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Objective The activity of brown adipose tissue is sensitive to changes in ambient temperature. A lower exposure to cold could result in an increased risk of developing diabetes at population level, although this factor has not yet been sufficiently studied. Design We studied 5072 subjects, participants in a national, cross-sectional population-based study representative of the Spanish adult population (Di@bet.es study). All subjects underwent a clinical, demographic and lifestyle survey, a physical examination and blood sampling (75 g oral glucose tolerance test). Insulin resistance was estimated with the homeostasis model assessment (HOMA-IR). The mean annual temperature (°C) in each individual municipality was collected from the Spanish National Meteorology Agency. Results Linear regression analysis showed a significant positive association between mean annual temperature and fasting plasma glucose (β: 0.087, P < 0.001), 2 h plasma glucose (β: 0.049, P = 0.008) and HOMA-IR (β: 0.046, P = 0.008) in multivariate adjusted models. Logistic regression analyses controlled by multiple socio-demographic variables, lifestyle, adiposity (BMI) and geographical elevation showed increasing odds ratios for prediabetes (WHO 1999), ORs 1, 1.26 (0.95-1.66), 1.08 (0.81-1.44) and 1.37 (1.01-1.85) P for trend = 0.086, diabetes (WHO 1999) ORs 1, 1.05 (0.79-1.39), 1.20 (0.91-1.59) and 1.39 (1.02-1.90) P = 0.037, and insulin resistance (HOMA-IR ≥75th percentile of the non-diabetic population): ORs 1, 1.03 (0.82-1.30), 1.22 (0.96-1.55), 1.26 (0.98-1.63) (P for trend = 0.046) as the mean annual temperature (into quartiles) rose. Conclusions Our study reports an association between ambient temperature and the prevalence of dysglycemia and insulin resistance in Spanish adults, consistent with the hypothesis that a lower exposure to cold could be associated with a higher risk of metabolic derangements.

Insulin resistance, i.e., decreased biological response to insulin, is a risk factor for many diseases, such as obesity, type 2 diabetes (T2DM), cardiovascular disease, polycystic ovary syndrome, some forms of cancer and neurodegenerative diseases. One of its main causes is chronic low-grade inflammation, mediated by the proinflammatory pathways, such as the c-Jun N-terminal kinase (JNK) pathway and the nuclear factor kappa B (NFκB) pathway. Interleukin (IL)-38 (IL-38) is a newly discovered cytokine that belongs to the IL-1 family. There are three hypothetical pathways through which IL-38 may bind to the specific receptors and inhibit their proinflammatory activity. Those pathways are associated with IL-36 receptor (IL-36R), IL-1 receptor accessory protein-like 1 (IL1RAPL1) and IL-1 receptor 1 (IL1R1). There are studies linking IL-38 to improve insulin sensitivity through the difference in serum IL-38 in patients with insulin resistance or the correlation of IL-38 concentrations with insulin resistance indexes. However, many questions still remain regarding the biological activity of IL-38 itself and its role in the pathogenesis of insulin resistance. The goal of this study is to showcase IL-38, its biological activity, hypothesized signaling pathways, connection with insulin resistance and future perspectives of research on IL-38. We present that IL-38 associated signaling can be a potential target for the treatment of insulin resistance and associated diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background and Aims: Non-alcoholic fatty liver disease (NAFLD) has been linked to type 2 diabetes (T2D), but also to hypothyroidism. Nevertheless, the relationship between thyroid function and NAFLD in diabetes is less clear. This study investigated associations between free thyroxine (fT4) or thyroid-stimulating hormone (TSH) and NAFLD in recent-onset diabetes., Methods: Participants with recent-onset type 1 diabetes (T1D, n = 358), T2D (n = 596) or without diabetes (CON, n = 175) of the German Diabetes Study (GDS), a prospective longitudinal cohort study, underwent Botnia clamp tests and assessment of fT4, TSH, fatty liver index (FLI) and in a representative subcohort 1 H-magnetic resonance spectroscopy., Results: First, fT4 levels were similar between T1D and T2D (p = .55), but higher than in CON (T1D: p < .01; T2D: p < .001), while TSH concentrations were not different between all groups. Next, fT4 correlated negatively with FLI and positively with insulin sensitivity only in T2D (ß = -.110, p < .01; ß = .126, p < .05), specifically in males (ß = -.117, p < .05; ß = .162; p < .01) upon adjustments for age, sex and BMI. However, correlations between fT4 and FLI lost statistical significance after adjustment for insulin sensitivity (T2D: ß = -.021, p = 0.67; males with T2D: ß = -.033; p = .56). TSH was associated positively with FLI only in male T2D before (ß = .116, p < .05), but not after adjustments for age and BMI (ß = .052; p = .30)., Conclusions: Steatosis risk correlates with lower thyroid function in T2D, which is mediated by insulin resistance and body mass, specifically in men, whereas no such relationship is present in T1D., (© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.)

Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed a GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-Related Traits Consortium. Discovery for genetic association was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested in models adjusted for age, sex, and BMI and in a model analyzing the combined influence of the genotype effect adjusted for BMI and the interaction effect between the genotype and BMI on ISI (model 3). In model 3, three variants reached genome-wide significance: rs13422522 (NYAP2; P = 8.87 × 10(-11)), rs12454712 (BCL2; P = 2.7 × 10(-8)), and rs10506418 (FAM19A2; P = 1.9 × 10(-8)). The association at NYAP2 was eliminated by conditioning on the known IRS1 insulin sensitivity locus; the BCL2 and FAM19A2 associations were independent of known cardiometabolic loci. In conclusion, we identified two novel loci and replicated known variants associated with insulin sensitivity. Further studies are needed to clarify the causal variant and function at the BCL2 and FAM19A2 loci., (© 2016 by the American Diabetes Association.)

The dyslipidemia associated with type 2 diabetes mellitus (T2DM) is an important risk factor for atherosclerotic cardiovascular disease. However, until now little attention has been paid to the role that the intestine might have. The aim of this research was to determine the relation between insulin resistance and intestinal de novo lipogenesis/lipoprotein synthesis in morbidly obese subjects and to study the effect of insulin on these processes. Jejunal mRNA expression of the different genes involved in the intestinal de novo lipogenesis/lipoprotein synthesis was analyzed in three groups of morbidly obese subjects: Group 1 with low insulin resistance (MO-low-IR), group 2 with high insulin resistance (MO-high-IR), and group 3 with T2DM and treatment with metformin (MO-metf-T2DM). In addition, intestinal epithelial cells (IECs) from MO-low-IR were incubated with different doses of insulin/glucose. In Group 2 (MO-high-IR), the jejunal mRNA expression levels of apo A-IV, ATP-citrate lyase (ACLY), pyruvate dehydrogenase (lipoamide) beta (PDHB), and sterol regulatory element-binding protein-1c (SREBP-1c) were significantly higher and acetyl-CoA carboxylase alpha (ACC1) and fatty-acid synthase lower than in Group 1 (MO-low-IR). In Group 3 (MO-metf-T2DM), only the ACLY and PDHB mRNA expressions were significantly higher than in Group 1 (MO-low-IR). The mRNA expression of most of the genes studied was significantly linked to insulin and glucose levels. The incubation of IEC with different doses of insulin and glucose produced a higher expression of diacylglycerol acyltransferase 2, microsomal triglyceride transfer protein, apo A-IV, SREBP-1c, and ACC1 when both, glucose and insulin, were at a high concentration. However, with only high insulin levels, there were higher apo A-IV, PDHB and SREBP-1c expressions, and a lower ACLY expression. In conclusion, the jejunum of MO-high-IR has a decreased mRNA expression of genes involved in de novo fatty-acid synthesis and an increase of genes involved in acetyl-CoA and lipoprotein synthesis. This effect is attenuated by metformin. In addition, the expression of most of the genes studied was found to be regulated by insulin.

The aim of the study was to analyze the association between aging and insulin resistance estimated by the homeostasis model assessment of insulin resistance (HOMA-IR). This work involved two studies: (1) the Di@bet.es study is a cross-sectional study including 4,948 subjects, comprising a representative sample of the adult Spanish population; (2) the Pizarra study is a population-based cohort study undertaken in Pizarra (Spain), in which 1,051 subjects were evaluated at baseline and 714 completed the 6-year follow-up study. Study variables included a clinical and demographic structured survey, a lifestyle survey, a physical examination, and an oral glucose tolerance test in subjects without diabetes. In the Di@bet.es study overall, an increase occurred in blood glucose until the age of 50, after which it remained stable (data adjusted for gender, body mass index, abnormal glucose regulation [AGR]). The HOMA-IR increased significantly with age (p = 0.01), due to a higher prevalence of obesity (p < 0.0001) and AGR (p < 0.001). In non-obese subjects without AGR, HOMA-IR values were not modified with age (p = 0.30), but they were with body mass index (p < 0.001). In the Pizarra study, the HOMA-IR was significantly lower after 6-year follow-up in the whole study population. Subjects with a HOMA-IR level higher than the 75th percentile at baseline were more likely to develop diabetes (OR 2.2, 95 % CI 1.2-3.9; p = 0.007) than subjects with a lower HOMA-IR. We concluded that age per se did not increase HOMA-IR levels, changes that might be related to higher rates of obesity and AGR in older subjects. The HOMA-IR was associated with an increased risk of developing type 2 diabetes 6 years later.

