mellitus (T2DM) patients were divided into 2 groups according to their waist to hip ratio. Metabolic parameters and Insulin resistance and the function of pancreatic β-cells were compared. Insulin resistance were calculated by HOMA-IR and the function of pancreatic β-cells were detected by HOMA-βand ISF-Arg. Results HOMA-IR index, HOMA-IS and ISF-Arg in WHR ≥0.85 (male) or 0.80 (female) group were significantly higher than that of WHR ＜ 0. 85 (male) or 0. 80 (female) group ( P ＜ 0. 01 ), whereas WHR ＜ 0. 85 (male) or 0. 8 ( female ) group had significantly higher fasting sugar levels and HbA1c and favorable lipid profile (P ＜ 0.05 ). Conclusion WHR is an useful parameter in roughly judging the function of β-cell and insulin resistance.     

Evaluation of pharmacists’ interventions on drug-related problems and drug costs in patients with cancer pain

Background

Drug-related problems (DRPs) prevent patients from fully benefiting from drug treatment. Unrelieved pain in patients with cancer is still widespread. Pharmacists can play a role in closely monitoring cancer patients, pain control maintenance, and patient consultation.

Objective

To evaluate the clinical effects and changes in drug costs of pharmacists’ interventions on patients with DRPs related to cancer pain.

Setting

An academic teaching hospital in Shanghai, China.

Methods

Patients with cancer pain admitted to Shanghai Tongren Hospital from October 2018 to February 2019 were randomized into the intervention and control groups. The Pharmaceutical Care Network Europe classification V8.02 was used to categorize DRPs treated with analgesics. Patients’ pain relief, the occurrence of adverse drug reactions, and drug cost-saving through the resolution of DRPs were evaluated.

Main outcome measure

Problems and causes of drug-related problems, interventions proposed, and outcome of pharmacy recommendations.

Results

A total of 172 patients were enrolled and randomized into the intervention group (n?=?86) and the control group (n?=?86). The pharmacist detected 66 DRPs in 48 patients (55.8%) of the intervention group, an average of 0.8 DRPs per patient. A total of 149 interventions were proposed by the pharmacist. Compared to the control group, the drug intervention produced more pain relief on the third day of analgesic treatment. In the intervention group, a total of 33 DRP interventions resulted in cost changes, saving a drug cost of $489.90, averaging $11.94 per intervention.

Conclusion

Our study suggests that pharmacy service in patients with cancer pain can resolve drug-related problems and reduce drug costs.

     

Dysfunction in the β2-adrenergic signal pathway in patients with insulin dependent diabetes mellitus (IDDM) and unawareness of hypoglycaemia

The majority of the impaired symptoms in hypoglycaemia unawareness, such as palpitations, tachycardia and tremor, are caused by increased release of adrenaline (ADR) and noradrenaline (NA), and induced by stimulation of -adrenergic receptors. Binding of ADR or NA to the -adrenergic receptor generates a signal, transmitted via a guanine nucleotide binding protein complex (G-protein), which in turn activates adenylate cyclase with increased production of cAMP. The aim of this study was to show whether IDDM-patients with hypoglycaemia unawareness had deficient coupling between ₂-adrenergic receptors and G-proteinscompared to IDDM-patients with hypoglycaemia awareness and healthy controls. The IDDM-patients were subgrouped as hypoglycaemia aware or unaware based on questionnaire answers, clinical information and the results of isoprenaline sensitivity tests. Mononuclear leukocytes (MNL) were isolated from venous blood. By saturation binding experiments, using [¹²⁵I]-(-)-iodopindolol ((-)-IPIN), total receptor number (B_max) and affinity (K_d) were determined. By displacement experiments the relative number of low-and high-affinity receptors for the -adrenergic agonist (-)-isoprenaline ((-)-ISO) were determined. We found no difference in B_max- or K_d-values for (-)-IPIN between the subgroups. However, there was a reduced capability to form high-affinity binding complexes with (-)-ISO in MNL from IDDM-patients with hypoglycaemia unawareness. It was concluded that hypoglycaemia unawareness in IDDM was associated with dysfunction of the proximal ₂-adrenergic signal pathway.     

Antidiabetic drugs present and future: will improving insulin resistance benefit cardiovascular risk in type 2 diabetes mellitus?

Results from the United Kingdom Prospective Diabetes Study showed that intensive treatment of type 2 (non-insulin-dependent) diabetes mellitus, with sulphonylureas or insulin, significantly reduced microvascular complications but did not have a significant effect on macrovascular complications after 10 years. Insulin resistance plays a key role in type 2 diabetes mellitus and is linked to a cluster of cardiovascular risk factors. Optimal treatment for type 2 diabetes mellitus should aim to improve insulin resistance and the associated cardiovascular risk factors in addition to achieving glycaemic control. Treatment with sulphonylureas or exogenous insulin improves glycaemic control by increasing insulin supplies rather than reducing insulin resistance. Metformin and the recently introduced thiazolidinediones have beneficial effects on reducing insulin resistance as well as providing glycaemic control. There is evidence that, like metformin, thiazolidinediones also improve cardiovascular risk factors such as dyslipidaemia and fibrinolysis. Whether these differences will translate into clinical benefit remains to be seen. The thiazolidinediones rosiglitazone and pioglitazone have been available in the US since 1999 (with pioglitazone also being available in Japan). Both products are now available to physicians in Europe.     

Relapse outcomes,safety, and treatment patterns in patients diagnosed with relapsing-remitting multiple sclerosis and initiated on subcutaneous interferon β-1a or dimethyl fumarate: a real-world study

Objective: To estimate real-world treatment patterns, safety, and relapse outcomes of subcutaneous (sc) interferon (IFN) β-1a (Rebif) vs dimethyl fumarate (DMF; Tecfidera), to treat relapsing-remitting multiple sclerosis (RRMS).

Methods: A US retrospective chart review of 450 randomly selected adults newly diagnosed with RRMS who received sc IFN β-1a (n?=?143) or DMF (n?=?307) was conducted. Patients were either (a) treatment-naïve, initiating first-line treatment with sc IFN β-1a or DMF, or (b) previously treated, switching to sc IFN β-1a or DMF. Two years’ follow-up data were captured. Patient characteristics, persistence, and adverse events between treatment groups were compared using t-tests or Chi-square tests. Kaplan-Meier curves with log-rank tests and Cox proportional hazards models were used to compare time to, and risk of non-persistence. Annualized Relapse Rates (ARR) were calculated using a robust variance Poisson model adjusting for covariates. Propensity scores were used to address possible selection bias.

Results: One hundred and twelve patients became non-persistent, most commonly due to an adverse event (n?=?37). No difference was observed in time to overall non-persistence between sc IFN β-1a and DMF patients. Among treatment-naïve patients, those receiving DMF had 2.4-times the risk (HR?=?2.439, 95% CI?=?1.007–5.917, p?=?.0483) of experiencing a discontinuation than patients receiving sc IFN β-1a. Non-persistent patients receiving DMF had 2.3-times the risk (HR?=?2.311, 95% CI?=?1.350–3.958, p?=?.0023) of experiencing an adverse event at a given time point than patients prescribed sc IFN β-1a. No differences in relapse risk or ARR between sc IFN β-1a- and DMF-treated patients were observed.

Conclusions: sc IFN β-1a-treated patients had comparable persistence and relapse outcomes, and better safety outcomes vs DMF-treated patients across 2 years.