Fatty liver index as a predictor for type 2 diabetes in subjects with normoglycemia in a nationwide cohort study.

Our aim was to evaluate whether fatty liver index (FLI) is associated with the risk of type 2 diabetes (T2DM) development within the Spanish adult population and according to their prediabetes status; additionally, to examine its incremental predictive value regarding traditional risk factors. A total of 2260 subjects (Prediabetes: 641 subjects, normoglycemia: 1619 subjects) from the Di@bet.es cohort study were studied. Socio-demographic, anthropometric, clinical data and survey on habits were recorded. An oral glucose tolerance test was performed and fasting determinations of glucose, lipids and insulin were made. FLI was calculated and classified into three categories: Low (< 30), intermediate (30-60) and high (> 60). In total, 143 people developed diabetes at follow-up. The presence of a high FLI category was in all cases a significant independent risk factor for the development of diabetes. The inclusion of FLI categories in prediction models based on different conventional T2DM risk factors significantly increase the prediction power of the models when all the population was considered. According to our results, FLI might be considered an early indicator of T2DM development even under normoglycemic condition. The data also suggest that FLI could provide additional information for the prediction of T2DM in models based on conventional risk factors.

Incidence of diabetes mellitus in Spain as results of the nation-wide cohort di@bet.es study.

Our aim was to determine the incidence of type 2 diabetes mellitus in a nation-wide population based cohort from Spain (di@bet.es study). The target was the Spanish population. In total 5072 people older than 18 years,were randomly selected from all over Spain). Socio-demographic and clinical data, survey on habits (physical activity and food consumption) and weight, height, waist, hip and blood pressure were recorder. A fasting blood draw and an oral glucose tolerance test were performed. Determinations of serum glucose were made. In the follow-up the same variables were collected and HbA1c was determined. A total of 2408 subjects participated in the follow-up. In total, 154 people developed diabetes (6.4% cumulative incidence in 7.5 years of follow-up). The incidence of diabetes adjusted for the structure of age and sex of the Spanish population was 11.6 cases/1000 person-years (IC95% = 11.1-12.1). The incidence of known diabetes was 3.7 cases/1000 person-years (IC95% = 2.8-4.6). The main risk factors for developing diabetes were the presence of prediabetes in cross-sectional study, age, male sex, obesity, central obesity, increase in weight, and family history of diabetes. This work provides data about population-based incidence rates of diabetes and associated risk factors in a nation-wide cohort of Spanish population.

Growth hormone-releasing hormone is produced by adipocytes and regulates lipolysis through growth hormone receptor.

BACKGROUND: Growth hormone-releasing hormone (GHRH) has a crucial role in growth hormone (GH) secretion, but little is known about its production by adipocytes and its involvement in adipocyte metabolism. OBJECTIVES: To determine whether GHRH and its receptor (GHRH-R) are present in human adipocytes and to study their levels in obesity. Also, to analyze the effects of GHRH on human adipocyte differentiation and lipolysis. METHODS: GHRH/GHRH-R and GH/GH-R mRNA expression levels were analyzed in human mature adipocytes from non-obese and morbidly obese subjects. Human mesenchymal stem cells (HMSC) were differentiated to adipocytes with GHRH (10-14-10-8 M). Adipocyte differentiation, lipolysis and gene expression were measured and the effect of GH-R silencing was determined. RESULTS: Mature adipocytes from morbidly obese subjects showed a higher expression of GHRH and GH-R, and a lower expression of GHRH-R and GH than non-obese subjects (P<0.05). A total of 10-14-10-10 M GHRH induced an inhibition of lipid accumulation and PPAR-γ expression (P<0.05), and an increase in glycerol release and HSL expression (P<0.05) in human differentiated adipocytes. A total of 10-12-10-8 M GHRH decreased GHRH-R expression in human differentiated adipocytes (P<0.05). A total of 10-10-10-8 M GHRH increased GH and GH-R expression in human differentiated adipocytes (P<0.05). The effects of GHRH at 10-10 M on adipocyte differentiation and lipolysis were blocked when GH-R expression was silenced. CONCLUSIONS: GHRH and GHRH-R are expressed in human adipocytes and are negatively associated. GHRH at low doses may exert an anti-obesity effect by inhibiting HMSC differentiation in adipocytes and by increasing adipocyte lipolysis in an autocrine or paracrine pathway. These effects are mediated by GH and GH-R.

