Subcutaneous fat loss is greater than visceral fat loss with diet and exercise, weight-loss promoting drugs and bariatric surgery: a critical review and meta-analysis.

Aim of this review is to compare visceral and subcutaneous fat loss with all available strategies (diet and exercise, weight-loss promoting agents and bariatric surgery). Eighty-nine studies, all full papers, were analyzed to evaluate visceral and subcutaneous fat changes, measured through ultrasound, computerized tomography, magnetic resonance imaging and expressed as thickness, weight, area and volume. Studies were included in a meta-analysis (random-effects model). Intervention effect (absolute and percent changes of visceral and subcutaneous fat) was expressed as standardized mean differences, with 95% confidence intervals. Publication bias was formally assessed. The result was that subcutaneous fat was greater than visceral fat when measured as area, volume and weight, not as thickness; decrease of subcutaneous fat was greater than visceral fat when measured as area, volume and weight, not as thickness; percent decrease of visceral fat was always greater than percent decrease of subcutaneous fat, with no differences between different strategies. No intervention preferentially targets visceral fat. Basal visceral fat depots are smaller than basal subcutaneous fat depots. Visceral fat loss is linked to subcutaneous fat loss. With all strategies, percent decrease of visceral fat prevails on subcutaneous fat loss.

Bariatric surgery and diabetic retinopathy: a systematic review and meta-analysis of controlled clinical studies.

BACKGROUND: Uncontrolled studies have indicated appearance or progression of diabetic retinopathy in obese diabetic patients after bariatric surgery. The aim of this systematic review and meta-analysis was to compare the rate of appearance, as well as progression or regression of diabetic retinopathy in studies comparing medical and surgical treatment of obese type 2 diabetes. METHODS AND FINDINGS: Intervention effect (new cases of retinopathy, and cases with any change of diabetic retinopathy score) was expressed as odds ratio (OR), with 95% confidence intervals (CIs); change of diabetic retinopathy score was expressed as standardized mean difference (SMD), with 95% CIs. Meta-analyses were performed by a random-effects model according to DerSimonian and Laird. Heterogeneity was assessed through Q and I2 statistics for each comparison, and potential sources of heterogeneity were discussed where appropriate. Appropriate methodology [preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement] was used. Seven studies were analyzed, and incident cases of retinopathy were fewer with bariatric surgery than with medical treatment; change of retinopathy score (three studies) was not different, while only two studies were available on numbers of patients showing progression or regression of retinopathy. Heterogeneity was not significant, and publication bias was not present. CONCLUSIONS: Bariatric surgery seems to prevent new cases of diabetic retinopathy, but available studies are not sufficient to support progression or regression of retinopathy. Further studies are needed to draw firm conclusions on the effect of bariatric surgery on diabetic retinopathy.

Prevention of type 2 diabetes; a systematic review and meta-analysis of different intervention strategies.

AIM: Different intervention strategies can prevent type 2 diabetes (T2DM). Aim of the present systematic review and meta-analysis was to evaluate the effectiveness of different strategies. METHODS: Studies were grouped into 15 different strategies: 1: diet plus physical activity; 2: physical activity; 3-6: anti-diabetic drugs [glitazones, metformin, beta-cell stimulating drugs (sulphanylureas, glinides), alfa-glucosidase inhibitors]; 7-8: cardiovascular drugs (ACE inhibitors, ARB, calcium antagonists); 9-14 [diets, lipid-affecting drugs (orlistat, bezafibrate), vitamins, micronutrients, estrogens, alcohol, coffee]; 15: bariatric surgery. Only controlled studies were included in the analysis, whether randomized, non-randomized, observational studies, whether primarily designed to assess incident cases of diabetes, or performed with other purposes, such as control of hypertension, of ischemic heart disease or prevention of cardiovascular events. Appropriate methodology [preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement] was used. Seventy-one studies (490 813 subjects), published as full papers, were analysed to identify predictors of new cases of T2DM, and were included in a meta-analysis (random-effects model) to study the effect of different strategies. Intervention effect (new cases of diabetes) was expressed as odds ratio (OR), with 95% confidence intervals (C.I.s). Publication bias was formally assessed. RESULTS: Body mass index was in the overweight range for 13 groups, obese or morbidly obese in lipid-affecting drugs and in bariatric surgery. Non-surgical strategies, except for beta-cell stimulating drugs, estrogens and vitamins, were able to prevent T2DM, with different effectiveness, from 0.37 (C.I. 0.26-0.52) to 0.85 (C.I. 0.77-0.93); the most effective strategy was bariatric surgery in morbidly obese subjects [0.16 (C.I. 0.11,0.24)]. At meta-regression analysis, age of subjects and amount of weight lost were associated with effectiveness of intervention. CONCLUSIONS: These data indicate that several strategies prevent T2DM, making it possible to make a choice for the individual subject.

