Obesity is a chronic disease. Positioning statement of the Diabetes, Obesity and Nutrition Workgroup of the Spanish Society of Internal Medicine (SEMI) for an approach centred on individuals with obesity. / La obesidad es una enfermedad crónica. Posicionamiento del grupo de trabajo de Diabetes, Obesidad y Nutrición de la Sociedad Española de Medicina Interna (SEMI) por un abordaje centrado en la persona con obesidad.

INTRODUCTION: Obesity is a chronic, complex and multifactorial metabolic disease involved in the development of chronic noncommunicable diseases such as type 2 diabetes mellitus, cardiovascular disease and cancer. The care of individuals with obesity is an essential part of the holistic approach provided by internal medicine to patients. MATERIAL AND METHODS: Between September 2019 and January 2020, we distributed an online survey to the members of the Spanish Society of Internal Medicine. We prepared a Strengths, Weaknesses, Opportunities, and Threats analysis using the responses and, using the nominal group technique, developed the recommendations. RESULTS: We obtained 599 responses. The respondents mean age was 44.4±11 years, and 52.1% were women. Some 91.8% of the internists evaluate their patients to rule out the comorbidities associated with obesity, mainly type 2 diabetes mellitus (96.2%), cardiovascular disease (88.9%) and obesity-associated hypoventilation syndrome (73%), among others. Some 79.9% provided indications on lifestyle changes. Some 64.1% and 74.9% of the respondents knew the indications for the drugs and bariatric surgery, respectively. Some 93.8% and 83% of the respondents considered obesity and excess weight a chronic disease, and 88.7% considered it a disease of specific interest to internists, who should take an active and leading role in its treatment (85.3%). CONCLUSIONS: The objective of the present document is to determine the degree of understanding and sensitivity of internists regarding the management of obesity and to develop a consensus of recommendations for the Spanish Society of Internal Medicine based on the scientific evidence and the opinion of its members.

Dietary fat may modulate adipose tissue homeostasis through the processes of autophagy and apoptosis.

PURPOSE: Obesity increases the risk of cardiovascular disease, type 2 diabetes mellitus and cancer development. Autophagy and apoptosis are critical processes for development and homeostasis in multicellular organisms and have been linked to a variety of disorders. We aimed to investigate whether the quantity and quality of dietary fat can influence these processes in the adipose tissue of obese people. METHODS: A randomized, controlled trial within the LIPGENE study assigned 39 obese people with metabolic syndrome to 1 of 4 diets: (a) a high-saturated fatty acid diet, (b) a high-monounsaturated fatty acid (HMUFA) diet, and (c, d) two low-fat, high-complex carbohydrate diets supplemented with long-chain n-3 polyunsaturated fatty acids (LFHCC n-3) or placebo (LFHCC), for 12 weeks each. RESULTS: We found an increase in the expression of autophagy-related BECN1 and ATG7 genes after the long-term consumption of the HMUFA diet (p = 0.001 and p = 0.004, respectively) and an increase in the expression of the apoptosis-related CASP3 gene after the long-term consumption of the LFHCC and LFHCC n-3 diets (p = 0.001 and p = 0.029, respectively). CASP3 and CASP7 gene expression changes correlated with HOMA index. CONCLUSION: Our results suggest that the processes of autophagy and apoptosis in adipose tissue may be modified by diet and that the consumption of a diet rich in monounsaturated fat may contribute to adipose tissue homeostasis by increasing autophagy. They also reinforce the notion that apoptosis in adipose tissue is linked to insulin resistance. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT00429195.

Hepatic insulin resistance both in prediabetic and diabetic patients determines postprandial lipoprotein metabolism: from the CORDIOPREV study.

