Young Hispanics at risk of type 2 diabetes display endothelial activation, subclinical inflammation and alterations of coagulation and fibrinolysis

Background: Hispanics have a high rate of diabetes that exposes them to an increased risk of cardiovascular disease. We hypothesized that many of the pathophysiological mechanisms that cause atherosclerotic disease may be present in young Hispanics who do not have clinical diabetes but are at increased risk of developing it. Methods: We studied 36 young Hispanic adults without diabetes (ages 18–40). Seventeen participants were at increased risk of developing type 2 diabetes given by overweight and a family history of diabetes on one or both parents (at risk group). Nineteen participants with normal body-mass index and no parental history of diabetes constituted the control group. We measured and compared plasma markers of endothelial dysfunction, disturbed coagulation and fibrinolysis, subclinical inflammation and adipose tissue dysfunction in the at risk and control groups. Results: Participants at risk of diabetes were more insulin-resistant according to different indicators, and had significantly higher levels of soluble intercellular adhesion molecule-1 (sICAM-1), tissue plasminogen activator (tPA), inhibitor of plasminogen activator-1 (PAi-1), high sensitivity C-reactive protein and free fatty acids, signaling the presence of multiple proatherogenic alterations despite the absence of overt diabetes. Levels of the prothrombotic molecule PAi-1 were most elevated in participants who were not only at risk of diabetes by the study definition, but also abdominally obese. Conclusions: Young adult Hispanics at risk of type 2 diabetes but without overt disease already bear considerably high levels of markers reflecting processes that lead to the development of atherosclerotic cardiovascular disease

primary prevention of cardiovascular disease and type 2 diabetes in patients at metabolic risk an endocrine society clinical practice guideline

Objective: The objective was to develop clinical practice guidelines for the primary prevention of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) in patients at metabolic risk. Conclusions: Healthcare providers should incorporate into their practice concrete measures to reduce the risk of developing CVD and T2DM. These include the regular screening and identification of patients at metabolic risk (at higher risk for both CVD and T2DM) with measurement of blood pressure, waist circumference, fasting lipid profile, and fasting glucose. All patients identified as having metabolic risk should undergo 10-yr global risk assessment for either CVD or coronary heart disease. This scoring will determine the targets of therapy for reduction of apolipoprotein B-containing lipoproteins. Careful attention should be given to the treatment of elevated blood pressure to the targets outlined in this guideline. The prothrombotic state associated with metabolic risk should be treated with lifestyle modification measures and in appropriate individuals with low-dose aspirin prophylaxis. Patients with prediabetes (impaired glucose tolerance or impaired fasting glucose) should be screened at 1- to 2-yr intervals for the development of diabetes with either measurement of fasting plasma glucose or a 2-h oral glucose tolerance test. For the prevention of CVD and T2DM, we recommend that priority be given to lifestyle management.Thisincludesantiatherogenicdietarymodification,aprogramofincreasedphysicalactivity, andweightreduction.Effortstopromotelifestylemodificationshouldbeconsideredanimportant component of the medical management of patients to reduce the risk of both CVD and T2DM. (J Clin Endocrinol Metab 93: 3671–3689, 2008

Endocrine-disrupting effects of cattle feedlot effluent on an aquatic sentinel species, the fathead minnow.

Over the last decade, research has examined the endocrine-disrupting action of various environmental pollutants, including hormones, pharmaceuticals, and surfactants, in sewage treatment plant effluent. Responding to the growth of concentrated animal feeding operations (CAFOs) and the pollutants present in their wastewater (e.g., nutrients, pharmaceuticals, and hormones), the U.S. Environmental Protection Agency developed a new rule that tightens the regulation of CAFOs. In this study, we collected wild fathead minnows (Pimephales promelas) exposed to feedlot effluent (FLE) and observed significant alterations in their reproductive biology. Male fish were demasculinized (having lower testicular testosterone synthesis, altered head morphometrics, and smaller testis size). Defeminization of females, as evidenced by a decreased estrogen:androgen ratio of in vitro steroid hormone synthesis, was also documented. We did not observe characteristics in either male or female fish indicative of exposure to environmental estrogens. Using cells transfected with the human androgen receptor, we detected potent androgenic responses from the FLE. Taken together, our morphologic, endocrinologic, and in vitro gene activation assay data suggest two hypotheses: a) there are potent androgenic substance(s) in the FLE, and/or b) there is a complex mixture of androgenic and estrogenic substances that alter the hypothalamic-pituitary-gonadal axis, inhibiting the release of gonadotropin-releasing hormone or gonadotropins. This is the first study demonstrating that the endocrine and reproductive systems of wild fish can be adversely affected by FLE. Future studies are needed to further investigate the effects of agricultural runoff and to identify the biologically active agents, whether natural or pharmaceutical in origin

Per- and polyfluoroalkyl substances and kidney function: Follow-up results from the Diabetes Prevention Program trial

