Prevalence of adiposity-based chronic disease and its association with anthropometric and clinical indices: a cross-sectional study.

The present study aimed to determine the prevalence of adiposity-based chronic disease (ABCD) and its association with anthropometric indices in the Mexican population. A cross-sectional study was conducted in 514 adults seen at a clinical research unit. The American Association of Clinical Endocrinology/AACE/ACE criteria were used to diagnose ABCD by first identifying subjects with BMI ≥ 25 kg/m2 and those with BMI of 23-24·9 kg/m2 and waist circumference ≥ 80 cm in women or ≥ 90 cm in men. The presence of metabolic and clinical complications associated with adiposity, such as factors related to metabolic syndrome, prediabetes, type 2 diabetes, dyslipidaemia and arterial hypertension, were subsequently evaluated. Anthropometric indices related to cardiometabolic risk factors were then determined. The results showed the prevalence of ABCD was 87·4 % in total, 91·5 % in men and 86 % in women. The prevalence of ABCD stage 0 was 2·4 %, stage 1 was 33·7 % and stage 2 was 51·3 %. The prevalence of obesity according to BMI was 57·6 %. The waist/hip circumference index (prevalence ratio (PR) = 7·57; 95 % CI 1·52, 37·5) and the conicity index (PR = 3·46; 95 % CI 1·34, 8·93) were better predictors of ABCD, while appendicular skeletal mass % and skeletal muscle mass % decreased the risk of developing ABCD (PR = 0·93; 95 % CI 0·90, 0·96; and PR = 0·95; 95 % CI 0·93, 0·98). In conclusion, the prevalence of ABCD in our study was 87·4 %. This prevalence increased with age. It is important to emphasise that one out of two subjects had severe obesity-related complications (ABCD stage 2).

Effect of the BCAT2 polymorphism (rs11548193) on plasma branched-chain amino acid concentrations after dietary intervention in subjects with obesity and insulin resistance.

Branched-chain amino acids (BCAA) are considered markers of insulin resistance (IR) in subjects with obesity. In this study, we evaluated whether the presence of the SNP of the branched-chain aminotransferase 2 (BCAT2) gene can modify the effect of a dietary intervention (DI) on the plasma concentration of BCAA in subjects with obesity and IR. A prospective cohort study of adult subjects with obesity, BMI ≥ 30 kg/m2, homeostatic model assessment-insulin resistance (HOMA-IR ≥ 2·5) no diagnosed chronic disease, underwent a DI with an energy restriction of 3140 kJ/d and nutritional education for 1 month. Anthropometric measurements, body composition, blood pressure, resting energy expenditure, oral glucose tolerance test results, serum biochemical parameters and the plasma amino acid profile were evaluated before and after the DI. SNP were assessed by the TaqMan SNP genotyping assay. A total of eighty-two subjects were included, and fifteen subjects with a BCAT2 SNP had a greater reduction in leucine, isoleucine, valine and the sum of BCAA. Those subjects also had a greater reduction in skeletal muscle mass, fat-free mass, total body water, blood pressure, muscle strength and biochemical parameters after 1 month of the DI and adjusting for age and sex. This study demonstrated that the presence of the BCAT2 SNP promotes a greater reduction in plasma BCAA concentration after adjusting for age and sex, in subjects with obesity and IR after a 1-month energy-restricted DI.

Effect of the intake of dietary protein on insulin resistance in subjects with obesity: a randomized controlled clinical trial.