BACKGROUND/AIMS: Previous evidences have shown the presence of a prolonged and exaggerated postprandial response in type 2 diabetes mellitus (T2DM) and its relation with an increase of cardiovascular risk. However, the response in prediabetes population has not been established. The objective was to analyze the degree of postprandial lipemia response in the CORDIOPREV clinical trial (NCT00924937) according to the diabetic status. METHODS: 1002 patients were submitted to an oral fat load test meal (OFTT) with 0.7 g fat/kg body weight [12 % saturated fatty acids (SFA), 10 % polyunsaturated fatty acids (PUFA), 43 % monounsaturated fatty acids (MUFA), 10 % protein and 25 % carbohydrates]. Serial blood test analyzing lipid fractions were drawn at 0, 1, 2, 3 and 4 h during postprandial state. Postprandial triglycerides (TG) concentration at any point >2.5 mmol/L (220 mg/dL) has been established as undesirable response. We explored the dynamic response in 57 non-diabetic, 364 prediabetic and 581 type 2 diabetic patients. Additionally, the postprandial response was evaluated according to basal insulin resistance subgroups in patients non-diabetic and diabetic without pharmacological treatment (N = 642). RESULTS: Prevalence of undesirable postprandial TG was 35 % in non-diabetic, 48 % in prediabetic and 59 % in diabetic subgroup, respectively (p < 0.001). Interestingly, prediabetic patients displayed higher plasma TG and large triacylglycerol-rich lipoproteins (TRLs-TG) postprandial response compared with those non-diabetic patients (p < 0.001 and p = 0.003 respectively). Moreover, the area under the curve (AUC) of TG and AUC of TRLs-TG was greater in the prediabetic group compared with non-diabetic patients (p < 0.001 and p < 0.005 respectively). Patients with liver insulin resistance (liver-IR) showed higher postprandial response of TG compared with those patients with muscle-IR or without any insulin-resistance respectively (p < 0.001). CONCLUSIONS: Our findings demonstrate that prediabetic patients show a lower phenotypic flexibility after external aggression, such as OFTT compared with nondiabetic patients. The postprandial response increases progressively according to non-diabetic, prediabetic and type 2 diabetic state and it is higher in patients with liver insulin-resistance. To identify this subgroup of patients is important to treat more intensively in order to avoid future cardiometabolic complications.

A gene variation (rs12691) in the CCAT/enhancer binding protein α modulates glucose metabolism in metabolic syndrome.

BACKGROUND AND AIMS: CCAAT/enhancer-binding protein alpha (CEBPA) is a transcription factor involved in adipogenesis and energy homeostasis. Caloric restriction reduces CEBPA protein expression in patients with metabolic syndrome (MetS). A previous report linked rs12691 SNP in CEBPA to altered concentration of fasting triglycerides. Our objective was to assess the effects of rs12691 in glucose metabolism in Metabolic Syndrome (MetS) patients. METHODS AND RESULTS: Glucose metabolism was assessed by static (glucose, insulin, adiponectin, leptin and resistin plasma concentrations) and dynamic (disposition index, insulin sensitivity index, HOMA-IR and acute insulin response to glucose) indices, performed at baseline and after 12 weeks of 4 dietary interventions (high saturated fatty acid (SFA), high monounsaturated fatty acid (MUFA), low-fat and low-fat-high-n3 polyunsaturated fatty acid (PUFA)) in 486 subjects with MetS. Carriers of the minor A allele of rs12691 had altered disposition index (p = 0.0003), lower acute insulin response (p = 0.005) and a lower insulin sensitivity index (p = 0.025) indicating a lower insulin sensitivity and a lower insulin secretion, at baseline and at the end of the diets. Furthermore, A allele carriers displayed lower HDL concentration. CONCLUSION: The presence of the A allele of rs12691 influences glucose metabolism of MetS patients.

Body mass interacts with fat quality to determine the postprandial lipoprotein response in healthy young adults.

