Metabolomic profiling of the Dietary Approaches to Stop Hypertension diet provides novel insights for the nutritional epidemiology of type 2 diabetes mellitus.

Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet is inversely associated with type 2 diabetes mellitus (T2DM) risk. Metabolic changes due to DASH adherence and their potential relationship with incident T2DM have not been described. The objective is to determine metabolite clusters associated with adherence to a DASH-like diet in the Insulin Resistance Atherosclerosis Study cohort and explore if the clusters predicted 5-year incidence of T2DM.

NT-proBNP by Itself Predicts Death and Cardiovascular Events in High-Risk Patients With Type 2 Diabetes Mellitus.

Background NT-proBNP (N-terminal pro-B-type natriuretic peptide) improves the discriminatory ability of risk-prediction models in type 2 diabetes mellitus (T2DM) but is not yet used in clinical practice. We assessed the discriminatory strength of NT-proBNP by itself for death and cardiovascular events in high-risk patients with T2DM. Methods and Results Cox proportional hazards were used to create a base model formed by 20 variables.

Three-question set from Michigan Neuropathy Screening Instrument adds independent prognostic information on cardiovascular outcomes: analysis of ALTITUDE trial.

Aims/hypothesis: The self-administered Michigan Neuropathy Screening Instrument (MNSI) is used to diagnose diabetic peripheral neuropathy. We examined whether the MNSI might also provide information on risk of death and cardiovascular outcomes.

Methods: In this post hoc analysis of the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE) trial, we divided 8463 participants with type 2 diabetes and chronic kidney disease (CKD) and/or cardiovascular disease (CVD) into independent training (n = 3252) and validation (n = 5211) sets.

Individual serum saturated fatty acids and markers of chronic subclinical inflammation: the Insulin Resistance Atherosclerosis Study.

Recent evidence has documented distinct effects of individual saturated FAs (SFAs) on cardiometabolic outcomes, with potential protective effects from odd- and very long-chain SFAs (VLSFAs). Cross-sectional and prospective associations of individual serum SFAs (12:0, 14:0, 15:0, 16:0, 18:0, 20:0, 22:0, and total SFA) with proinflammatory biomarkers and adiponectin were investigated in 555 adults from the IRAS. Principal component analysis (PCA) of proinflammatory markers yielded three clusters: principal component (PC) 1: fibrinogen, white cell count, C-reactive protein; PC 2: plasminogen activator inhibitor-1 (PAI-1), TNF-α, IL-18; PC 3: IL-6 and IL-8.

Association of Directly Measured Plasma Free 25(OH)D With Insulin Sensitivity and Secretion: The IRAS Family Study.

Objectives: We aimed to compare the associations of directly measured plasma free 25-hydroxyvitamin D [25(OH)D] and total 25(OH)D concentrations with insulin sensitivity (SI) and β-cell function in nondiabetic Hispanics and African Americans. We hypothesized that directly measured free 25(OH)D would be more strongly associated with these measures of glucose homeostasis and that associations would differ by race.

Design: We studied 1189 nondiabetic participants in the Insulin Resistance Atherosclerosis Study Family Study using data from baseline examinations from 2000 to 2002.

Noncardiovascular deaths are more common than cardiovascular deaths in patients with cardiovascular disease or cardiovascular risk factors and impaired glucose tolerance: Insights from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial.

Background: Patients with impaired glucose tolerance have an elevated risk of cardiovascular (CV) death; however, the causes and risk factors associated with non-CV deaths are poorly understood.

Methods: The NAVIGATOR trial enrolled 9,306 participants with impaired glucose tolerance and CV disease or at high CV risk, with a median follow-up of 6.4years.

Updated risk factors should be used to predict development of diabetes.

Aims: Predicting incident diabetes could inform treatment strategies for diabetes prevention, but the incremental benefit of recalculating risk using updated risk factors is unknown. We used baseline and 1-year data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) Trial to compare diabetes risk prediction using historical or updated clinical information.

Methods: Among non-diabetic participants reaching 1year of follow-up in NAVIGATOR, we compared the performance of the published baseline diabetes risk model with a "landmark" model incorporating risk factors updated at the 1-year time point.

Effect of valsartan on kidney outcomes in people with impaired glucose tolerance.

Aims: To examine the effect of valsartan on kidney outcomes in patients with impaired glucose tolerance (IGT).