PURPOSE: We compared the effect of diets with different amounts and sources of dietary protein on insulin sensitivity (IS) in subjects with obesity and insulin resistance (IR). METHODS: Eighty subjects with obesity (BMI ≥ 30 kg/m2) and IR (Matsuda index < 4.3 and HOMA-IR ≥ 2.5) over 18 years old were randomized to four groups for a one-month period: a normal protein diet (< 20%) with a predominance of animal protein (Animal NP) or vegetable protein (Vegetable NP) and a high-protein diet (25-30%) with a predominance of animal protein (Animal HP) or vegetable protein (Vegetable HP). Baseline and final measurements of body weight, body composition, biochemical parameters, blood pressure (BP), resting energy expenditure and plasma amino acid profiles were performed. RESULTS: Body weight, BMI and waist circumference decreased in all groups. Interestingly, the IS improved more in the Animal HP (Matsuda index; 1.39 vs 2.58, P = 0.003) and in the Vegetable HP groups (Matsuda index; 1.44 vs 3.14, P < 0.0001) after one month. The fat mass, triglyceride levels, C-reactive protein levels and the leptin/adiponectin index decreased; while, the skeletal muscle mass increased in the Animal and Vegetable HP groups. The BP decreased in all groups except the Animal NP group. CONCLUSION: Our study demonstrates that a high-protein hypocaloric diets improves IS by 60-90% after one month in subjects with obesity and IR, regardless of weight loss and the source of protein, either animal or vegetable. TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov (NCT03627104), August 13, 2018.

Association of BCAT2 and BCKDH polymorphisms with clinical, anthropometric and biochemical parameters in young adults.

BACKGROUND AND AIM: Circulating amino acids are modified by sex, body mass index (BMI) and insulin resistance (IR). However, whether the presence of genetic variants in branched-chain amino acid (BCAA) catabolic enzymes modifies circulating amino acids is still unknown. Thus, we determined the frequency of two genetic variants, one in the branched-chain aminotransferase 2 (BCAT2) gene (rs11548193), and one in the branched-chain ketoacid dehydrogenase (BCKDH) gene (rs45500792), and elucidated their impact on circulating amino acid levels together with clinical, anthropometric and biochemical parameters. METHODS AND RESULTS: We performed a cross-sectional comparative study in which we recruited 1612 young adults (749 women and 863 men) aged 19.7 ± 2.1 years and with a BMI of 24.9 ± 4.7 kg/m2. Participants underwent clinical evaluation and provided blood samples for DNA extraction and biochemical analysis. The single nucleotide polymorphisms (SNPs) were determined by allelic discrimination using real-time polymerase chain reaction (PCR). The frequencies of the less common alleles were 15.2 % for BCAT2 and 9.83 % for BCKDH. The subjects with either the BCAT2 or BCKDH SNPs displayed no differences in the evaluated parameters compared with subjects homozygotes for the most common allele at each SNP. However, subjects with both SNPs had higher body weight, BMI, blood pressure, glucose, and circulating levels of aspartate, isoleucine, methionine, and proline than the subjects homozygotes for the most common allele (P < 0.05, One-way ANOVA). CONCLUSION: Our findings suggest that the joint presence of both the BCAT2 rs11548193 and BCKDH rs45500792 SNPs induces metabolic alterations that are not observed in subjects without either SNP.

Genetic risk score for insulin resistance based on gene variants associated to amino acid metabolism in young adults.

Circulating concentration of arginine, alanine, aspartate, isoleucine, leucine, phenylalanine, proline, tyrosine, taurine and valine are increased in subjects with insulin resistance, which could in part be attributed to the presence of single nucleotide polymorphisms (SNPs) within genes associated with amino acid metabolism. Thus, the aim of this work was to develop a Genetic Risk Score (GRS) for insulin resistance in young adults based on SNPs present in genes related to amino acid metabolism. We performed a cross-sectional study that included 452 subjects over 18 years of age. Anthropometric, clinical, and biochemical parameters were assessed including measurement of serum amino acids by high performance liquid chromatography. Eighteen SNPs were genotyped by allelic discrimination. Of these, ten were found to be in Hardy-Weinberg equilibrium, and only four were used to construct the GRS through multiple linear regression modeling. The GRS was calculated using the number of risk alleles of the SNPs in HGD, PRODH, DLD and SLC7A9 genes. Subjects with high GRS (≥ 0.836) had higher levels of glucose, insulin, homeostatic model assessment- insulin resistance (HOMA-IR), total cholesterol and triglycerides, and lower levels of arginine than subjects with low GRS (p < 0.05). The application of a GRS based on variants within genes associated to amino acid metabolism may be useful for the early identification of subjects at increased risk of insulin resistance.

