The potential role of dietary advanced glycation endproducts in the development of chronic non-infectious diseases: a narrative review.

Increasing clinical and experimental evidence accumulated during the past few decades supports an important role for dietary advanced glycation endproducts (AGE) in the pathogenesis of many chronic non-infectious diseases, such as type 2 diabetes, CVD and others, that are reaching epidemic proportions in the Western world. Although AGE are compounds widely recognised as generated in excess in the body in diabetic patients, the potential importance of exogenous AGE, mostly of dietary origin, has been largely ignored in the general nutrition audience. In the present review we aim to describe dietary AGE, their mechanisms of formation and absorption into the body as well as their main mechanisms of action. We will present in detail current evidence of their potential role in the development of several chronic non-infectious clinical conditions, some general suggestions on how to restrict them in the diet and evidence regarding the potential benefits of lowering their consumption.

Acceptability of self-sampling and human papillomavirus testing among non-attenders of cervical cancer screening programs in El Salvador.

In a cross-sectional study carried out in El Salvador between February 2016 and July 2017, self-sampling and human papillomavirus (HPV) testing was found to be highly acceptable among 2019 women who had not attended a cervical cancer screening in at least 3 years. Within this population, HPV positivity rates differed according to age, marital status, number of children, and lifetime sexual partners. The proportion of women who tested HPV positive or who were diagnosed with cervical intraepithelial neoplasia grade 2 (CIN2) or more severe diagnoses (CIN2+) was similar to the general population of the area. Among the reasons for failing to participate in previous screening programs, non-attending women described logistic concerns, but also erroneous beliefs regarding HPV and cervical cancer, misconceptions regarding the screening procedure, discomfort with male providers, and confidentiality fears. The aim of this study was to identify opportunities and challenges that emerged from the use of self-sampling and HPV testing as part of a public cervical cancer control effort in a low-resource setting.

Premature loss of muscle mass and function in type 2 diabetes.

INTRODUCTION: Muscle mass and function are among the most relevant factors that contribute to an optimal quality of life, and are strong predictors of mortality in the elderly. Loss of lean tissues and deterioration of muscle function have been described as one of the many complications of type 2 diabetes mellitus (DM2), but most studies do not isolate age as an intervening factor. AIM: To study whether adult DM2 patients up to 60years of age have decreased muscle mass and function compared with healthy non-diabetic (ND) subjects of similar age. METHODOLOGY: Appendicular fat-free mass (ApFFM) by dual X-ray absorptiometry (DEXA), handgrip strength (HS), quadriceps strength (QS), 12 min walking capacity (12MW) and the Timed Up and Go test (TUG) were measured in 100 DM2 patients and 39 ND controls. Muscle quality, or the ratio between lean mass and muscle strength of upper and lower limbs, and the functional limitations associated with pain and stiffness assessed according to the Western Ontario and McMaster Universities Arthrosis Index (WOMAC) were also recorded. Specific tests were performed to rule out microvascular diabetic complications (retinal and peripheral nerves), metabolic control, kidney function and vitamin D status and examine their association with ApFFM and function. RESULTS: ApFFM was significantly higher among DM2 female patients and lower among diabetic men. However opposite results were obtained when individual values were corrected for body mass index (BMI), specifically among women, who were more likely to be obese. As for muscle strength and global functionality tests, significantly better performances in TUG, 12MW, QS and HS were observed among ND subjects of both sexes. These differences prevailed even after excluding diabetic patients with microvascular complications as well as those with more than 10years of diabetes. Muscle quality was also significantly better among ND women. Higher scores of pain and stiffness in the WOMAC scale correlated with 12MW and TUG in both groups but did not correlate with ApFFM. CONCLUSIONS: We found a clear deterioration of lean mass and muscle functions among adult DM2 patients of up to 60years old, independent of length of disease, metabolic control, vitamin D status and presence of microvascular complications and pain.

Effect of weight maintenance or gain in a 10 years period over telomere length, sirtuin 1 and 6 expression and carotid intima media thickness.

