Longitudinal changes in Mediterranean diet and transition between different obesity phenotypes.

BACKGROUND & AIMS: Little is known about the impact of specific dietary patterns on the development of obesity phenotypes. We aimed to determine the association of longitudinal changes in adherence to the traditional Mediterranean diet (MedDiet) with the transition between different obesity phenotypes. METHODS: Data of 5801 older men and women at high cardiovascular risk from PREDIMED trial were used. Adherence to MedDiet was measured with the validated 14p-Mediterranean Diet Adherence Screener (MEDAS). Using the simultaneous combination of metabolic health- and body size-related parameters participants were categorized into one of four phenotypes: metabolically healthy and abnormal obese (MHO and MAO), metabolically healthy and abnormal non-obese (MHNO and MANO). Cox regression models with yearly repeated measures during 5-year of follow-up were built with use of Markov chain assumption. RESULTS: Each 2-point increase in MEDAS was associated with the following transitions: in MAO participants, with a 16% (95% CI 3-31%) greater likelihood of becoming MHO; in MHO participants with a 14% (3-23%) lower risk of becoming MAO; in MHNO participants with a 18% (5-30%) lower risk of becoming MHO. In MANO women, but not in men, MEDAS was associated with 20% (5-38%) greater likely of becoming MHNO (p for interaction by gender 0.014). No other significant associations were observed. CONCLUSIONS: Better adherence to the traditional MedDiet is associated with transitions to healthier phenotypes, promoting metabolic health improvement in MAO, MANO (only in women), and MHO, as well as protecting against obesity incidence in MHNO subjects.

[Incidence of type 1 diabetes in Navarre (2009-2016): higher in the southern regions of the autonomous community]. / Incidencia de diabetes tipo 1 en Navarra (2009-2016): mayor en la zona sur de la comunidad.

BACKGROUND: Geographical and seasonal variations of type 1 diabetes (T1D) are useful for establishing the key ethio-pathogenic factors of the disease. The present work seeks to analyze the incidence rates of T1D in Navarre for the 2009-2016 period, its geographical distribution and seasonal variations in birth and diagnosis in affected persons. METHODS: Prospective study with one primary and three secondary sources. The completeness of the registry, determined using the capture-recapture method, was 96.08%. The confidence intervals of zone and onset season incidence rates were determined assuming an underlying Poisson distribution. Adjusted effect of onset age, sex, onset season and geographical area over changes in incidence rates were analyzed using a Poisson regression model. Comparison among areas was carried out after the corresponding adjustments of incidence by the indirect standardization method. RESULTS: Four hundred and twenty-eight new cases were detected (incidence= 8.36/100,000 inhabitants per year, CI95%: 7.58-9.19). The disease is predominant in males (63% of patients). The incidence in children under 15 years was higher than in adults (21.54, CI95%: 18.43-25.02 vs. 5.94, CI95%: 5.23-6.71; p<0.001). Incidence was highest in the four southern regions of Navarre, most of the cases being in winter and spring. No differences were found regarding birth season over incidence. CONCLUSION: Navarre maintains a high T1D incidence in childhood that decreases progressively with age. Sex, age group, geographical zone and onset season are independently associated with the incidence rates observed in the study.

Sex and age differences in the achievement of control targets in patients with type 2 diabetes: results from a population-based study in a South European region.

BACKGROUND: We aimed to determine the degree to which control targets of glycaemia and cardiovascular risk factors were achieved among patients with type 2 diabetes and to investigate sex- and age-related differences in this population. METHODS: This cross-sectional, population-based study was conducted in Spain. Glycated hemoglobin (HbA1c), blood pressure, LDL-c, HDL-c, triglycerides, BMI, and smoking history were obtained from electronic clinical primary care records (n = 32,638 cases). The proportions of patients who met control targets were determined according to sex and age groups. Comparisons between groups were conducted with t-tests for continuous variables, tests for trends in proportions for categorical and ordinal variables, and Pearson's chi-square tests and binary logistic regression models for categorical variables. RESULTS: The overall proportions of patients with type 2 diabetes who met the target objectives for HbA1c (<7 %, 53 mmol/mol), blood pressure (130/80 mmHg), and LDL-cholesterol (100 mg/dl) were 60, 40 and 41 %, respectively. Women were less likely than men to meet the control targets of HbA1c (59 vs 61 %), LDL (35 vs 45 %), and HDL (58 vs 78 %). Patients under 65 years of age presented poorer control than older age groups. Only a minority of patients with type 2 diabetes met the composite target objectives for glycemic control, blood pressure, and LDL. CONCLUSIONS: There are differential gaps in the control results of female patients and younger patients, which should prompt improvements in case management and care. There is room for further improvement in the cardiometabolic control of patients with type 2 diabetes.