A New Approach to Personalized Nutrition: Postprandial Glycemic Response and its Relationship to Gut Microbiota.

A prolonged and elevated postprandial glucose response (PPGR) is now considered a main factor contributing for the development of metabolic syndrome and type 2 diabetes, which could be prevented by dietary interventions. However, dietary recommendations to prevent alterations in PPGR have not always been successful. New evidence has supported that PPGR is not only dependent of dietary factors like the content of carbohydrates, or the glycemic index of the foods, but is also dependent on genetics, body composition, gut microbiota, among others. In recent years, continuous glucose monitoring has made it possible to establish predictions on the effect of different dietary foods on PPGRs through machine learning methods, which use algorithms that integrate genetic, biochemical, physiological and gut microbiota variables for identifying associations between them and clinical variables with aim of personalize dietary recommendations. This has allowed to improve the concept of personalized nutrition, since it is now possible to recommend through these predictions specific dietary foods to prevent elevated PPGRs that are highly variable among individuals. Additional components that can enrich the predictive algorithms are findings of nutrigenomics, nutrigenetics and metabolomics. Thus, this review aims to summarize the evidence of the components that integrate personalized nutrition focused on the prevention of PPGRs, and to show the future of personalized nutrition by laying the groundwork for the development of individualized dietary management and its impact on the improvement of metabolic diseases.

Modulation of MicroRNAs and Exosomal MicroRNAs after Dietary Interventions for Obesity and Insulin Resistance: A Narrative Review.

MicroRNAs (miRNAs) are small noncoding RNAs approximately 22 nucleotides in length. Their main function is to regulate gene expression at the posttranscriptional level by inhibiting the translation of messenger RNAs (mRNAs). miRNAs originate in the cell nucleus from specific genes, where they can perform their function. However, they can also be found in serum, plasma, or other body fluids travelling within vesicles called exosomes and/or bound to proteins or other particles such as lipoproteins. miRNAs can form complexes outside the cell where they are synthesized, mediating paracrine and endocrine communication between different tissues. In this way, they can modulate the gene expression and function of distal cells. It is known that the expression of miRNAs can be affected by multiple factors, such as the nutritional or pathological state of the individual, or even in conditions such as obesity, insulin resistance, or after any dietary intervention. In this review, we will analyse miRNAs whose expression and circulation are affected in conditions of obesity and insulin resistance, as well as the changes generated after a dietary intervention, with the purpose of identifying new possible biomarkers of early response to nutritional treatment in these conditions.

Effect of the Melanocortin 4-Receptor Ile269Asn Mutation on Weight Loss Response to Dietary, Phentermine and Bariatric Surgery Interventions.

The loss of function melanocortin 4-receptor (MC4R) Ile269Asn mutation has been proposed as one of the most important genetic contributors to obesity in the Mexican population. However, whether patients bearing this mutation respond differently to weight loss treatments is unknown. We tested the association of this mutation with obesity in 1683 Mexican adults, and compared the response of mutation carriers and non-carriers to three different weight loss interventions: dietary restriction intervention, phentermine 30 mg/day treatment, and Roux-en-Y gastric bypass (RYGB) surgery. The Ile269Asn mutation was associated with obesity [OR = 3.8, 95% CI (1.5-9.7), p = 0.005]. Regarding interventions, in the dietary restriction group only two patients were MC4R Ile269Asn mutation carriers. After 1 month of treatment, both mutation carriers lost weight: -4.0 kg (-2.9%) in patient 1, and -1.8 kg (-1.5%) in patient 2; similar to the mean weight loss observed in six non-carrier subjects (-2.9 kg; -2.8%). Phentermine treatment produced similar weight loss in six carriers (-12.7 kg; 15.5%) and 18 non-carriers (-11.3 kg; 13.6%) after 6 months of pharmacological treatment. RYGB also caused similar weight loss in seven carriers (29.9%) and 24 non-carriers (27.8%), 6 months after surgery. Our findings suggest that while the presence of a single MC4R loss of function Ile269Asn allele significantly increases obesity risk, the presence of at least one functional MC4R allele seems sufficient to allow short-term weight loss in response to dietary restriction, phentermine and RYGB. Thus, these three different interventions may be useful for the short-term treatment of obesity in MC4R Ile269Asn mutation carriers.