Methods: In a double-blind randomized trial, 9306 patients with IGT were assigned to valsartan (160 mg daily) or placebo. The co-primary endpoints were the development of diabetes and two composite cardiovascular outcomes.

Novel Protein Glycan-Derived Markers of Systemic Inflammation and C-Reactive Protein in Relation to Glycemia, Insulin Resistance, and Insulin Secretion.

Objective: N-acetylglucosamine/galactosamine (GlycA) and sialic acid (GlycB) moieties of glycosylated serum proteins are nonspecific measures of inflammation, but conclusive data on their relationship with insulin resistance or insulin secretion are missing. Therefore, we aimed to examine the relation of GlycA, GlycB, and C-reactive protein (CRP) to direct measures of insulin sensitivity (insulin sensitivity index [S]) and insulin secretion (acute insulin response [AIR]).

Research Design And Methods: This study used cross-sectional analyses and included 1,225 participants with and without type 2 diabetes in the Insulin Resistance Atherosclerosis Study (IRAS).

Branched-Chain Amino Acids and Insulin Metabolism: The Insulin Resistance Atherosclerosis Study (IRAS).

Objective: Recent studies using untargeted metabolomics approaches have suggested that plasma branched-chain amino acids (BCAAs) are associated with incident diabetes. However, little is known about the role of plasma BCAAs in metabolic abnormalities underlying diabetes and whether these relationships are consistent across ethnic populations at high risk for diabetes. We investigated the associations of BCAAs with insulin sensitivity (SI), acute insulin response (AIR), and metabolic clearance of insulin (MCRI) in a multiethnic cohort.

Lipoprotein heterogeneity may help to detect individuals with insulin resistance.

Aims/hypothesis: The triacylglycerol (TG)-to-HDL-cholesterol ratio has been shown to detect insulin resistance. However, the added predictive value of a more comprehensive assessment of lipoprotein composition is unknown.

Methods: We analysed cross-sectional data from 882 non-diabetic participants in the Insulin Resistance Atherosclerosis Study (IRAS).

Prospective relationships between body weight and physical activity: an observational analysis from the NAVIGATOR study.

Objectives: While bidirectional relationships exist between body weight and physical activity, direction of causality remains uncertain and previous studies have been limited by self-reported activity or weight and small sample size. We investigated the prospective relationships between weight and physical activity.

Design: Observational analysis of data from the Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) study, a double-blinded randomised clinical trial of nateglinide and valsartan, respectively.

Mortality following a cardiovascular or renal event in patients with type 2 diabetes in the ALTITUDE trial.

Aims: Patients with type 2 diabetes mellitus (T2DM) are at high risk of developing cardiovascular (CV) and renal disease. We examined the burden of, and risk of death following, CV and renal events in the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE), a randomized trial of alikiren vs. placebo.

Improving Adiponectin Levels in Individuals With Diabetes and Obesity: Insights From Look AHEAD.

Objective: This study investigated whether fitness changes resulting from lifestyle interventions for weight loss may independently contribute to the improvement of low adiponectin levels in obese individuals with diabetes.

Research Design And Methods: Look AHEAD (Action for Health in Diabetes) randomized overweight/obese individuals with type 2 diabetes to intensive lifestyle intervention (ILI) for weight loss or to diabetes support and education (DSE). Total and high-molecular weight adiponectin (adiponectins), weight, and cardiorespiratory fitness (submaximal exercise stress test) were measured in 1,397 participants at baseline and at 1 year, when ILI was most intense.

Lack of significant association between serum inflammatory cytokine profiles and the presence of colorectal adenoma.

Background: Inflammatory cytokines in the colonic microenvironment have been shown to increase with advance colorectal cancer disease state. However, the contribution of inflammatory cytokines to pre-malignant disease, such as the formation of adenomas, is unclear.

Methods: Using the Milliplex® MAP Human Cytokine/ Chemokine Magnetic Bead Panel Immunoassay, serum cytokine and chemokine profiles were assayed among participants without an adenoma (n = 97) and those with an adenoma (n = 97) enrolled in the NCI-funded Insulin Resistance Atherosclerosis Colon Study.

Glycated hemoglobin levels are mostly dependent on nonglycemic parameters in 9398 Finnish men without diabetes.

Context: Determinants of the variance in glycated hemoglobin (HbA1c) among individuals without type 2 diabetes remain largely unknown.

Objective: We investigated the determinants of HbA1c, fasting plasma glucose, and 2-hour glucose in an oral glucose tolerance test and the associations of these glycemic markers with insulin sensitivity and insulin secretion in Finnish men without type 2 diabetes.