[Incidence of type 1 diabetes in Navarre, 2009-2012]. / Incidencia de la diabetes tipo 1 en Navarra, 2009-2012.

BACKGROUND: A north-south gradient for the incidence of type 1 diabetes (DM1) has been described in Europe, with higher incidence in the northern countries. The aim of this study is to describe the incidence data for DM1 in Navarre from 2009-2012, regardless of age at diagnosis, including geographical distribution and age and sex characteristics. PATIENTS AND METHODS: Prospective study, based on one primary and three secondary sources. Completeness of records was assessed, using the capture-recapture method, at 98.42%. Incidence was compared between different gender and age groups by estimating the incidence ratio using Poisson regression methods. To compare the incidence between the different geographical areas, adjustments were made to the values obtained by the indirect standardization method. RESULTS: A total of 216 cases were detected (incidence: 8.4/100,000 population/year; 95 % CI: 7.3-9.5). Incidence was higher in children than in adults, although the number of new cases was highest in those aged over 15. The age group with the highest incidence was 10 to 14 years; however, the highest percentage of patients fell in the 15 to 29-year-old group. Incidence was higher in men than in women. The incidence rates in the three southern regions were generally higher than the mean for Navarre. CONCLUSIONS: Navarre has a very high incidence of DM1 in children and adults aged 15 to 29. DM1 is more common in men and shows some geographic variability.

Influence of age at diagnosis on glycaemic control evolution in patients with type 1 diabetes.

AIM: The objective of this study was to describe the relationship between age at onset, with no age limits, and glycaemic control evolution from the time of onset in patients with type 1 diabetes (T1D). METHODS: This observational retrospective follow-up study included 716 patients with T1D onset between 1990 and 2008 treated at the Navarre Hospital Complex. The mean (SD) follow-up lasted 10.1 (5.3) years. Information on their HbA(1c) levels was collected at onset and every year thereafter. Generalized additive mixed models and linear models were used, with patients' annual HbA1c levels as the response variable and the number of years since onset together with age at onset as covariates. RESULTS: The evolution of glycaemic control is not linear and differs across all age groups. Children reach their highest values in adolescence, while patients with onset at ages 10-15 years stabilize their HbA(1c) values after 7 or 8 years. In adults, it is notable that an age of onset ≥ 45 years is associated with the worst control. CONCLUSION: A non-linear increase in HbA(1c) levels can be observed from the time of T1D diagnosis, with significant differences across all age groups.

[Descriptive study of transexuality in Navarre]. / Estudio descriptivo de la transexualidad en Navarra.

BACKGROUND: Transexuality has been recognized in Navarre as a clinical entity that must be attended to in a multidisciplinary form in the Navarre Health Service. METHODS: An analysis was made of the epidemiological data of 35 subjects who have attended the Navarre Transexual and Intersex Unit (UNATI - Unidad Navarra de Transexuales e Intersexos) since April 2011. The variables related to socio-demographic parameters, transexuality and treatment were collected. RESULTS: The average age was 37.3 years. Sixty-five point seven percent of the subjects were born in Spain. Seventy-one point four percent of the users are feminine transsexuals. At present 62.9% of the subjects are receiving hormonal treatment. Amongst the feminine transexuals 20% have had a mamoplasty, 4% have had a vaginoplasty and 20% have had both operations. Ten percent of the masculine transsexuals have had a mastectomy, 10% have had a hysterectomy with double anexectomy and 10% have had both operations. CONCLUSIONS: The majority of the transsexuals in Navarre are being evaluated in the UNATI. More feminine transsexuals have attended than masculine ones. The feminine transsexuals more frequently have reassignation surgery, while the masculine ones have extirpative surgery.