Objective: Thyroid hormone receptor-beta resistance has been associated with metabolic traits. THRA gene sequencing of an obese woman (index case) who presented as empirical thyroid hormone receptor-α (THRA) resistance, disclosed a polymorphism (rs12939700) in a critical region involved in TRα alternative processing., Design and Subjects: THRA gene variants were evaluated in three independent europid populations (i) in two population cohorts at baseline (n=3417 and n=2265), 6 years later (n=2139) and (ii) in 4734 high cardiovascular risk subjects (HCVR, PREDIMED trial)., Results: The minor allele of the index case polymorphism (rs12939700), despite having a very low frequency (4%), was significantly associated with higher body mass index (BMI) (P=0.042) in HCVR subjects. A more frequent THRA polymorphism (rs1568400) was associated with higher BMI in subjects from the population (P=0.00008 and P=0.05) after adjusting for several confounders. Rs1568400 was also strongly associated with fasting triglycerides (P dominant=3.99 × 10(-5)). In the same sample, 6 years later, age and sex-adjusted risk of developing obesity was significantly increased in GG homozygotes (odds ratio 2.93 (95% confidence interval, 1.05-6.95)). In contrast, no association between rs1568400 and BMI was observed in HCVR subjects, in whom obesity was highly prevalent. This might be explained by the presence of an interaction (P <0.001) among the rs1568400 variant, BMI and saturated fat intake. Only when saturated fat intake was high (>24.5 g d(-1)), GG carriers showed a significantly higher BMI than A carriers after controlling for energy intake and physical activity., Conclusions: THRA gene polymorphisms are associated with obesity development. This is a novel observation linking the THRA locus to metabolic phenotypes.

Objective: The study aim was to identify changes in duodenal gene expression associated with the development of insulin resistance according to the BMI of women., Methods: Duodenal samples were assessed by microarray in four groups of women, nonobese women and women with severe obesity, with both low and high insulin resistance., Results: There was a group of shared downregulated differentially expressed genes (DEGs) related to tissue homeostasis and antimicrobial humoral response in women with higher insulin resistance both with severe obesity and without obesity. In the exclusive DEGs found in severe obesity, downregulated DEGs related to the regulation of the defense response to bacterium and cell adhesion, involving pathways related to the immune system, inflammation, and xenobiotic metabolism, were observed. In the exclusive DEGs from nonobese women with higher insulin resistance, upregulated DEGs mainly related to the regulation of lipoprotein lipase activity, very low-density lipoprotein particle remodeling, lipid metabolic process, antigen processing, and the presentation of peptide antigen were found., Conclusions: Independent of BMI, higher insulin resistance was associated with a downregulation of duodenal DEGs mainly related to the immune system, inflammation, and xenobiotic metabolism. Also, intestinal lipoprotein metabolism may have a certain relevance in the regulation of insulin resistance in nonobese women., (© 2020 The Obesity Society.)

Background: Although high-sensitivity C-reactive protein (hs-CRP) is currently used as a risk marker of cardiovascular disease, it has been suggested that genetic, clinical, biochemical or environmental factors could modify hs-CRP levels. The aim of this study was to investigate sources of interindividual hs-CRP variability in the Spanish population., Materials and Methods: A representative sample of the Spanish population within the di@bet.es study was used. Study variables included a clinical and demographic structured survey, a lifestyle survey, a physical examination, plasmatic hs-CRP and other biochemical parameters., Results: Median and interquartile range of plasma hs-CRP values were 1·73 ± 2·75 mg/dL. Thirty per cent of the study population had hs-CRP levels above 3 mg/dL and 38% from 1 to 3 mg/dL. Body mass index was the strongest factor associated with moderate and high hs-CRP levels. Age, sex, waist-to-hip ratio, weight increase, plasma lipid levels, glucose metabolism (HOMA-IR and abnormal glucose regulation categories), pharmacological treatment (lipid-lowering agents, psychotropic drugs and levothyroxine), smoking, physical activity, different dietary patterns, quality of life and educational level were all significantly associated with hs-CRP levels. Interactions were observed between variables. These interactions modulated the effect of previously described factors on hs-CRP., Conclusions: Thirty per cent of the Spanish population have hs-CRP levels considered to represent a cardiovascular risk. Different clinical, anthropometric, biochemical and environmental variables modulate hs-CRP levels. In addition, multiple interactions between variables complicate the interpretation of hs-CRP values., (© 2012 The Authors. European Journal of Clinical Investigation © 2012 Stichting European Society for Clinical Investigation Journal Foundation.)

Summary: The main objective was to evaluate the association between SNPs and haplotypes of the FABP1-4 genes and type 2 diabetes, as well as its interaction with fat intake, in one general Spanish population. The association was replicated in a second population in which HOMA index was also evaluated., Methods: 1217 unrelated individuals were selected from a population-based study [Hortega study: 605 women; mean age 54 y; 7.8% with type 2 diabetes]. The replication population included 805 subjects from Segovia, a neighboring region of Spain (446 females; mean age 52 y; 10.3% with type 2 diabetes). DM2 mellitus was defined in a similar way in both studies. Fifteen SNPs previously associated with metabolic traits or with potential influence in the gene expression within the FABP1-4 genes were genotyped with SNPlex and tested. Age, sex and BMI were used as covariates in the logistic regression model., Results: One polymorphism (rs2197076) and two haplotypes of the FABP-1 showed a strong association with the risk of DM2 in the original population. This association was further confirmed in the second population as well as in the pooled sample. None of the other analyzed variants in FABP2, FABP3 and FABP4 genes were associated. There was not a formal interaction between rs2197076 and fat intake. A significant association between the rs2197076 and the haplotypes of the FABP1 and HOMA-IR was also present in the replication population., Conclusions: The study supports the role of common variants of the FABP-1 gene in the development of type 2 diabetes in Caucasians.

Background: Different studies, mostly cross-sectional, have found an association between low levels of thyroid hormones, even within the normal range, and a greater body mass index. The aim of this study was to determine the association between thyroid function and the risk for obesity., Materials and Methods: In this population-based prospective study, measurements were made of anthropometric parameters, thyroid hormone function and urinary iodine in a cohort of the Pizarra Study (n = 937), and repeated 6 years later (n = 784). At the second point, measurements were also made of leptin and adiponectin., Results: Among the persons who were not obese at the start of the study, the odds ratio (OR) of becoming obese for those in the fourth quartile (Q(4)) for free triiodothyronine (FT3) (versus those in Q(1)) was 2·94 (1·46-5·90) (P = 0·005). The OR of becoming obese in persons in Q(4) of FT4 (versus those in Q(1)) was 3·06 (1·23-7·43) (P = 0·01). Those persons in Q(4) of weight gain had a higher FT3 at the 6-year follow-up than those whose weight gain was in Q(1) (P < 0·001). Leptin correlated with thyrotropin (β = 0·58, P = 0·001) and the FT4 (β = -1·12, P = 0·005). Adiponectin correlated with FT3 (r = -0·24, P < 0·001). The urinary iodine correlated negatively with both the BMI (β = -0·08, P = 0·01) and the increase in weight (β = -0·08, P = 0·04)., Conclusions: The changes in the thyroid hormones could be the consequence, rather than the cause, of the increase in weight. The same pathophysiological mechanisms that induce obesity might also be modifying the thyroid hormone pattern., (© 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation.)

Animal studies have revealed the association between stearoyl-CoA desaturase 1 (SCD1) and obesity and insulin resistance. However, only a few studies have been undertaken in humans. We studied SCD1 in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) from morbidly obese patients and their association with insulin resistance, sterol regulatory element binding protein-1 (SREBP-1) and ATPase p97, proteins involved in SCD1 synthesis and degradation. The insulin resistance was calculated in 40 morbidly obese patients and 11 overweight controls. Measurements were made of VAT and SAT SCD1, SREBP-1 and ATPase p97 mRNA expression and protein levels. VAT and SAT SCD1 mRNA expression levels in the morbidly obese patients were significantly lower than in the controls (P = 0.006), whereas SCD1 protein levels were significantly higher (P < 0.001). In the morbidly obese patients, the VAT SCD1 protein levels were decreased in patients with higher insulin resistance (P = 0.007). However, SAT SCD1 protein levels were increased in morbidly obese patients with higher insulin resistance (P < 0.05). Multiple linear regressions in the morbidly obese patients showed that the variable associated with the SCD1 protein levels in VAT was insulin resistance, and the variables associated with SCD1 protein levels in SAT were body mass index (BMI) and ATPase p97. In conclusion, these data suggest that the regulation of SCD1 is altered in individuals with morbid obesity and that the SCD1 protein has a different regulation in the two adipose tissues, as well as being closely linked to the degree of insulin resistance.