Serum amino acid concentrations are modified by age, insulin resistance, and BCAT2 rs11548193 and BCKDH rs45500792 polymorphisms in subjects with obesity.

BACKGROUND & AIMS: The amino acid profile of young adults is modified by sex, body mass index (BMI) and insulin resistance (IR). However, we do not know if age or the presence of specific polymorphisms in the genes of BCAT2 and BCKDH contribute to changes in the amino acid profile, especially in subjects with obesity. Therefore, we have evaluated the effect of age, the presence of IR and the polymorphisms of BCAT2 rs11548193 and BCKDH rs45500792 on the concentration of amino acids in subjects with obesity. METHODS: This was a cross-sectional study conducted with 487 subjects with obesity. Participants underwent a physical examination in which their clinical history was obtained and a blood sample was taken for biochemical, hormonal, and DNA analysis. RESULTS: Adults <30 years old with obesity had higher levels of alanine, arginine, aspartate, histidine, leucine, lysine, methionine, phenylalanine, proline, serine and valine than adults ≥30 years old. Interestingly, regardless of age, we found that arginine, aspartate, serine decreased, while proline and tyrosine increased in the presence of IR; tyrosine and sum of branched-chain amino acids (∑BCAA) were the amino acids that increased in the presence of BCAT2 rs11548193 and BCKDH rs45500792 polymorphisms. CONCLUSIONS: We found that the amino acid profiles of subjects with obesity are differentially modified by age, the presence of IR, and the presence of the BCAT2 rs11548193 and BCKDH rs45500792 polymorphisms.

Genistein stimulates insulin sensitivity through gut microbiota reshaping and skeletal muscle AMPK activation in obese subjects.

OBJECTIVE: Obesity is associated with metabolic abnormalities, including insulin resistance and dyslipidemias. Previous studies demonstrated that genistein intake modifies the gut microbiota in mice by selectively increasing Akkermansia muciniphila, leading to reduction of metabolic endotoxemia and insulin sensitivity. However, it is not known whether the consumption of genistein in humans with obesity could modify the gut microbiota reducing the metabolic endotoxemia and insulin sensitivity. RESEARCH DESIGN AND METHODS: 45 participants with a Homeostatic Model Assessment (HOMA) index greater than 2.5 and body mass indices of ≥30 and≤40 kg/m2 were studied. Patients were randomly distributed to consume (1) placebo treatment or (2) genistein capsules (50 mg/day) for 2 months. Blood samples were taken to evaluate glucose concentration, lipid profile and serum insulin. Insulin resistance was determined by means of the HOMA for insulin resistance (HOMA-IR) index and by an oral glucose tolerance test. After 2 months, the same variables were assessed including a serum metabolomic analysis, gut microbiota, and a skeletal muscle biopsy was obtained to study the gene expression of fatty acid oxidation. RESULTS: In the present study, we show that the consumption of genistein for 2 months reduced insulin resistance in subjects with obesity, accompanied by a modification of the gut microbiota taxonomy, particularly by an increase in the Verrucomicrobia phylum. In addition, subjects showed a reduction in metabolic endotoxemia and an increase in 5'-adenosine monophosphate-activated protein kinase phosphorylation and expression of genes involved in fatty acid oxidation in skeletal muscle. As a result, there was an increase in circulating metabolites of ß-oxidation and ω-oxidation, acyl-carnitines and ketone bodies. CONCLUSIONS: Change in the gut microbiota was accompanied by an improvement in insulin resistance and an increase in skeletal muscle fatty acid oxidation. Therefore, genistein could be used as a part of dietary strategies to control the abnormalities associated with obesity, particularly insulin resistance; however, long-term studies are needed.