The reduction of the metabolyc syndrome in Navarra-Spain (RESMENA-S) study: a multidisciplinary strategy based on chrononutrition and nutritional education, together with dietetic and psychological control.

INTRODUCTION: The high prevalence of metabolic syndrome (MS) in Spain requires additional efforts for prevention and treatment. OBJECTIVE: The study RESMENA-S aims to improve clinical criteria and biomarkers associated with MS though an integral therapy approach. METHODS: The study is a randomized prospective parallel design in which is expected to participate a total of 100 individuals. The RESMENA-S group (n = 50) is a personalized weight loss (30% energy restriction) diet, with a macronutrient distribution (carbohydrate / fat / protein) of 40/30/30, high meal frequency (7 / day), low glycemic index/load and high antioxidant capacity as well as a high adherence to the Mediterranean diet. The control group (n = 50) is assigned to a diet with the same energy restriction and based on the American Heart Association pattern. Both experimental groups are under dietary and psychological control during 8 weeks. Likewise, for an additional period of 16 weeks of self-control, is expected that volunteers will follow the same pattern but with no dietary advice. RESULTS: Anthropometrical data and body composition determinations as well as blood and urine samples are being collected at the beginning and end of each phase. This project is registered at www.clinicaltrials.gov with the number NCT01087086 and count with the Research Ethics Committee of the University of Navarra approval (065/2009). CONCLUSIONS: Intervention trials to promote the adoption of dietary patterns and healthy lifestyle are of great importance to identify the outcomes and nutritional mechanisms that might explain the link between obesity, metabolic syndrome and associated complications.

[Glucocorticoid hypofunction in myotonic dystrophy]. / Hipofunción glucocorticoide en la distrofia miotónica.

INTRODUCTION: Myotonic dystrophy (DM1) is an autosomal dominant disorder whose genetic defect consists of the amplification of an unstable CTG trinucleotide repeat in the 3' untranslated region of the dystrophia myotonica protein kinase gene (DMPK). This is a multi-systemic disease with a well-known endocrinological repercussion. With respect to the adrenal function variable results have been described, although lately they are interpreted as indicators of a hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. MATERIAL AND METHODS: Twenty-five patients (13 men and 12 women) with DM1 were recruited. They were analysed for: basal cortisol and ACTH, stimulus test with 0.25 mg of ACTH for cortisol and CRH test for cortisol and ACTH. Similarly, the degree of expansion of CTG was evaluated by Southern blot and PCR. Twenty-five healthy individuals, comparable by age and sex, were studied as a control group; the CRH test was carried out on 11 of them. RESULT: One patient was diagnosed with primary non-autoimmune adrenal failure. In the rest of the cases there were no differences between the basal ACTH of patients and controls, and the cortisol response to ACTH was normal. The patients showed a lower level of basal cortisol (p<0.01) and also showed, following stimulation with CRH, a lower cortisol response (p<0.05) with higher average values of ACTH. CONCLUSIONS: Our data differs from the latest publications and point to an adrenal hypofunction due to lack of efficacy of the ACTH on its receptor or at the post-receptor level. We suggest that the etiology might be related to the underlying defect in the gene that codifies DMPK.

[Paraneoplastic hormonal syndromes]. / Síndromes hormonales paraneoplásicos.

We can define paraneoplastic syndromes as a combination of effects occurring far from the original location of the tumour and independently from the local repercussion of its metastases. Paraneoplastic hormonal syndromes depend on the secretion of hormonal peptides or their precursors, cytokines and, more rarely, thyroidal hormones and Vitamin D, which act in an endocrine, paracrine or autocrine way. Sometimes, paraneoplastic syndromes can be more serious than the consequences of the primary tumour itself and can precede, develop in parallel, or follow the manifestations of this tumour. It is important to recognise a paraneoplastic hormonal syndrome for several reasons, amongst which we would draw attention to three: 1) It can lead to the diagnosis of a previously undetected, underlying malign or benign neoplasia; 2) It can dominate the clinical picture and thus lead to errors with respect to the origin and type of primary tumour; and 3) It can follow the clinical course of the underlying tumour and thus be useful for monitoring its evolution. The molecular mechanisms responsible for the development of these syndromes are not well-known, but it is believed that they might be inherent to the mutations responsible for the primary tumour or depend on epigenetic factors such as methylation. In this review, we consider the following paraneoplastic hormonal syndromes: malign hypercalcaemia, hyponatraemia (inappropiate secretion of the antidiuretic hormone), ectopic Cushing's syndrome, ectopic acromegaly, hypoglycaemia due to tumours different from those of the islet cells and paraneoplastic gynaecomastia; we make a brief final reference to other hormones (calcitonin, somatostatin, and VIP).

