An exploratory retrospective assessment of a quantitative measure of diabetes risk: medical management and patient impact in a primary care setting.

Background: Primary care providers with limited time and resources bear a heavy responsibility for chronic disease prevention or progression. Reliable clinical tools are needed to risk stratify patients for more targeted care. This exploratory study examined the care of patients who had been risk stratified regarding their likelihood of clinically progressing to type 2 diabetes.

Comparison of accuracy of diabetes risk score and components of the metabolic syndrome in assessing risk of incident type 2 diabetes in Inter99 cohort.

Background: Given the increasing worldwide incidence of diabetes, methods to assess diabetes risk which would identify those at highest risk are needed. We compared two risk-stratification approaches for incident type 2 diabetes mellitus (T2DM); factors of metabolic syndrome (MetS) and a previously developed diabetes risk score, PreDx® Diabetes Risk Score (DRS). DRS assesses 5 yr risk of incident T2DM based on the measurement of 7 biomarkers in fasting blood.

Cost-effectiveness of risk stratification for preventing type 2 diabetes using a multi-marker diabetes risk score.

Background: Personalized medicine requires diagnostic tests that stratify patients into distinct groups that may differentially benefit from targeted treatment approaches. This study compared the costs and benefits of two approaches for identifying those at high risk of developing type 2 diabetes for entry into a diabetes prevention program. The first approach identified high risk patients using impaired fasting glucose (IFG).

Metabolic syndrome components are associated with future medical costs independent of cardiovascular hospitalization and incident diabetes.

Background: Higher medical care costs have been associated with the number of metabolic syndrome components present, but the association with future medical costs has not been described. Furthermore, the independent cost contribution of each component alone and in combination with other components is unknown.

Methods: We identified 57,420 nondiabetic adults aged ≥30 with all metabolic syndrome components measured in 2003-2004 and with 5 years of follow-up data available.

Diabetes incidence for all possible combinations of metabolic syndrome components.

Aims: Because metabolic syndrome (MetS) is defined as any three of five criteria, not all persons with MetS have the same risk factors. Whether the combinations of criteria confer equal diabetes risk is unknown.

Methods: We identified 58,056 non-diabetic adults age >=30 with all MetS components measured in 2003-2004.

Validation of a multimarker model for assessing risk of type 2 diabetes from a five-year prospective study of 6784 Danish people (Inter99).

Background: Improved identification of subjects at high risk for development of type 2 diabetes would allow preventive interventions to be targeted toward individuals most likely to benefit. In previous research, predictive biomarkers were identified and used to develop multivariate models to assess an individual's risk of developing diabetes. Here we describe the training and validation of the PreDx Diabetes Risk Score (DRS) model in a clinical laboratory setting using baseline serum samples from subjects in the Inter99 cohort, a population-based primary prevention study of cardiovascular disease.

Development of a type 2 diabetes risk model from a panel of serum biomarkers from the Inter99 cohort.

Objective: The purpose of this study was to develop a model for assessing the 5-year risk of developing type 2 diabetes from a panel of 64 circulating candidate biomarkers.

Research Design And Methods: Subjects were selected from the Inter99 cohort, a longitudinal population-based study of approximately 6,600 Danes in a nested case-control design with the primary outcome of 5-year conversion to type 2 diabetes. Nondiabetic subjects, aged >or=39 years, with BMI >or=25 kg/m(2) at baseline were selected.

CHIR-124, a novel potent inhibitor of Chk1, potentiates the cytotoxicity of topoisomerase I poisons in vitro and in vivo.

Purpose: Chk1 kinase is a critical regulator of both S and G(2)-M phase cell cycle checkpoints in response to DNA damage. This study aimed to evaluate the biochemical, cellular, and antitumor effects of a novel Chk1 inhibitor, CHIR124.

Experimental Design: CHIR-124 was evaluated for its ability to abrogate cell cycle checkpoints, to potentiate cytotoxicity, and to inhibit Chk1-mediated signaling induced by topoisomerase I poisons in human tumor cell line and xenograft models.

Development of a screening assay for surrogate markers of CHK1 inhibitor-induced cell cycle release.

Chk1 is a key regulator of the S and G2/M checkpoints and is activated following DNA damage by agents such as the topoisomerase I inhibitor camptothecin (CPT). It has been proposed that Chk1 inhibitors used in combination with such a DNA damaging agent to treat tumors would potentiate cytotoxicity and increase the therapeutic index, particularly in tumors lacking functional p53. The aim of this study was to determine whether gene expression analysis could be used to inform lead optimization of a novel series of Chk1 inhibitors.