Vascular effects of rapid-acting insulin analogs in the diabetic patient: a review

The insulin analogs lispro, aspart, and glulisine are the only commercially available rapid-acting insulins to treat diabetes. We review the evidence for treating hyperglycemia, using insulin, and specifically using rapid-acting analogs in diabetic individuals, on the prevention of vascular events. We review the beneficial effects of insulin on the vascular system, which include vasodilation and anti-inflammatory actions. The effects of treating hyperglycemia and intensive blood glucose control on vascular outcomes are reviewed

The Wandering Jew

Sheet music contains anti-Black, racist language, stereotypes, and/or imagry. Contains advertisements and/or short musical examples of pieces being sold by publisher.https://digitalcommons.library.umaine.edu/mmb-vp/6860/thumbnail.jp

Examining correlates of treatment satisfaction for injectable insulin in type 2 diabetes: lessons learned from a clinical trial comparing biphasic and basal analogues

BACKGROUND: Successfully managing diabetes is a complex process that includes addressing issues of drug efficacy, safety and treatment satisfaction. Additionally, the combined impact of patient/disease characteristics and treatment outcomes on treatment satisfaction is not well understood. The purpose of this study was to examine the impact of age, weight, gender, co-morbid conditions, diabetes history, treatment burden, efficacy (HbA(1c)) and side effects (weight gain, hypoglycemic events) on patients' appraisal of treatment satisfaction using linear regression models. METHODS: Data from a multi-center, randomized clinical trial comparing the efficacy/safety of biphasic insulin aspart 70/30 (BIAsp 70/30) vs. glargine (Glar) among insulin naïve type 2 patients were analyzed. Subjects were between ages 18–75, with baseline HbA(1c )> 8% and BMI ≤ 40 kg/m(2 )(N = 233). Treatment satisfaction was assessed by the Insulin Treatment Satisfaction Questionnaire (ITSQ). RESULTS: When factors were examined independently, multiple significant relationships (age, co-morbidity, hypoglycemic events, and weight gain) with overall and/or domains of treatment satisfaction were found. However, when all significant relationships were examined together, only neuropathy, treatment efficacy, and number of hypoglycemic events maintained their previous significance. CONCLUSION: By examining predictors independently, significant relationships were identified. However, not all findings remained significant when examined in combination with each other. Thus, to more accurately characterize the impact of factors on treatment satisfaction, a more comprehensive approach may be necessary. By improving patient treatment satisfaction, the efficacy of treatments, as well as critical treatment outcomes such as compliance and cost of care should be improved

Impact of Bromocriptine-QR Therapy on Glycemic Control and Daily Insulin Requirement in Type 2 Diabetes Mellitus Subjects Whose Dysglycemia Is Poorly Controlled on High-Dose Insulin: A Pilot Study

Background:. The concurrent use of a postprandial insulin sensitizing agent, such as bromocriptine-QR, a quick release formulation of bromocriptine, a dopamine D2 receptor agonist, may offer a strategy to improve glycemic control and limit/reduce insulin requirement in type 2 diabetes (T2DM) patients on high-dose insulin. This open label pilot study evaluated this potential utility of bromocriptine-QR. Methods:. Ten T2DM subjects on metformin (1-2 gm/day) and high-dose (TDID ≥ 65 U/day) basal-bolus insulin were enrolled to receive once daily (morning) bromocriptine-QR (1.6–4.8 mg/day) for 24 weeks. Subjects with at least one postbaseline HbA1c measurement (N = 8) were analyzed for change from baseline HbA1c, TDID, and postprandial glucose area under the curve of a four-hour mixed meal tolerance test (MMTT). Results:. Compared to the baseline, average HbA1c decreased 1.76% (9.74 ± 0.56 to 7.98 ± 0.36, P = 0.01), average TDID decreased 27% (199 ± 33 to 147 ± 31, P = 0.009), and MMTT AUC60–240 decreased 32% (P = 0.04) over the treatment period. The decline in HbA1c and TDID was observed at 8 weeks and sustained over the remaining 16-week study duration. Conclusion:. In this study, bromocriptine-QR therapy improved glycemic control and meal tolerance while reducing insulin requirement in T2DM subjects poorly controlled on high-dose insulin therapy