Influence of two polymorphisms of the tumoral necrosis factor-alpha gene on the obesity phenotype.

Several populational-based studies have suggested an association between tumoral necrosis factor-alpha (TNF-alpha) polymorphisms and obesity-related phenotypes. Therefore, this study aimed at assessing the situation (frequency and associated phenotype) of two TNF-alpha common polymorphisms in a Spanish population. In a case-control design study, a group of Spanish subjects (n=313) were genotyped for the TNF-alpha G/A -308 and -238 polymorphisms. Obese subjects (cases) were compared with lean individuals (controls) according to body mass index (BMI; cases: BMI >30 kg/m2, controls: BMI <25 kg/m2). Waist-to-hip ratio, body composition and some metabolic indicators were assessed. The frequency of the -308A allele (0.14) and -238A allele (0.09) was similar to those previously reported in other Caucasian populations. Interestingly, cases with the -308A allele of the TNF-alpha gene have significantly higher hip and waist circumferences (p<0.05), BMI (p<0.01) and body fat mass (p<0.05) values than obese individuals carrying the -308G allele, but not the waist-to-hip ratio. No apparent influence of the -308A polymorphism on other metabolic indicators (insulin and leptin levels) was found. We could not detect any association between the substitution at position -238 polymorphism of the TNF-alpha gene and obesity anthropometrical phenotypes in this Spanish population, despite some differences in plasma leptin. These results support the hypothesis that the G/A -308 polymorphism of the TNF-alpha gene is associated with a higher BMI as well as hip ad waist circumferences, particularly on female bearers, while no influence on such measurements was found for the G/A -238 TNF-alpha gene polymorphism, but only an effect on leptinaemia.

[Influence of the polymorphism 03826 A --> G in the UCP1 gene on the components of metabolic syndrome]. / Influencia del polimorfismo -3826 A --> G en el gen de la UCP1 sobre los componentes del síndrome metabólico.

BACKGROUND: The uncoupling protein UCP1 has been related to the development and/or maintenance of obesity through its involvement in regulating energy balance. The role of this mitochondrial protein in humans is uncertain due to the scarce presence of the brown adipose tissue in the adult individual. The polymorphism -3826 A/G of the UCP1 alone or in conjunction with the mutation Trp64Arg of the adrenergic receptor b3 has been associated with obesity, diabetes mellitus and related diseases although with contradictory results. With the aim of determining the influence of polymorphism -3826 A/G of the UCP1 on the classical components of the metabolic syndrome in our population, we studied 159 obese individuals and 154 of normal weight, with a study design of cases and controls. In all of them Body Mass Index (BMI), hip/waist index, % of body fat, arterial tension (AT), lipidic profile, leptine, basal glucemia and basal insulinemia were determined. Similarly, the presence of the above mentioned mutation of the UCPI gene was analysed. RESULTS: Significant differences were obtained in all of the variables studied between obese (cases) and normal weight (controls). Within the obese group, polymorphism -3826 A/G of the UCP1 gene (n=53) was associated with a greater BMI (p=0.03), greater percentage of body fat (p=0.04) and higher AT both systolic (p=0.009) and diastolic (p=0.02). There were no statistically significant differences in any of the other indices evaluated. CONCLUSION: The fundamental factor that influences the components of the metabolic syndrome is obesity. However, the polymorphism -3826 A/G of the UCP1 gene is associated with a greater degree of obesity and very high figures of AT.

A novel nonsense mutation in the melanocortin-4 receptor associated with obesity in a Spanish population.