Design And Setting: The design and setting were the cross-sectional population-based Metabolic Syndrome in Men study including 10 197 Finnish men, aged 45-70 years, and randomly selected from the population register of Kuopio, Eastern Finland.

Usefulness of measuring both body mass index and waist circumference for the estimation of visceral adiposity and related cardiometabolic risk profile (from the INSPIRE ME IAA study).

Despite its well-documented relation with visceral adiposity (VAT) and cardiometabolic risk (CMR), whether waist circumference (WC) should be measured in addition to body mass index (BMI) remains debated. This study tested the relevance of adding WC to BMI for the estimation of VAT and CMR. In the International Study of Prediction of Intra-abdominal Adiposity and Its Relationship with Cardiometabolic Risk/Intra-abdominal Adiposity, 297 physicians recruited 4,504 patients (29 countries).

Serum pentadecanoic acid (15:0), a short-term marker of dairy food intake, is inversely associated with incident type 2 diabetes and its underlying disorders.

Background: Growing evidence suggests that dairy consumption is associated with lower type 2 diabetes risk. However, observational studies have reported inconsistent results, and few have examined dairy's association with the underlying disorders of insulin resistance and β-cell dysfunction.

Objective: We investigated the association of the dairy fatty acid biomarkers pentadecanoic acid (15:0) and trans-palmitoleic acid (trans 16:1n-7) with type 2 diabetes traits by evaluating 1) prospective associations with incident diabetes after 5 y of follow-up and 2) cross-sectional associations with directly measured insulin resistance and β-cell dysfunction.

Fasting and OGTT-derived measures of insulin resistance as compared with the euglycemic-hyperinsulinemic clamp in nondiabetic Finnish offspring of type 2 diabetic individuals.

Context: It remains to be established which surrogate marker is the most predictive of insulin resistance.

Objective: We evaluated the incremental value of the Matsuda insulin sensitivity index (ISI) to homeostasis model assessment of insulin resistance (HOMA-IR) for detecting insulin resistance.

Design And Setting: This was a cross-sectional analysis of the EUGENE2 Kuopio cohort.

Fiber intake and plasminogen activator inhibitor-1 in type 2 diabetes: Look AHEAD (Action for Health in Diabetes) trial findings at baseline and year 1.

Plasminogen activator inhibitor 1 (PAI-1) is elevated in obese individuals with type 2 diabetes and may contribute, independently of traditional factors, to increased cardiovascular disease risk. Fiber intake may decrease PAI-1 levels. We examined the associations of fiber intake and its changes with PAI-1 before and during an intensive lifestyle intervention (ILI) for weight loss in 1,701 Look AHEAD (Action for Health in Diabetes) participants with dietary, fitness, and PAI-1 data at baseline and 1 year.

Calcium and phosphate concentrations and future development of type 2 diabetes: the Insulin Resistance Atherosclerosis Study.

Aims/hypothesis: Low phosphate and high calcium concentrations have been linked to altered glucose tolerance and reduced insulin sensitivity in non-diabetic individuals. The aim of this study was to examine the relationships of calcium and phosphate levels and the calcium-phosphate product with the development of type 2 diabetes.

Methods: Participants were 863 African-Americans, Hispanics and non-Hispanic whites in the Insulin Resistance Atherosclerosis Study who were free of diabetes at baseline.

Impact of baseline physical activity and diet behavior on metabolic syndrome in a pharmaceutical trial: results from NAVIGATOR.

Objective: The cardiometabolic risk cluster metabolic syndrome (MS) includes ≥3 of elevated fasting glucose, hypertension, elevated triglycerides, reduced high-density lipoprotein cholesterol (HDL-c), and increased waist circumference. Each can be affected by physical activity and diet. Our objective was to determine whether determine whether baseline physical activity and/or diet behavior impact MS in the course of a large pharmaceutical trial.

Disproportionately elevated proinsulinemia is observed at modestly elevated glucose levels within the normoglycemic range.

We aimed to evaluate disproportional proinsulinemia in the pre-diabetic state by analyzing the cross-sectional differences between proinsulin (PI) ratios across the entire range of fasting and 2-h plasma glucose. The study sample was 1,016 participants in the insulin resistance atherosclerosis study, who had no previous diagnosis of diabetes. Insulin sensitivity index (SI) and acute insulin response (AIR) were measured by the frequently sampled intravenous glucose tolerance test.