BACKGROUND AND AIMS: Postprandial lipemia predicts the evolution of cardiovascular disease. Obesity is associated with an increase in the magnitude of postprandial lipemia. Our objective was to evaluate the influence of body mass index (BMI) on the effects of acute ingestion of different types of fat on the postprandial lipemic response. METHODS AND RESULTS: Twenty-one healthy men followed a 4-week baseline diet and then consumed three fat-loaded meals that included 1g fat/kg body wt (65%fat) according to a randomized crossover design. The compositions of the three meals were olive oil meal (22% saturated fatty acids (SFA), 38% monounsaturated fatty acids (MUFA), 4% polyunsaturated fatty acids (PUFA)); butter meal (35% SFA, 22% MUFA, 4% PUFA); walnuts meal (20% SFA, 24% MUFA, 16% PUFA, and 4% α-linolenic acid). Higher-weight (HW) subjects (BMI greater than the median 26.18 kg/m(2), n = 11) presented higher incremental area under the curve (iAUC) for triglycerides (TG), both in large- and small-TG rich lipoproteins (TRL) than lower-weight (LW) subjects (BMI<26.18 kg/m(2), n = 10) (p<0.05), and a similar trend for plasma TG (p = 0.084). Moreover, HW subjects presented higher concentrations for small TRL-cholesterol and small TRL-TG in different timepoints of the postprandial lipemia after the intake of enriched walnuts or butter meals compared with the olive oil-enriched meal (p < 0.05) No significant differences were observed between the three types of meals in the postprandial response of LW subjects. CONCLUSION: HW subjects present a greater postprandial response than LW subjects, and they benefit from the consumption of monounsaturated fatty acids from olive oil, to lower their levels of TRL particles during the postprandial state.

Consumption of diets with different type of fat influences triacylglycerols-rich lipoproteins particle number and size during the postprandial state.

BACKGROUND AND AIMS: Previous evidence suggests that dietary fat could influence the composition and size of triacylglycerols-rich lipoproteins (TRL). In a controlled intervention study on healthy subjects, we evaluated the influence of 3 dietary interventions, with different types of fat on postprandial TRL particle size and number. METHODS AND RESULTS: Volunteers followed three different diets for four weeks each, according to a randomized crossover design. Western diet: 15% protein, 47% carbohydrates (CHO), 38% fat (22% saturated fatty acid (SFA)); Mediterranean diet: 15% protein, 47% CHO, 38% fat (24% monounsaturated fatty acid (MUFA)); high CHO enriched with ALNA diet: 15% protein, 55% CHO, <30% fat (8% polyunsaturated fatty acid (PUFA)). After a 12-h fast, volunteers consumed a breakfast with 1g fat and 7 mg cholesterol per kg body weight and a fat composition similar to that consumed in each of the diets: Butter meal: 35% SFA; Olive oil meal: 36% MUFA; Walnut meal: 16% PUFA, 4% α-linolenic acid. Tryglicerides (TG) in TRL (large and small TRL) were determined by ultracentrifugation and size and number of lipoprotein particles were measured with Nuclear Magnetic Resonance Spectroscopy at different time points. The olive oil meal reduced the number of total TRL postprandial particles compared with the other meals (P=0.002). Moreover, the olive oil meal also increased the TRL particle size compared with the walnut meal (P=0.001). CONCLUSION: Our data showed that short-term intake of the Mediterranean diet and the acute intake of an olive oil meal lead to the formation of a reduced number and higher-size TRL particle compared with other fat sources. These novel findings have implications for understanding the postprandial lipoprotein mechanisms, and could favour the lower cardiovascular risk in Mediterranean countries.

Obesity is a chronic disease. Positioning statement of the Diabetes, Obesity and Nutrition Workgroup of the Spanish Society of Internal Medicine (SEMI) for an approach centred on individuals with obesity.

BACKGROUND: Obesity is a chronic, complex and multifactorial metabolic disease involved in the development of chronic noncommunicable diseases such as type 2 diabetes mellitus, cardiovascular disease and cancer. The care of individuals with obesity is an essential part of the holistic approach provided by internal medicine to patients. MATERIAL AND METHODS: Between September 2019 and January 2020, we distributed an online survey to the members of the Spanish Society of Internal Medicine. We prepared a Strengths, Weaknesses, Opportunities, and Threats analysis using the responses and, using the nominal group technique, developed the recommendations. RESULTS: We obtained 599 responses. The respondents mean age was 44.4 ±â€¯11 years, and 52.1% were women. Some 91.8% of the internists evaluate their patients to rule out the comorbidities associated with obesity, mainly type 2 diabetes mellitus (96.2%), cardiovascular disease (88.9%) and obesity-associated hypoventilation syndrome (73%), among others. Some 79.9% provided indications on lifestyle changes. Some 64.1% and 74.9% of the respondents knew the indications for the drugs and bariatric surgery, respectively. Some 93.8% and 83% of the respondents considered obesity and excess weight a chronic disease, and 88.7% considered it a disease of specific interest to internists, who should take an active and leading role in its treatment (85.3%). CONCLUSIONS: The objective of the present document is to determine the degree of understanding and sensitivity of internists regarding the management of obesity and to develop a consensus of recommendations for the Spanish Society of Internal Medicine based on the scientific evidence and the opinion of its members.