BACKGROUND: In recent years, several groups have reported dominant inheritance of obesity conferred by missense, nonsense and frameshift mutations in the melanocortin 4 receptor gene (MC4R). Hence, MC4R is involved in the most common monogenic form of human obesity described so far. OBJECTIVES: In this context, we screened a Spanish population, composed of obese subjects and normal weight controls, for mutations in the MC4-R by single-strand conformational polymorphism (SSCP). SUBJECTS AND METHODS: Overall 313 individuals, 159 obese subjects (body mass index: BMI: 37.6 kg/m(2), 95% CI: 36.7-38.5 kg/m(2)) and 154 normal weight control subjects (BMI: 22.3 kg/m(2), 95% CI: 22.0-22.6 kg/m(2)) were screened for MC4-R mutations. RESULTS: We detected a novel nonsense mutation at codon 16 of the MC4-R in an obese female (BMI: 30.0 kg/m(2)) and a previously described missense mutation (Val-253-Ile) located within the sixth trans-membrane domain of the MC4-R in a normal weight individual (BMI: 19.0 kg/m(2)). The polymorphism Val-103-Ile was detected in one obese individual, while four subjects (two cases and two controls) with the polymorphism Ile-251-Leu were found. CONCLUSIONS: We have identified a novel nonsense mutation (Trp-16-Stop) that, based on previously described frameshift and nonsense mutations, most likely results in dominantly inherited obesity. Within this Spanish population, the frequency of the Ile-251-Leu polymorphism of the MC4R was similar in obese and control subjects (about 1.3%), while the polymorphism Val-103-Ile was only detected in an obese individual (0.6%).

The risk of obesity and the Trp64Arg polymorphism of the beta(3)-adrenergic receptor: effect modification by age.

AIM: To examine the association between the risk of obesity and the Trp64Arg polymorphism of the beta(3)-adrenergic receptor gene. METHODS: A case-control study was conducted. The case series encompassed 159 subjects with a body mass index >30 kg/m(2) (obesity) and no other major diseases except for type 2 diabetes, and the controls were 154 healthy subjects with a body mass index <25 kg/m(2). 313 Spanish subjects between 20 and 60 years of age were screened for the Trp64Arg mutation. RESULTS: The prevalence of the Trp64Arg mutation was similar among cases (19.5%) and control subjects (16.2%). The association between the risk of obesity and the Trp64Arg mutation was estimated using multivariate logistic regression. A higher odds ratio of 3.84 (95% CI 1.33-11.12) for the mutation was found among younger individuals (20-35 years), while no increased risk was apparent among older participants (35-60 years). Moreover, when the model was adjusted for gender, age, and leisure-time physical activity, the product-term for interaction (effect modification) between age and the presence of the Trp64Arg mutation was statistically significant (likelihood ratio test p = 0.035). CONCLUSION: Individuals aged 20-35 years who are Trp64Arg carriers had a substantially higher risk of developing obesity, independent of their sex or leisure-time physical activity.

Beta(2)-adrenergic receptor mutation and abdominal obesity risk: effect modification by gender and HDL-cholesterol.

OBJECTIVE AND DESIGN: A case-control study was conducted to examine the association between the 27Glu polymorphism of the beta(2)-adrenergic receptor gene (ADRB2) and the risk of abdominal obesity (defined by a waist/hip ratio: WHR higher than 0.85). METHODS: The case series encompassed 112 obese subjects with body mass index (BMI) > 30 kg/m(2) and WHR > 0.85 and no other major disease except for type 2 diabetes, while the controls were 127 healthy subjects, BMI < 25 kg/m(2) and WHR < 0.85. RESULTS: The association between the risk of abdominal obesity and the 27Glu polymorphism was estimated using multivariate logistic regression. A higher crude odds ratio (OR) of 4.08 (95 % confidence interval: 0.98-16.3) for the 27Glu allele was found among men, while no increased risk was apparent among female participants. Moreover, when the model was adjusted for age, male subjects carriers of the 27Glu allele had a significant ten-fold higher risk of abdominal obesity (OR = 10.31; 95 % CI: 1.4-76.8) and the product-term for the interaction (effect modification) between gender and the ADRB2 mutation was near to the limits of statistical significance (Likelihood ratio test p = 0.056). Interestingly, we also found an effect modification with higher OR among individuals with low HDL-cholesterol (< 1.5 mmol/l) after adjustment for age and gender (OR = 2.87 95 % CI 1.09-7.50) and the product-term for interaction between the 27Glu allele and HDL-cholesterol was statistically significant (Likelihood ratio test p = 0.003). CONCLUSIONS: Our results showed that the 27Glu allele of the ADRB2 gene appears to be a risk factor for abdominal obesity among male subjects, specially among those with lower HDL-cholesterol levels.

