Prevalence of diabetes mellitus and impaired glucose metabolism in the adult population of the Basque Country, Spain.

AIMS: To assess the prevalence of diabetes mellitus and impaired glucose metabolism in the Basque Country and their relationship with cardiovascular risk factors. METHODS: A population-based, cross-sectional, cluster sampling design study was carried out in an adult (≥18 years) Basque population. A total of 847 participants completed a questionnaire on personal and family medical history and lifestyle. Anthropometric variables and blood pressure were measured and biochemical analysis and an oral glucose tolerance test (75 g) were also performed. RESULTS: The total prevalence of diabetes was 10.6% (95% CI 8.65-12.95). Among them 6.3% (95% CI 4.79-8.22) had previously been diagnosed and 4.3% (95% CI 3.04-5.92) were not aware that they had diabetes. Impaired glucose tolerance was present in 7.2% (95% CI 5.53-9.15) and impaired fasting glucose in 3.8% (95% CI 2.64-5.37) of the population. In total, 21.6% of the population had some type of glucose metabolism disturbance, with a higher rate among men (28.3 vs 16.3%; P<0.001) and with the rate increasing with age. Risk factors independently associated with the development of diabetes were: male sex [odds ratio 4.58 (95% CI 2.34-8.97)]; abdominal obesity [odds ratio 2.80 (95% CI 1.47-5.36)]; high triglyceride levels [odds ratio 2.46 (95% CI 1.26-4.81)]; hypertension [odds ratio 2.40 (95% CI 1.16-4.96)]; family history of diabetes [odds ratio 2.30 (95% CI 1.25-4.24)]; high LDL cholesterol levels [odds ratio 1.83 (95% CI 1.01-3.31)] and older age [odds ratio 1.08 (95% CI 1.05-1.10)]. CONCLUSIONS: The prevalence of diabetes in the Basque Country was lower than in Spain and was independently associated with family history of diabetes and with cardiovascular risk factors such as abdominal obesity, hypertension, high LDL cholesterol levels and high triglyceride levels, which were also observed in those with prediabetes.

Diagnosis and treatment of multiple endocrine neoplasia type 1 (MEN1).

Multiple endocrine neoplasia type 1 (MEN1; formerly known as Wermer syndrome) is a rare disorder characterized by the combined occurrence of two or more tumors involving parathyroid, pancreatic islets and anterior pituitary glands; some other tumors have also been described. In most cases it is inherited in an autosomic dominant manner but it may occur sporadically. The MEN1 gene (MEN1) is located on chromosome 11q13, it is composed of ten exons that encode a 610 amino acid protein called menin. Menin, with no homology to any other known protein, interacts with several different proteins and plays an important role in regulation of cell growth, cell cycle, genome stability and synapse plasticity. Familiar MEN1 has a high degree of penetrance with clinical or biochemical manifestations of the disease in 80% and 98%, respectively, by the fifth decade. Clinical manifestations are related to tumor localizations and their secretory products. Hyperparathyroidism is the most common feature of MEN1 (95% of patients), pancreatic islet tumors or pancreatic NET (neuroendocrine tumor) occur in 40-70% and pituitary tumors in 30-40% of MEN 1 patients. In addition, other tumors, such as adrenal cortical tumors, carcinoid tumors, lipomas, angiofibromas, colagenomas and meningiomas may be present. Occurrence of de novo mutations appear in 10% of all patients with MEN1. A correlation between genotype and phenotype has not been found and, even more, combinations of these tumors may be different in members of the same family. Untreated patients have a decreased life expectancy, with a 50% probability of death by the age of 50 years and the cause of death is mostly directly related to MEN1, being the most important causes malignant pancreatic neuroendocrine tumors (NET) and thymic carcinoids. Treatment for each type of endocrine tumor is generally similar as in non-MEN1 associated tumors, but results are less successful according to multiplicity of tumors, higher metastatic disease, larger and more aggressive tumors and more resistant to treatment. The prognosis might improve by preclinical tumor diagnosis and appropriated treatment.

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 of diabetes mellitus and impaired glucose regulation in Spain: the Di@bet.es Study.

