Ankle-brachial Index and Incident Diabetes Mellitus: The Atherosclerosis Risk in Communities (ARIC) Study.

Introduction: Individuals with peripheral artery disease (PAD) often have reduced physical function and activity, which may increase the future risk of diabetes. Although diabetes is a risk factor of PAD, whether low ankle-brachial index (ABI) predates diabetes has not been studied. Methods: We examined the association of ABI with incident diabetes after accounting for potential confounders using Cox proportional hazards models in the ARIC Study. ABI was measured on a randomly selected leg in 12,247 black and white participants without prevalent diabetes at baseline (1987-1989). Incident diabetes cases were identified by glucose measurements (fasting ≥126 mg/dl or non-fasting ≥200 mg/dl) at subsequent three visits (1990-92, 1993-95, and 1996-98) and self-reported diagnosis or medication use at those visits or during annual phone interview through 2011. Results: A total of 3,305 participants developed diabetes during a median of 21 years of follow-up. Participants with low (≤0.90) and borderline low (0.91-1.00) ABI had 30-40% higher risk of future diabetes as compared to those with ABI of 1.10-1.20 in the demographically adjusted model. The associations were attenuated after further adjustment for other potential confounders but remained significant for ABI 0.90-1.00 (HR=1.17, 95%CI 1.04-1.31) and marginally significant for ABI ≤0.90 (HR=1.19, 0.99-1.43). Although the association was largely consistent across demographic and clinical subgroups, we observed borderline significant interaction for hypertension status and fasting glucose, with a stronger association between ABI and diabetes risk in participants without hypertension and those with normal fasting compared to their counterparts. Conclusions: Low ABI was modestly but independently associated with increased risk of incident diabetes in the general population. Clinical attention should be paid to the glucose trajectory among people with low ABI

Sampling strategies and integrated reconstruction for reducing distortion and boundary slice aliasing in high-resolution 3D diffusion MRI

Purpose: To develop a new method for high-fidelity, high-resolution 3D multi-slab diffusion MRI with minimal distortion and boundary slice aliasing. Methods: Our method modifies 3D multi-slab imaging to integrate blip-reversed acquisitions for distortion correction and oversampling in the slice direction (kz) for reducing boundary slice aliasing. Our aim is to achieve robust acceleration to keep the scan time the same as conventional 3D multi-slab acquisitions, in which data are acquired with a single direction of blip traversal and without kz-oversampling. We employ a two-stage reconstruction. In the first stage, the blip-up/down images are respectively reconstructed and analyzed to produce a field map for each diffusion direction. In the second stage, the blip-reversed data and the field map are incorporated into a joint reconstruction to produce images that are corrected for distortion and boundary slice aliasing. Results: We conducted experiments at 7T in six healthy subjects. Stage 1 reconstruction produces images from highly under-sampled data (R = 7.2) with sufficient quality to provide accurate field map estimation. Stage 2 joint reconstruction substantially reduces distortion artifacts with comparable quality to fully-sampled blip-reversed results (2.4× scan time). Whole-brain in-vivo results acquired at 1.22 mm and 1.05 mm isotropic resolutions demonstrate improved anatomical fidelity compared to conventional 3D multi-slab imaging. Data demonstrate good reliability and reproducibility of the proposed method over multiple subjects. Conclusion: The proposed acquisition and reconstruction framework provide major reductions in distortion and boundary slice aliasing for 3D multi-slab diffusion MRI without increasing the scan time, which can potentially produce high-quality, high-resolution diffusion MRI

Hybrid-space reconstruction with add-on distortion correction for simultaneous multi-slab diffusion MRI