A 16-week comparison of the novel insulin analog insulin glargine (HOE 901) and NPH human insulin used with insulin lispro in patients with type 1 diabetes

WSTĘP. Ocena bezpieczeństwa i skuteczności glarginy, długodziałającego analogu insuliny ludzkiej, jako składnika insulinoterapii opartej na wielokrotnych wstrzyknięciach u chorych na cukrzycę typu 1. MATERIAŁ I METODY. Chorych na cukrzycę typu 1 leczonych wielokrotnymi wstrzyknięciami insuliny (ludzka insulina NPH oraz bolusy insuliny lispro) randomizowano do grupy leczonej glarginą (HOE 901), długodziałającym analogiem insuliny, podawaną raz dziennie (n = 310) albo do grupy leczonej insuliną NPH (n = 309) jako insuliną podstawową i kontynuowano podawanie bolusów insuliny lispro. Badanie trwało 16 tygodni i było badaniem otwartym. Chorzy otrzymywali insulinę NPH według dotychczasowego schematu, to znaczy 1 lub 2 razy dziennie, natomiast chorzy randomizowani do grupy leczonej glarginą otrzymywali ją raz dziennie wieczorem. WYNIKI. U chorych otrzymujących glarginę glikemia na czczo według pomiarów domowych była znamiennie niższa niż u wszystkich osób leczonych insuliną NPH (średnio: &#8211;42,0 &plusmn; 4,7 i &#8211;12,4 &plusmn; 4,7 mg/dl [&#8211;2,33 &plusmn; 0,26 i &#8211;0,69 &plusmn; 0,26 mmol/l]; p = 0,0001). Te różnice pojawiały się dość wcześnie i utrzymywały się do końca badania. Założoną glikemię 119 mg/dl (< 6,6 mmol/l) uzyskało więcej chorych leczonych glarginą (29,6%) niż insuliną NPH (16,8%). Nie stwierdzono jednak różnic dotyczących stężenia hemoglobiny glikowanej. Leczenie glarginą wiązało się również z wyraźnie mniejszymi wahaniami glikemii na czczo (p = 0,0124). Nie obserwowano różnic w częstości objawowej hipoglikemii, także nocnej. Również objawy niepożądane były podobne w obu grupach, z wyjątkiem większej bolesności w miejscu wstrzyknięcia w grupie chorych otrzymujących glarginę (6,1 vs 0,3% dla osób otrzymujących insulinę NPH). Masa ciała zwiększyła się o 0,12 kg u pacjentów leczonych glarginą i o 0,54 kg u pacjentów leczonych insuliną NPH (p = 0,034). WNIOSKI. Stosowanie glarginy raz dziennie jako insuliny podstawowej wydaje się leczeniem bezpiecznym i co najmniej tak samo efektywnym jak leczenie insuliną NPH stosowaną 1 lub 2 razy dziennie u chorych na cukrzycę typu 1 leczonych bolusami insuliny lispro.OBJECTIVE. To determine the safety and efficacy of the long-acting insulin analog, insulin glargine, as a component of basal bolus therapy in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS. Patients with type 1 diabetes receiving basal-bolus insulin treatment with NPH human insulin and insulin lispro were randomized to receive insulin glargine (HOE 901), a long-acting basal insulin analog, once a day (n = 310) or NPH human insulin (n = 309) as basal treatment with continued bolus insulin lispro for 16 weeks in an open-label study. NPH insulin patients maintained their prior schedule of administration once or twice a day, whereas insulin glargine patients received basal insulin once a day at bedtime. RESULTS. Compared with all NPH insulin patients, insulin glargine patients had significant decreases in fasting blood glucose measured at home (means &#177; SEM, 42.0&#177; &#177; 4.7 vs. 12.4 &#177; 4.7 mg/dl [&#150;2.33 &#177; 0.26 vs. 0.69 &#177; 0.26 mmol/l]; P = 0.0001). These differences were evident early and persisted throughout the study. More patients in the insulin glargine group (29.6%) than in the NPH group (16.8%) reached a target fasting blood glucose of 119 mg/dl (6.6 mmol/l). However, there were no differences between the groups with respect to change in GHb. Insulin glargine treatment was also associated with a significant decrease in the variability of fasting blood glucose values (P = 0.0124). No differences in the occurrence of symptomatic hypoglycemia, including nocturnal hypoglycemia, were observed. Overall, adverse events were similar in the two treatment groups with the exception of injection site pain, which was more common in the insulin glargine group (6.1%) than in the NPH group (0.3%). Weight gain was 0.12 kg in insulin glargine patients and 0.54 kg in NPH insulin patients (P = 0.034). CONCLUSIONS. Basal insulin therapy with insulin glargine once a day appears to be as safe and at least as effective as using NPH insulin once or twice a day in maintaining glycemic control in patients with type 1 diabetes receiving basal-bolus insulin treatment with insulin lispro