Background: The elongase of long chain fatty acids family 6 (ELOVL6) is an enzyme that specifically catalyzes the elongation of saturated and monounsaturated fatty acids with 12, 14 and 16 carbons. ELOVL6 is expressed in lipogenic tissues and it is regulated by sterol regulatory element binding protein 1 (SREBP-1)., Objective: We investigated whether ELOVL6 genetic variation is associated with insulin sensitivity in a population from southern Spain., Design: We undertook a prospective, population-based study collecting phenotypic, metabolic, nutritional and genetic information. Measurements were made of weight and height and the body mass index (BMI) was calculated. Insulin resistance was measured by homeostasis model assessment. The type of dietary fat was assessed from samples of cooking oil taken from the participants' kitchens and analyzed by gas chromatography. Five SNPs of the ELOVL6 gene were analyzed by SNPlex., Results: Carriers of the minor alleles of the SNPs rs9997926 and rs6824447 had a lower risk of having high HOMA&#95;IR, whereas carriers of the minor allele rs17041272 had a higher risk of being insulin resistant. An interaction was detected between the rs6824447 polymorphism and the intake of oil in relation with insulin resistance, such that carriers of this minor allele who consumed sunflower oil had lower HOMA&#95;IR than those who did not have this allele (P = 0.001)., Conclusions: Genetic variations in the ELOVL6 gene were associated with insulin sensitivity in this population-based study.

Hyperuricaemia is one of the components of metabolic syndrome. Both oxidative stress and hyperinsulinism are important variables in the genesis of this syndrome and have a close association with uric acid (UA). We evaluated the effect of an oral glucose challenge on UA concentrations. The study included 656 persons aged 18 to 65 years. Glycaemia, insulin, UA and plasma proteins were measured at baseline and 120 min after an oral glucose tolerance test (OGTT). The baseline sample also included measurements of total cholesterol, triacylglycerol (TAG) and HDL-cholesterol. Insulin resistance was calculated with the homeostasis model assessment. UA levels were significantly lower after the OGTT (281.93 (sd 92.19) v. 267.48 (sd 90.40) micromol/l; P < 0.0001). Subjects with a drop in UA concentrations >40.86 micromol/l (>75th percentile) had higher plasma TAG levels (P = 0.0001), baseline insulin (P = 0.02) and greater insulin resistance (P = 0.034). Women with a difference in plasma concentrations of UA above the 75th percentile had higher baseline insulin levels (P = 0.019), concentration of plasma TAG (P = 0.0001) and a greater insulin resistance index (P = 0.029), whereas the only significant difference in men was the level of TAG. Multiple regression analysis showed that the basal TAG levels, insulin at 120 min, glycaemia at 120 min and waist:hip ratio significantly predicted the variance in the UA difference (r2 0.077). Levels of UA were significantly lower after the OGTT and the individuals with the greatest decrease in UA levels are those who have greater insulin resistance and higher TAG levels.

Background: The intestinal fatty acid-binding protein (FABP2) is involved in the intracellular transport and metabolism of fatty acids and may affect insulin sensitivity and glucose metabolism., Objective: The objective was to study the effect of interaction between the Ala54Thr polymorphism of the FABP2 gene (FABP2) and the type of dietary cooking oil used on peripheral insulin sensitivity in a population from southern Spain., Design: The study was cross-sectional. Anthropometric measurements were obtained for 1226 persons aged 18-65 y selected randomly from the municipal census of Pizarra, Spain. An oral-glucose-tolerance test was given to 1020 of these persons. Insulin resistance was measured by homeostasis model assessment. Samples of the cooking oil being used were taken from the kitchens of a random subset of 538 persons., Results: Persons who consumed sunflower oil and who also had the Thr54 variant had higher insulin resistance than did those who consumed olive oil (P = 0.01). We detected an interaction between the Ala54Thr polymorphism and the type of oil consumed that accounted for the variance in insulin resistance (P = 0.02)., Conclusions: The effect of dietary fatty acids on the populational pattern of insulin resistance is not independent of the Ala54Thr polymorphism of FABP2. An interaction existed between this polymorphism and the intake of dietary fats in a population with a high intake of monounsaturated fatty acids.

Aims/hypothesis: Decreased sensing of the innate immune system may lead to chronic activation of the inflammatory cascade. We hypothesised that mannan-binding lectin (MBL) deficiency may confer risk of obesity and insulin resistance., Materials and Methods: We performed a cross-sectional study of MBL protein concentration (n=434) and MBL2 gene mutations (exon 1) (n=759) in association with obesity, markers of inflammation and insulin action (euglycaemic clamp, n=113), and a longitudinal study of MBL protein before and after weight loss in obese patients (n=10). We also studied the effects of MBL in vitro in muscle cells and circulating MBL-A (mouse equivalent of human MBL) in a mouse model., Results: Among 434 consecutive non-diabetic men, the age-adjusted serum MBL concentration was lower in obese subjects than in lean subjects (median: 959 microg/ml [interquartile range: 116.8-2,044 microg/ml] vs 1,365 [467-2,513] microg/ml; p=0.01) and was accompanied by increased serum inflammatory markers. Insulin action correlated significantly with serum MBL (r=0.49, p<0.0001). Serum MBL concentration increased by a median of 110.2% after weight loss. The change in serum concentration of MBL was positively associated with the increase in insulin sensitivity (r=0.713, p=0.021). At least one MBL2 gene mutation was present in 48.2% of obese vs 39.3% of non-obese subjects (p=0.037). The plasma concentration of MBL-A was lower in insulin-resistant obese ob/ob mice, as was the glucose/insulin ratio. Incubation of rat soleus muscle with human MBL markedly increased fatty acid oxidation., Conclusions/interpretation: These findings suggest that MBL, previously thought only to be involved in inflammation and immune system function, affects metabolic pathways.

Objective: Few epidemiological studies have examined the relationship of dietary fatty acids, especially MUFA, with the interrelation between insulin secretion and insulin resistance. We assessed the relation of dietary fatty acids with insulin secretion in a free-living population., Design and Setting: This cross-sectional, population-based study was undertaken in Pizarra, a small town in Spain., Subjects and Methods: Anthropometrical data were collected for 1226 persons selected randomly from the municipal census, 538 of whom (randomly chosen) were given a prospective, quantitative, 7-day nutritional questionnaire. The fatty acid composition of the serum phospholipids was used as a biological marker of the type of fat consumed. Beta-cell function (betaCFI) and insulin-resistance index (IRI) were estimated by the Homeostasis Model Assessment., Results: To determine which factors influence the variability of the betaCFI, we analyzed the variance of the betaCFI according to sex, the presence of carbohydrate metabolism disorders and the different components of the diet, adjusting the models for age, body mass index (BMI) and IRI. The dietary MUFA and polyunsaturated fatty acids (PUFA) contributed to the variability of the betaCFI, whereas only the proportion of serum phospholipid MUFA, but neither the saturated fatty acids nor the PUFA accounted for part of the variability of the betaCFI in a multiple regression analysis., Conclusion: The results of this population-based study corroborate the results of other clinical and experimental studies suggesting a favorable relationship of MUFA with beta-cell insulin secretion., Sponsorship: Fondo de Investigación Sanitaria, Junta de Andalucía and the Asociación Maimónides.

Activation of the PPAR gamma 2 gene (PPARG2) improves the action of insulin and its lipid metabolism. We examined the association between Pro12Ala polymorphism of PPARG2, type 2 diabetes mellitus (DM2), and peripheral insulin sensitivity in a population with a high intake of oleic acid. A cross-sectional, population-based study was undertaken in Pizarra, a small town in the province of Malaga in southern Spain. A total of 538 subjects, aged 18-65 y, were selected randomly from the municipal census. All subjects underwent a clinical, anthropometrical, and biochemical evaluation, including an oral glucose tolerance test and Pro12Ala polymorphism of PPARG2. Insulin resistance was measured by homeostasis model assessment. Those subjects with the Ala-12 allele had an odds ratio for impaired fasting glucose of 0.55, for impaired glucose tolerance of 0.59, and for DM2 of 0.30. The intake of monounsaturated fatty acids (MUFA) contributed to the variance of the homeostasis model assessment insulin resistance index (HOMA IR) (P = 0.04), with a 2-way interaction between the Ala-12 allele of PPARG2 and the intake of MUFA (P = 0.005). The results suggest the existence of an interaction between Pro12Ala polymorphism of PPARG2 and dietary MUFA, such that obese people with the Ala-12 allele have higher HOMA IR values, especially if their intake of MUFA is low.

The aim of this study was to evaluate patterns of insulin resistance in the general population. The study was cross sectional. Clinical, anthropometric, and lipid measurements were made in 1226 persons aged 18-65 years. An oral glucose tolerance test (OGTT) was performed in 1020 subjects, with insulin levels determined at baseline and after 2 h. The homeostasis model assessment insulin resistance index (HOMA IR) and HOMA beta-cell function were calculated. Compared with subjects with normal glucose tolerance, the groups with abnormal OGTT had different baseline insulinemia, 2 h post OGTT insulinemia, HOMA IR and HOMA beta-cell indices. Serum insulin levels at baseline and 2 h after OGTT showed a characteristic pattern for each category of glucose tolerance, resulting from the different insulin responses. In the subjects with normal glucose tolerance, the pattern of the relationships between both types of serum insulin levels was exactly the same, so that it was possible to determine risk groups according to the ratio of baseline serum insulin/2 h insulin. HOMA IR and HOMA beta-cell were significantly associated with the risk of impaired fasting glucose, previously unknown diabetes mellitus, and known diabetes mellitus. These results support the rationale for introducing preventive measures against insulin resistance in the general population.