Purpose: This study aims to propose a model-based reconstruction algorithm for simultaneous multi-slab diffusion MRI acquired with blipped-CAIPI gradients (blipped-SMSlab), which can also incorporate distortion correction. Methods: We formulate blipped-SMSlab in a 4D k-space with kz gradients for the intra-slab slice encoding and km (blipped-CAIPI) gradients for the inter-slab encoding. Because kz and km gradients share the same physical axis, the blipped-CAIPI gradients introduce phase interference in the z-km domain while motion induces phase variations in the kz-m domain. Thus, our previous k-space-based reconstruction would need multiple steps to transform data back and forth between k-space and image space for phase correction. Here we propose a model-based hybrid-space reconstruction algorithm to correct the phase errors simultaneously. Moreover, the proposed algorithm is combined with distortion correction, and jointly reconstructs data acquired with the blip-up/down acquisition to reduce the g-factor penalty. Results: The blipped-CAIPI-induced phase interference is corrected by the hybrid-space reconstruction. Blipped-CAIPI can reduce the g-factor penalty compared to the non-blipped acquisition in the basic reconstruction. Additionally, the joint reconstruction simultaneously corrects the image distortions and improves the 1/g-factors by around 50%. Furthermore, through the joint reconstruction, SMSlab acquisitions without the blipped-CAIPI gradients also show comparable correction performance with blipped-SMSlab. Conclusion: The proposed model-based hybrid-space reconstruction can reconstruct blipped-SMSlab diffusion MRI successfully. Its extension to a joint reconstruction of the blip-up/down acquisition can correct EPI distortions and further reduce the g-factor penalty compared with the separate reconstruction.Comment: 10 figures+tables, 8 supplementary figure

Ankle-brachial index and incident diabetes mellitus: the atherosclerosis risk in communities (ARIC) study

Abstract Background Individuals with peripheral artery disease (PAD) often have reduced physical activity, which may increase the future risk of diabetes mellitus. Although diabetes is a risk factor for PAD, whether low ankle-brachial index (ABI) predates diabetes has not been studied. Methods We examined the association of ABI with incident diabetes using Cox proportional hazards models in the ARIC Study. ABI was measured in 12,247 black and white participants without prevalent diabetes at baseline (1987–1989). Incident diabetes cases were identified by blood glucose levels at three subsequent visits (1990–92, 1993–95, and 1996–98) or self-reported physician diagnosis or medication use at those visits or during annual phone interview afterward through 2011. Results A total of 3305 participants developed diabetes during a median of 21 years of follow-up. Participants with low (≤0.90) and borderline low (0.91–1.00) ABI had 30–40% higher risk of future diabetes as compared to those with ABI of 1.10–1.20 in the demographically adjusted model. The associations were attenuated after further adjustment for other potential confounders but remained significant for ABI 0.91–1.00 (HR = 1.17, 95% CI 1.04–1.31) and marginally significant for ABI ≤ 0.90 (HR = 1.19, 0.99–1.43). Although the association was largely consistent across subgroups, a stronger association was seen in participants without hypertension, those with normal fasting glucose, and those with a history of stroke compared to their counterparts. Conclusions Low ABI was modestly but independently associated with increased risk of incident diabetes in the general population. Clinical attention should be paid to the glucose trajectory among people with low ABI but without diabetes

Sex Differences in Associations of Adiposity Measures and Insulin Resistance in US Hispanic/Latino Youth: The Hispanic Community Children's Health Study/Study of Latino Youth (SOL Youth)