Olive oil and health: summary of the II international conference on olive oil and health consensus report, Jaén and Córdoba (Spain) 2008.

Olive oil (OO) is the most representative food of the traditional Mediterranean Diet (MedDiet). Increasing evidence suggests that monounsaturated fatty acids (MUFA) as a nutrient, OO as a food, and the MedDiet as a food pattern are associated with a decreased risk of cardiovascular disease, obesity, metabolic syndrome, type 2 diabetes and hypertension. A MedDiet rich in OO and OO per se has been shown to improve cardiovascular risk factors, such as lipid profiles, blood pressure, postprandial hyperlipidemia, endothelial dysfunction, oxidative stress, and antithrombotic profiles. Some of these beneficial effects can be attributed to the OO minor components. Therefore, the definition of the MedDiet should include OO. Phenolic compounds in OO have shown antioxidant and anti-inflammatory properties, prevent lipoperoxidation, induce favorable changes of lipid profile, improve endothelial function, and disclose antithrombotic properties. Observational studies from Mediterranean cohorts have suggested that dietary MUFA may be protective against age-related cognitive decline and Alzheimer's disease. Recent studies consistently support the concept that the OO-rich MedDiet is compatible with healthier aging and increased longevity. In countries where the population adheres to the MedDiet, such as Spain, Greece and Italy, and OO is the principal source of fat, rates of cancer incidence are lower than in northern European countries. Experimental and human cellular studies have provided new evidence on the potential protective effect of OO on cancer. Furthermore, results of case-control and cohort studies suggest that MUFA intake including OO is associated with a reduction in cancer risk (mainly breast, colorectal and prostate cancers).

Chronic effects of a high-fat diet enriched with virgin olive oil and a low-fat diet enriched with alpha-linolenic acid on postprandial endothelial function in healthy men.

Traditional cardiovascular risk factors are associated with endothelial dysfunction. The vascular endothelium plays a key role in local vascular tone regulation and can be modulated by dietary fat. We propose to determine the chronic effect of three diets with different fat compositions on postprandial endothelial function and inflammatory biomarkers. Twenty healthy men followed three 4-week diets in a randomised cross-over design: a Western diet, rich in saturated fat (22% SFA, 12% MUFA and 0.4% alpha-linolenic acid (ALA), all fractions are % of energy); a Mediterranean diet, rich in MUFA ( < 10 % SFA, 24 % MUFA and 0.4% ALA); a low-fat diet enriched in ALA ( < 10% SFA, 12% MUFA and 2% ALA). At the end of each dietary period all subjects underwent a postprandial study. Plasma concentrations of lipid parameters, soluble intercellular cell-adhesion molecule-1, soluble vascular cell-adhesion molecule-1 (sVCAM-1), nitrates and nitrites (NOx) and endothelial function studied by laser Doppler were examined at 0, 2, 4, 6 and 8 h. The endothelium-dependent vasodilatory response was greater 4 h after the ingestion of the MUFA-rich diet than after the SFA or ALA low-fat diets (P = 0.031). The 4 h postprandial plasma sVCAM-1 levels were lower after the MUFA meals than after the ALA low-fat diet (P = 0.043). The bioavailability of NOx was higher following the MUFA diet than after the SFA and ALA low-fat diets (P = 0.027). We found no differences in the other parameters measured. Chronic ingestion of a Mediterranean diet avoids the postprandial deterioration of endothelial function associated with Westernised diets in healthy individuals.

A carbohydrate-rich diet reduces LDL size in QQ homozygotes for the Gln 192Arg polymorphism of the paraoxonase 1 gene.

