OBJECTIVE -We measured plasma markers of endothelial dysfunction, vascular inflammation, and pro-coagulation in obese Hispanic/Latino children and adolescents with normal glucose tolerance and determined their relationship to body composition and indexes of glucose and lipid metabolism. RESEARCH DESIGN AND METHODS-A total of 38 lean or obese Hispanic children and adolescents (10 -18 years of age) were selected. The overweight group (n ϭ 21) had a BMI Ͼ85th percentile for their age and sex, and the lean group (n ϭ 17) had a BMI between the 25th and 50th percentiles. Studies included an oral glucose tolerance test, measurements of plasma glucose and lipids, several markers of endothelial function and inflammation, and determination of body composition by dual X-ray absorptiometry.RESULTS -The obese group had higher systolic blood pressure and plasma triglycerides and was more insulin resistant than the lean group. The obese group also had higher plasma soluble intercellular adhesion molecule (259.5 Ϯ 60.0 vs. 223.2 Ϯ 47.5 ng/ml, P ϭ 0.047), tumor necrosis factor-␣ (2.57 Ϯ 1.1 vs. 1.74 Ϯ 0.6 pg/ml, P ϭ 0.008), high-sensitivity C-reactive protein (2.0 vs. 0.13 mg/l, P Ͻ 0.0001), plasminogen-activated inhibitor-1 (47.0 Ϯ 35.7 vs. 12.0 Ϯ 5.2 ng/ml, P Ͻ 0.0001), tissue plasminogen activator (6.1 Ϯ 1.9 vs. 4.1 Ϯ 0.8 ng/ml, P ϭ 0.001), and white blood cell count (6.9 vs. 5.3 ϫ 10 3 , P ϭ 0.031) and lower levels of adiponectin (8.7 Ϯ 3.3 vs. 12.6 Ϯ 5.2 g/ml, P ϭ 0.022). No significant differences were observed for soluble vascular cell adhesion molecule or interleukin-6. CONCLUSIONS -Overweight Hispanic children and adolescents with normal glucose tolerance exhibit increased plasma markers of endothelial dysfunction and subclinical inflammation in association with obesity and insulin resistance. These abnormalities may predispose them to the development of type 2 diabetes and cardiovascular disease.

Chronic kidney disease (CKD) is an important global health problem that affects 8-15% of the population according to epidemiological studies done in different countries. Essential to prevention is the knowledge of the environmental factors associated with this disease, and heavy metals such as lead and cadmium are clearly associated with kidney injury and CKD progression. Arsenic is one of the most abundant contaminants in water and soil, and many epidemiological studies have found an association between arsenic and type 2 diabetes mellitus, hypertension and cancer; however, there is a scarcity of epidemiological studies about its association with kidney disease, and the evidence linking urinary arsenic excretion with CKD, higher urinary excretion of low molecular proteins, albuminuria or other markers of renal in injury is still limited, and more studies are necessary to characterize the role of arsenic on renal injury and CKD progression. Global efforts to reduce arsenic exposure remain important and research is also needed to determine whether specific therapies are beneficial in susceptible populations.

High circulating levels of the hormone prolactin (PRL) protect against experimental diabetic retinopathy (DR) due to the retinal accumulation of vasoinhibin, a PRL fragment that inhibits blood vessel permeability and growth. A phase 2 clinical trial is investigating a new therapy for DR based on elevating serum PRL levels with levosulpiride, a prokinetic dopamine D2 receptor blocker. Here, we tested whether levosulpiride-induced hyperprolactinemia elevates PRL and vasoinhibin in the vitreous of volunteer patients with proliferative DR (PDR) undergoing elective pars plana vitrectomy. Methods: Patients were randomized to receive placebo (lactose pill, orally TID; n = 19) or levosulpiride (25 mg orally TID; n = 18) for the 7 days before vitrectomy. Vitreous samples from untreated non-diabetic (n = 10) and PDR (n = 17) patients were also studied. Results: Levosulpiride elevated the systemic (101 ± 13 [SEM] vs. 9.2 ± 1.3 ng/mL, P < 0.0001) and vitreous (3.2 ± 0.4 vs. 1.5 ± 0.2 ng/mL, P < 0.0001) levels of PRL, and both levels were directly correlated (r = 0.58, P < 0.0002). The vitreous from nondiabetic patients or from PDR patients treated with levosulpiride, but not from placebotreated PDR patients, inhibited the basic fibroblast growth factor (bFGF)-and vascular endothelial growth factor (VEGF)-induced proliferation of endothelial cells in culture. Vasoinhibin-neutralizing antibodies reduced the vitreous antiangiogenic effect. Matrix metalloproteases (MMPs) in the vitreous cleaved PRL to vasoinhibin, and their activity was higher in non-diabetic than in PDR patients. Conclusions: Levosulpiride increases the levels of PRL in the vitreous of PDR patients and promotes its MMP-mediated conversion to vasoinhibin, which can inhibit angiogenesis in DR. Translational Relevance: These findings support the potential therapeutic benefit of levosulpiride against vision loss in diabetes.

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