Aim: To evaluate the relation between type of dietary fatty acid and degree of insulin resistance., Design: A cross-sectional study., Methods: Anthropometrical data were measured in 538 subjects, aged 18-65 Years, selected randomly from the municipal census of Pizarra (Spain). An oral glucose tolerance test (OGTT) was given to all subjects and measurements were made of glycemia, insulinemia and the proportion of fatty acids in plasma phospholipids. Insulin resistance (IR) was estimated by homeostasis model assessment. Samples of cooking oil being used were obtained from the kitchens. The strength of association between variables was measured by calculating the odds ratio (OR) from logistic models, and the relationships were measured by linear correlation coefficients., Results: Insulin resistance was significantly less in people who used olive oil compared with those who used sunflower oil or a mixture. Statistical significance remained in the group of people with normal OGTT after adjusting for obesity. In the whole sample, IR correlated negatively with the concentration of oleic acid (r=-0.11; P=0.02) and positively with that of linoleic acid (r=0.10; P=0.02) from the cooking oil. In subjects with normal OGTT, IR correlated negatively with oleic acid from cooking oil (r=-0.17; P=0.004) and from plasma phospholipids (r=-0.11; P=0.01) and positively with the concentration of linoleic acid in cooking oil (r=0.18; P=0.004) and plasma phospholipids (r=0.12; P=0.005). The risk (OR) of having raised IR was significantly lower in people who consumed olive oil, either alone (OR=0.50) or mixed (OR=0.52) compared with those who consumed only sunflower oil., Conclusion: There is an association between the intake of oleic acid, the composition of oleic acid in plasma phospholipids and peripheral insulin action.

Background: Systemic inflammation (SI) and insulin resistance (IR) are correlated to the progression of gastrointestinal (GI) cancer. Therefore, this study aimed to analyze the potential clinical value of the C-reactive protein-triglyceride-glucose index (CTI) in relation to SI and IR in patients with GI cancer. Methods: This prospective cohort study included patients with GI cancer. Patient data were collected from Fujian Cancer Hospital as an external validation cohort. Prognostic AUC, time-dependent ROC curve, C-index, and calibration curve analyses were used to predict the efficacy and accuracy of CTI survival prediction. Multivariate survival analysis was performed to evaluate the potential prognostic value of the CTI. Multiple logistic regression was performed to evaluate the relationship between the CTI and 90-day and 180-day mortalities. Results: We divided 1520 patients with GI cancer (mean age, 60.39 ± 11.3 years; male sex, 67%) into a training cohort and internal validation cohort; the external validation cohort included 476 patients. Prognostic AUC, time-dependent ROC curve, C-index, and calibration curve analyses of all cohorts indicated that the CTI could reliably and accurately predict the short- and long-term survival outcomes of patients with GI cancer. Multivariate survival analysis showed that for each standard deviation increase in the CTI, the risk of death increased by 32%, 21%, and 40% in the training, internal validation, and external validation cohorts, respectively. A high CTI was correlated to worse survival in patients with GI cancer (training cohort, hazard ratio [HR]=1.67, 95% confidence interval [CI]=1.35–2.08; internal validation cohort, HR=1.51, 95% CI=1.07–2.14, and external validation cohort, HR=1.59, 95% CI=1.18–2.13). In different tumor subgroups, a high CTI predicted worse survival outcomes for upper GI cancer (HR=1.54, 95% CI=1.18–2.01) and lower GI cancer (HR=1.98, 95% CI=1.36–2.86). Multivariate logistic regression analysis showed that a high CTI was positively correlated with 90-day (odds ratio [OR]=3.25, 95% CI=1.75–6.23) and 180-day mortalities (OR=2.66, 95% CI=1.72–4.15). Conclusions: The CTI is related to SI and IR and can predict the short- and long-term prognosis of patients with GI cancer. Evaluation of the CTI could provide clinicians with an effective tool for predicting the prognosis of patients with GI cancer. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=31813 , identifier ChiCTR1800020329. [ABSTRACT FROM AUTHOR]

Background: Apolipoprotein (apo) C-III is involved in several processes that increase triglyceride levels, inflammation, and insulin resistance. Four of its proteoforms have been the focus of several studies and have shown differential associations with cardiovascular risk biomarkers, mostly lipids. However, there are other proteoforms of apoC-III that have not yet been investigated in detail. The aim of this study was to evaluate the associations of seven apoC-III proteoforms with a comprehensive set of biomarkers, including lipid metabolism, inflammation, and glucose homeostasis. Methods: Seven apoC-III proteoforms (apoC-III0a, apoC-III0b, apoC-III1, apoC-III1d, apoC-III2, apoC-III2d, and apoC-III0f) were measured using a mass spectrometry immunoassay in 875 participants from the cross-sectional study of the Di@bet.es cohort. The complete lipoprotein profile was obtained via the Liposcale test, and the proton nuclear magnetic resonance (1H-NMR)-assessed glycoprotein signals were also obtained as biomarkers of inflammation. Results: Three proteoform ratios (apoC-III2d, apoC-III2, and apoC-III0f normalized to apoC-III1) showed protective associations with most of the cardiovascular risk biomarkers in comparison with total apoC-III in linear regression models and were negatively associated with triglycerides (β=-0.173, p < 0.001; β=-0.297, p < 0.001; β=-0.223, p = 0.002), very low-density (VLDL) particle concentration (β=-0.133, p < 0.001; β=-0.265, p < 0.001; β=-0.203, p < 0.001), GlycA (β=-0.148, p < 0.001; β=-0.263, p < 0.001; β=-0.211, p < 0.001) and homeostatic model assessment of insulin resistance (HOMA-IR) (β=-0.096, p = 0.003; β=-0.199, p < 0.001; β=-0.114, p = 0.002). These associations were partly independent of total apoC-III concentrations. Participants with high levels of these proteoforms had a lower prevalence of cardiometabolic disorders, such as type 2 diabetes (p = 0.022), obesity (p = 0.001), and metabolic syndrome (p = 0.013). Conclusions: While apoC-III is positively associated with biomarkers of cardiometabolic risk, the proportions of three apoC-III proteoforms show opposite associations, independent of total apoC-III concentrations. Measuring not only apoC-III but also the proportions of apoC-III proteoforms can provide valuable information since individuals with similar levels of total apoC-III could display opposite lipid profiles depending on the proportion of apoC-III proteoforms. [ABSTRACT FROM AUTHOR]

Background: Male obesity is one of the most associated factors with substandard testosterone levels. However, there is growing evidence linking low testosterone levels to insulin resistance and diabetic complications. We aimed to study the impact of diabetes mellitus on testosterone levels and to assess the correlation of various clinical and biochemical factors with hypogonadism. Subjects and methods: This case-control study was conducted on 160 adult males categorized into four equal groups (40 each); Group A: lean men with T2DM, Group B: obese with T2DM, Group C: lean with normal glycemic profile, Group D: obese with normal glycemic profile. Serum total testosterone (TT), SHBG and HbA1c have been measured. Free testosterone (cFT) and HOMA-IR were calculated. Results: A significant negative correlation of serum TT and cFTwith BMI (r -0.16, p 0.04/ r -0.26, p < 0.001, respectively) and with waist circumference (WC) (r -0.23, p 0.003 and r -0.3, p < 0.001, respectively). A significant decrease in TT and cFT in the diabetes group versus the non-diabetes one (p < 0.001 for both). TT level was significantly lower in the diabetic lean group than in the non-diabetic lean (p < 0.001), and even significantly lower than in the non-diabetic obese (p < 0.001). TT level in the diabetic obese group was lower than in the non-diabetic obese (p < 0.001). The same for cFT level, lower in the diabetic lean group than in non-diabetic lean (p < 0.001) and lower in the diabetic obese than in the non-diabetic obese (p < 0.001). Concomitant significant reduction in SHBG in the diabetes group (p < 0.001). Linear regression analysis revealed that TT significantly correlated with HOMA-IR. HOMA-IR with WC, age and the duration of diabetes correlated significantly with cFT. In our model, HOMA-IR and HbA1c accounted for approximately 51.3% of TT variability (adjusted R-squared 0.513). Conclusions: The impact of T2DM on serum testosterone levels was more significant than that of obesity. Our study showed a decrease in SHBG together with cFT among the diabetes group. Hypogonadism is significantly correlated to insulin resistance and poor glycemic control, which implies another perspective on the impact of suboptimal glycemic control on the development of hypogonadism. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD), which is a prevalent hepatic condition worldwide, is expected to develop into the leading reason for end-stage fatty liver in the forthcoming decades. Incorporating rapeseed oil into a balanced diet may be beneficial in improving NAFLD. The goal of this trial was to evaluate the impact of substituting ghee with rapeseed oil on primary outcomes such as fatty liver and liver enzymes, as well as on secondary outcomes including glycaemic variables, lipid profile and anthropometric measurements in individuals with NAFLD. Over 12 weeks, 110 patients (seventy men and forty women; BMI (mean) 28·2 (sd 1·6 kg/m2); mean age 42 (sd 9·6) years), who daily consumed ghee, were assigned to the intervention or control group through random allocation. The intervention group was advised to substitute ghee with rapeseed oil in the same amount. The control group continued the consumption of ghee and was instructed to adhere to a healthy diet. Results showed a significant reduction in the steatosis in the intervention group in comparison with the control group (P < 0·001). However, a significant change in the levels of alanine aminotransferase (–14·4 μg/l), γ-glutamyl transferase (–1·8 μg/l), TAG (–39·7 mg/dl), total cholesterol (–17·2 mg/dl), LDL (–7·5 mg/dl), fasting blood glucose (–7·5 mg/dl), insulin (–3·05 mU/l), Homeostatic Model Assessment for Insulin Resistance (–0·9), Quantitative Insulin-Sensitivity Check Index (+0·01), weight (–4·3 kg), BMI (–0·04 kg/m2), waist (–5·6 cm) and waist:height ratio (–0·04) was seen in the intervention group. The consumption of rapeseed oil instead of ghee caused improvements in liver steatosis and enzymes, glycaemic variables and anthropometric measurements among individuals with NAFLD. [ABSTRACT FROM AUTHOR]

