A plant-based diet for the prevention and treatment of type 2 diabetes
The prevalence of type 2 diabetes is rising worldwide, especially in older adults. Diet and lifestyle, particularly plant-based diets, are effective tools for type 2 diabetes prevention and management. Plant-based diets are eating patterns that emphasize legumes, whole grains, vegetables, fruits, nuts, and seeds and discourage most or all animal products. Cohort studies strongly support the role of plant-based diets, and food and nutrient components of plant-based diets, in reducing the risk of type 2 diabetes. Evidence from observational and interventional studies demonstrates the benefits of plant-based diets in treating type 2 diabetes and reducing key diabetes-related macrovascular and microvascular complications. Optimal macronutrient ratios for preventing and treating type 2 diabetes are controversial; the focus should instead be on eating patterns and actual foods. However, the evidence does suggest that the type and source of carbohydrate (unrefined versus refined), fats (monounsaturated and polyunsaturated versus saturated and trans), and protein (plant versus animal) play a major role in the prevention and management of type 2 diabetes. Multiple potential mechanisms underlie the benefits of a plant-based diet in ameliorating insulin resistance, including promotion of a healthy body weight, increases in fiber and phytonutrients, food-microbiome interactions, and decreases in saturated fat, advanced glycation endproducts, nitrosamines, and heme iron.
Amniotic fluid inhibits Toll-like receptor 4 signaling in the fetal and neonatal intestinal epithelium
The fetal intestinal mucosa is characterized by elevated Toll-like receptor 4 (TLR4) expression, which can lead to the development of necrotizing enterocolitis (NEC)--a devastating inflammatory disease of the premature intestine--upon exposure to microbes. To define endogenous strategies that could reduce TLR4 signaling, we hypothesized that amniotic fluid can inhibit TLR4 signaling within the fetal intestine and attenuate experimental NEC, and we sought to determine the mechanisms involved. We show here that microinjection of amniotic fluid into the fetal (embryonic day 18.5) gastrointestinal tract reduced LPS-mediated signaling within the fetal intestinal mucosa. Amniotic fluid is abundant in EGF, which we show is required for its inhibitory effects on TLR4 signaling via peroxisome proliferator-activated receptor, because inhibition of EGF receptor (EGFR) with cetuximab or EGF-depleted amniotic fluid blocked the inhibitory effects of amniotic fluid on TLR4, whereas amniotic fluid did not prevent TLR4 signaling in EGFR- or peroxisome proliferator-activated receptor gamma-deficient enterocytes or in mice deficient in intestinal epithelial EGFR, and purified EGF attenuated the exaggerated intestinal mucosal TLR4 signaling in wild-type mice. Moreover, amniotic fluid-mediated TLR4 inhibition reduced the severity of NEC in mice through EGFR activation. Strikingly, NEC development in both mice and humans was associated with reduced EGFR expression that was restored upon the administration of amniotic fluid in mice or recovery from NEC in humans, suggesting that a lack of amniotic fluid-mediated EGFR signaling could predispose to NEC. These findings may explain the unique susceptibility of premature infants to the development of NEC and offer therapeutic approaches to this devastating disease.