Other aspects of bariatric surgery: liver steatosis, ferritin and cholesterol metabolism.

Bariatric surgery developed in the late 1970 to treat severe hyperlipidemias in overweight individuals, not necessarily obese. Several techniques have been developed, and the concept has come first of a surgery for morbid obesity, then of a cure for diabetes in morbid obesity. There are other aspects of bariatric surgery that deserve attention, beyond BMI and diabetes, such as hypertension, poor life expectancy, increased prevalence of cancer, congestive heart failure, social inadequacy. The aim of this presentation is to review some recent development in clinical research, in the fields of liver steatosis, ferritin metabolism, and cholesterol metabolism. Liver steatosis, also called fatty liver encompasses a graduation of diseases with different clinical relevance and prognosis. NAFLD correlates with atherosclerosis, insulin resistance and diabetes mellitus. There is now evidence that weight loss, obtained through diet or restrictive surgery, reduces the prevalence (and the severity) of NAFLD. An other issue is represented by serum ferritin concentrations, that are strongly associated with fibrosis, portal and lobular inflammation in NAFLD patients, especially in the presence of obesity. Body iron contributes to excess oxidative stress already at non iron overload concentrations. Moreover, serum ferritin is an important and independent predictor of the development of diabetes. Weight loss is accompanied by reduction of ferritin, more after restrictive than malabsorptive surgery. Metabolic changes are greater after malabsorptive or mixed surgery than after purely restrictive surgery, and this has been ascribed to a greater weight loss. Studies comparing the two kinds of surgery indicate that, for the same amount of weight loss, decrease of cholesterol is greater with the former than with the latter techniques, and this difference is mainly due to a greater reduction of intestinal absorption of cholesterol. In the choice of surgery for the single patient, among other aspects, malabsorptive surgery seems to be more indicated in subjects with hyperlipidemia, especially with high cholesterol levels.

La cirugía bariátrica se desarrolló a finales de la década de los 70 para tratar la hiperlipidemia severa en personas con sobrepeso, no necesariamente obesos. A lo largo de los años se han desarrollado varias técnicas quirúrgicas que han sido utilizadas en primer lugar en la obesidad mórbida y posteriormente en el tratamiento de la diabetes. Hay otros aspectos de la cirugía bariátrica que merecen atención más allá del IMC y la diabetes, como la hipertensión, la pobre esperanza de vida, una mayor prevalencia de cáncer, insuficiencia cardíaca e inadaptación social. El objetivo de este artículo es revisar los recientes avances clínicos en campos de investigación relacionados con la esteatosis hepática, el metabolismo de ferritina y el metabolismo del colesterol. La esteatosis hepática, también llamada hígado graso abarca una serie de las enfermedades con diferente pronóstico y relevancia clínica. El Hígado Graso No Alcohólico (NAFLD siglas en ingles) se correlaciona con la aterosclerosis, resistencia a la insulina y diabetes mellitus. Hoy en día existen evidencias de que la pérdida de peso que se obtiene a través de la dieta o cirugía restrictiva, reduce la prevalencia (y la gravedad) de la NAFLD. Otro tema de estudio incluye las concentraciones de ferritina sérica, que están fuertemente asociadas con la fibrosis e inflamación lobular y portal en pacientes con NAFLD, especialmente en presencia de obesidad. El exceso de hierro corporal en obesos contribuye a un aumento del estrés oxidativo debido a una sobrecarga en su concentración. Por otra parte, la ferritina sérica es un indicador importante e independiente del desarrollo de la diabetes. La pérdida de peso se acompaña de una disminución de la ferritina. Esta disminución es más evidente tras una cirugía restrictiva que tras una malabsortiva. Los cambios metabólicos son mayores después de una cirugía malabsortiva o mixta que tras una cirugía puramente restrictiva, y esto se ha atribuido a una mayor pérdida de peso. Estudios que comparan los dos tipos de cirugía indican que, para la mismo índice de pérdida de peso, la disminución de colesterol es mayor con las primeras técnicas que con las últimas, y esta diferencia se debe principalmente a una mayor reducción de la absorción intestinal del colesterol. En la elección de la cirugía para un paciente concreto, entre otros aspectos, la cirugía de malabsorción parece estar más indicada en sujetos con hiperlipemia, especialmente con altos niveles de colesterol.