Context The cardiometabolic significance of subclinical liver fat in otherwise healthy individuals is unclear. Objective This work aimed to evaluate the association of hepatic steatosis/fibrosis with cardiometabolic risk markers and incident prediabetes among healthy adults. Methods This is a post hoc analysis of data from the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study. The participants underwent assessments, including clinical examination, oral glucose tolerance test, insulin sensitivity, insulin secretion, plasma high-sensitivity C-reactive protein (hsCRP), and adiponectin levels, with the primary outcome of incident prediabetes during 5-year follow-up. Liver steatosis and fibrosis were assessed using the hepatic steatosis index (HSI) and the Fibrosis-4 (Fib-4) index, and participants were stratified by baseline quartiles (Q) of each index. Results Among 343 (193 African American, 150 European American) participants (mean age 44.2 ± 10.6 years, body mass index 30.2 ± 7.28, fasting glucose 91.8 ± 6.80 mg/dL, and 2-hour glucose 125 ± 26.5 mg/dL), the mean baseline HSI was 39.7 ± 8.21 and Fib-4 index was 0.80 ± 0.41. Baseline HSI correlated with insulin sensitivity (r = −0.44; P <.0001), hsCRP (r = 0.37; P <.0001), and adiponectin (r = −0.24; P <.0001), as did Fib-4 index: insulin sensitivity (r = 0.14; P =.046), hsCRP (r = −0.17; P =.0021), adiponectin (r = −0.22; P <.0001). During 5 years of follow-up, prediabetes occurred in 16.2%, 21.6%, 31.5%, and 30.6% among participants in Q1 to Q4 of baseline HSI, respectively (log-rank P =.02). The prediabetes hazard ratio was 1.138 (95% CI, 1.027-1.261) for baseline HSI. Conclusion Among initially normoglycemic individuals, hepatic steatosis predicted progression to prediabetes, probably via mechanisms that involve insulin resistance and inflammation. [ABSTRACT FROM AUTHOR]

Metformin is a highly effective medication for managing type 2 diabetes mellitus. Recent studies have shown that it has significant therapeutic benefits in various organ systems, particularly the liver. Although the effects of metformin on metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis are still being debated, it has positive effects on cirrhosis and anti-tumoral properties, which can help prevent the development of hepatocellular carcinoma. Furthermore, it has been proven to improve insulin resistance and dyslipidaemia, commonly associated with liver diseases. While more studies are needed to fully determine the safety and effectiveness of metformin use in liver diseases, the results are highly promising. Indeed, metformin has a terrific potential for extending its full therapeutic properties beyond its traditional use in managing diabetes. [ABSTRACT FROM AUTHOR]

Insulin resistance (IR) is an important risk factor for cardiovascular diseases, and the triglyceride-glucose index (TyG index) is a potential IR biomarker. Evidence also suggests that fat intake may modulate IR status, but this relationship remains unclear. Thus, the present study aimed to analyze the relationship between the TyG index and isocaloric replacement of macronutrients, including the profile of dietary fatty acids in individuals at cardiometabolic risk. This cross-sectional study enrolled 264 individuals at cardiometabolic risk (age 43.1 ± 16.3 years) who participated in a nutritional intervention study (ReBEC, id: RBR-5n4y2g). The baseline demographic, anthropometric, clinical, dietary, and lifestyle data were used. The TyG index was calculated using the formula ln [fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2]. Multivariate nutrient density models were used to analyze isocaloric replacement of fatty acids (as 5% of energy). The chance of having a high TyG index (TyG index >8.83, median value) was decreased by 60% after replacing 5% of the energy intake of polyunsaturated fatty acid (PUFA), saturated fatty acid (SFA), and trans fatty acid (TFA) with monounsaturated fatty acid (MUFA) or PUFA and SFA with protein. Isocaloric replacement of PUFA, SFA, and TFA with MUFA and protein was associated with lower chances of having a high TyG index. These results indicate the importance of macronutrient and dietary fat profiles in the dietary planning of individuals at cardiometabolic risk. [ABSTRACT FROM AUTHOR]

Midlife women experience changes in cardiometabolic, physical, and psychosocial health during menopause that negatively impacts their overall quality of life. Factors that contribute to these increases in cardiometabolic risk include weight gain as well as increases in fat mass (particularly abdominal adiposity), insulin resistance, and vascular dysfunction. Other deleterious changes in physical health (e. g. reduced sleep health, bone density, and balance) as well as changes in psychosocial health (e. g. mood, anxiety, and depression) often coincide and are linked to these increases in cardiometabolic risk. Physical activity and exercise are important lifestyle components that have been demonstrated to improve cardiometabolic, physical, and psychosocial health, yet physical activity and exercise is known to decline during perimenopause and into the postmenopausal years. In this narrative review, we summarize these changes in overall health during menopause as well as how declining physical activity contributes to these changes. Additionally, we discuss how incorporating physical activity and exercise during menopause can potentially ameliorate health declines. We conclude that there exists a significant, positive impact of physical activity on cardiometabolic, physical, and psychological health among midlife women, particularly if undertaken during the perimenopausal and postmenopausal years. [ABSTRACT FROM AUTHOR]

Background: Vitamin D deficiency (VDD) increases the risk for type 2 diabetes mellitus (T2DM), which might be related to insulin resistance (IR). We aimed to explore the association between the triglyceride-glucose (TyG) index, a reliable indicator of IR, and VDD in patients with T2DM. Methods: There were 1034 participants with T2DM enrolled in the Second Xiangya Hospital of Central South University. The TyG index was calculated as ln (fasting triglyceride (TG, mg/dL) × fasting blood glucose (mg/dL)/2). VDD was defined as 25-hydroxyvitamin D [25(OH)D] level <50 nmol/L. Results: Correlation analysis showed a negative association between the TyG index and 25(OH)D level. After adjustments for clinical and laboratory parameters, it was revealed that when taking the Q1 quartile of TyG index as a reference, an increasing trend of VDD prevalence was presented in the other three groups divided by TyG index quartiles, where the OR (95% CI) was 1.708 (1.132–2.576) for Q2, 2.041 (1.315–3.169) for Q3, and 2.543 (1.520–4.253) for Q4 (all p < 0.05). Conclusions: Patients with higher TyG index were more likely to have an increased risk of VDD in T2DM population, which may be related to IR. [ABSTRACT FROM AUTHOR]

Most cells release extracellular vesicles (EVs) that can be detected circulating in blood. We and others have shown that the microRNA contents of these vesicles induce transcriptomic changes in acceptor cells, contributing to the adjustment of metabolic homeostasis in response to environmental demands. Here, we explore the potential for modulating obesity- and exercise-derived EV-microRNAs to treat the metabolic dysfunction associated with obesity in mice. Treatment with EV-miRNAs alleviated glucose intolerance and insulin resistance in obese mice to an extent similar to that of high-intensity interval training, although only exercise improved cardiorespiratory fitness and decreased body weight. Mechanistically, EV-miRNAs decreased fatty acid and cholesterol biosynthesis pathways in the liver, reducing hepatic steatosis and increasing insulin sensitivity, resulting in decreased glycemia and triglyceridemia. Our data suggest that manipulation of EV-miRNAs may be a viable strategy to alleviate metabolic dysfunction in obese and diabetic patients who are unable to exercise, although actual physical activity is needed to improve cardiorespiratory fitness. [ABSTRACT FROM AUTHOR]