Paraoxonase 1 (PON 1) is an esterase with antioxidant properties that is present in HDL. Gln192Arg polymorphism (also named Q192R or Q/R) of the PON 1 gene that encodes this protein defines two alleles (Q and R). The R allele has been associated with higher cardiovascular risk. LDL size and susceptibility to oxidation also have been identified as cardiovascular risk factors. Our objective was to determine whether genetic variations in the Gln192Arg polymorphism influence LDL size and susceptibility to oxidation after the consumption of diets with different fat content. In our experiments, the participants (n = 98) underwent three 4-wk diets--one, saturated fat-enriched (SAT); another, monounsaturated fat-enriched (MONO); and a third, carbohydrate-enriched (CHO). We observed that LDL were smaller in the QQ group after the CHO diet vs. the SAT (P < 0.01) and MONO diets (P < 0.03). No differences in LDL size were found in QR/RR subjects. When we analyzed lag time of oxidation of LDL, we found that when carriers of the R allele (QR/RR) received the MONO diet, the lag period of LDL oxidation was longer as compared with the CHO diet. Otherwise, we found no differences in QQ homozygotes when we evaluated the lag time of oxidation of LDL after the three diets. These results suggest that the Glnl92Arg polymorphism of the paraoxonase gene influences LDL size and susceptibility to oxidation in response to diet.

The postprandial inflammatory response after ingestion of heated oils in obese persons is reduced by the presence of phenol compounds.

SCOPE: Heating during the process of cooking alters the chemical properties of foods and may affect subsequent postprandial inflammation. We tested the effects of four meals rich in different oils subjected to heating on the postprandial inflammatory metabolism of peripheral blood mononuclear cells (PBMCs). METHODS AND RESULTS: Twenty obese participants received four breakfasts following a randomized crossover design, consisting of milk and muffins made with different oils (virgin olive oil (VOO), sunflower oil (SFO), and a mixture of seeds oil (SFO/canola oil) with added either dimethylpolysiloxane (SOD), or natural antioxidants from olive mill wastewater alperujo (phenols; SOP)), previously subjected to 20 heating cycles. Postprandial inflammatory status in PBMCs was assessed by the activation of nuclear NF-κB, the concentration in cytoplasm of the NF-κB inhibitor (IκB-α), the mRNA levels of NF-κB subunits and activators (p65, IKKß, and IKKα) and other inflammatory molecules (TNF-α, IL-1ß, IL-6, MIF, and JNK), and lipopolysaccharide (LPS) levels. VOO and SOP breakfasts reduced NF-κB activation, increased IκB-α, and decreased LPS plasma concentration. SFO increased IKKα, IKKß, p65, IL-1b, IL-6, MIF, and JNK mRNA levels, and plasma LPS. CONCLUSION: Oils rich in phenols, whether natural (VOO) or artificially added (SOP), reduce postprandial inflammation, compared with seed oil (sunflower).

A low-fat high-carbohydrate diet supplemented with long-chain n-3 PUFA reduces the risk of the metabolic syndrome.

OBJECTIVE: Dietary changes are major factor in determining cardiovascular risk. We assessed the effects of isoenergetic diets with different fat quantity and quality on the incidence and regression of the metabolic syndrome (MetS) from the LIPGENE project. METHODS AND DESIGN: Clinical intervention study: the patients (n=337) were randomly assigned to one of four diets for 12 weeks each: two high fat diets, one rich in saturated fat (HSFA) and the other rich in monounsaturated fat (HMUFA), and two low fat diets, one high in complex carbohydrates (LFHCC) supplemented with 1.24g/day of long-chain n-3 polyunsaturated fatty acids (LFHCC n-3) and the other LFHCC diet with placebo (LFHCC). MEASUREMENTS: the effects on MetS risk criteria were recorded before and after the intervention period. RESULTS: An enlarged waist circumference (≥88cm for women and ≥102cm for men) was present among 95% of the participants, 88% had elevated blood pressure (>130/85mm Hg or antihypertensive drugs), 77% had elevated fasting plasma glucose (≥5.55mmol/L), 51% were hypertriacylglycerolemic (≥1.7mmol/L), and 72% had low HDL cholesterol (<1.0mmol/L for men, and <1.3mmol/L for women). The prevalence of enlarged waist circumference, hypertension and hypertriacylglycerolemia were reduced after the LFHCC n-3 diet (p<0.05). Thus the prevalence of MetS fell by 20.5% after LFHCC n-3 diet compared with the HSFA (10.6%), HMUFA (12%) diet or LFHCC (10.4%) diets (p<0.028). CONCLUSIONS: The consumption of a low-fat high-carbohydrate supplemented with n-3 diet reduced the risk of MetS as compared with isoenergetic high-fat (HSFA and HMUFA) and LFHCC diets.