Resistin regulates pituitary lipid metabolism and inflammation in vivo and in vitro.

The adipokine resistin is an insulin-antagonizing factor that also plays a regulatory role in inflammation, immunity, food intake, and gonadal function and also regulates growth hormone (GH) secretion in rat adenopituitary cells cultures with the adipokine. Although adipose tissue is the primary source of resistin, it is also expressed in other tissues, including the pituitary. The aim of this study is to investigate the possible action of resistin on the lipid metabolism in the pituitary gland in vivo (rats in two different nutritional status, fed and fast, treated with resistin on acute and a chronic way) and in vitro (adenopituitary cell cultures treated with the adipokine). Here, by a combination of in vivo and in vitro experimental models, we demonstrated that central acute and chronic administration of resistin enhance mRNA levels of the lipid metabolic enzymes which participated on lipolysis and moreover inhibiting mRNA levels of the lipid metabolic enzymes involved in lipogenesis. Taken together, our results demonstrate for the first time that resistin has a regulatory role on lipid metabolism in the pituitary gland providing a novel insight in relation to the mechanism by which this adipokine can participate in the integrated control of lipid metabolism.

Children whose diet contained olive oil had a lower likelihood of increasing their body mass index Z-score over 1 year.

OBJECTIVE: Changes in eating habits may be influential in the ever-increasing rate of childhood obesity. Our aim was to determine whether those children who consume olive oil have a lower risk of weight gain compared with children who consume other oils. DESIGN AND METHODS: The study included 18 girls and 74 boys, all aged 13-166 months. A survey was completed for each subject about eating habits and physical activity. A sample of subcutaneous adipose tissue was also obtained for cellular study. Data were recorded on the mean size of the adipocytes, the number of preadipocytes, and the concentration of particular fatty acids. The weight and height of the children were measured 13 months later. RESULTS: The likelihood that after 1 year the children would have increased their body mass index (BMI) Z-score above the initial score was less in the children who consumed only olive oil (odds ratio (OR)=0.22; 95% confidence interval (CI): 0.08-0.63; P=0.005). These results remained after adjusting for age, physical activity and BMI (OR=0.19; 95% CI: 0.06-0.61; P=0.005) and after adjusting for age, physical activity and adipocyte volume (OR=0.15; 95% CI: 0.04-0.52; P=0.003). CONCLUSIONS: Diets with mono unsaturated fatty acid (MUFA)-rich olive oil could reduce the risk of obesity in childhood.

Jejunal wall triglyceride concentration of morbidly obese persons is lower in those with type 2 diabetes mellitus.

The overproduction of intestinal lipoproteins may contribute to the dyslipidemia found in diabetes. We studied the influence of diabetes on the fasting jejunal lipid content and its association with plasma lipids and the expression of genes involved in the synthesis and secretion of these lipoproteins. The study was undertaken in 27 morbidly obese persons, 12 of whom had type 2 diabetes mellitus (T2DM). The morbidly obese persons with diabetes had higher levels of chylomicron (CM) triglycerides (P < 0.001) and apolipoprotein (apo)B48 (P = 0.012). The jejunum samples obtained from the subjects with diabetes had a lower jejunal triglyceride content (P = 0.012) and angiopoietin-like protein 4 (ANGPTL4) mRNA expression (P = 0.043). However, the apoA-IV mRNA expression was significantly greater (P = 0.036). The jejunal triglyceride content correlated negatively with apoA-IV mRNA expression (r = -0.587, P = 0.027). The variables that explained the jejunal triglyceride content in a multiple linear regression model were the insulin resistance state and the apoA-IV mRNA expression. Our results show that the morbidly obese subjects with diabetes had lower jejunal lipid content and that this correlated negatively with apoA-IV mRNA expression. These findings show that the jejunum appears to play an active role in lipid homeostasis in the fasting state.

