Sonia Gaztambide

Estudio prospectivo a 10 años sobre la incidencia y factores de riesgo de diabetes mellitus tipo 2

Fundamento Conocer la incidencia de diabetes mellitus tipo 2 en nuestro medio y los posibles factores de riesgo implicados. Pacientes y metodo Estudio prospectivo a 10 anos realizado en Lejona (Vizcaya) en una poblacion de mas de 30 anos de edad (n = 584). Tras un estudio de prevalencia efectuado en 1985, se revaluo 10 anos mas tarde a la misma poblacion. Se recogieron datos sobre edad, sexo, indice de masa corporal, antecedentes familiares de diabetes, presion arterial sistolica y diastolica y glucemia en sangre capilar tras sobrecarga oral de glucosa que se valoro segun criterios de la Organizacion Mundial de la Salud. Resultados La incidencia anual acumulada de diabetes mellitus tipo 2 fue de 8 casos/1.000 personas. En modelos multivariados de regresion logistica, la tolerancia anormal a la glucosa resulto ser el predictor mas importante (OR = 4,17; intervalo confianza del 95%: 1,80-9,63). La edad y el sexo tambien resultaron predictores significativos (p < 0,05) y casi significativos los antecedentes familiares de diabetes mellitus tipo 2 (p = 0,057). No lo fue el indice de masa corporal, aunque su incremento fue mayor en los enfermos que progresaron a diabetes mellitus tipo 2 frente a los que no. Conclusiones La incidencia acumulada de diabetes mellitus tipo 2 en Lejona fue similar a la encontrada en otros paises europeos. La presencia de tolerancia anormal a la glucosa y cifras mas elevadas de glucemia favorecen la progresion a diabetes mellitus tipo 2. El incremento del indice de masa corporal parece desempenar un papel precipitante en la progresion a diabetes mellitus tipo 2.

Conserved extended haplotypes discriminate HLA-DR3-homozygous Basque patients with type 1 diabetes mellitus and celiac disease

The major susceptibility locus for type 1 diabetes mellitus (T1D) maps to the human lymphocyte antigen (HLA) class II region in the major histocompatibility complex on chromosome 6p21. In southern European populations, like the Basques, the greatest risk to T1D is associated with DR3 homo- and heterozygosity and is comparable to that of DR3/DR4, the highest risk genotype in northern European populations. Celiac disease (CD) is another DR3-associated autoimmune disorder showing certain overlap with T1D that has been explained by the involvement of common genetic determinants, a situation more frequent in DR3-rich populations, like the Basques. As both T1D- and CD-associated HLA alleles are part of conserved extended haplotypes (CEH), we compared DR3-homozygous T1D and CD patients to determine whether CEHs were equally distributed between both disorders or there was a differential contribution of different haplotypes. We observed a very pronounced distribution bias (P<10−5) of the two major DR3 CEHs, with DR3-B18 predominating in T1D and DR3-B8 in CD. Additionally, high-density single nucleotide polymorphism (SNP) analysis of the complete CEH [A*30-B*18-MICA*4-F1C30-DRB1*0301-DQB1*0201-DPB1*0202] revealed extraordinary conservation throughout the 4.9 Mbp analyzed supporting the existence of additional diabetogenic variants (other than HLA-DRB1*0301-DQB1*0201), conserved within the DR3-B18 CEH (but not in other DR3 haplotypes) that could explain its enhanced diabetogenicity.

Novel mutations in MEN1, CDKN1B and AIP genes in patients with multiple endocrine neoplasia type 1 syndrome in Spain

Context  Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant disorder mostly owing to a genetic defect in MEN1 gene. Not all patients with MEN1 phenotype present a defect in this gene. Thus, other genes like CDKN and AIP have been showed to be involved in MEN1‐like patients.

Iodine intake in the adult population. Di@bet.es study

BACKGROUND & AIMS To date no nation-wide study has yet been undertaken in Spain to estimate the iodine deficiency. The aim was to evaluate iodine intake and its conditioning factors in a representative sample of the whole adult population. METHODS The Di@bet.es Study is a national, cross-sectional, population-based survey conducted in 2009-2010 in Spain. RESULTS The median urinary iodine (UI) was 117.2 μg/L. Iodized salt (IS) was consumed by 43.9% of the population. The median UI in those who consumed IS and in those who did not consume IS was 131.1 and 110.8 μg/L respectively (p<0.0001). The likelihood of having UI levels above 100 μg/L was significantly associated with the intake of IS (OR=1.47) and milk at least once a day (OR=1.22). Within each individual autonomous communities, the median UI levels in those who consumed IS correlated significantly with the median levels of those who did not consume IS (r=0.76, p=0.001). CONCLUSIONS Though strictly speaking, Spain should be considered within the category of a country having an adequate iodine intake, the current value is too close to the cut point and does not guarantee that those groups with a greater need for iodine will have the required intake of iodine.