Pleiotropic effects of TCF7L2 gene variants and its modulation in the metabolic syndrome: from the LIPGENE study.

AIMS/HYPOTHESIS: Variants of the TCF7L2 gene predict the development of type 2 diabetes mellitus (T2DM). We investigated the associations between gene variants of TCF7L2 and clinical features of the metabolic syndrome (MetS) (an entity often preceding T2DM), and their interaction with non-genetic factors, including plasma saturated fatty acids (SFA) concentration and insulin resistance (IR). METHODS: Fasting lipid profiles, insulin sensitivity, insulin secretion, anthropometrics, blood pressure and 10 gene variations of the TCF7L2 gene were determined in 450 subjects with MetS. RESULTS: Several single nucleotide polymorphisms (SNP) showed phenotypic associations independent of SFA or IR. Carriers of the rare T allele of rs7903146, and of three other SNPs in linkage disequilibrium with rs7903146, had lower blood pressure and insulin secretion. High IR and the presence of the T-allele of rs7903146 acted synergistically to define those with reduced insulin secretion. Carriers of the minor allele of rs290481 exhibited an altered lipid profile, with increased plasma levels of apolipoprotein B, non-esterified fatty acids, cholesterol and apolipoprotein B in triglyceride rich lipoproteins, and LDL cholesterol. Carriers of the minor allele of rs11196224 that had higher plasma SFA levels showed elevated procoagulant/proinflammatory biomarkers, impaired insulin secretion and increased IR, whereas carriers of the minor allele of rs17685538 with high plasma SFA levels exhibited higher blood pressure. CONCLUSIONS/INTERPRETATION: SNP in the TCF7L2 gene are associated with differences in insulin secretion, blood pressure, blood lipids and coagulation in MetS patients, and may be modulated by SFA in plasma or IR.

The -675 4G/5G polymorphism at the Plasminogen Activator Inhibitor 1 (PAI-1) gene modulates plasma Plasminogen Activator Inhibitor 1 concentrations in response to dietary fat consumption.

The objective of the study was to determine whether Plasminogen Activator Inhibitor Type 1 (PAI-1) -675 4G/5G polymorphism is associated with the response of functional plasma PAI-1 concentrations to changes in the amount and quality of dietary fat in healthy subjects. PAI-1 is the major inhibitor of fibrinolysis, and a lower level of fibrinolytic activity could be implicated in an increased risk of IHD. Fifty-nine healthy Spanish volunteers (ten 4G/4G homozygotes, twenty-eight heterozygotes 4G/5G and twenty-one 5G/5G homozygotes) consumed three diets for periods of 4 weeks each: a SFA-rich diet (38 % fat, 20 % SFA), followed by a carbohydrate-rich diet (30 % fat, 55 % carbohydrate) and a MUFA-rich diet (38 % fat, 22 % MUFA) according to a randomized crossover design. At the end of each dietary period plasma lipid and functional plasma PAI-1 concentrations were determined. Subjects carrying the 4G allele (4G/4G and 4G/5G) showed a significant decrease in PAI-1 concentrations after the MUFA diet, compared with the SFA-rich and carbohydrate-rich diets (genotype x diet interaction: P = 0.028). 5G/5G homozygotes had the lowest plasma PAI-1 concentrations compared with 4G/4G and 4G/5G subjects (genotype: P = 0.002), without any changes as a result of the amount and the quality of the dietary fat. In summary, no differences in plasma PAI-1 concentration response were found after changes in dietary fat intake in 5G/5G homozygotes, although these subjects displayed the lowest concentrations of PAI-1. On the other hand, carriers of the 4G allele are more likely to hyper-respond to the presence of MUFA in the diet because of a greater decrease in PAI-1 concentrations.