Context: US Hispanic/Latino youth are disproportionally affected by the obesity and diabetes. Objective: We examined associations of adiposity measures with insulin resistance (IR) and hyperglycemia and the influences of sex and pubertal development on these associations. Design, Setting, and Participants: We performed a cross-sectional analysis of 1223 8- to 16-year-old Hispanic/Latino youth from a community-based study in the United States (SOL Youth). Main Outcome Measures: We measured IR (≥75th percentile of sex-specific Homeostatic Model Assessment of Insulin Resistance) and hyperglycemia (fasting glucose ≥100 mg/dL or hemoglobin a1c ≥5.7%). Results: In boys, body mass index (BMI) showed the strongest association with IR [prevalence ratio (PR), 2.10; 95% confidence interval (CI), 1.87 to 2.36 per standard deviation], which was not statistically different compared with body fat percentage (%BF) (PR, 2.03; 95% CI, 1.81 to 2.29) and waist circumference (WC) (PR, 1.89; 95% CI, 1.67 to 2.13) but was significantly stronger compared with fat mass index (FMI) (PR, 1.79; 95% CI, 1.63 to 1.96), waist-to-hip ratio (WHR) (PR, 1.32; 95% CI, 1.21 to 1.44), and waist-to-height ratio (WHtR) (PR, 1.76; 95% CI, 1.54 to 2.01) (P for difference, <0.05). In girls, %BF (PR, 2.73; 95% CI, 2.34 to 3.20) showed a significantly stronger association with IR compared with BMI (PR, 1.48; 95% CI, 1.29 to 1.70), FMI (PR, 1.71; 95% CI, 1.49 to 1.95), WC (PR, 1.96; 95% CI, 1.70 to 2.27), WHR (PR, 1.95; 95% CI, 1.70 to 2.23), and WHtR (PR, 1.79; 95% CI, 1.53 to 2.09) (P for difference, <0.003). Associations between adiposity measures and IR were generally stronger among children in puberty versus those who had completed puberty, with significant interactions for WC and WHtR in boys and for BMI in girls (P for interaction, <0.01). Adiposity measures were modestly associated with hyperglycemia (PR, 1.14 to 1.25), with no interactions with sex or pubertal status. Conclusions: Sex and puberty may influence associations between adiposity measures and IR in US Hispanic/Latino youth. Multiple adiposity measures are needed to better assess IR risk between boys and girls according to pubertal status

Objectively Measured Sedentary Time and Cardiovascular Risk Factor Control in US Hispanics/Latinos With Diabetes Mellitus: Results From the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

BACKGROUND: Cardiovascular disease (CVD) risk factor control is a cornerstone of diabetes mellitus management. Little is known about relationships of objectively measured sedentary time and physical activity with major CVD risk factor control in individuals with diabetes mellitus. We examined associations of objectively measured sedentary time and moderate-to-vigorous physical activity with reaching major CVD risk factor control goals among US Hispanic/Latino adults with diabetes mellitus. METHODS AND RESULTS: This cross-sectional analysis included 1699 participants with diabetes mellitus from the Hispanic Community Health Study/Study of Latinos (2008-2011). Logistic regression models were used to estimate the odds ratios (ORs) of meeting the following 5 major CVD risk factor control goals: hemoglobin A1c 40/50 mg/dL for men/women. After adjustment for covariates including moderate-to-vigorous physical activity, less sedentary time was associated with increased odds of reaching hemoglobin A1c (OR=1.76 [95% CI: 1.10, 2.82]) and triglyceride control goals (OR=2.16 [1.36, 3.46]), and reaching ≥3 CVD risk factor control goals (OR=2.08 [1.34, 3.23]) (all ORs for comparisons of extreme tertiles of sedentary time). Moderate-to-vigorous physical activity was not associated with reaching any CVD risk factor control goals. Substituting 60-min/day of sedentary time with light-intensity physical activity was associated with increased odds of reaching hemoglobin A1c (OR=1.18 [1.04, 1.35]), high-density lipoprotein cholesterol (OR=1.17 [1.04, 1.32]), and triglyceride (OR=1.20 [1.05, 1.36]) control goals. CONCLUSIONS: Among US Hispanic/Latino adults with diabetes mellitus, less sedentary time, but not moderate-to-vigorous physical activity, was associated with improved CVD risk factor control, specifically in reaching hemoglobin A1c and triglyceride control goals

Relationship between area mortgage foreclosures, homeownership, and cardiovascular disease risk factors: The Hispanic Community Health Study/Study of Latinos

Abstract Background The risk of mortgage foreclosure disproportionately burdens Hispanic/Latino populations perpetuating racial disparities in health. In this study, we examined the relationship between area-level mortgage foreclosure risk, homeownership, and the prevalence of cardiovascular disease risk factors among participants of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Methods HCHS/SOL participants were age 18–74 years when recruited from four U.S. metropolitan areas. Mortgage foreclosure risk was obtained from the U.S. Department of Housing and Urban Development. Homeownership, sociodemographic factors, and cardiovascular disease risk factors were measured at baseline interview between 2008 and 2011. There were 13,856 individuals contributing to the analysis (median age 39 years old, 53% female). Results Renters in high foreclosure risk areas had a higher prevalence of hypertension and hypercholesterolemia but no association with smoking status compared to renters in low foreclosure risk areas. Renters were more likely to smoke cigarettes than homeowners. Conclusion Among US Hispanic/Latinos in urban cities, area foreclosure and homeownership have implications for risk of cardiovascular disease