Drug development in Alzheimer’s disease: The path to 2025

The global impact of Alzheimer’s disease (AD) continues to increase, and focused efforts are needed to address this immense public health challenge. National leaders have set a goal to prevent or effectively treat AD by 2025. In this paper, we discuss the path to 2025, and what is feasible in this time frame given the realities and challenges of AD drug development, with a focus on disease-modifying therapies (DMTs). Under the current conditions, only drugs currently in late Phase 1 or later will have a chance of being approved by 2025. If pipeline attrition rates remain high, only a few compounds at best will meet this time frame. There is an opportunity to reduce the time and risk of AD drug development through an improvement in trial design; better trial infrastructure; disease registries of well-characterized participant cohorts to help with more rapid enrollment of appropriate study populations; validated biomarkers to better detect disease, determine risk and monitor disease progression as well as predict disease response; more sensitive clinical assessment tools; and faster regulatory review. To implement change requires efforts to build awareness, educate and foster engagement; increase funding for both basic and clinical research; reduce fragmented environments and systems; increase learning from successes and failures; promote data standardization and increase wider data sharing; understand AD at the basic biology level; and rapidly translate new knowledge into clinical development. Improved mechanistic understanding of disease onset and progression is central to more efficient AD drug development and will lead to improved therapeutic approaches and targets. The opportunity for more than a few new therapies by 2025 is small. Accelerating research and clinical development efforts and bringing DMTs to market sooner would have a significant impact on the future societal burden of AD. As these steps are put in place and plans come to fruition, e.g., approval of a DMT, it can be predicted that momentum will build, the process will be self-sustaining, and the path to 2025, and beyond, becomes clearer

Comparison of a Novel Insulin Bolus-Patch with Pen/Syringe Injection to Deliver Mealtime Insulin for Efficacy, Preference, and Quality of Life in Adults with Diabetes: A Randomized, Crossover, Multicenter Study