Obesity induces insulin resistance, chronic inflammation, oxidative stress, and neurocognitive impairment. Avocado oil (AO) has antioxidants and anti-inflammatory effects. This study evaluated the effect of AO supplementation on obese mice in the adipose tissue, muscle, liver, and hippocampus. Male C57BL/6J mice received a standard and high-fat diet (20 weeks) and then were supplemented with AO (4 mL/kg of body weight, 90 days) and divided into the following groups: control (control), control + avocado oil (control + AO), diet-induced obesity (DIO), and diet-induced obesity + avocado oil (DIO + AO) (n = 10/group). AO supplementation was found to improve insulin sensitivity and decrease hepatic fat accumulation and serum triglyceride levels in DIO mice. AO improved cognitive performance and did not affect mood parameters. Oxidative marker levels were decreased in DIO + AO mice in all the tissues and were concomitant with increased catalase and superoxide dismutase activities in the epididymal adipose tissue and quadriceps, as well as increased catalase activity in the liver. AO in obese animals further induced reductions in TNF-α and IL-1β expressions in the epididymal adipose tissue and quadriceps. These results suggest that AO supplementation has the potential to be an effective strategy for combating the effects of obesity in rats, and human studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Background. Insulin resistance is the major sign of etiology and pathogenesis of type 2 diabetes mellitus and metabolic syndrome and can precede its development for many years. Early identifying the beginning of insulin resistance in children is important to prevent diabetes mellitus in adult life. The purpose was to identify metabolic and somatic changes in children with insulin resistance. Material and methods. Out of 182 children of the general sample, who was estimated fasting plasma insulin and glucose, HOMA-IR, and glucose/insulin ratio, 2 groups were formed: group 1 — children with IR — 56 (30.8 %) and group 2 — 126 (69.2 %) children with normal insulin sensitivity. In children anthropometric data, lipid metabolism (total cholesterol, triglycerides, HDL-C, LDL-C, VLDL-C), blood pressure, leptin were determined. Results. From examined subjects 56 children were generally obese (BMI > 95th percentile), 71 children were abdominally obese (WC > 90th percentile), 55 children were with normal body mass (BMI < 90th percentile). Insulin resistance was identified in 21 (37.5 %) children with general obesity more rarely, than in 38 (39.4 %) children with abdominal obesity (p = .049) and in 7 (12.7 %) children with normal BMI (p = .003). In insulin-resistant children BMI, waist and hip circumference was larger than in children with normal insulin sensitivity. The lipid profile in children with different insulin sensitivity did not differ, but in insulin-resistant children an association of basal glucose with TG/HDL-C ratio (r = .53; p = .001), blood insulin with TG (r = .34; p = .018), and TG/HDL-C ratio (r = .54; p = .001) was estimated. The HOMA-IR significantly correlated with VLD-C (r = .40; p = .005), TG (r = .49; p = .001), TG/HDL-C ratio (r = .43; p = .002). The glucose/insulin ratio was in significant association with the TG/non-HDL-C ratio. The incidence of hypetension (> 95th percentile) diagnosis in insulin-resistant children was by 33.8 % higher (p = .001). Blood leptin concentration was 1.8 falled higher in insulin-resistant children and significantly correlates with waist circumference, fasting insulin, HOMA-IR, and diastolic blood pressure. Conclusions. Insulin resistance is related to cardiometabolic risks, such as general and abdominal obesity, hypertension, dyslipidemia, hyperleptinemia, and leptin resistance, and is a screening biomarker for children and adolescents with an increased risk of cardiometabolic diseases. [ABSTRACT FROM AUTHOR]

Background: Little is known about the relation between morbid obesity and duodenal transcriptomic changes. We aimed to identify intestinal genes that may be associated with the development of obesity regardless of the degree of insulin resistance (IR) of patients. Material and Methods: Duodenal samples were assessed by microarray in three groups of women: non-obese women and women with morbid obesity with low and high IR. Results: We identified differentially expressed genes (DEGs) associated with morbid obesity, regardless of IR degree, related to digestion and lipid metabolism, defense response and inflammatory processes, maintenance of the gastrointestinal epithelium, wound healing and homeostasis, and the development of gastrointestinal cancer. However, other DEGs depended on the IR degree. We mainly found an upregulation of genes involved in the response to external organisms, hypoxia, and wound healing functions in women with morbid obesity and low IR. Conclusions: Regardless of the degree of IR, morbid obesity is associated with an altered expression of genes related to intestinal defenses, antimicrobial and immune responses, and gastrointestinal cancer. Our data also suggest a deficient duodenal immune and antimicrobial response in women with high IR. [ABSTRACT FROM AUTHOR]

Background: Thyroid hormone (TH) regulates metabolic pathways which may interfere with insulin action. There is limited knowledge on adipose tissue (AT) and skeletal muscle (SM) expression of genes associated with TH action in relation to insulin sensitivity. The aim of this study was to analyze AT and SM expression of the genes associated with TH action in subjects with different degree of insulin sensitivity and the regulation of these genes by insulin and free fatty acids (FFA). Methods: The study group comprised 72 euthyroid male subjects: 36 normal weight subjects and 36 overweight/obese subjects. Two-hour hyperinsulinemic–euglycemic clamp and tissue biopsies were performed. In the subgroup of 20 subjects, 9 normal weight subjects and 11 overweight/obese subjects, clamp was prolonged to 6 hours and another clamp with Intralipid/heparin infusion was performed after 1 week. Tissue biopsies were performed before and after each clamp. Results: Overweight/obese subjects had higher AT DIO2, DIO3, and NCOR1, lower AT THRA and PPARGC1A, higher SM NCOR1, and lower SM DIO2, DIO3, PPARGC1A, and ATP2A2 expression. In AT, DIO2 and PPARGC1A increased, whereas NCOR1 and FOXO1 decreased after the clamp only in normal weight individuals. DIO3 decreased in both groups. In SM, NCOR1 decreased, whereas PPARGC1A and ATP2A2 increased after the clamp only in normal weight individuals. Tissue THRA and THRB decreased in both groups. Intralipid/heparin abolished these effects. Conclusions: Alterations in AT and SM expression of TH-related gene indicate a decreased tissue TH action in obesity. Inability to increase TH-related gene expression in obesity and during FFA oversupply may contribute to the aggravation of lipotoxicity. [ABSTRACT FROM AUTHOR]

Context: The role of androgen excess as a contributing factor to abnormal glucose metabolism (AGM) and insulin resistance in women remains controversial.Objective: To investigate whether hyperandrogenemia (HA) estimated by serum testosterone (T) level and free androgen index (FAI) at ages 31 and 46 years is associated with insulin resistance, insulin secretion and AGM by age 46.Design: Prospective study including 5889 females followed at ages 31 and 46 years.Setting: General community.Participants: Women with HA were compared with normoandrogenic women at ages 31 and 46 years.Intervention: None.Main Outcome Measurements: AGM, including prediabetes and type 2 diabetes mellitus, homeostatic model assessments of insulin resistance (HOMA-IR) and of pancreatic β-cell function (HOMA-B).Results: At age 31 years, HA women displayed increased HOMA-IR (P = 0.002), HOMA-B (P = 0.007), and higher fasting insulin (P = 0.03) than normoandrogenic women after adjusting for body mass index (BMI). At age 46 years, there was a nonsignificant trend toward higher fasting glucose (P = 0.07) and glycated hemoglobin A1 (P = 0.07) levels in HA women. Women in the highest T quartile (odds ratio [OR] = 1.80; 95%CI, 1.15-2.82) at age 31 years and in the 2 highest FAI quartiles at ages 31 (Q4: OR = 3.76; 95% CI, 2.24-6.32) and 46 (Q4: OR = 2.79; 95% CI, 1.74-4.46) years had increased risk for AGM, independently of BMI, when compared with women in Q1. SHBG was inversely associated with AGM (at age 31 years: Q4: OR = 0.37; 95% CI, 0.23-0.60, at age 46 years: Q4: OR = 0.28; 95% CI, 0.17-0.44).Conclusion: Hyperandrogenemia and low SHBG in early and middle age associates with AGM independently of BMI. [ABSTRACT FROM AUTHOR]

Aims: The association of strictly defined metabolic healthy obese (MHO) with subclinical cardiac function was unclear. Our study aims to examine the role of MHO in subclinical cardiac dysfunction in a Chinese population. Methods and results: The study subjects were recruited from Danyang from 2017 to 2019. Obesity was defined by body mass index (BMI) categories (normal weight, overweight and obesity). Metabolic health was strictly defined as having neither any of the guidelines recommended metabolic syndrome components nor insulin resistance. Thus, subjects were grouped by BMI categories and metabolic health status as six groups. Preclinical systolic (global longitudinal strain [GLS]) and diastolic function were assessed by 2D speckle tracking, and transmitral and tissue Doppler imaging, respectively. The 2757 participants (mean age ± standard deviation, 52.7 ± 11.7 years) included 1613 (58.5%) women, 999 (36.2%) obese, 2080 (75.4%) metabolically unhealthy and 93 (3.4%) MHO participants. After adjustment for covariates, the trend was similar for left ventricular (LV) ejection fraction (Ptrend ≥ 0.07) but significantly worse for GLS, e′ and E/e′ (Ptrend ≤ 0.02) across the six groups or passing from normal weight to obese individuals irrespective of metabolic status. MHO participants had lower GLS (20.4 vs. 21.4%) and e′ (9.6 vs. 10.6 cm/s) compared with controls (P < 0.0001) but had similar GLS (P = 0.47) compared with metabolically unhealthy obese (MUO). Regardless of obesity status, metabolically unhealthy participants had worse diastolic function compared with their metabolically healthy counterparts (P ≤ 0.0004). Compared with controls, MHO individuals were at higher risk of subclinical LV systolic dysfunction (OR = 3.44, 95% CI = 1.25–9.49, P = 0.02). These results were robust to sensitivity analysis. Conclusions: MHO was substantially associated with worse subclinical systolic function although early diastolic dysfunction seemed to be more accentuated in MUO. [ABSTRACT FROM AUTHOR]

