Eli Lilly and Company

About: Eli Lilly and Company is a company organization based out in Indianapolis, Indiana, United States. It is known for research contribution in the topics: Population & Receptor. The organization has 17826 authors who have published 22835 publications receiving 946714 citations. The organization is also known as: Eli Lily.

The next generation of therapeutics for chronic kidney disease

Abstract: Chronic kidney disease (CKD) represents a leading cause of death in the United States. There is no cure for this disease, with current treatment strategies relying on blood pressure control through blockade of the renin-angiotensin system. Such approaches only delay the development of end-stage kidney disease and can be associated with serious side effects. Recent identification of several novel mechanisms contributing to CKD development - including vascular changes, loss of podocytes and renal epithelial cells, matrix deposition, inflammation and metabolic dysregulation - has revealed new potential therapeutic approaches for CKD. This Review assesses emerging strategies and agents for CKD treatment, highlighting the associated challenges in their clinical development.

Association of an interleukin 1α polymorphism with Alzheimer’s disease

Abstract: Background: Retrospective epidemiologic studies suggest that individuals exposed to anti-inflammatory agents such as nonsteroidal anti-inflammatory drugs have a lower probability of developing AD as well as an older age at onset for the illness. Neuroinflammation may play an important role in the pathogenesis of AD. Interleukin 1 (IL-1), a potent proinflammatory cytokine, is colocalized immunohistochemically to neuritic plaques, a requisite neuropathologic feature for AD. A polymorphism in the 5′-flanking regulatory region at −889 of the IL-1α gene (a C-to-T transition designated as IL-1A[−889] allele 2) may cause an overexpression of IL-1α, a finding shown to be associated with inflammatory diseases. The IL-1A(−889) allele 2 polymorphism may be associated with AD pathogenesis. Methods: A total of 259 patients with AD and 192 nondemented control subjects were included from two different centers (Indianapolis, IN, and Munich, Germany). Genotyping for APOE alleles and IL-1A(−889) allele 2 was performed by PCR-based amplification followed by restrictive endonuclease digestion. Statistical analyses were conducted by center-, gender group-, and age group–stratified Mantel–Haenszel odds ratios, CI, and p values. Results: The allele frequency of IL-1A(−889) allele 2 was 46% in clinically diagnosed patients with probable AD versus 34% in control subjects from the combined centers. Conclusion: The authors found an increased risk for AD with an estimated Mantel–Haenszel odds ratio of 1.68 (95% CI 1.1 to 2.6; p = 0.022) for heterozygous carriers and 7.2 (95% CI 2.0 to 24.5; p = 0.003) for individuals homozygous for IL-1A(−889) allele 2. They found no evidence for an interaction between the IL-1A and the apoE e4 polymorphisms (carriers and homozygotes), age, or gender with regard to conferred risk. The data strongly support an association between the IL-1A(−889) allele 2, especially in homozygotes, and later-onset AD.

Neurodegeneration Across Stages of Cognitive Decline in Parkinson Disease

Abstract: Objective To assess regions and patterns of brain atrophy in patients with Parkinson disease (PD) with normal cognition (PD-NC), mild cognitive impairment (PD-MCI), and dementia-level cognitive deficits (PDD). Design Images were quantified using a region-of-interest approach and voxel-based morphometry analysis. We used a high-dimensional pattern classification approach to delineate brain regions that collectively formed the Spatial Pattern of Abnormalities for Recognition of PDD. Setting The Parkinson's Disease and Movement Disorders Center at the University of Pennsylvania. Subjects Eighty-four PD patients (61 PD-NC, 12 PD-MCI, and 11 PDD) and 23 healthy control subjects (HCs) underwent magnetic resonance imaging of the brain. Results The PD-NC patients did not demonstrate significant brain atrophy compared with HCs. Compared with PD-NC patients, PD-MCI patients had hippocampal atrophy (β = −0.37; P = .001), and PDD patients demonstrated hippocampal (β = −0.32; P = .004) and additional medial temporal lobe atrophy (β = −0.36; P = .003). The PD-MCI patients had a different pattern of atrophy compared with PD-NC patients (P = .04) and a similar pattern to that of PDD patients (P = .81), characterized by hippocampal, prefrontal cortex gray and white matter, occipital lobe gray and white matter, and parietal lobe white matter atrophy. In nondemented PD patients, there was a correlation between memory-encoding performance and hippocampal volume. Conclusions Hippocampal atrophy is a biomarker of initial cognitive decline in PD, including impaired memory encoding and storage, suggesting heterogeneity in the neural substrate of memory impairment. Use of a pattern classification approach may allow identification of diffuse regions of cortical gray and white matter atrophy early in the course of cognitive decline.

Advancing Insulin Therapy in Type 2 Diabetes Previously Treated With Glargine Plus Oral Agents Prandial premixed (insulin lispro protamine suspension/lispro) versus basal/bolus (glargine/lispro) therapy

Abstract: OBJECTIVE: Compare two analog insulin therapies (prandial premixed therapy [PPT] vs. basal bolus therapy [BBT]) in type 2 diabetes patients previously treated with insulin glargine (≥30 units/d) + oral agents, with the aim of demonstrating non-inferiority of PPT to BBT. RESEARCH DESIGN AND METHODS: Patients were randomized to PPT (lispro mix 50/50; 50% insulin lispro protamine suspension [ILPS], 50% lispro; n=187) tid with meals or BBT (glargine at bedtime + mealtime lispro; n=187) in a 24-wk, multicenter, open-label, non-inferiority trial. Investigators could replace lispro mix 50/50 with lispro mix 75/25 at the evening meal if fasting PG target was unachievable. RESULTS: Baseline A1C was similar (PPT 8.8%, BBT 8.9%, P=0.598). At wk 24, A1C was lower with BBT (6.78 vs. 6.95%, P=0.021). A1C was reduced significantly from baseline for both therapies (P CONCLUSIONS: While non-inferiority of PPT to BBT was not demonstrated, findings on A1C reduction, % achieving A1C targets, hypoglycemia, and number of required injections should be considered in the individual decision-making process of advancing insulin replacement to PPT vs. BBT in type 2 diabetes.