Endocrine Profile and Phenotype-(Epi)Genotype Correlation in Spanish Patients with Pseudohypoparathyroidism

CONTEXT Recent advances in genetics and epigenetics have revealed an overlap between molecular and clinical features of pseudohypoparathyroidism (PHP) subtypes, broadening the previous spectrum of PHP genotype-phenotype correlations and indicating limitations of the current classification of the disease. OBJECTIVES The aim of the study was to screen patients with clinical diagnoses of PHP type I or pseudo-PHP for underlying molecular defects and explore possible correlations between molecular findings and clinical features. PATIENTS AND METHODS We investigated the GNAS locus at the molecular level in 72 affected patients (46 women and 26 men) from 56 nonrelated families. Clinical data were obtained for 63 of these patients (38 women and 25 men). RESULTS The molecular analysis showed that 35 patients carried structural mutations, 32 had loss of methylation, and 2 had a 2q37 deletion but did not reveal any (epi)mutation for 3 patients. Comparing these results and the clinical data, we observed that a younger age at diagnosis was associated with structural defects at the GNAS gene and epigenetic defects with a diagnosis later in life (9.19 ± 1.64 vs 24.57 ± 2.28 years, P < .0001). CONCLUSIONS This first global review of PHP in Spain highlights the importance of a detailed clinical and genetic study of each patient and the integrated analysis of the findings from the two approaches. It may also help geneticists and clinicians to raise the suspicion of PHP earlier, reach more accurate diagnoses, and provide patients with PHP and their families with useful genetic information and counseling, thereby improving outcomes and quality of life.

RET Cys634Arg mutation confers a more aggressive multiple endocrine neoplasia type 2A phenotype than Cys634Tyr mutation

OBJECTIVE Specific germline mutations in the RET proto-oncogene are correlated with clinical features in multiple endocrine neoplasia type 2A (MEN2A); however, data are scarce regarding differences in clinical profiles dependent on the type of nucleotide and amino acid substitution at the same codon. We aimed to analyse differences in clinical risk profiles and outcomes among different amino acids encoded by codon 634. DESIGN The study was retrospective and multicentric. METHODS We collected data included in the Spanish Online National Database from patients with MEN2A carrying a RET proto-oncogene mutation on codon 634. The mean follow-up time was 7.6±6.9 years (1-32). RESULTS Patients (n=173) from 49 unrelated families were C634Y carriers, and 26 patients from eight different families had C634R mutation. We found higher penetrance of medullary thyroid carcinoma, phaeochromocytoma and hyperparathyroidism (P<0.001, P=0.007 and P<0.001 respectively) in C634R carriers than in C634Y carriers. The Kaplan-Meier estimate of cumulative lymph node and distant metastases rates showed that these events occurred earlier in patients harbouring the C634R mutation (P<0.001). A multivariate adjusted Cox regression analysis indicated that the C634R mutation was an independent factor for persistent/recurrent disease (hazard ratio, 3.17; 95% CI: 1.66-6.03; P<0.001). CONCLUSIONS Our results suggest that there could be clinical differences caused by different amino acid substitutions at codon 634; specifically, the C634R mutation was associated with a more aggressive MEN2A phenotype than the C634Y mutation.

Olive oil has a beneficial effect on impaired glucose regulation and other cardiometabolic risk factors. Di@bet.es study.

Background:Despite the marked increase in cardiovascular risk factors in Spain in recent years, the prevalence and incidence of cardiovascular diseases have not risen as expected. Our objective is to examine the association between consumption of olive oil and the presence of cardiometabolic risk factors in the context of a large study representative of the Spanish population.Subjects and methods:A population-based, cross-sectional, cluster sampling study was conducted. The target population was the whole Spanish population. A total of 4572 individuals aged ⩾18 years in 100 clusters (health centers) were randomly selected with a probability proportional to population size. The main outcome measures were clinical and demographic structured survey, lifestyle survey, physical examination (weight, height, body mass index, waist, hip and blood pressure) and oral glucose tolerance test (OGTT) (75 g).Results:Around 90% of the Spanish population use olive oil, at least for dressing, and slightly fewer for cooking or frying. The preference for olive oil is related to age, educational level, alcohol intake, body mass index and serum glucose, insulin and lipids. People who consume olive oil (vs sunflower oil) had a lower risk of obesity (odds ratio (OR)=0.62 (95% confidence interval (CI)=0.41–0.93, P=0.02)), impaired glucose regulation (OR=0.49 (95% CI=0.28–0.86, P=0.04)), hypertriglyceridemia (OR=0.53 (95% CI=0.33–0.84, P=0.03)) and low HDL cholesterol levels (OR=0.40 (95% CI=0.26–0.59, P=0.0001)).Conclusions:The results show that consumption of olive oil has a beneficial effect on different cardiovascular risk factors, particularly in the presence of obesity, impaired glucose tolerance or a sedentary lifestyle.