Background: Endogenous sex hormones and sex hormone-binding globulins (SHBG) determine the risk of occurrence of Type 2 diabetes mellitus (T2DM) in postmenopausal (PM) women. Aims: To investigate the association between sex hormones (estradiol and testosterone) and SHBG with plasma glucose, fasting insulin levels, HbA1c, and homeostasis model assessment insulin resistance (HOMA-IR) and also to investigate independent role of sex hormones in the occurrence of T2DM among PM. Settings and Design: Cross-sectional case–control study. Subjects and Methods: The present study was conducted in Endocrinology department Guwahati, Medical College, Assam, India. The participants included cases – PM women with T2DM (n = 100) and controls – Healthy PM women (n = 86). The medical history, clinical examination, and investigations including total testosterone, serum estradiol, SHBG, free testosterone index, high sensitivity C-reactive protein (hs-CRP), lipid profile, fasting insulin, fasting plasma glucose (FPG), and postprandial plasma glucose (PPPG) were done and analyzed. HOMA-IR was calculated. Statistical Analysis: Pearson correlation between sex hormone level and SHBG with plasma glucose, HbA1c, fasting insulin, hs-CRP, and HOMA-IR was seen. Multivariance logistic analysis was done to find the independent association between sex hormones/SHBG and the occurrence of T2 DM. P < 0.05 was considered statistically significant. Results: Among the cases, a significant positive correlation was found between total testosterone/free testosterone index with waist circumference, FPG PPPG, HbA1c, fasting insulin, and HOMA-IR, and a significant negative correlation was found between SHBG and FPG, PPPG, HbA1c, fasting insulin, and HOMA-IR (P < 0.01). The logistic analysis showed total testosterone levels and SHBG are independently associated with the occurrence of T2 DM among PM (P < 0.01). Conclusion: SHBG and testosterone levels in PM can be a risk marker for the development of T2DM. [ABSTRACT FROM AUTHOR]

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Obesity in youth is associated with increased risk of metabolic disorders. Adipose tissue hormones are involved in body-weight regulation. Among these, apelin is recognized as an insulin-sensitizer adipokine. Data on apelin levels in obese children and its relation to insulin-sensitivity are limited. We aimed to evaluate apelin levels in relation to obesity and insulin sensitivity in a large cohort of overweight/obese children and adolescents. Furthermore, these youths were reevaluated after a median 6.5 years of follow-up, thus allowing assessing changes in apelin levels in relation to increasing age and weight changes. Clinical data in 909 children and adolescents were collected between 2007 and 2010. Two hundred and one were reexamined at a median 6.5 years of follow-up. All subjects at baseline and at follow-up underwent an OGTT. Apelin levels were measured on sera by ELISA method. At baseline, lower apelin levels were associated with increasing age and puberty (Tanner ≥II 0.67 ± 0.96 ng/mL vs. Tanner I 0.89 ± 1.13 ng/mL, p <.002), but not with body-weight. At follow-up, apelin levels in the 201 subjects reexamined were significantly lower than at baseline (0.45 ± 0.77 ng/mL at follow-up, 0.68 ± 0.95 ng/mL baseline, p <.001), confirming the effects of age and puberty. Body-weight did not affect apelin levels. Multiple regression analysis confirmed that sex and puberty were associated with lower apelin levels, independently from age and insulin-sensitivity. Apelin levels decrease significantly with pubertal development, whilst body-weight in children and adolescents did not determine changes in apelin. Reduced levels of apelin in children and adolescents may therefore represent a necessary response to maintain the "physiological" insulin resistance of puberty. Abbreviations: ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; G: glucose; BMI: Body mass index; DBP: Diastolic blood pressure; ELISA: enzyme-linked immunosorbent assay; HDL-C: High-density lipoprotein-cholesterol; HOMA-B: Homeostatic model assessment for beta-cell function; HOMA-IR: Homeostatic model assessment of insulin-resistance; INS: Insulin; ISI: insulin-sensitivity index; LDL-C: Low-density lipoprotein cholesterol; NW: normal weight; OB: obese; OGTT: oral glucose tolerance test; OW: overweight; SBP: Systolic blood pressure; TC: Total cholesterol; TGs: Triglycerides [ABSTRACT FROM AUTHOR]

Background and Purpose: Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and abnormalities in insulin production. Apelin is associated with insulin resistance. According to the anti-diabetic properties of curcumin, the purpose of this study was to compare the effects of curcumin and nano-curcumin intake on insulin resistance and serum levels of fasting blood sugar (FBS), Apelin, and lipid profile (cholesterol, triglyceride, LDL, HDL and VLDL) in T2DM rats. Materials and Methods: Forty-eight male Wistar rats were divided into six groups: Control, diabetic, diabetic treated with two doses of curcumin (100 and 200 mg/kg) and diabetic treated with two doses of nano-curcumin (100 and 200 mg/kg). Induction of T2DM was performed by intraperitoneal injection of Nicotinamide (110 mg/kg) and Streptozotocin (45 mg/kg) in the fasting state. Rats received different doses of nano-curcumin and curcumin by gavage (daily) for 28 days. At the end of the intervention period, insulin resistance and serum levels of FBS, apelin and lipid profiles were measured. Results: Insulin resistance and serum levels of FBS, Apelin, cholesterol, triglycerides, LDL, and VLDL were significantly decreased in diabetic rats treated with curcumin and nano-curcumin (p< 0.05) so that nano-curcumin in reducing lipid profile is more effective than curcumin (P< 0.05). Serum level of HDL in nano-curcumin groups was significantly higher than diabetic and curcumin groups (p< 0.05). Also, with increasing insulin resistance, serum level of apelin increased (P< 0.05). Conclusion: The therapeutic effects of curcumin and nano-curcumin were effective in decreasing insulin resistance, serum levels of FBS, apelin and lipid profile. The dose of 100 mg/kg nano-curcumin was more effective in reducing lipid profile. [ABSTRACT FROM AUTHOR]

This study investigated the endurance exercise-induced changes in lesser known adipokines (visfatin, chemerin, apelin, semaphorin 3 C) related to obesity and metabolism, and their correlations with the changes in the parameters of obesity and glucose homeostasis. Forty metabolically healthy obese young males were randomly assigned to control group (C, n = 12) or exercise group (Ex, n = 28). The subjects in Ex participated in a 8-week supervised endurance exercise training program, comprised of four sessions of treadmill running at 65–70% of VO2max per week. Serum levels of visfatin, chemerin, apelin, and semaphorin 3 C were significantly decreased in Ex. At baseline, apelin and semaphorin 3 C appeared to be correlated with obesity measures, including body mass index, % total fat and trunk fat, and waist circumference. Exercise-induced changes in these obesity measures significantly correlated with the changes in chemerin and semaphorin 3 C. Basal chemerin, apelin and semaphorin 3 C correlated with glucose homeostasis parameters, including fasting plasma glucose, fasting plasma insulin, homeostasis model assessment of insulin resistance and β-cell function, and quantitative insulin-sensitivity check index to different extents. Furthermore, the changes in apelin and semaphorin 3 C well predicted the improvements in glycemic parameters. We suggest that semaphorin 3 C is a novel adipokine involved in pathophysiology of obesity and metabolism, and that it is a biomarker representing an exercise-induced improvement in metabolically healthy obese young males. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is associated with increased risk of cardiovascular disease (CVD). In insulin resistant states such as the metabolic syndrome, overproduction and impaired clearance of liver-derived very-low-density lipoproteins and gut-derived chylomicrons (CMs) contribute to hypertriglyceridemia and elevated atherogenic remnant lipoproteins. Although ingested fat is the major stimulus of CM secretion, intestinal lipid handling and ultimately CM secretory rate is determined by numerous additional regulatory inputs including nutrients, hormones and neural signals that fine tune CM secretion during fasted and fed states. Insulin resistance and T2D represent perturbed metabolic states in which intestinal sensitivity to key regulatory hormones such as insulin, leptin and glucagon-like peptide-1 (GLP-1) may be altered, contributing to increased CM secretion. In this review, we describe the evidence from human and animal models demonstrating increased CM secretion in insulin resistance and T2D and discuss the molecular mechanisms underlying these effects. Several novel compounds are in various stages of preclinical and clinical investigation to modulate intestinal CM synthesis and secretion. Their efficacy, safety and therapeutic utility are discussed. Similarly, the effects of currently approved lipid modulating therapies such as statins, ezetimibe, fibrates, and PCSK9 inhibitors on intestinal CM production are discussed. The intricacies of intestinal CM production are an active area of research that may yield novel therapies to prevent atherosclerotic CVD in insulin resistance and T2D. [ABSTRACT FROM AUTHOR]

Palmitic acid is a saturated fatty acid whose blood concentration is elevated in obese patients. This causes inflammatory responses, where toll-like receptors (TLR), TLR2 and TLR4, play an important role. Nevertheless, palmitic acid is not only a TLR agonist. In the cell, this fatty acid is converted into phospholipids, diacylglycerol and ceramides. They trigger the activation of various signaling pathways that are common for LPS-mediated TLR4 activation. In particular, metabolic products of palmitic acid affect the activation of various PKCs, ER stress and cause an increase in ROS generation. Thanks to this, palmitic acid also strengthens the TLR4-induced signaling. In this review, we discuss the mechanisms of inflammatory response induced by palmitic acid. In particular, we focus on describing its effect on ER stress and IRE1α, and the mechanisms of NF-κB activation. We also present the mechanisms of inflammasome NLRP3 activation and the effect of palmitic acid on enhanced inflammatory response by increasing the expression of FABP4/aP2. Finally, we focus on the consequences of inflammatory responses, in particular, the effect of TNF-α, IL-1β and IL-6 on insulin resistance. Due to the high importance of macrophages and the production of proinflammatory cytokines by them, this work mainly focuses on these cells. [ABSTRACT FROM AUTHOR]