BACKGROUND: Lack of weight gain throughout adult life could mimic the beneficial effects of energy restriction in humans. The present study aimed to assess the effects of weight stability or gain, over a period of 10 years, on telomere length, sirtuin 1 and 6 expression, and carotid intima media thickness. METHODS: We studied 148 healthy adults (age range 20-59 years; 101 females) who had an objective record of their weight 10 years before. They were classified as weight losers, weight maintainers, weight gainers and extreme weight gainers. A fasting blood sample was obtained for routine laboratory and isolation of peripheral blood mononuclear cells, to extract DNA and RNA, and to measure telomere length and sirtuin 1 and 6 expression, respectively. Carotid intima media thickness was measured by ultrasound. Body composition was measured by Dual-energy X-ray absorptiometry. RESULTS: In the 10-year period, 24 participants lost weight (17 females), 65 maintained weight (41 females), 25 gained weight (15 females) and 34 were extreme weight gainers (28 females). Female weight gainers had a higher body mass index, waist circumference, total body fat and homeostatic model assessment insulin resistance. Male weight gainers had a higher hip circumference and total body fat. No differences in telomere length, sirtuin 1 expression and carotid intima media thickness were observed between weight gainers and maintainers. CONCLUSIONS: No effect of weight maintenance or gain was observed on metabolic and vascular markers of ageing.

Dietary intake increases serum levels of carboxymethil-lysine (CML) in diabetic patients.

INTRODUCTION: Advanced glycation end products are produced endogenously, in association with hyperglycemia and oxidative stress. They can also be generated during cooking or food processing and, once absorbed, alter protein function and promote inflammation. METHODS: We selected 40 healthy male subjects, 17 patients with type 2 diabetes of both sexes and 15 patients with type 1 diabetes of both sexes. Each participant underwent both a food frequency questionnaire (FFQ) and 24-hour dietary recall specially adapted for measuring CML intake, anthropometry, measurement of blood pressure and biochemical parameters in blood and urine. RESULTS: Serum CML levels were significantly higher in patients with diabetes compared to healthy subjects (p 0.04), showing a direct relationship between dietary intake and serum levels of CML in T2D patients (r 0.53 p 0.03). sCML levels correlated positively with length of diabetes mellitus, and inversely with body mass index (BMI). The most important dietary factor contributing to raise CML levels in these patients with diabetes was the consumption of milk powder. CONCLUSION: Serum levels of CML were found to be higher among diabetic subjects, associated to length of diabetes as expected, but also with the ingestion of foods containing higher amounts of ML. The consumption of milk powder in this group is a major determinant of increased serum levels.

Proliferation and differentiation of human adipocyte precursor cells: differences between the preperitoneal and subcutaneous compartments.

Human adipocyte precursor cells (APC) have been characterized in their proliferation and differentiation potential from subcutaneous, omental, and mesenteric depots, mostly from morbidly obese patients. Cells from the preperitoneal adipose compartment have not been characterized yet, least of all when obtained from normal weight subjects. The aim was to compare proliferation and differentiation of subcutaneous (SC) and preperitoneal (PP) APC derived from adipose tissue in healthy subjects with different body mass. SC and PP adipose tissue was obtained during surgery of inguinal hernias in five healthy non-obese subjects and three obese otherwise healthy men. APC, obtained by collagenase digestion, were cultured. Proliferation was assayed by cell counting and differentiation by oil red O staining and flow cytometry using Nile Red staining. Proliferation of SC was higher than PP APC. Such differences between both compartments were even higher in APC obtained from obese patients. Conversely PP APC differentiated earlier in vitro compared with SC cells. These results agree with published data on fat cell proliferation. However regarding differentiation, our data show that APC from deeper depots (in this case PP) differentiate earlier than subcutaneous APC. This is different to previous studies performed in mesenteric or omental adipose tissue.

[Quality of life of patients subjected to gastric bypass more than one year ago: influence of socioeconomic status]. / Calidad de vida en pacientes operadas de bypass gástrico hace más de un año: Influencia del nivel socioeconómico.