AIMS/HYPOTHESIS: The Di@bet.es Study is the first national study in Spain to examine the prevalence of diabetes and impaired glucose regulation. METHODS: A population-based, cross-sectional, cluster sampling study was carried out, with target population being the entire Spanish population. Five thousand and seventy-two participants in 100 clusters (health centres or the equivalent in each region) were randomly selected with a probability proportional to population size. Participation rate was 55.8%. Study variables were a clinical and demographic structured survey, lifestyle survey, physical examination (weight, height, BMI, waist and hip circumference, blood pressure) and OGTT (75 g). RESULTS: Almost 30% of the study population had some carbohydrate disturbance. The overall prevalence of diabetes mellitus adjusted for age and sex was 13.8% (95% CI 12.8, 14.7%), of which about half had unknown diabetes: 6.0% (95% CI 5.4, 6.7%). The age- and sex-adjusted prevalence rates of isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT) and combined IFG-IGT were 3.4% (95% CI 2.9, 4.0%), 9.2% (95% CI 8.2, 10.2%) and 2.2% (95% CI 1.7, 2.7%), respectively. The prevalence of diabetes and impaired glucose regulation increased significantly with age (p < 0.0001), and was higher in men than in women (p < 0.001). CONCLUSIONS/INTERPRETATION: The Di@bet.es Study shows, for the first time, the prevalence rates of diabetes and impaired glucose regulation in a representative sample of the Spanish population.

Results from a national survey on the management of primary hyperparathyroidism.

BACKGROUND: Management of primary hyperparathyroidism (PHPT) continues to be challenging. At the Third International Workshop on PHPT, recent data on this disease were reviewed and new clinical recommendations were developed. There are few data on the influence of new guidelines in clinical practice. AIM: We designed an online survey that was sent to all Spanish hospital endocrinology services. METHODS: The questionnaire included 28 questions about diagnosis and management of PHPT. Ninety-nine of 131 sites (76%), giving health coverage to 70% of Spanish population, completed the survey. RESULTS: The reported incidence of PHPT was 9.95/100,000 person-years. Heighty percent of patients were asymptomatic. Each center performed a median (Q1, Q3) of 12 (6, 20) parathyroidectomies/year. The median (Q1, Q3) percentage of curative interventions (at first trial) was 90% (80, 95). The main reasons for not performing surgery were, by decreasing frequency: surgery contraindication, patient's refusal, loss of monitoring, limited surgery experience. Localization techniques were used in 83% of cases. The main criteria for parathyroidectomy in asymptomatic patients were Ca≥2.875 mmol/l (79%), Tscore ≤-2.5 SD at any site (91%), age <50 yr (80%) and glomerular filtration rate <60 ml/min/1.73 m 2 (82%). Minimally invasive surgery was performed in 42% of centers. Frequency of biochemistry and bone density determinations for non-surgically managed patients was in accordance with international guidelines. CONCLUSIONS: The clinical practice of Spanish endocrinologists is consistent with the recommendations of the guidelines from the Third International Workshop for the management of PHPT.

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.

Exploring the diabetogenicity of the HLA-B18-DR3 CEH: independent association with T1D genetic risk close to HLA-DOA.

The objective of this study was to identify additional diabetes susceptibility markers in the MHC that could be responsible for the differential diabetogenicity of different HLA-DR3 CEHs. High-resolution SNP genotyping of the MHC was carried out in 15 type 1 diabetes (T1D) patients and 39 non-diabetic controls, homozygous for DR3-DQ2 and with one copy of the A(*)30-B(*)18-MICA(*)4-F1C30-DRB1(*)0301-DQB1(*)0201-DPB1(*)0202 HLA haplotype. Significantly associated SNPs were replicated in an independent sample of 554 T1D patients and 841 controls without HLA matching. Electrophoretic mobility shift assay was used to show a functional effect of an associated SNP. Seven SNPs showed evidence of association in the initial discovery experiment. Upon replication, only rs419434 (upstream HLA-DOA gene) remained significant. A functional variant (rs432375) in complete LD with rs419434 was shown to affect USF-1 binding and could be responsible for the association signal in the region. We have identified a new susceptibility locus within the MHC with a modest contribution to T1D (OR=1.93; CI: 1.52-2.44; P=10(-8)) that is independent of HLA-DRB1 locus.