Other aspects of bariatric surgery: liver steatosis, ferritin and cholesterol metabolism / Otros aspectos de la cirugía bariátrica: esteatosis hepática, metabolismo de ferritina y colesterol

Bariatric surgery developed in the late 1970 to treat severe hyperlipidemias in overweight individuals, not necessarily obese. Several techniques have been developed, and the concept has come first of a surgery for morbid obesity, then of a cure for diabetes in morbid obesity. There are other aspects of bariatric surgery that deserve attention, beyond BMI and diabetes, such as hypertension, poor life expectancy, increased prevalence of cancer, congestive heart failure, social inadequacy. The aim of this presentation is to review some recent development in clinical research, in the fields of liver steatosis, ferritin metabolism, and cholesterol metabolism. Liver steatosis, also called fatty liver encompasses a graduation of diseases with different clinical relevance and prognosis. NAFLD correlates with atherosclerosis, insulin resistance and diabetes mellitus. There is now evidence that weight loss, obtained through diet or restrictive surgery, reduces the prevalence (and the severity) of NAFLD. An other issue is represented by serum ferritin concentrations, that are strongly associated with fibrosis, portal and lobular inflammation in NAFLD patients, especially in the presence of obesity. Body iron contributes to excess oxidative stress already at non iron overload concentrations. Moreover, serum ferritin is an important and independent predictor of the development of diabetes. Weight loss is accompanied by reduction of ferritin, more after restrictive than malabsorptive surgery. Metabolic changes are greater after malabsorptive or mixed surgery than after purely restrictive surgery, and this has been ascribed to a greater weight loss. Studies comparing the two kinds of surgery indicate that, for the same amount of weight loss, decrease of cholesterol is greater with the former than with the latter techniques, and this difference is mainly due to a greater reduction of intestinal absorption of cholesterol. In the choice of surgery for the single patient, among other aspects, malabsorptive surgery seems to be more indicated in subjects with hyperlipidemia, especially with high cholesterol levels (AU)

La cirugía bariátrica se desarrolló a finales de la década de los 70 para tratar la hiperlipidemia severa en personas con sobrepeso, no necesariamente obesos. A lo largo de los años se han desarrollado varias técnicas quirúrgicas que han sido utilizadas en primer lugar en la obesidad mórbida y posteriormente en el tratamiento de la diabetes. Hay otros aspectos de la cirugía bariátrica que merecen atención más allá del IMC y la diabetes, como la hipertensión, la pobre esperanza de vida, una mayor prevalencia de cáncer, insuficiencia cardíaca e inadaptación social. El objetivo de este artículo es revisar los recientes avances clínicos en campos de investigación relacionados con la esteatosis hepática, el metabolismo de ferritina y el metabolismo del colesterol. La esteatosis hepática, también llamada hígado graso abarca una serie de las enfermedades con diferente pronóstico y relevancia clínica. El Hígado Graso No Alcohólico (NAFLD siglas en ingles) se correlaciona con la aterosclerosis, resistencia a la insulina y diabetes mellitus. Hoy en día existen evidencias de que la pérdida de peso que se obtiene a través de la dieta o cirugía restrictiva, reduce la prevalencia (y la gravedad) de la NAFLD. Otro tema de estudio incluye las concentraciones de ferritina sérica, que están fuertemente asociadas con la fibrosis e inflamación lobular y portal en pacientes con NAFLD, especialmente en presencia de obesidad. El exceso de hierro corporal en obesos contribuye a un aumento del estrés oxidativo debido a una sobrecarga en su concentración. Por otra parte, la ferritina sérica es un indicador importante e independiente del desarrollo de la diabetes. La pérdida de peso se acompaña de una disminución de la ferritina. Esta disminución es más evidente tras una cirugía restrictiva que tras una malabsortiva. Los cambios metabólicos son mayores después de una cirugía malabsortiva o mixta que tras una cirugía puramente restrictiva, y esto se ha atribuido a una mayor pérdida de peso. Estudios que comparan los dos tipos de cirugía indican que, para la mismo índice de pérdida de peso, la disminución de colesterol es mayor con las primeras técnicas que con las últimas, y esta diferencia se debe principalmente a una mayor reducción de la absorción intestinal del colesterol. En la elección de la cirugía para un paciente concreto, entre otros aspectos, la cirugía de malabsorción parece estar más indicada en sujetos con hiperlipemia, especialmente con altos niveles de colesterol (AU)

High pressure liquid chromatography and electrospray ionization mass spectrometry are advantageously integrated into a two-levels approach to detection and identification of haemoglobin variants.

Detecting and correctly identifying haemoglobin (Hb) variants is typically achieved by a two-levels laboratory approach. We report our experience in dealing with 91 Hb variants, including a number of frequent and a few rare variants. Screening included akaline agarose gel electrophoresis (AGE), ion-exchange automated high-performance liquid chromatography (HPLC) and a test for deoxyhaemoglobin solubility. Identification was based on electrospray ionization-mass spectrometry (ESI-MS). Our results confirmed the advantages of HPLC over AGE for screening, because of the occurrence of some electrophoretically 'silent' variants. ESI-MS permitted the definitive identification of 90 of the 91 variants included in the study, in some cases (e.g. HbS) through the application of a simple protocol (direct injection of the sample), in other cases requiring the application of more demanding procedures (purification of the variant chain and peptide analysis after enzymatic or chemical cleavage). In an additional case (Hb J-Oxford), ESI-MS assay did not lead to definitive identification, but gave indications for designing the appropriate primers to focus DNA sequence analysis on the specific region of the gene. Deoxyhaemoglobin solubility test was positive only in the presence of HbS. We conclude that HPLC and ESI-MS are advantageously integrated into a two-level analytical system for the detection and confirmation of variant Hbs.

