Dietary AGEs as Exogenous Boosters of Inflammation

Most chronic modern non-transmissible diseases seem to begin as the result of low-grade inflammation extending over prolonged periods of time. The importance of diet as a source of many pro-inflammatory compounds that could create and sustain such a low-grade inflammatory state cannot be ignored, particularly since we are constantly exposed to them during the day. The focus of this review is on specific components of the diet associated with inflammation, specifically advanced glycation end products (AGEs) that form during thermal processing of food. AGEs are also generated in the body in normal physiology and are widely recognized as increased in diabetes, but many people are unaware of the potential importance of exogenous AGEs ingested in food. We review experimental models, epidemiologic data, and small clinical trials that suggest an important association between dietary intake of these compounds and development of an inflammatory and pro-oxidative state that is conducive to chronic diseases. We compare dietary intake of AGEs with other widely known dietary patterns, such as the Mediterranean and the Dietary Approaches to Stop Hypertension (DASH) diets, as well as the Dietary Inflammation Index (DII). Finally, we delineate in detail the pathophysiological mechanisms induced by dietary AGEs, both direct (i.e., non-receptor-mediated) and indirect (receptor-mediated

D-lactate and Low Molecular AGEs Are Elevated in Obese Adolescents: Evidence for Carbonyl Stress in Adolescent Obesity

Glycation and carbonyl stress produced by methylglyoxal (MG) as a consequence of triose flux in glycolysis has been implicated in the etiology of metabolic syndrome and diabetes complications. An integrated estimation of MG flux is provided by measuring concentrations of its catabolite D-lactate in serum. However, no studies have explored the pathway in childhood obesity. Objective: Study serum concentrations of D-lactate and low molecular weight advanced glycation end-products (LMWAGE) in lean vs adolescents with obesity. Material and Methods: We conducted a cross-sectional study of 30 lean and 30 obese adolescents between the ages of 15-19 years. D-lactate was measured kinetically in serum ultrafiltrates by an adaptation of a colorimetric method from Sigma. Total and LMW-AGEs were measured by fluorescence (Excitation: λ 370 nm, Emission: λ 440 nm). The Ethical Committee of the Institution approved this study and informed consent was obtained from the participant adolescents and their parents. Results: The obesity group showed significantly (* p \u3c 0.01, ** p \u3c 0.001) higher levels of: % body fat 35.0 ± 9**, systolic BP 116.0 ± 8.1 mmHg** and diastolic BP, 72.9 ± 7.1*mmHg, waist 96.1 ± 11.6 cm** and hip circumferences 110.2 ± 8 cm**, HbA1c 5.1 ± 0.6*. D-lactate was 4.5 +/- 2.5 nmol/l in controls vs 7.4 +/- 4.2 vs. nmol/l in obese subjects **. LMW/total AGE were 0.48 (0.44-052) AU in controls vs 0.61 (0.55-0.67) AU in obese subjects**. Conclusions: D-lactate levels and LMW-AGEs are higher (64% and 27% respectively) in adolescents with obesity as compared to lean controls. Our data is compatible with the presence of an increased production of MG associated with protein modification that results in LMW-AGE (partial proteolysis of AGE proteins) increases in serum. This increased carbonyl stress may be of etiological significance. Sources of Research Support: Project supported by DAIP Universidad de Guanajuato (project 011/2015) and Touro Universit

Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes

Penetrance of variants in monogenic disease and clinical utility of common polygenic variation has not been well explored on a large-scale. Here, the authors use exome sequencing data from 77,184 individuals to generate penetrance estimates and assess the utility of polygenic variation in risk prediction of monogenic variants

Los Conceptos en Evolución sobre Diabetes Los Conceptos en Evolución sobre Diabetes

Important concepts on diabetes Mellitus have evolved recently. The concepts and practical applications on the metabolic syndrome have been questioned, yet the importance of its components is unchanged. The actual definition of prediabetes is also under scrutiny, and its utility for the identification of the preclinical stage of diabetes seems of limited utility. Insulin resistance is no longer considered the principal factor underlying diabetes, however non-alcoholic fatty liver disease is identified as frequent and important associated pathology. Deficient insulin secretion is now considered a sine qua non condition for the installation of diabetes, but the main cause of it is yet to be recognized. In recent months about fifteen genes associated to type 2 diabetes have been identified, but they can only account for about fifteen percent of the variability on the installation of disease. The importance of perinatal imprinting and the influence of early alimentary experiences for the future appearance of diabetes and the cardiovascular risk are now under reconsideration. The importance of feeding on the appearance of metabolic alterations, now focus attention on the food content of advanced glycosilation end products (AGEs) and the trans- fatty acids. These factors may also be significant for the physiopathology and clinical course of diabetes mellitus. Los conceptos sobre la diabetes mellitus tipo 2 han evolucionado rápidamente. Actualmente se cuestionan las bases conceptuales y la utilidad práctica del síndrome metabólico, aunque la importancia de sus componentes sigue vigente. La defi nición actual de la prediabetes también parece endeble, como un medio para identifi car la etapa preclínica de la enfermedad. La resistencia a la insulina aunque ya no se identifi ca como la causa principal de la diabetes mellitus, tiene un componente muy importante que debe ser considerado, que es el hígado graso no alcohólico. Por otra parte la defi ciente secreción de insulina se considera la condición sine qua non para la instalación de la diabetes mellitus tipo 2, pero su defecto principal no ha sido identifi cado aunque si diversos factores coadyuvantes. Se han identificado cerca de 15 genes asociados a la enfermedad, pero se calcula que solo explican cerca del 15% de su variabilidad. Por ello se explora la importancia de las improntas perinatales, como el peso al nacer, las condiciones metabólicas de la madre y la alimentación el primer año de vida. La importancia de la alimentación tanto en calidad como en cantidad, ahora se examina con más detalle mediante el estudio del efecto de la ingesta de AGEs (productos finales de glucosilación avanzada) y los ácidos grasos trans, que parecen participar en la fisiopatología y el curso clínico de la diabetes. </span