BACKGROUND: The study of the effects of bariatric surgery on quality of life in patients of different socioeconomic levels (SEL) is worthwhile. AIM: To study quality of life (QoL), eating behavior, depressive symptoms and sexuality in patients subjected to a gastric bypass (GBP) more than 1 year before. MATERIAL AND METHODS: The sample was composed of 33 GPB patients (19 high SEL and 14 low SEL), and 27 non-operated women (18 high SEL and 9 low SEL) of similar weight and age, as controls. Assessment included medical history anthropometry radiological densitometry. Eating behavior was assessed using the three factor eating questionnaire, quality of life using SF-36 and the Bariatric Analysis of Reporting Outcome System (BAROS) depressive symptoms were assessed using the Beck scale version II and sexual behavior using the female sexual function index (FSFI). RESULTS: QoL was lower in operated patients from low SEL, especially when compared to high SEL control women. Operated patients had a predominantly restrictive pattern of eating behavior Eating behavior disorders were detected in 5 of 33 operated patients versus 4 of 27 controls (p =ns). Sexual function was absent or dysfunctional in 22 operated versus 8 controls (p =0,02). No significant differences were observed for depressive symptoms, between operated patients and controls. CONCLUSIONS: In the long term, QoL of bariatric patients, especially those from low SEL, is inferior to control women and Chilean general population. Operated patients have restrictive eating patterns and lower sexual satisfaction indexes. Frequency of depressive symptoms was high both in bariatric and control women.

Calidad de vida en pacientes operadas de bypass gástrico hace más de un año: Influencia del nivel socioeconómico / Quality of life of patients subjected to gastric bypass more than one year ago: Influence of socioeconomic status

Background: The study of the effects of bariatric surgery on quality of life in patients of different socioeconomic levels (SEL) is worthwhile. Aim: To study quality of life (QoL), eating behavior, depressive symptoms and sexuality in patients subjected to a gastric bypass (GBP) more than 1 year before. Material and methods: The sample was composed of 33 GPB patients (19 high SEL and 14 low SEL), and 27 non-operated women (18 high SEL and 9 low SEL) of similar weight and age, as controls. Assessment included medical history anthropometry radiological densitometry. Eating behavior was assessed using the three factor eating questionnaire, quality of life using SF-36 and the Bariatric Analysis of Reporting Outcome System (BAROS) depressive symptoms were assessed using the Beck scale version II and sexual behavior using the female sexual function index (FSFI). Results: QoL was lower in operated patients from low SEL, especially when compared to high SEL control women. Operated patients had a predominantly restrictive pattern of eating behavior. Eating behavior disorders were detected in 5 of 33 operated patients versus 4 of 27 controls (p =ns). Sexual function was absent or dysfunctional in 22 operated versus 8 controls (p =0,02). No significant differences were observed for depressive symptoms, between operated patients and controls. Conclusions: In the long term, QoL of bariatric patients, especially those from low SEL, is inferior to control women and Chilean general population. Operated patients have restrictive eating patterns and lower sexual satisfaction indexes. Frequency of depressive symptoms was high both in bariatric and control women.

Fluorescent serum and urinary advanced glycoxidation end-products in non- diabetic subjects.

INTRODUCTION: Advanced glycoxidation end-products (AGEs) are involved in age-related conditions and diabetic complications. Diet intake contributes to their circulating concentrations. AIM: To measure serum and urinary AGEs in non-diabetic volunteers and relate their concentration to body composition, blood chemistry and dietary ingestion. METHODS: We studied 41 adult men (31 middle-aged adults and 10 elderly). A nutritional assessment including a dietary recall designed for detection of AGE ingestion (specifically carboxymethyl-lysine(CML)), and anthropometric measurements were performed. Also serum lipoproteins, insulin, glucose, leptin and C reactive protein (CRP). AGEs were measured in serum and urine samples using size exclusion chromatography and flow injection assay (FIA); the technical procedures were first employed in 11 heterogeneous diabetics, as positive controls for this methodology. RESULTS: Serum and urinary chromatograms indicated that areas under the curve were not different in younger compared with elderly adults. AGEs did not correlate with dietary intake, body composition, nor metabolic parameters, however they correlated significantly with renal function and CRP concentration. DISCUSSION: In these non-diabetic volunteers, with low CML intake, serum and urinary concentration of AGEs were not related to dietary intake. AGEs were related to renal function and CRP, but not to body composition, lipoproteins, insulin and glucose.

