Elehazara Rubio-Martín

Vitamin D deficiency in Spain: a population-based cohort study

Background:Vitamin D deficiency is common worldwide. No homogenous reference values have yet been established and no studies of values have been conducted in Spain involving a large number of participants.Objective:To study the population concentrations of vitamin D in a representative sample of the Spanish population.Subjects/Methods:The study involved two cohorts from Spain, the Asturias study and the Pizarra study, which are two prospective, population-based studies involving 2260 participants. In 1262 subjects (age: 20–83 years) we studied 25-hydroxyvitamin D, intact parathyroid hormone (iPTH), calcium, phosphorus and creatinine.Results:The median population values of 25-hydroxyvitamin D and iPTH were 22.46 ng/ml and 42.29 pg/ml, respectively. The values of 25-hydroxyvitamin D were significantly higher in summer and correlated with age (β=−0.05±0.01, P<0.0001), creatinine (β=6.42±1.17, P<0.0001) and iPTH (−0.07±0.01, P<0.0001), but not with calcium, phosphorus or sex. The increase in iPTH with age was seen whatever the values of 25-hydroxyvitamin D, and was greater in the older persons. The concentration of iPTH rose continuously with effect from 25-hydroxyvitamin D values below ≈30 ng/ml. Values above ≈35 ng/ml were associated with a significantly lower concentration of iPTH.Conclusions:One-third (33.9%) of the Spanish population may be at risk for Vitamin D deficiency. The 25-hydroxyvitamin D values above 30 ng/ml can safely discard ‘hyper PTH’. The increase in iPTH concentration is greater in older persons for similar values of 25-hydroxyvitamin D.

Vitamin D and incidence of diabetes: A prospective cohort study

BACKGROUND & AIMS To investigate the relationship between levels of 25-hydroxyvitamin D and the incidence of type 2 diabetes in a Spanish population. METHODS We undertook a population-based prospective study in a population from southern Spain. The first phase of the study (1996-1998) included 1226 individuals. Of this original cohort, 988 persons were reassessed in 2002-2004 and 961 in 2005-2007. Measurements were made of 25-hydroxyvitamin D and intact parathyroid hormone in 2002-2004 and an oral glucose tolerance test was done in three time points. RESULTS The incidence of diabetes in subjects with 25-hydroxyvitamin D levels ≤ 18.5 ng/mL (percentile 25) was 12.4% vs 4.7% in subjects with levels >18.5 ng/mL. The likelihood of having diabetes during the four years of follow-up was significantly lower in the subjects with higher levels of 25-hydroxyvitamin D [OR = 0.17 (0.05-0.61)]. None of the subjects with levels higher than 30 ng/mL developed diabetes. CONCLUSION In this prospective study, we found a significant inverse association between serum 25-hydroxyvitamin D levels and the risk for type 2 diabetes in a population from the south of Spain.

Methylation levels of the SCD1 gene promoter and LINE-1 repeat region are associated with weight change: An intervention study

SCOPE Epigenetic processes may be affected by environmental factors. DNA methylation measured in LINE-1 elements (LINE-1, long interspersed nucleotide element-1) correlates with LINE-1 DNA methylation. Variations in stearoyl CoA desaturase (SCD) activity (a key enzyme in the fatty acid metabolism) may be involved in various processes that can lead to diseases such as obesity. We evaluated whether changes in diet after a nutritional intervention would be associated with changes in LINE-1 DNA methylation and/or specific methylation of SCD1 gene promoter. METHODS AND RESULTS DESIGN Prospective cohort intervention study with a control group. We recorded phenotypic, anthropometric, biochemical, and nutritional information at baseline and 1 year later. DNA methylation was quantified by pyrosequencing. LINE-1 DNA methylation and SCD1 gene promoter methylation levels were similar at the beginning of the study in both populations, whereas after a year these levels were higher in the control group (p < 0.001). In the intervention group, those subjects who lost weight showed higher levels of SCD1 gene promoter methylation after the intervention. Subjects with lower adherence to a Mediterranean diet experienced larger changes in LINE-1 methylation. CONCLUSION DNA methylation levels were associated with weight change and with adherence to a Mediterranean diet.

