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OBJECTIVE: Adolescents with type 1 diabetes (T1DM) must consider multiple factors in diet planning, including glycemic control and cardiovascular disease prevention, while ensuring adequate nutrition for growth. We examined diet composition, quality, and compliance for two dietary patterns - the traditional Dietary Approaches to Stop Hypertension (DASH) and a modified version of DASH in this population. METHODS AND FINDINGS: Two feeding studies were conducted. First, adolescents with T1DM consumed their usual diet for 3 days followed by traditional DASH for 6 days. Next, DASH menus were adjusted to align with T1DM nutrition guidelines, and this modified DASH for Diabetes (DASH-D) was tested on a new group of adolescents with T1DM for 6 days, following 3 days of usual diet. Usual diet was measured via 24-hr dietary recalls. Dietary composition of DASH-D was compared to DASH and usual diet. Eighteen adolescents (9/group) participated. Compared to usual diet, intake of protein, fiber, fruit, vegetables, lean meats, and low-fat dairy were higher, while saturated fat and added sugar were lower, in DASH-D. Percent energy from fat was higher, and from carbohydrate lower, in DASH-D versus traditional DASH, with food group intake reflecting these patterns. Participants consumed 87% of foods provided for DASH, and 98% of foods provided for DASH-D. In both DASH iterations, participants met national guidelines for fat, saturated fat, fiber, and fruit/vegetable intake, while usual diet fell short of these recommendations. CONCLUSIONS: The novel DASH-D pattern meets guidelines and may be a viable option for achieving nutrition goals for adolescents with T1DM.
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OBJECTIVE: PAR2 (protease-activated receptor 2)-dependent signaling results in augmented inflammation and has been implicated in the pathogenesis of several autoimmune conditions. The objective of this study was to determine the effect of PAR2 deficiency on the development of atherosclerosis. APPROACH AND RESULTS: PAR2 mRNA and protein expression is increased in human carotid artery and mouse aortic arch atheroma versus control carotid and aortic arch arteries, respectively. To determine the effect of PAR2 deficiency on atherosclerosis, male and female low-density lipoprotein receptor-deficient (Ldlr-/-) mice (8-12 weeks old) that were Par2+/+ or Par2-/- were fed a fat- and cholesterol-enriched diet for 12 or 24 weeks. PAR2 deficiency attenuated atherosclerosis in the aortic sinus and aortic root after 12 and 24 weeks. PAR2 deficiency did not alter total plasma cholesterol concentrations or lipoprotein distributions. Bone marrow transplantation showed that PAR2 on nonhematopoietic cells contributed to atherosclerosis. PAR2 deficiency significantly attenuated levels of the chemokines Ccl2 and Cxcl1 in the circulation and macrophage content in atherosclerotic lesions. Mechanistic studies using isolated primary vascular smooth muscle cells showed that PAR2 deficiency is associated with reduced Ccl2 and Cxcl1 mRNA expression and protein release into the supernatant resulting in less monocyte migration. CONCLUSIONS: Our results indicate that PAR2 deficiency is associated with attenuation of atherosclerosis and may reduce lesion progression by blunting Ccl2- and Cxcl1-induced monocyte infiltration.