Per- and polyfluoroalkyl substances (PFAS) are ubiquitously detected in populations worldwide and may hinder kidney function. The objective of the study was to determine longitudinal associations of plasma PFAS concentrations with estimated glomerular filtration rate (eGFR) and evaluate whether a lifestyle intervention modify the associations. We studied 875 participants initially randomized to the lifestyle or placebo arms in the Diabetes Prevention Program (DPP, 1996–2002) trial and Outcomes Study (DPPOS, 2002–2014). We ran generalized linear mixed models accounting a priori covariates to evaluate the associations between baseline PFAS concentrations and repeated measures of eGFR, separately, for six PFAS (PFOS, PFOA, PFHxS, EtFOSAA, MeFOSAA, PFNA); then used quantile-based g-computation to evaluate the effects of the six PFAS chemicals as a mixture. The cohort was 64.9% female; 73.4% 40–64 years-old; 29.4% with hypertension; 50.5% randomized to lifestyle intervention and 49.5% to placebo and had similar plasma PFAS concentrations as the general U.S. population in 1999–2000. Most participants had normal kidney function (eGFR \u3e 90 mL/min/1.73 m2) over the approximately 14 years of follow-up. We found that plasma PFAS concentrations during DPP were inversely associated with eGFR during DPPOS follow-up. Each quartile increase in baseline plasma concentration of the 6 PFAS as a mixture was associated with 2.26 mL/min/1.73 m2 lower eGFR (95% CI: −4.12, −0.39) at DPPOS Year 5, approximately 9 years since DPP randomization and PFAS measurements. The lifestyle intervention did not modify associations, but inverse associations were stronger among participants with hypertension at baseline. Among prediabetic adults, we found inverse associations between baseline plasma PFAS concentrations and measures of eGFR throughout 14 years of follow-up. The lifestyle intervention of diet, exercise and behavioral changes did not modify the associations, but persons with hypertension may have heightened susceptibility

February 1967 Conference Issue

Massachusetts Turf and Lawn Grass CouncilBetter Turf Through Research and Educatio

Brachial Artery Responses to Ambient Pollution, Temperature, and Humidity in People with Type 2 Diabetes: A Repeated-Measures Study

Background: Extreme weather and air pollution are associated with increased cardiovascular risk in people with diabetes. Objectives: In a population with diabetes, we conducted a novel assessment of vascular brachial artery responses both to ambient pollution and to weather (temperature and water vapor pressure, a measure of humidity). Methods: Sixty-four 49- to 85-year-old Boston residents with type 2 diabetes completed up to five study visits (279 repeated measures). Brachial artery diameter (BAD) was measured by ultrasound before and after brachial artery occlusion [i.e., flow-mediated dilation (FMD)] and before and after nitroglycerin-mediated dilation (NMD). Ambient concentrations of fine particulate mass (PM2.5), black carbon (BC), organic carbon (OC), elemental carbon, particle number, and sulfate were measured at our monitoring site; ambient concentrations of carbon monoxide, nitrogen dioxide, and ozone were obtained from state monitors. Particle exposure in the home and during each trip to the clinic (home/trip exposure) was measured continuously and as a 5-day integrated sample. We used linear models with fixed effects for participants, adjusting for date, season, temperature, and water vapor pressure on the day of each visit, to estimate associations between our outcomes and interquartile range increases in exposure. Results: Baseline BAD was negatively associated with particle pollution, including home/trip–integrated BC (–0.02 mm; 95% CI: –0.04, –0.003, for a 0.28 μg/m3 increase in BC), OC (–0.08 mm; 95% CI: –0.14, –0.03, for a 1.61 μg/m3 increase) as well as PM2.5, 5-day average ambient PM2.5, and BC. BAD was positively associated with ambient temperature and water vapor pressure. However, exposures were not consistently associated with FMD or NMD. Conclusion: Brachial artery diameter, a predictor of cardiovascular risk, decreased in association with particle pollution and increased in association with ambient temperature in our study population of adults with type 2 diabetes. Citation: Zanobetti A, Luttmann-Gibson H, Horton ES, Cohen A, Coull BA, Hoffmann B, Schwartz JD, Mittleman MA, Li Y, Stone PH, de Souza C, Lamparello B, Koutrakis P, Gold DR. 2014. Brachial artery responses to ambient pollution, temperature, and humidity in people with type 2 diabetes: a repeated-measures study. Environ Health Perspect 122:242–248; http://dx.doi.org/10.1289/ehp.120613

Comprehensive Analysis of Established Dyslipidemia-Associated Loci in the Diabetes Prevention Program

Background-We assessed whether 234 established dyslipidemia-associated loci modify the effects of metformin treatment and lifestyle intervention (versus placebo control) on lipid and lipid subfraction levels in the Diabetes Prevention Program randomized controlled trial. Methods and Results-We tested gene treatment interactions in relation to baseline-adjusted follow-up blood lipid concentrations (high-density lipoprotein [HDL] and low-density lipoprotein-cholesterol, total cholesterol, and triglycerides) and lipoprotein subfraction particle concentrations and size in 2993 participants with pre-diabetes. Of the previously reported single-nucleotide polymorphism associations, 32.5% replicated at PP>1.1×10-16) with their respective baseline traits for all but 2 traits. Lifestyle modified the effect of the genetic risk score for large HDL particle numbers, such that each risk allele of the genetic risk scores was associated with lower concentrations of large HDL particles at follow-up in the lifestyle arm (β=-0.11 μmol/L per genetic risk scores risk allele; 95% confidence interval,-0.188 to-0.033; P=5×10-3; Pinteraction=1×10-3 for lifestyle versus placebo), but not in the metformin or placebo arms (P>0.05). In the lifestyle arm, participants with high genetic risk had more favorable or similar trait levels at 1-year compared with participants at lower genetic risk at baseline for 17 of the 20 traits. Conclusions-Improvements in large HDL particle concentrations conferred by lifestyle may be diminished by genetic factors. Lifestyle intervention, however, was successful in offsetting unfavorable genetic loading for most lipid traits. Clinical Trial Registration-URL: https://www.clinicaltrials.gov. Unique Identifier: NCT00004992