Elevated plasma concentration of apolipoprotein B-48 (apoB-48) is an independent risk factor of cardiovascular disease. Stearoyl-CoA desaturase-1 (SCD1) is a rate-limiting lipogenic enzyme and a key regulator of fuel metabolism. The aim of this study was to analyse associations between clinical, biochemical, and genetic factors and different apoB-48 levels in subjects at increased cardiometabolic risk. We examined 220 subjects exhibiting at least one metabolic syndrome (MetS) component. In conjunction with basic clinical, anthropometric and laboratory measurements, we analysed various polymorphisms of stearoyl-CoA desaturase-1 (SCD1). Subjects were divided into two groups according to the median apoB-48 level: (1) high apoB-48 (≥ 7.9 mg/l, N = 112) and (2) low apoB-48 (< 7.9 mg/l, N = 108). Neither group differed significantly in anthropometric measures. High plasma apoB-48 levels were associated with increased systolic blood pressure (+3 %; P < 0.05), MetS prevalence (59.8 vs. 32.4 %; P < 0.001), small-dense LDL frequency (46.4 vs. 20.4 %; P < 0.001), triglycerides (+97 %; P < 0.001), non-HDLcholesterol (+27 %; P < 0.001), and lower concentrations of HDL-cholesterol (-11 %; P < 0.01). This group was further characterized by a higher HOMA-IR index (+54 %; P < 0.001) and increased concentrations of conjugated dienes (+11 %; P < 0.001) and oxidatively modified LDL (+ 38 %; P < 0.05). Lower frequencies of SCD1 minor genotypes (rs2167444, rs508384, P < 0.05) were observed in subjects with elevated plasma concentrations of apoB-48. Elevated plasma concentrations of apoB-48 are associated with an adverse lipid profile, higher systolic blood pressure, insulin resistance, and oxidative stress. Lower proportions of minor SCD1 genotypes (rs2167444, rs508384) implicate the role of genetic factors in the pathogenesis of elevated levels of apoB-48. [ABSTRACT FROM AUTHOR]

Purpose: Type 2 diabetes mellitus (T2DM) is characterized by both impaired pancreatic β-cell function (BCF) and insulin resistance. In the etiology of T2DM, BCF basically determines whether a person with a certain degree of insulin resistance develops T2DM, as β-cells are able to compensatorily increase insulin secretion. The effects of dietary intake on BCF are largely unknown. Our study aim was to investigate whether dietary macronutrient intake predicts BCF. Methods: Prospective data (median follow-up 7 years) of 303 individuals recruited from the CODAM study population (aged 40–70 years, 39% women) were analyzed. BCF was measured by C-peptide deconvolution and physiological modeling of data from a 5-point, 75-g, 2-h oral glucose tolerance test. Macronutrient intake was estimated by a 178-item Food Frequency Questionnaire. Results: Associations adjusted for relevant covariates of baseline macronutrient intake with model-derived parameters describing BCF (glucose sensitivity, rate sensitivity or potentiation) or C-peptidogenic index were detected for trans fat [standardized regression coefficient (95%-CI) glucose sensitivity − 0.14 (− 0.26, − 0.01)] per g, cholesterol [potentiation 0.20 (0.02, 0.37)] per 100 mg, dietary fiber [glucose sensitivity 0.21 (0.08, 0.33)] per 10 g, MUFA glucose sensitivity 0.16 (0.02, 0.31) per 10 g, and polysaccharide [potentiation − 0.24 (− 0.43, − 0.05), C-peptidogenic index − 0.16 (− 0.29 − 0.03); odds ratio lowest versus highest tertile (95%-CI) rate sensitivity 1.51 (1.06, 2.15)) per 50 g. Conclusions: In this population at high risk for developing T2DM, polysaccharide and trans fat intake were associated with worse BCF, whereas increased intake of MUFA, dietary cholesterol, and fiber were associated with better BCF. [ABSTRACT FROM AUTHOR]

Summary: Objective: Metabolically healthy individuals are known to be resistant to cardiovascular disease development. However, a considerable fraction of those individuals shows deteriorated metabolic health over time. Although skeletal muscle is the primary insulin‐responsive target organ, a longitudinal investigation of the skeletal muscle mass in relation to the development of metabolically unhealthy phenotype has not been performed. We aimed to evaluate whether greater skeletal muscle mass is an independent protective factor for the development of metabolically unhealthy phenotype. Design, Participants and Measurements: We conducted a retrospective cohort study with 9033 metabolically healthy volunteers who underwent routine health examinations in 2012 and a follow‐up examination in 2016. Obesity was defined as Asian‐Pacific body mass index criterion ≥25 kg/m2. Subjects with fewer than two risk factors (elevated blood pressure, triglyceride, glucose, high‐sensitivity C‐reactive protein, insulin resistance and decreased high‐density lipoprotein cholesterol levels) were characterized as metabolically healthy using Wildman criteria. Results: At the 4‐year follow‐up, approximately one‐fourth of the nonobese participants and half of the participants with obesity showed metabolic deterioration. In nonobese men and women, higher appendicular skeletal muscle mass (ASM)/weight at baseline was significantly associated with decreased risk of metabolic deterioration. Compared to the lowest quartile of ASM/weight, the adjusted odds ratios (95% confidence intervals) of the highest quartile were 0.68 (0.52‐0.89) in nonobese men and 0.64 (0.46‐0.90) in nonobese women. However, this association was not observed in obese subjects. Conclusions: Greater skeletal muscle mass at baseline is significantly associated with maintenance of metabolically healthy status, especially in nonobese individuals. [ABSTRACT FROM AUTHOR]

The mechanisms underlying the oversecretion of apolipoprotein (apo)B-48-containing triglyceride-rich lipoproteins (TRL) in insulin-resistance (IR) states in humans remain to be fully understood. The objective of this study was to evaluate the association between the plasma levels of insulin and glucose and the intestinal expression of key genes involved in chylomicron metabolism in a large sample of nondiabetic men displaying various degrees of IR. Duodenal biopsies were obtained by gastroduodenoscopy in 127 men free of intestinal disease. Gene expression was measured using quantitative PCR in duodenal samples. Plasma insulin and glucose concentrations were measured in the fasting state. Postprandial TRL apoB-48 kinetics were measured using a primed-constant infusion of L-[5,5,5-D3]leucine for 12 h in a subgroup of 75 subjects maintained in a constant fed state. Plasma insulin levels were negatively associated with intestinal expression of ACS1 (standard β = -0.20, P = 0.007), DGAT1 (β = -0.18, P = 0.001), DGAT2 (β = -0.20, P = 0.02), and MTP (β = -0.27, P = 0.0005), whereas glucose levels were positively associated with MTP expression (β = 0.15, P = 0.04) independent of age, BMI, waist circumference, dietary intake, and duodenal expression of SREBP1c. Insulin levels, but not glucose concentrations, were positively correlated with postprandial TRL apoB-48 production rate (r = 0.24, P = 0.04) and pool size (r = 0.27, P = 0.03). In conclusion, plasma insulin and glucose levels are differentially associated with the expression of key genes involved in chylomicron metabolism. These results suggest that alterations in intestinal lipoprotein metabolism associated with IR may be regulated by plasma levels of both insulin and glucose concurrently and are therefore likely modified by the onset of insulin insufficiency. NEW & NOTEWORTHY We demonstrate that plasma insulin and glucose levels are differentially associated with the expression of key genes involved in chylomicron metabolism in men. For instance, intestinal expression of MTP is negatively associated with plasma insulin concentrations and positively associated with plasma glucose concentrations. Alterations in intestinal lipoprotein metabolism associated with insulin resistance may be regulated by plasma levels of both insulin and glucose concurrently and are therefore likely modified by the onset of insulin insufficiency. [ABSTRACT FROM AUTHOR]

Introduction: Metabolic heterogeneity among obese individuals is thought to translate into variations in cardiovascular risk. Identifying obese people with an unfavourable metabolic profile may allow preventive strategies to be targeted at high-risk groups. This study aimed to identify clinical, biochemical and immunological differences between insulin-sensitive and insulin-resistant obese subgroups, to understand the population-specific pathophysiological basis of the adverse cardiovascular risk profile in the latter group.Methods: Cardiovascular risk indicators, including anthropometric parameters, blood pressure, acanthosis nigricans area, and related biochemical, endocrine and inflammatory markers, were determined in 255 healthy South Asian volunteers aged 18-45 years, with a 2:1 ratio of obese/overweight to normal-weight individuals. Lifetime atherosclerotic cardiovascular disease (ASCVD) risk was also calculated.Results: Body mass index (BMI) and insulin sensitivity-based tertiles independently showed incremental trends in waist-hip ratio, skinfold thickness, acanthosis nigricans area, blood pressure, serum lipids, hepatic enzymes, adipokines, inflammatory markers and ten-year ASCVD risk. The anthropometric, biochemical and inflammatory parameters of obese insulin-sensitive and obese insulin-resistant groups differed significantly. Extreme group analysis after excluding the middle tertiles of both insulin resistance and BMI also showed significant difference in anthropometric indicators of cardiovascular risk and estimated lifetime ASCVD risk between the two obese subgroups.Conclusion: Obese insulin-sensitive individuals had a favourable metabolic profile compared to the obese insulin-resistant group. The most consistent discriminative factor between these phenotypic classes was anthropometric parameters, which underscores the importance of clinical parameters as cardiovascular risk indicators in obesity. [ABSTRACT FROM AUTHOR]