[Glycemic and insulin indices of tube feeding formulas in healthy adults]. / Determinación de los índices glicémicos y de insulina en fórmulas para alimentación enteral en adultos sanos.

BACKGROUND: In acute illnesses, plasma glucose levels are often increased and generally parallel the severity of stress. Hyperglycemia caused by reduced insulin sensitivity and reduced insulin secretion is associated with increased susceptibility to infections. Maintaining blood glucose levels at or below 110 mg/dl reduces morbidity and mortality in critically ill patients. AIM: To measure the glucose and insulin responses of four commercially available enteral formulas compared with a standard meal reference product. MATERIAL AND METHODS: The glycemic index (GI) and the insulin index (II) were determined in a randomized, cross over protocol in 38 healthy volunteers between 18 and 46 years of age. Each subject underwent five tests: three with the standard meal (bread) and two with the study products. The enteral formulas were Clinutren HPR (whole protein of high protein value), Crucial (casein peptide based formula), Peptamen, (whey peptide based formula), Glytrol (formula for diabetics with whole protein with fiber). Each study product was evaluated 10 times. RESULTS: The diabetic formula and the high protein energy dense formulas induced a significantly lower GI (p <0.02) compared with the standard meal. The GI response did not appear to be due to enhanced insulin secretion. The other tested formulas had lower GI than the standard meal, but in addition they exhibited increased II The whey based peptide formulation produced the highest insulin response (p <0.03). CONCLUSIONS: Both GI and II are related to the concentration, form and type of protein contained in the enteral formula. The whey peptide formulation produced a low GI with the highest insulin index. Based on the low GI of these enteral products, all can be useful to provide nutritional support during metabolic stress, without adding an additional challenge to blood glucose management.

Determinación de los índices glicémicos y de insulina en fórmulas para alimentación enteral en adultos sanos / Glycemic and insulin indices of tube feeding formulas in healthy adults

Background: In acute illnesses, plasma glucose levels are often increased and generally parallel the severity of stress. Hyperglycemia caused by reduced insulin sensitivity and reduced insulin secretion is associated with increased susceptibility to infections. Maintaining blood glucose levels at or below 110 mg/dl reduces morbidity and mortality in critically ill patients. Aim: To measure the glucose and insulin responses of four commercially available enteral formulas compared with a standard meal reference product. Material and Methods: The glycemic index (GI) and the insulin index (II) were determined in a randomized, cross over protocol in 38 healthy volunteers between 18 and 46 years of age. Each subject underwent five tests: three with the standard meal (bread) and two with the study products. The enteral formulas were Clinutren HPR (whole protein of high protein value), Crucial® (casein peptide based formula), Peptamen®, (whey peptide based formula), Glytrol® (formula for diabetics with whole protein with fiber). Each study product was evaluated 10 times. Results: The diabetic formula and the high protein energy dense formulas induced a significantly lower GI (p <0.02) compared with the standard meal. The GI response did not appear to be due to enhanced insulin secretion. The other tested formulas had lower GI than the standard meal, but in addition they exhibited increased II The whey based peptide formulation produced the highest insulin response (p <0.03). Conclusions: Both GI and II are related to the concentration, form and type of protein contained in the enteral formula. The whey peptide formulation produced a low GI with the highest insulin index. Based on the low GI of these enteral products, all can be useful to provide nutritional support during metabolic stress, without adding an additional challenge to blood glucose management.

