运动对抵抗素水平的影响及与胰岛素抵抗改善的相关性

在简要概述抵抗素生物学的基础上,对近年国内外有关运动与抵抗素的研究文献进行了回顾。注意到无论运动对抵抗素水平是否有影响,但可提高胰岛素敏感性,至于运动改善IR是否通过降低抵抗水平这一机制实现尚难以确定,且研究较少。     

邹承鲁：攀登前人没有攀登过的高峰

邹承鲁院士是我国著名的生物化学家,长期从事蛋白质结构与功能研究。他参加发起人工合成胰岛素工作,并负责胰岛素A、B两条肽链的拆合,为结晶牛胰岛素的人工全合成作出了重要贡献。他建立了蛋白质必需基团的化学修饰和活性丧失的定量关系公式,以及确定必需基团数的作图方法;提出了酶活性部位柔性假说,将蛋白质变性研究从以结构研究为主推向结构与功能密切结合的水平。本文通过梳理邹承鲁院士的几个重要科学发现,试图展示其在科研实践中所表现出的勇攀高峰、敢为人先的创新精神。     

Long-term health economic benefits of sensor-augmented pump therapy vs continuous subcutaneous insulin infusion alone in type 1 diabetes: a UK perspective

Aims/hypothesis:

Continuous subcutaneous insulin infusion (CSII) is an important treatment option for type 1 diabetes patients unable to achieve adequate glycemic control with multiple daily injections (MDI). Combining CSII with continuous glucose monitoring (CGM) in sensor-augmented pump therapy (SAP) with a low glucose-suspend (LGS) feature may further improve glycemic control and reduce the frequency of hypoglycemia. A cost-effectiveness analysis of SAP?+?LGS vs CSII plus self-monitoring of blood glucose (SMBG) was performed to determine the health economic benefits of SAP?+?LGS in type 1 diabetes patients using CSII in the UK.

Methods:

Cost-effectiveness analysis was performed using the CORE diabetes model. Treatment effects were sourced from the literature, where SAP?+?LGS was associated with a projected HbA_1c reduction of ?1.49% vs ?0.62% for CSII, and a reduced frequency of severe hypoglycemia. The time horizon was that of patient lifetimes; future costs and clinical outcomes were discounted at 3.5% and 1.5% per annum, respectively.

Results:

Projected outcomes showed that SAP?+?LGS was associated with higher mean quality-adjusted life expectancy (17.9 vs 14.9 quality-adjusted life years [QALYs], SAP?+?LGS vs CSII), and higher life expectancy (23.8 vs 21.9 years), but higher mean lifetime direct costs (GBP 125,559 vs GBP 88,991), leading to an incremental cost-effectiveness ratio (ICER) of GBP 12,233 per QALY gained for SAP?+?LGS vs CSII. Findings of the base-case analysis remained robust in sensitivity analyses.

Conclusions/interpretation:

For UK-based type 1 diabetes patients with poor glycemic control, the use of SAP?+?LGS is likely to be cost-effective compared with CSII plus SMBG.     

Cost-effectiveness of continuous subcutaneous insulin infusion in people with type 2 diabetes in the Netherlands

Aims: Up to 30% of insulin-treated type 2 diabetes patients are unable to achieve HbA1c targets despite optimization of insulin multiple daily injections (MDI). For these patients the use of continuous subcutaneous insulin infusion (CSII) represents a useful but under-utilized alternative. The aim of the present analysis was to examine the cost-effectiveness of initiating CSII in type 2 diabetes patients failing to achieve good glycemic control on MDI in the Netherlands. Methods: Long-term projections were made using the IMS CORE Diabetes Model. Clinical input data were sourced from the OpT2mise trial. The analysis was performed over a lifetime time horizon. The discount rates applied to future costs and clinical outcomes were 4% and 1.5% per annum, respectively. Results: CSII was associated with improved quality-adjusted life expectancy compared with MDI (9.38 quality-adjusted life years [QALYs] vs 8.95 QALYs, respectively). The breakdown of costs indicated that ～50% of costs were attributable to diabetes-related complications. Higher acquisition costs of CSII vs MDI were partially offset by the reduction in complications. The ICER was estimated at EUR 62,895 per QALY gained and EUR 60,474 per QALY gained when indirect costs were included. Conclusions: In the Netherlands, CSII represents a cost-effective option in patients with type 2 diabetes who continue to have poorly-controlled HbA1c despite optimization of MDI. Since the ICER falls below the willingness-to-pay threshold of EUR 80,000 per QALY gained, CSII is likely to represent good-value for money in the treatment of poorly-controlled T2D patients compared with MDI.     