[Complications of obesity]. / Complicaciones de la obesidad.

Obesity, which was evaluated positively in our culture in past periods and which was even considered by some to be merely an aesthetic question, is a disease with serious consequences for the health of the person suffering from it, and for the economy of those who have to meet its costs. Its present prevalence in Spain is situated around 13% and, if we can trust the forecasts established for other western countries such as the USA, it will increase to become the epidemic of the present century. The consequences of excess weight on the cardiovascular, respiratory, digestive, osteoarticular, reproductive and endocrine-metabolic systems are well known, as well as the relation between obesity and some types of cancer. As a general rule, it is worth bearing in mind that the greatest complications will correspond to the greater overweight (morbid obesity and severe obesity) and that age, the duration of ponderal excess and the distribution of the additional fat also have an influence, given that android/visceral/abdominal obesity is accompanied by the so-called insulin resistance syndrome. It is thus usually accompanied by hypertension, dyslipemia, alterations of hydrocarbonate tolerance and coagulation, elements involved as a whole in cardio-vascular morbi-mortality.

Relationship between lactose digestion, gastrointestinal transit time and symptoms in lactose malabsorbers after dairy consumption.

BACKGROUND: The relationship of symptoms with objective measurements, as well as some of the mechanisms involved in lactose tolerance after yoghurt consumption, remain unclear. METHODS: The trial had a double-blind design in which 22 lactose malabsorbers received 25 g daily lactose in fresh (living bacteria > 108 cfu/g) yoghurt or heated (< 102 cfu/g) yoghurt for 15 days, followed by a cross-over (15 days) after a wash-out period (14 days). The lactose digestion was determined by the breath H2 test, the gastric emptying (GE) with a 13C-acetate breath test and the revealed transit time (OCTT) by 15N-lactose-ureide test. Subjects reported their gastrointestinal symptoms (GIS) in a validated questionnaire. RESULTS: Breath H2 test indicated more effective lactose digestion after fresh yoghurt intake. The OCTT was shorter after heated yoghurt ingestion as compared with the fresh. There was lower severity of GIS (P < 0.05) after fresh yoghurt intake, and this showed an inverse correlation with OCTT (P < 0.05). CONCLUSIONS: Delayed orocoecal transit time was associated with fewer gastrointestinal symptoms. The improved lactose digestion and tolerance of fresh yoghurt should be mainly attributed to the presence of living bacteria.

Postprandial de novo lipogenesis and metabolic changes induced by a high-carbohydrate, low-fat meal in lean and overweight men.

BACKGROUND: Adjustments of carbohydrate intake and oxidation occur in both normal-weight and overweight individuals. Nevertheless, the contribution of carbohydrates to the accumulation of fat through either reduction of fat oxidation or stimulation of fat synthesis in obesity remains poorly investigated. OBJECTIVE: The objective of this study was to assess the postprandial metabolic changes and the fractional hepatic de novo lipogenesis (DNL) induced by a high-carbohydrate, low-fat meal in lean and overweight young men. DESIGN: A high-carbohydrate, low-fat meal was administered to 6 lean and 7 overweight men after a 17.5-h fast. During the fasting and postprandial periods, energy expenditure (EE), macronutrient oxidation, diet-induced thermogenesis, and serum insulin, glucose, triacylglycerol, and fatty acids were measured. To determine DNL, [1-13C]sodium acetate was infused and the mass isotopomer distribution analysis method was applied. RESULTS: After intake of the high-carbohydrate meal, the overweight men had hyperinsulinemia and higher fatty acid and triacylglycerol concentrations than did the lean men. The overweight group showed a greater EE, whereas there was no significant difference in carbohydrate oxidation between the groups. Nevertheless, the overweight men had a marginally higher protein oxidation and a lower lipid oxidation than did the lean men. DNL was significantly higher before and after meal intake in the overweight men and was positively associated with fasting serum glucose and insulin concentrations. Furthermore, postprandial DNL was positively correlated with body fat mass, EE, and triacylglycerol. CONCLUSION: After a high-carbohydrate, low-fat meal, overweight men had a lower fat oxidation and a higher fractional hepatic fat synthesis than did lean men.