Fluorescent serum and urinary advanced glycoxidation end-products in non- diabetic subjects

Introduction: Advanced glycoxidation end-products (AGEs) are involved in age-related conditions and diabetic complications. Diet intake contributes to their circulating concentrations. Aim: To measure serum and urinary AGEs in non-diabetic volunteers and relate their concentration to body composition, blood chemistry and dietary ingesti¢n. Methods: We studied 41 adult men (31 middle-aged adults and 10 elderly). A nutritional assessment including a dietary recall designed for detection of AGE ingesti¢n (specifically carboxymethyl-lysine(CML)), and anthropometric measurements were performed. Also serum lipoproteins, insulin, glucose, leptin and C reactive protein (CRP). AGEs were measured in serum and urine samples using size exclusion chromatography and flow injection assay (FIA); the technical procedures were first employed in 11 heterogeneous diabetics, as positive controls for this methodology. Results: Serum and urinary chromatograms indicated that areas under the curve were not different in younger compared with elderly adults. AGEs did not correlate with dietary intake, body composition, nor metabolic parameters, however they correlated significantly with renal function and CRP concentration. Discussion: In these non-diabetic volunteers, with low CML intake, serum and urinary concentration of AGEs were not related to dietary intake. AGEs were related to renal function and CRP, but not to body composition, lipoproteins, insulin and glucose.

[Weight maintenance in humans. Could it mimic calorie restriction of animal models?]. / La mantención de peso en humanos podría ser equivalente a la restricción calórica de los modelos animales?

BACKGROUND: Energy restriction (ER) extends life span in animals, by decreasing oxidative stress. AIM: To compare adiposity, metabolic variables and DNA oxidative damage, among adults, reporting a constant body weight (weight maintainers), versus those reporting a progressive increase (weight gainers). SUBJECTS AND METHODS: Clinical history, dietary recall, anthropometric measures, abdominal CT scan and fasting blood samples (to measure lipoproteins, glucose and insulin), were obtained in 44 males. These subjects were classified as weight maintainers if they had a change in weight of 3 kg or less in the last 10 years, or weight gainers, if they had a weight increment of more than 6 kg, in the same lapse. Oxidative damage was assessed by 8-hydroxydeoxyguanosine (8-OHdG), in DNA extracted from circulating lymphocytes, in 5 weight maintainers, 8 weight gainers and 5 healthy elders. RESULTS: Energy Intake was 18% higher in weight gainers (p <0.01). Adiposity and central fat were higher among weight gainers (p <0.01). Abdominal fat correlated with serum lipoproteins, glucose and insulin sensitivity, assessed by the Homeostasis Model Assessment (HOMA). 8-OHdG levels did not differ between groups. CONCLUSIONS: The analysis of weight change based on the clinical history correlates with actual body composition, thus it may be a reliable indicator of long term energy Intake. This method could be comparable to weight clamp models employed in animals to study aging.

[A review of the epidemiology of multiple sclerosis in Mexico]. / Revisión de la epidemiología de la esclerosis múltiple en México.

OBJECTIVE: To review the epidemiological information on multiple sclerosis in Mexico. DEVELOPMENT AND CONCLUSIONS: The results of the few epidemiological studies on multiple sclerosis show a prevalence of 1.5/100,000 inhabitants, a figure which is not in concordance with studies carried out by institutions, which indicates an increase in the frequency of new cases. This information is not necessarily due to a true increase in prevalence. Possibly this increase is related to improved methodology for clinical and paraclinical diagnosis, especially the use of magnetic resonance. There is a need for descriptive and analytical epidemiological studies to obtain precise data on this. At present, the Mexican Group for the study of Multiple Sclerosis and The Mexican Association for the study of Multiple Sclerosis are using a questionnaire designed and validated for Mexico in order to determine the clinical characteristics and the prevalence of multiple sclerosis. The results will be available in the near future to improve knowledge regarding the epidemiology of this disorder and its economic impact on the Mexican health systems.

[The importance of folic acid in current medicine]. / Importancia del ácido fólico en la medicina actual.

Lately, folic acid deficiency is gaining a predominant role in the pathogenesis of congenital malformations and cardiovascular diseases in adults. The planning of individual and population preventive strategies for these diseases must consider this deficiency. This paper reviews the anatomical, biochemical and molecular bases of neural tube defects and cardiovascular diseases in adults. In these two frequent diseases, folic acid supplementation has shown a clear cut protective effect.