Nutritional regulation of interleukin-6 release from adipocytes.

BACKGROUND AND AIMS: As interleukin-6 (IL-6) has an important role in general metabolism with high circulating levels in obesity and other associated diseases, the factors regulating its synthesis and release have been considered possible therapeutic targets and have recently been studied. We examined the influence of three different diets, each having a different fatty acid composition--saturated, monounsaturated or polyunsaturated (coconut oil, olive oil and sunflower oil diets), on IL-6 release from rat adipocytes, and the interaction between diet and other regulatory factors of IL-6 release, such as epinephrine. METHODS: A group of rats was assigned to one of the three different diets, each with a significantly different concentration of saturated, monounsaturated and polyunsaturated fatty acids. Samples were taken from the omental adipose tissue for measurement of the triacylglycerol fatty acid composition of the tissues and for adipocyte isolation. IL-6 release from adipocytes was measured in vitro, under nonstimulated conditions and also with two concentrations of epinephrine in the medium. RESULTS: Animals fed with the olive oil diet showed lower values of IL-6 release with and without epinephrine stimulation. IL-6 release from adipocytes varied according to the diet, but not according to epinephrine dose. However, a significant interaction was found between the epinephrine dose and the diet in IL-6 release regulation. CONCLUSIONS: IL-6 release from adipocytes was markedly regulated by the dietary fatty acid composition, even under epinephrine stimulation, with lower values of IL-6 release in the olive oil diet. The study also showed that epinephrine regulation of IL-6 release was related to the diet.

Suplementación con ácidos grasos poliinsaturados a largo plazo en pacientes con fibrosis quística / Long term polyunsaturated fatty acid supplement in patients with cystic fibrosis

Objetivo: valorar el efecto de la suplementación oral de una combinación a dosis bajas de diversos ácidos grasos sobre parámetros respiratorios e inflamatorios en pacientes adultos con fibrosis quística(FQ).Método: 17 pacientes recibieron diariamente: 324 mg de ácido eicosapentaenoico (EPA), 216 mg de docosahexaenoico (DHA),480 mg de linoleico (LIN) y 258 mg de gammalinolénico (GLA)durante un año. Se valoraron parámetros espirométricos, número y gravedad de las reagudizaciones respiratorias, uso de antibióticos y marcadores inflamatorios. Resultados: se ha observado un incremento de parámetros espirométricos, así como una reducción estadísticamente significativa en el número de reagudizaciones (totales y graves) y en los días totales de tratamiento antibiótico, comparado con el año previo a la suplementación. Concomitantemente se observó una reducción significativa de los niveles del factor de necrosis tumoral alfa (TNF alfa)así como un incremento de los receptores solubles del TNF alfa. Conclusiones: la suplementación con una mezcla definida de ácidos grasos durante un año parece mejorar parámetros espirométricos, clínicos (menor número de reagudizaciones y tandas de antibióticos)e inflamatorios en pacientes adultos con FQ (AU)

Objective: to evaluate the effect of a combination of low doses oral supplement of various fatty acids on respiratory and inflammatory parameters in adult patients with cystic fibrosis (CF). Method: 17 patients received: 324 mg of eicosapentaenoic acid(EPA), 216 mg of docosahexaenoic acid (DHA), 480 mg of linoleicacid (LIN) and 258 mg of gamma-linolenic acid (GLA) daily during a one-year period. The parameters evaluated included spirometry, number and severity of the acute respiratory attacks, use of antibiotics and inflammatory markers. Results: an increase in spirometry parameters was observed, as well as a statistically significant reduction in the number of acute respiratory attacks (total and severe) and in the total number of days of antibiotic treatment, compared with the year prior to taking the supplement. At the same time, there was a reduction in the levels of the alpha tumor necrosis factor (alpha TNF), as well as an increase of the soluble receptors of alpha TNF. Conclusions: supplements with a specific mix of fatty acids for the period of one year appears to improve spirometry, clinical (lower number of the acute respiratory attacks and rounds of antibiotics) and inflammatory parameters in adults with CF (AU)

Incidence of obesity is lower in persons who consume olive oil.