Evaluating drug cost per responder and number needed to treat associated with lixisenatide on top of glargine when compared to rapid-acting insulin intensification regimens on top of glargine,in patients with type 2 diabetes in the UK,Italy, and Spain

Objectives: This study investigated the cost per responder and number needed to treat (NNT) in type 2 diabetes mellitus (T2DM) patients for lixisenatide compared to insulin intensification regimens using composite endpoints in the UK, Italy, and Spain.

Methods: Efficacy and safety outcomes were obtained from GetGoal Duo-2, a 26-week phase 3 trial comparing lixisenatide vs insulin glulisine (IG) once daily (QD) and three times daily (TID). Response at week 26 was extrapolated to 52 weeks, assuming a maintained treatment effect, based on long-term evidence in other T2DM populations. Responders were defined using composite end-points, based on an HbA1c threshold and/or no weight gain and/or no hypoglycemia. The HbA1c threshold was varied in sensitivity analyses. Annual treatment costs were estimated in euros (1 GBP?=?1.26 EUR), including drug acquisition and resource use costs. Cost per responder was computed by dividing annual treatment costs per patient by the proportion of responders.

Results: Lixisenatide was associated with the lowest cost per responder for all composite end-points that included a weight-related component. For the main composite end-point of HbA1c ≤7.5% AND no weight gain AND no symptomatic hypoglycemia, cost per responder results were: UK: 6,867€, 8,746€, and 12,410€; Italy: 7,057€, 9,160€, and 12,844€; Spain: 8,370€, 11,365€, and 17,038€, for lixisenatide, IG QD, and TID, respectively. The NNT analysis showed that, for every 6.85 and 5.86 patients treated with lixisenatide, there was approximately one additional responder compared to IG QD and TID, respectively.

Limitations: A limitation of the clinical inputs is the lack of 52-week trial data from GetGoal Duo-2, which led to the assumption of a maintained treatment effect from week 26 to 52.

Conclusions: This analysis suggests lixisenatide is an efficient economic resource allocation in the UK, Italy, and Spain.     

Evaluation of a patient self-directed mealtime insulin titration algorithm: a US payer perspective

Objective To model the potential economic impact of implementing the AUTONOMY once daily (Q1D) patient self-titration mealtime insulin dosing algorithm vs standard of care (SOC) among a population of patients with Type 2 diabetes living in the US.

Methods Three validated models were used in this analysis: The Treatment Transitions Model (TTM) was used to generate the primary results, while both the Archimedes (AM) and IMS Core Diabetes Models (IMS) were used to test the veracity of the primary results produced by TTM. Models used data from a ‘real world’ representative sample of patients (2012 US National Health and Nutrition Examination Survey) that matched the characteristics of US patients enrolled in the randomized controlled trial ‘AUTONOMY’ cohort. The base-case time horizon was 10 years.

Results The modeling results from TTM demonstrated that total costs in the base-case were reduced by $1732, with savings predicted to occur as early as year 1. Results from the three models were consistent, showing a reduction in total costs for all sensitivity analyses.

Limitations Data from short-term clinical trials were used to develop long-term projections. The nature of such extrapolation leads to increased uncertainty.

Conclusion The results from all three models indicate that the AUTONOMY Q1D algorithm has the potential to abate total costs as early as the first year.     