Functional Analysis of six novel ORFs on the left arm of Chromosome XII of Saccharomyces cerevisiae reveals three of them responding to S-starvation.

Six novel Open Reading Frames (ORFs) located on the left arm of the chromosome XII (YLL061w, YLL060c, YLL059c, YLL058w, YLL057c and YLL056c) have been analysed using either short-flanking homology (SFH) or long-flanking homology (LFH) gene replacement. Sporulation and tetrad analysis showed none of these ORFs to be essential for vegetative growth. The standard EUROFAN growth tests failed to reveal any obvious phenotypes resulting from deletion of each of the ORFs. Bioinformatic analysis revealed that YLL061w is probably an amino acid permease for S-methylmethionine and that YLL060c encodes a glutathione transferase which is involved in cellular detoxification, while YLL058w may play a role in sulphur-containing amino-acid metabolism, YLL057c in sulphonate catabolism and YLL056c in stress response. The transcription of three ORFs (YLL061w, YLL057c and YLL056c) has been shown to increase more than 10-fold under sulphate starvation. Replacement cassettes, comprising the kanMX marker flanked by each ORF's promoter and terminator regions, were cloned into pUG7. All the cognate clones, were generated using direct PCR products amplified from genomic DNA or using gap-repair. All clones and strains produced have been deposited in the EUROFAN genetic stock centre (EUROSCARF, Frankfurt).

Functional analysis of eight open reading frames on chromosomes XII and XIV of Saccharomyces cerevisiae.

Deletion, together with basic functional and bioinformatic analyses has been carried out on eight novel ORFs discovered during the sequencing of the Saccharomyces cerevisiae genome. Six ORFs (YLL049w, YLL051c, YLL052c, YLL053c, YLL054c and YLL055w) located on the left arm, and one (YLR130c) on the right arm, of chromosome XII, and an eighth ORF (YNL331c) on the left arm of the chromosome XIV, have been investigated. ORFs were deleted by the SFH-PCR gene-replacement strategy. Basic functional analysis revealed no obvious phenotype for any of the eight ORFs. Bioinformatic analysis, however, revealed possible functions for seven of the ORFs on the basis of the amino acid sequence similarity of their predicted protein products to those of proteins with known functions. ORF YLL051c (FRE6) shows similarity to iron transport proteins, such as ferric reductase. YLL052c and YLL053c appear to be aquaporins. The product of YLL054c (Yll054p) is highly similar to the oleate-specific transcriptional activator protein (Pip2p), which is involved in the peroxisomal induction pathway (pip). ORF YLL055w is similar to Dal5p, allantoate permease, and may play role in allantoin transport. YLR130c (ZRT2) is a low-affinity zinc transporter protein. YNL331c is also named AAD14, which is induced by chemicals that induce oxidative stress by depleting the cell of glutathione.

Functional analysis of six novel ORFs on the left arm of chromosome XII in Saccharomyces cerevisiae reveals two essential genes, one of which is under cell-cycle control.

Six novel Open Reading Frames (ORFs) located on the left arm of chromosome XII (YLL044w, YLL042c, YLL040c, YLL038c, YLL035w and YLL034c) have been analysed using short-flanking homology (SFH) gene replacement. Sporulation and tetrad analysis showed that YLL035w and YLL034c are essential for cell growth; yll035w spores arrested after two or three cell divisions, while the majority of yll034c spores stopped growth within two cell cycles after germination. Complementation of the yll035w deletion with its cognate clone, and a promoter-substitution experiment, indicated that the promoter of YLL035w may lie within the adjacent ORF, YLL036c. Transcriptional analysis demonstrated that YLL035w is under cell-cycle regulation. Bioinformatic analyses produced significant matches between YLL034c and mammalian valosin and many other ATPases. The standard EUROFAN growth tests failed to reveal obvious phenotypes resulting from deletion of any of the four non-essential ORFs. Replacement cassettes, comprising the kanMX marker flanked by each ORF's promoter and terminator regions, were cloned into pUG7. All the cognate clones, except for YLL040c, were generated using direct PCR products amplified from genomic DNA or using gap-repair. All clones and strains produced have been deposited in the EUROFAN genetic stock centre (EUROSCARF, Frankfurt).