Single Nucleotide Polymorphisms of 8 Inflammation-related Genes and their Associations with Smoking-related Cancers

Tobacco smoke and its metabolites are carcinogens that increase tissue oxidative stress and induce target tissue inflammation. We hypothesized that genetic variation of inflammatory pathway genes plays a role in tobacco-related carcinogenesis and is modified by tobacco smoking. We evaluated the association of 12 single nucleotide polymorphisms of 8 inflammation-related genes with tobacco-related cancers (lung, oropharynx, larynx, esophagus, stomach, liver, bladder, and kidney) using 3 case-control studies from: Los Angeles (population-based; 611 lung and 553 upper aero-digestive tract cancer cases and 1,040 controls), Taixing, China (population-based; 218 esophagus, 206 stomach, 204 liver cancer cases, and 415 controls), and Memorial Sloan-Kettering Cancer Center (hospital-based; 227 bladder cancer cases and 211 controls). After adjusting for age, education, ethnicity, gender, and tobacco smoking, IL10 rs1800871 was inversely associated with oropharyngeal cancer (CT+TT vs. CC adjusted odds ratio [aOR]: 0.69, 95% confidence interval [CI]: 0.50-0.95), and was positively associated with lung cancer among never smokers (TT vs. CT+CC aOR: 2.5, 95% CI: 1.3-5.1) and inversely with oropharyngeal cancer among ever smokers (CT+TT vs. CC aOR: 0.63, 95% CI: 0.41-0.95). Among all pooled never smokers (588 cases and 816 controls), TNF rs1799964 was inversely associated with smoking-related cancer (CC vs. CT+TT aOR: 0.36, 95% CI: 0.17-0.77). Bayesian correction for multiple comparisons suggests that chance is unlikely to explain our findings (although epigenetic mechanisms may be in effect), which support our hypotheses, suggesting that IL10 rs1800871 is a susceptibility marker for oropharyngeal and lung cancers, and that TNF rs1799964 is associated with smoking-related cancers among never smokers. © 2010 UICC

pRb Inactivation in Mammary Cells Reveals Common Mechanisms for Tumor Initiation and Progression in Divergent Epithelia

Retinoblastoma 1 (pRb) and the related pocket proteins, retinoblastoma-like 1 (p107) and retinoblastoma-like 2 (p130) (pRb(f), collectively), play a pivotal role in regulating eukaryotic cell cycle progression, apoptosis, and terminal differentiation. While aberrations in the pRb-signaling pathway are common in human cancers, the consequence of pRb(f) loss in the mammary gland has not been directly assayed in vivo. We reported previously that inactivating these critical cell cycle regulators in divergent cell types, either brain epithelium or astrocytes, abrogates the cell cycle restriction point, leading to increased cell proliferation and apoptosis, and predisposing to cancer. Here we report that mouse mammary epithelium is similar in its requirements for pRb(f) function; Rb(f) inactivation by T(121), a fragment of SV40 T antigen that binds to and inactivates pRb(f) proteins, increases proliferation and apoptosis. Mammary adenocarcinomas form within 16 mo. Most apoptosis is regulated by p53, which has no impact on proliferation, and heterozygosity for a p53 null allele significantly shortens tumor latency. Most tumors in p53 heterozygous mice undergo loss of the wild-type p53 allele. We show that the mechanism of p53 loss of heterozygosity is not simply the consequence of Chromosome 11 aneuploidy and further that chromosomal instability subsequent to p53 loss is minimal. The mechanisms for pRb and p53 tumor suppression in the epithelia of two distinct tissues, mammary gland and brain, are indistinguishable. Further, this study has produced a highly penetrant breast cancer model based on aberrations commonly observed in the human disease