糖脂消对胰岛素抵抗高血压大鼠基因表达谱的影响

目的:利用基因芯片技术探讨糖脂消对胰岛素抵抗高血压大鼠基因表达谱的变化,研究糖脂消治疗胰岛素抵抗高血压的作用机制。方法:用高果糖饲料诱发SD大鼠胰岛素抵抗模型,给予糖脂消口服后,用基因芯片分别检测高果糖组、治疗组,计算机软件分析后,观察基因表达的变化。结果:治疗组表达差异的基因有95条,新基因有23条,已知基因34条。结论:糖脂消可以改变其基因表达谱,为进一步探讨糖脂消治疗作用创造了条件。     

Healthcare utilization changes in relation to treatment intensification with insulin aspart in patients with type 2 diabetes. Data from a large US managed-care organization

ABSTRACT

Objective: Most patients with type 2 diabetes eventually require exogenous insulin therapy to achieve good glycemic control due to the progressive nature of the disease. Insulin aspart is a rapid-acting insulin analog developed for prandial use. This study aimed to illustrate the implications on healthcare costs of adding insulin aspart to basal therapy in a real-world setting.

Methods: Patients with type 2 diabetes who intensified previous basal therapy with insulin aspart were identified from a large commercial US healthcare data source between April 2007 and September 2008. Patients were required to have received basal insulin treatment with or without concomitant oral antidiabetic (OAD) therapy for at least 90 days pre- and post-initiation of insulin aspart. Wilcoxon signed-rank test and McNemar's test were used for continuous and categorical variables, respectively, to analyze the difference of self-comparison between pre- and post insulin aspart add-on.

Results: In total, 1,739 patients with an average age of 56 years were identified, of whom 55% were male. After initiation of insulin aspart, a significant improvement in glycemic control was observed (change in HbA_1c: –0.5%, p=0.0013). Similarly, a reduction of 0.4% in HbA_1c was observed for the subpopulation of 151 patients, who had both pre-and post-index HbA_1c data (p=0.0085). Also, significantly fewer patients used OADs after insulin aspart initiation (56 vs. 64%, p< 0.0001). Overall and diabetes-related healthcare costs also significantly decreased by $2,283 and $2,028, respectively (p≤0.0001). Diabetes-related inpatient visits appear to be the main contributor to total cost (46%); however, after initiation of insulin aspart the number of inpatient visits decreased by 0.50 visits/patient/year (p< 0.05). This decrease was reflected in a large reduction in cost related to inpatient visits ($3,019/patient).

Limitations: A regression to the mean effect may be associated with this pre-post comparison. The ability to make conclusions regarding cause and effect may be limited due to the retrospective design of this study.

Conclusions: Patients with type 2 diabetes achieved better glycemic control and needed less OAD treatment after adding insulin aspart to previous basal therapy. Furthermore, patients experienced on average reduced healthcare utilization after initiation of insulin aspart, which resulted in significant cost savings.     

Resource utilisation and costs in patients with type 2 diabetes mellitus treated with insulin glargine or conventional basal insulin under real-world conditions in Germany: LIVE-SPP study

Objective: To assess and compare the total costs relevant to diabetes care in patients with type 2 diabetes mellitus (T2D) treated at specialised diabetes practices with either insulin glargine- or conventional basal insulin (neutral protamine Hagedorn [NPH])-based therapies from the German statutory health insurance (SHI) perspective.

Methods: The Long Acting Insulin Glargine Versus NPH Cost Evaluation in Specialised Practices (LIVE-SPP) study is an observational, retrolective, multicentre longitudinal cost comparison in adults with T2D. Costs were evaluated from the German SHI perspective based on official 2005 prices. Average total costs per patient for insulin glargine-versus NPH-based therapies were compared using multivariate general linear modelling. Sensitivity analyses were performed by varying the main cost factors by ± 25%.

Results: Patients (n=1,024, 512 patients per cohort) were on average 62 years of age, with an average 8-year diabetes history at study start. The average unadjusted total annual costs per patient were €1,868.41 (95% CI 1,744.27–1,992.56) for insulin glargine-based vs. €2,063.72 (95% CI 1,922.91–2,204.54) for NPH-based therapies. Average adjusted total annual costs per patient between insulin glargine- (€1,241.13) and NPH-based therapies (€1,607.86) were statistically significantly different (p=0.0004). The economic advantage for insulin glargine-based therapies resulted mainly from fewer blood glucose measurements and other diabetes-related materials (e.g. needles). The savings remained stable in one-way sensitivity analyses.

Conclusions: The LIVE-SPP study suggests that insulin glargine-based therapies may offer an economic advantage over NPH-based therapies.