We undertook a population-based cohort study in Pizarra (Spain). Anthropometric and nutritional variables were recorded for 613 persons. The type of fat used was determined by measurement of the fatty acids contained in cooking oil. Serum fatty acid was used as a biological marker of the type of fat consumed. Obesity incidence in persons who were not obese at baseline was greater in those who consumed sunflower oil (Group 1: 41.5 (95% CI, 25.4-67.8) cases per 1000 person-years) than in those who consumed olive oil or a mixture of oils (Group 2: 17.3 (95% CI, 11.6-25.8) cases per 1000 person-years). The risk of developing obesity over 6 years, adjusted for age, sex, physical activity, smoking, instruction level, energy intake and baseline BMI, was 2.3 (95% CI, 1.06-5.02) in group 1 compared with that in group 2. The increase in the prevalence of obesity in the free-living population is associated with the type of fatty acids in the diet.

The -30G>A polymorphism of the glucokinase gene promoter is associated with obesity in a population from southern Spain.

The aim of this study was to test the hypothesis of an association between the -30G>A polymorphism of the promoter of the glucokinase gene and the prevalence and incidence of obesity. We studied the -30G>A polymorphism of the glucokinase gene promoter in 981 persons, of whom 866 were seen again 6 years later. All the persons underwent an oral glucose-tolerance test and the BMI (weight/height(2)) was recorded. The -30G>A polymorphism of the glucokinase gene promoter was studied using RFLP-PCR. At the initial study, the probability of having a BMI > or =25 in carriers of the A allele was significantly lower than expected by chance (odds ratio (OR) = 0.63; 95% confidence interval (CI) = 0.456-0.885). In those persons with a BMI > or =30 at the first study, the probability at 6 years of losing weight (reaching a BMI < 30) was greater in carriers of the A allele (OR = 0.22; 95% CI = 0.087-0.576). The increase in weight over these 6 years, taken as a continuous variable, was significantly less only in those persons who were originally obese (P = 0.018). In conclusion, in a population from southern Spain, carriers of the A allele of the -30G>A polymorphism in the promoter of the glucokinase gene had a lower risk for obesity and the likelihood of losing weight was greater in those obese persons who had the A allele (GA or AA).

Incidence of type 2 diabetes in southern Spain (Pizarra Study).

BACKGROUND: Few European studies have used an oral glucose tolerance test (OGTT) to examine the incidence of type 2 diabetes. We determined the incidence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and type 2 diabetes in a population from southern Spain. MATERIAL AND METHODS: A population-based cohort study was undertaken in Pizarra, Spain. Baseline data were recorded on age, sex, weight, height, waist and hip circumferences, and diabetes status for 1051 persons, of whom 910 were free of type 2 diabetes (at-risk sample). Of these, 714 completed the 6-year follow-up study. Body mass index, waist-to-hip ratio and weight increase since baseline were calculated. The homeostasis model assessment equations were used to estimate the indices of insulin resistance and beta-cell function. Each person received an OGTT at baseline and after 6 years. RESULTS: Type 2 diabetes developed in 81 people for a total of 4253 person-years, representing an incidence of 19.1 cases per 1000 person-years (95% confidence interval, 15.3-23.6). Age and the presence of obesity, central obesity and carbohydrate metabolism disorders [IFG (cut off = 100 mg dL(-1), capillary blood glucose level), IGT or both] at baseline were significant markers for the onset of type 2 diabetes during follow-up. After adjusting for these variables, multivariate analysis showed weight increase, waist-to-hip ratio and the indices of insulin resistance and beta-cell function were significantly associated with the risk for type 2 diabetes. CONCLUSIONS: The incidence of type 2 diabetes in a population from southern Spain is high. It is probably associated with the high prevalence of obesity and weight increase in this population.

Dietary fatty acids and insulin secretion: a population-based study.

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.