Role of cholinergic muscarinic pathways on the free fatty acid inhibition of GH responses to GHRH in normal men.

In order to explore the mechanisms by which free fatty acids (FFA) inhibit GH secretion, we studied the effect of the acetylcholinesterase inhibitor pyridostigmine (120 mg p. o.) on the FFA blockade of GH responses to the administration of GHRH (100 μg i. v.) in seven normal subjects. GHRH‐induced GH secretion was significantly reduced following elevation of circulating FFA levels by lipid‐heparin infusion and significantly potentiated by previous pyridostigmine treatment. Peak GH levels following combined administration of pyridostigmine plus lipid—heparin plus GHRH were significantly higher (P < 0.01) than after GHRH alone and significantly lower than after pyridostigmine plus GHRH (P < 0.01). In conclusion, central cholinergic activation by pyridostigmine, with the presumed reduction in somatostatin discharge, reversed the blocking effect of FFA on GHRH‐stimulated GH release. Conversely, FFA were able to reduce even a maximal GH stimulation by pyridostigmine plus GHRH.

Mediterranean diet adherence in individuals with prediabetes and unknown diabetes: the Di@bet.es Study.

Background and Aims: Mediterranean diet (MedDiet) is causally related to diabetes and is a dietary pattern recommended to individuals with diabetes. We investigated MedDiet adherence in individuals with prediabetes and unknown (PREDM/UKDM) or known diabetes (KDM) compared to those with normal glucose metabolism (NORMAL). Methods: This was a national, population-based, cross-sectional, cluster-sampling study. MedDiet adherence was scored (MedScore, mean ± SD 24 ± 5) using a qualitative food frequency questionnaire. Logistic regression was used to examine the association between MedScore and PREDM/UKDM or KDM versus control subjects. Results: We evaluated 5,076 individuals. Mean age was 50 years, 57% were female, 826 (582/244) were PREDM/UKDM, 478 were KDM and 3,772 were NORMAL. Mean age increased across MedScore tertiles (46, 51 and 56 years, p < 0.0001). Higher age-adjusted adherence to MedDiet (5-unit increment in the MedScore) was associated with lower and nondifferent odds (OR, 95% CI) of prevalent PREDM/UKDM (0.88, 0.81-0.96, p = 0.001) and KDM (0.97, 0.87-1.07, p = 0.279), respectively, compared to individuals in the NORMAL group. Conclusions: In a representative sample of the whole Spanish population, MedDiet adherence is independently associated with PREDM/UKDM. Therapeutic intervention may be, in part, responsible for the lack of differences in adherence observed between the KDM and NORMAL groups. However, reverse causation bias cannot be ruled out in cross-sectional studies.

Prevalence, Diagnosis, Treatment, and Control of Hypertension in Spain. Results of the Di@bet.es Study.

INTRODUCTION AND OBJECTIVES Di@bet.es is a national study designed to estimate the prevalence of diabetes mellitus and other cardiovascular risk factors in the Spanish adult population. The prevalence of hypertension and the degree to which it is recognized, treated, and controlled are described. METHODS The study included a sample of the Spanish population with 5048 adults aged ≥ 18 years. Patients were questioned and examined, with 3 blood pressure readings while seated and at rest to calculate the mean of the 3 readings. Hypertension was defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg and/or prescription for antihypertensive drug therapy. RESULTS Hypertension was found in 42.6% of the Spanish adult population aged ≥ 18 years and was more common among men (49.9%) than women (37.1%). The prevalence was higher among prediabetics (67.9%) and diabetics (79.4%). Undiagnosed hypertension was identified in 37.4% of patients and was more common in men (43.3%) than in women (31.5%). Among patients with known hypertension, 88.3% were receiving drug therapy. Well-controlled blood pressure was found in only 30% and was more common among women (24.9%) than men (16%). CONCLUSIONS The prevalence of hypertension in Spain is high, and a considerable percentage of hypertensive patients have still not been diagnosed. Hypertension is associated with diabetes and prediabetes, and although drug therapy is increasingly common, the degree of control has not improved and remains low. Population campaigns should be developed and promoted for hypertension prevention, detection, and treatment.