Type 2 Diabetes Mellitus is an increasing public health problem that poses a severe social and economic burden affecting both developed and developing countries. Defects in insulin signaling itself are among the earliest indications that an individual is predisposed to the development of insulin resistance and subsequently Type 2 Diabetes Mellitus. To date, however, the underlying molecular mechanisms which result in resistance to the actions of insulin are poorly understood. Furthermore, it has been shown that maternal obesity is associated with an increased risk of obesity and insulin resistance in the offspring. However, the genetic and/or epigenetic modifications within insulin-sensitive tissues such as the liver and skeletal muscle, which contribute to the insulin-resistant phenotype, still remain unknown. More importantly, a lack of in-depth understanding of how the early life environment can have long-lasting effects on health and increased risk of Type 2 Diabetes Mellitus in adulthood poses a major limitation to such efforts. The focus of the current review is thus to discuss recent experimental and human evidence of an epigenetic component associated with components of nutritional programming of Type 2 Diabetes Mellitus, including altered feeding behavior, adipose tissue, and pancreatic beta-cell dysfunction, and transgenerational risk transmission.

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Celiac disease is an autoimmune disorder that affects the small intestine. When gluten, a protein found in wheat, rye and barley is consumed, the immune system responds by targeting the small intestine and inhibiting the absorption of nutrients into the body. The objective was to evaluate the potential of anthocyanin‐rich plant extracts to protect human epithelial cells against a celiac toxic peptide (CTP). Healthy differentiated Caco‐2 epithelial like human cells were used to represent the intestine and treated with a known CTP from wheat protein, alpha‐gliadin H‐6712 Gliadorphin‐7, H‐Tyr‐Pro‐Gln‐Pro‐Gln‐Pro‐Phe‐OH (YPQPQPF). Anthocyanin‐rich extracts from fruits (red and purple grape), vegetables (purple sweet potato and purple carrot), grains (color corn, black rice, sorghum, and blue wheat), and legumes (black bean, black lentil, black peanut, and purple bean) were tested to evaluate their protective effects on Caco‐2 cells treated with CTP using a cell proliferation assay. The total monomeric anthocyanin were calculated as mg cyanidin‐3‐glucoside (C3G) equivalents (eq) per g of dry extract (DE), total polyphenols as mg gallic acid eq per g DE, and total tannins as mg catechin eq per g DE for each plant material. Cell protection was evaluated using 0.001–1 mg DE/mL in the presence of 25 mM CTP (C+) (IC95). A human inflammation array was performed comparing untreated Caco‐2 cells (C−) with Caco‐2 cells treated with C+, red corn acidified water extract (RAW), and purple corn acidified water extract (PAW) with additional ethyl acetate purification (PAWE) 1 mg/mL extract in the presence of C+. Total anthocyanin ranged from 0.0–287.5 (mg C3G eq/g DE), total polyphenols from 47.4–382.3 (mg gallic acid eq/g DE), and total tannins ranged from 0.2–9.4 (mg catechin eq/g DE) (p<0.05). Black rice had the highest amount of total anthocyanins and total polyphenols, while corn hybrid 6 was high in pelargonidin, catechin and had the highest tannins. PAW and black lentil presented a dose dependent response curve for cell protection. Corn hybrids increased protection (60–80%) except for hybrid 6 (pelargonidin, low acylated), purple corn pure water extract (PW) and PAW increased cell protection (60–78%) at low concentrations, and black peanut increased protection over 80% at low concentrations (p<0.05). PAWE exhibited a 3.6 fold decrease (FD) on granulocyte macrophage‐colony stimulating factor (GM‐CSF) while exhibited a modest but significant fold increase (FI) on metallopeptidase inhibitor 2 (TIMP‐2) (p<0.05). Both PAWE and RAW exhibited a modest fold increase (FI) on interleukin (IL) 6, while only RAW had a 4.3 FI on IL‐11. Interleukin 11 and TIMP‐2 are anti‐inflammatory while IL‐6 and GM‐CSF are pro‐inflammatory. The ability of anthocyanin‐rich plant extracts to inhibit CTP has positive implication for human health; these extracts could potentially decrease the occurrence of inflammation for gluten sensitive individuals.Support or Funding InformationHatch funding