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Aorta Torácica/metabolismo , Enfermedades de la Aorta/prevención & control , Aterosclerosis/prevención & control , Receptor PAR-2/deficiencia , Animales , Aorta Torácica/patología , Enfermedades de la Aorta/genética , Enfermedades de la Aorta/metabolismo , Enfermedades de la Aorta/patología , Aterosclerosis/genética , Aterosclerosis/metabolismo , Aterosclerosis/patología , Enfermedades de las Arterias Carótidas/genética , Enfermedades de las Arterias Carótidas/metabolismo , Enfermedades de las Arterias Carótidas/patología , Movimiento Celular , Células Cultivadas , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Quimiocina CXCL1/genética , Quimiocina CXCL1/metabolismo , Modelos Animales de Enfermedad , Femenino , Predisposición Genética a la Enfermedad , Humanos , Lípidos/sangre , Macrófagos/metabolismo , Macrófagos/patología , Masculino , Ratones Noqueados , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Fenotipo , Placa Aterosclerótica , Receptor PAR-1/deficiencia , Receptor PAR-1/genética , Receptor PAR-2/genética , Receptores Acoplados a Proteínas G/deficiencia , Receptores Acoplados a Proteínas G/genética , Receptores de LDL/deficiencia , Receptores de LDL/genéticaRESUMEN
Objective: Glucose variability (GV) independently increases risk for vascular events in patients with diabetes. The Dietary Approaches to Stop Hypertension (DASH) dietary pattern emphasizes fruits, vegetables, whole grains, lean meats, and low fat dairy and has the potential to reduce postprandial blood glucose (BG) excursions, however, its effect on GV is not known. The purpose of this work was to assess feasibility and collect preliminary data on the efficacy of the DASH diet on GV in adolescents with type 1 diabetes (T1D). Methods: Twenty one adolescents recruited from the Diabetes Center of Cincinnati Children's Hospital Medical Center with T1D (11-17y) participated in one of two phases of a controlled feeding study. The first phase tested the acceptability and blood glucose response to a traditional DASH diet (DASH) and the second phase tested a DASH diet specifically modified for diabetes (DASH-D) to improve glucose response to meals. For each phase, participants consumed first their usual diet, and then a controlled DASH diet while wearing continuous glucose monitoring (CGM) systems for 3 days of each diet. All foods were provided to the patients during the DASH dietary periods and 24 h dietary recalls were conducted during the usual diet periods to assess daily intake. Results: Sixteen participants (14.1 +/- 2.2y) were included in final analyses (DASH n=7, DASH-D n=9). Both DASH diets were significantly higher in fruits, vegetables, fiber, vitamin A, and % energy from protein than usual intakes. DASH was higher in carbohydrate (CHO) (60 vs. 50%) and lower in fat (21 vs. 36%) than usual intake, resulting in higher GV (Standard Deviation and Lability Index) and more low BG excursions (3 ± 2.8 vs. 7.1 ± 3.3, p=0.024). DASH-D was modified to better match CHO and fat content of patients' usual intakes in phase 1 (50/30/20 for CHO/fat/pro respectively, which resulted in no difference in GV between DASH-D and usual intake. There were also trends for lower average BG (144.1 vs. 168.9, p=0.072) and less percentage of time spent in the hyperglycemic range (39.3 ± 25.5 vs. 54.1 ± 19.4, p=0.07) on DASH-D compared to usual intake. Conclusion: The DASH dietary pattern tended to result in less hyperglycemia and an overall lower BG compared to usual care. Modifying a traditional DASH diet by increasing heart healthy fats improves glycemic response to DASH and may be beneficial for long term cardiovascular benefits in youth with T1D.
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BACKGROUND: Studies show that obese individuals have prolonged elevations in postprandial lipemia and an exacerbated inflammatory response to high fat meals, which can increase risk for cardiovascular diseases. As epidemiological studies indicate an association between type of fat and circulating inflammatory markers, the purpose of this study was to investigate the acute effect of different fat sources on inflammation and oxidative stress in overweight and obese individuals. METHODS: Eleven overweight and obese subjects consumed three high fat milkshakes rich in monounsaturated fat (MFA), saturated fat (SFA), or long-chain omega 3 polyunsaturated fat (O3FA) in random order. Blood samples collected at baseline, 1, 2, 4, and 6 hours postprandial were analyzed for markers of inflammation (soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), tumor necrosis factor- α (TNF-α), and C-reactive protein (CRP)), oxidative stress (8-epi-prostaglandin-F2α (8-epi) and nuclear factor-κB (NF-κB)), and metabolic factors (glucose, insulin, non-esterified free fatty acids, and triglycerides (TG)). RESULTS: O3FA enhanced NF-kB activation compared to SFA, but did not increase any inflammatory factors measured. Conversely, SFA led to higher ICAM-1 levels than MFA (p = 0.051), while MFA increased TG more than SFA (p < 0.05). CRP increased while TNF-α and 8-epi decreased with no difference between treatments. CONCLUSIONS: While most of the inflammatory factors measured had modest or no change following the meal, ICAM-1 and NF-κB responded differently by meal type. These results are provocative and suggest that type of fat in meals may differentially influence postprandial inflammation and endothelial activation.