Type 2 diabetes mellitus in relation to global LINE-1 DNA methylation in peripheral blood: A cohort study

In the last years, epigenetic processes have emerged as a promising area of complex diseases research. DNA methylation measured in Long Interspersed Nucleotide Element 1 (LINE-1) sequences has been considered a surrogate marker for global genome methylation. New findings have suggested the potential involvement of epigenetic mechanisms in Type 2 diabetes (T2DM) as a crucial interface between the effects of genetic predisposition and environmental influences. Our study evaluated whether global DNA methylation predicted increased risk from T2DM or other carbohydrate metabolism disorders in a cohort study. We used a prospective cohort intervention study and a control group. We collected phenotypic, anthropometric, biochemical, and nutritional information from all subjects. Global LINE-1 DNA methylation was quantified by pyrosequencing technology. Subjects that did not improve their carbohydrate metabolism status showed lower levels of global LINE-1 DNA methylation (63.9 ± 1.7 vs. 64.7 ± 2.4) and they practiced less intense physical activity (5.8% vs. 21.5%). Logistic regression analyses showed a significant association between LINE-1 DNA methylation and metabolic status after adjustment for sex, age, BMI, and physical activity. Our study showed that lower LINE-1 DNA methylation levels were associated with a higher risk metabolic status worsening, independent of other classic risk factors. This finding highlights the potential role for epigenetic biomarkers as predictors of T2DM risk or other related metabolic disorders.

Thyroid hormone levels predict the change in body weight: a prospective study.

Eur J Clin Invest 2011; 41 (11): 1202–1209

Night-time sleep duration and the incidence of obesity and type 2 diabetes. Findings from the prospective Pizarra study

BACKGROUND Several recent studies have related short sleep duration with different health problems, though the results related with the risk of obesity and type 2 diabetes (T2D) are far from conclusive. The aim of this study was to investigate the association between night-time sleep duration and the incidence of obesity and T2D in a prospective study with a follow-up of 11 years. MATERIAL AND METHODS The study comprised 1145 people evaluated in 1997-1998 and re-evaluated after 6 years and 11 years. At the three study points, subjects without known diabetes mellitus (KDM) were given an oral glucose tolerance test (OGTT). Anthropometric and biochemical variables were measured. The subjects were asked about their number of hours of night-time sleep. RESULTS After adjustment, the OR of becoming obese was significantly higher in subjects who slept ≤ 7 hours per night, at both the 6-year follow-up (OR = 1.99; 95% CI = 1.12-3.55) and the 11-year follow-up (OR = 2.73; 95% CI = 1.47-5.04). The incidence of T2D at the 6-year follow-up in subjects without T2D at baseline was higher in those who slept ≤ 7 hours per night (OR = 1.96; 95% CI = 1.10-3.50). However, this association was not independent of obesity, weight gain or abnormal glucose regulation at baseline. At the 11-year follow-up however there was no association between night-time sleep duration and the incidence of T2D. CONCLUSIONS The incidence of obesity over the 11-year follow-up increased in subjects with fewer hours of night-time sleep. The incidence of T2D according to the hours of night-time sleep depended on obesity and the carbohydrate metabolism phenotype.

Testosterone, SHBG and risk of type 2 diabetes in the second evaluation of the Pizarra cohort study

Eur J Clin Invest 2012; 42 (1): 79–85

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.

Effect of insulin analogues on 3t3-l1 adipogenesis and lipolysis

Eur J Clin Invest 2011; 41 (9): 979–986

Evolution of urinary iodine excretion over eleven years in an adult population

BACKGROUND & AIMS Few prospective cohort studies have evaluated dietary iodine intake and urinary iodine concentrations in the general adult population. We assess the evolution of urinary iodine excretion and factors that may influence it in an adult population followed for 11 years. METHODS A population-based cohort study was undertaken in Pizarra (Spain). In the three study phases (baseline (n = 886), and 6 (n = 788) and 11 years later (n = 501)), participants underwent an interview and a standardized clinical examination that included a food questionnaire, and thyroid hormone and urinary iodine determinations. Subjects with thyroid dysfunction, palpable goiter or urinary iodine excretion >400 μg/L were excluded. RESULTS Urinary iodine increased over the years (100.6 ± 70.0 μg/L at baseline vs. 125.4 ± 95.2 μg/L at 6 years and 141.6 ± 81.4 μg/L at 11 years; p < 0.0001). Urinary iodine was significantly higher in subjects who reported iodized salt consumption and in subjects with a higher intake of dairy products (p < 0.05). Consumption of iodized salt (Risk ratio (RR) = 1.23, 95% CI [1.01-2.05]) and dairy products (RR = 2.07, 95% CI [1.01-4.23]), and a baseline urinary iodine concentration ≥100 μg/L (RR = 1.26, 95% CI [1.04-1.53]) were significantly associated with urinary iodine concentrations ≥100 μg/L at 11 years. There is no correlation between thyroid function (TSH, free triiodothyronine or free thyroxine levels) and urinary iodine concentrations in conditions of iodine sufficiency. CONCLUSIONS The increase in urinary iodine concentrations over eleven years is associated with an increase in iodized salt intake and with the dairy products intake, and possibly with a higher iodine content of dairy products. However, individual variability in urinary iodine excretion was not fully explained by dietary iodine intake alone; previous urinary iodine concentrations were also important.