[New pieces in the puzzle of atherogenesis]. / Nuevas piezas en el puzzle de la aterogénesis.

The contribution of high serum levels of cholesterol to atherogenesis has been widely recognized, but the mechanisms are not completely clear. Numerous publications have emphasized that oxidized, but not native low-density lipoproteins, are the particles incorporated into the arterial wall. A group of receptors generically called "scavenger" (SR), actively bind these modified lipoproteins and incorporate them into monocytes-macrophages, in the arterial intima. SR are not down regulated by intracellular concentrations of cholesterol, thus accumulating huge amounts of lipids, transforming monocyte-macrophages into foam cells, predominant cell type of the fatty streak. The simultaneous cytokine production and migration of other cellular types progressively transform this initial lesion into the organized atherosclerotic plaque. In this setting SR, which are up-regulated by oxidized LDL, play a central promoting role. Its presence has been demonstrated in arterial plaques both in human and animal models, and its blockade protects animals from development or progression of atherosclerosis. In humans, elevated antibody titers to oxidized LDL in patients with coronary stenosis, and increased SR activity, in pro-atherogenic conditions such as haemodialysis, indicate that this model may operate as well, but the evidences are still not solid enough to definitively conclude that the oxidized-LDL-SR hypothesis is a finished puzzle.

Lipid turnover in alcoholics before and after an ethanol load.

Alcohol ingestion decreases plasma free fatty acids (FFAs) and lipid oxidation. This study was conducted to determine palmitate turnover in alcoholics during a short abstinence period and after an ethanol load and in a group of nonalcoholic control subjects, looking for correlations between palmitate turnover, FFA, acetate, and acetoacetate/beta hydroxybutyrate ratio (AKBR). Palmitate C14 turnover was studied in five alcoholics during early abstinence and after a 0.8 g/kg ethanol load, and in five nonalcoholic normal controls. Plasma levels of FFA, acetate, acetoacetate, and beta hydroxybutyrate were measured before and during the ethanol load. A needle hepatic biopsy was performed in alcoholics. FFA levels, palmitate flux, oxidation, and nonoxidative disposal were similar in alcoholics compared with control subjects, decreasing significantly after the ethanol load in both groups. AKBR and ketone bodies were similar in both groups in the basal period. After the alcohol infusion, AKBR decreased significantly. Acetoacetate levels did not change, and beta hydroxybutyrate and total ketone bodies increased significantly in alcoholics and control subjects. A positive correlation was found between FFA levels and palmitate flux. Liver biopsies showed mild changes in the patients studied. The similar inhibition of lipid turnover, FFA release, and the drop in AKBR observed after an alcohol load in alcoholics and control subjects suggest that this effect is mediated by alcohol metabolism and not by metabolic alterations present in alcoholics.

[Markers of hepatic fibrogenesis in alcoholic patients]. / Marcadores de fibrogénesis hepática en pacientes alcohólicos.

BACKGROUND: An elevation of serologic markers of hepatic fibrogenesis has been reported in liver diseases of different etiologies. Among these, the N-terminal type III procollagen (P-III-P) and the P1 proteolytic fragment of laminin (P1 laminin) increase in alcoholic liver damage, in proportion to the progression of this condition. AIM: To study serum levels of P-III-P and P1 laminin in asymptomatic alcoholics with and without liver damage and decompensated alcoholic cirrhotics, compared to normal controls. METHODS: Serum P-III-P and laminin levels were measured in asymptomatic alcoholics during detoxification treatment. Liver biopsies were obtained, in order to detect liver damage, which was graded with a numeric score, considering values over 6 as severe damage. Serum fibrogenesis markers were also measured in a group of decompensated alcoholic cirrhotics. RESULTS: P-III-P levels were significantly higher in cirrhotic patients compared to alcoholics with or without liver damage and to normal controls. Laminin was not different between groups. P-III-P did not correlate with histologic score in asymptomatic patients. CONCLUSIONS: In this study P-III-P and P1 laminin were not usefull discriminators of severe liver damage among asymptomatic alcoholics; their levels were found to rise significantly only when liver disease has become clinically evident.