Objective: This study compared the efficacy, safety, device satisfaction, and quality of life (QOL) in people with diabetes using an insulin bolus-patch versus current devices (pen/syringe) to deliver mealtime insulin. Research Design and Methods: Thirty-eight subjects with diabetes (26 with type 1 and 12 with type 2) were randomized to bolus-patch or current injection device (55% pen and 45% syringe) to deliver mealtime insulin in a multicenter, 6-week crossover study. Efficacy was assessed by equivalence in mean daily seven-point blood glucose (MDBG). Safety assessments included severe hypoglycemia episodes, adverse device effects (ADEs), and adverse events (AEs). Device satisfaction was determined by the validated Insulin Delivery System Rating Questionnaire (IDSRQ) and QOL by the validated Diabetes Specific QOL Scale (DSQOLS). Results: Using bolus-patch, MDBG (mean•SE) was equivalent to that using pen/syringe (8.61+/-0.28 vs. 9.02+/-0.26-mmol/L; P=0.098). SD of the seven-point blood glucose measurements was lower using bolus-patch (3.18+/-0.18 vs. 3.63+/-0.17 mmol/L; P=0.004), as was the coefficient of variation (CV) (37.2+/-1.7 vs. 40.3+/-1.7%; P=0.046). Hemoglobin A1c, 1,5-anhydroglucitol, fructosamine, and insulin use were similar between groups. There were no severe hypoglycemia episodes or serious ADEs. Between-device AEs were comparable. Subjects scored better on six of seven subscales on the DSQOLS and five of six subscales on the IDSRQ while using bolus-patch versus pen/syringe. At study completion, 76% of subjects would choose to switch to bolus-patch (P=0.001). Conclusions: Delivery of mealtime insulin with bolus-patch compared with pen/syringe resulted in equivalent MDBG, lower SD and CV of seven-point blood glucose measurements, good safety, significant device satisfaction, and improved QOL.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90477/1/dia-2E2011-2E0047.pd

Haptoglobin Genotype and the Rate of Renal Function Decline in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study

Many patients with type 1 diabetes develop renal disease despite moderately good metabolic control, suggesting other risk factors may play a role. Recent evidence suggests that the haptoglobin (HP) 2-2 genotype, which codes for a protein with reduced antioxidant activity, may predict renal function decline in type 1 diabetes. We examined this hypothesis in 1,303 Caucasian participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. HP genotype was determined by polyacrylamide gel electrophoresis. Glomerular filtration rate was estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and albumin excretion based on timed urine samples. Participants were followed up for a mean of 22 years. HP genotype was significantly associated with the development of sustained estimated glomerular filtration rate (GFR) \u3c60 mL/min/1.73 m2and with end-stage renal disease (ESRD), with HP 2-2 having greater risk than HP 2-1 and 1-1. No association was seen with albuminuria. Although there was no treatment group interaction, the associations were only significant in the conventional treatment group, where events rates were much higher. We conclude that the HP genotype is significantly associated with the development of reduced GFR and ESRD in the DCCT/EDIC study

Looking ahead: forecasting and planning for the longer-range future, April 1, 2, and 3, 2005

This repository item contains a single issue of the Pardee Conference Series, a publication series that began publishing in 2006 by the Boston University Frederick S. Pardee Center for the Study of the Longer-Range Future. This was the Center's spring Conference that took place during April 1, 2, and 3, 2005.The conference allowed for many highly esteemed scholars and professionals from a broad range of fields to come together to discuss strategies designed for the 21st century and beyond. The speakers and discussants covered a broad range of subjects including: long-term policy analysis, forecasting for business and investment, the National Intelligence Council Global Trends 2020 report, Europe’s transition from the Marshal plan to the EU, forecasting global transitions, foreign policy planning, and forecasting for defense

Financing Direct Democracy: Revisiting the Research on Campaign Spending and Citizen Initiatives

The conventional view in the direct democracy literature is that spending against a measure is more effective than spending in favor of a measure, but the empirical results underlying this conclusion have been questioned by recent research. We argue that the conventional finding is driven by the endogenous nature of campaign spending: initiative proponents spend more when their ballot measure is likely to fail. We address this endogeneity by using an instrumental variables approach to analyze a comprehensive dataset of ballot propositions in California from 1976 to 2004. We find that both support and opposition spending on citizen initiatives have strong, statistically significant, and countervailing effects. We confirm this finding by looking at time series data from early polling on a subset of these measures. Both analyses show that spending in favor of citizen initiatives substantially increases their chances of passage, just as opposition spending decreases this likelihood