Identification of a novel nonsense mutation and a missense substitution in the vasopressin-neurophysin II gene in two Spanish kindreds with familial neurohypophyseal diabetes insipidus.

Familial neurohypophyseal diabetes insipidus (FNDI) is an autosomal dominant disease caused by deficiency in the antidiuretic hormone arginine vasopressin (AVP) encoded by the AVP-neurophysin II (AVP-NPII) gene on chromosome 20p13. In this study, we analyzed two families with FNDI using direct automated fluorescent, solid phase, single-stranded DNA sequencing of PCR-amplified AVP-NPII DNA. In one of the families, affected individuals presented a novel nonsense mutation in exon 3 of the gene, consisting in a G to T transition at nucleotide 2101, which produces a stop signal in codon 82 (Glu) of NPII. The premature termination eliminates part of the C-terminal domain of NPII, including a cysteine residue in position 85, which could be involved in the correct folding of the prohormone. In the second family, a G279A substitution at position -1 of the signal peptide was observed in all affected individuals. This missense mutation, which replaces Ala with Thr, is frequent among FNDI patients and is thought to reduce the efficiency of cleavage by signal peptidases.

Nonadherence and osteoporosis treatment preferences of older women: a qualitative study.

BACKGROUND: Physicians must have an understanding of patients' medication beliefs in order to enhance medication adherence. To increase understanding, this study examined how beliefs about medication and four osteoporosis treatments influenced treatment selection and adherence. METHODS: Six focus groups, three with 28 African Americans and one with 11 non-Hispanic white women, were conducted in English. Two groups with 16 Hispanics were conducted in Spanish. The convenience sample was recruited from senior centers and housing in lower socioeconomic geographic areas. The average age was 74.8 +/- 1.1 years. RESULTS: Adherence was associated with recognition of the serious consequences of nonadherence, realization of the beneficial effects, and the belief that medicines are not harmful. Doubts about physicians' competence to prescribe appropriate drugs were also revealed. Women who thought they were unlikely to fracture or perceived fracture outcomes as not severe chose no treatment. If they identified a need, they weighed benefits against the attendant risks to find the best alternative among the affordable options. Price considerations eliminated raloxifene and alendronate. Consideration of side effects eliminated estrogen and raloxifene. Calcium was viewed as a low-cost, low-risk alternative. Those who could afford alendronate and who viewed its side effects as preventable preferred it. Benefit and risk assessments may have been biased by fear of cancer and thromboembolic events. CONCLUSIONS: Women's beliefs about necessity of treatment, medication safety, cost of treatment, and treatment goals appear critical to osteoporosis treatment selection and adherence.

[10-year prospective study on the incidence and risk factors for type 2 diabetes mellitus]. / Estudio prospectivo a 10 años sobre la incidencia y factores de riesgo de diabetes mellitus tipo 2.

BACKGROUND: The aims of this study were to determine the incidence of diabetes mellitus type 2 and to define the associated risk factors. PATIENTS AND METHOD: A 10-year prospective study was done over 584 people identified by screening of the Lejona (Vizcaya, Spain) adult population in 1985. Data on age, sex, body mass index, family history of diabetes mellitus and blood pressure were collected. Also an oral glucose tolerance test was done following the criteria recommended by the WHO. RESULTS: Age-adjusted cumulative incidence per year was 8 per 1,000 persons. In a multivariate logistic regression analysis, impaired glucose tolerance was the major predictor of worsening to diabetes (relative risk 4.17; 95% confidence interval 1.80-9.63). Age and sex were also statistically significant predictors (p < 0.05), and family history of diabetes was almost significant (p = 0.057). Body mass index was not an independent and significant risk factor in this study. However, the rise in body mass index was larger in those who progressed to diabetes mellitus type 2 than in those who did not. CONCLUSIONS: The incidence of diabetes mellitus type 2 found in Lejona was similar to that reported in other european countries. Subjects having impaired glucose tolerance as well as those with elevated blood glucose levels are at higher risk of worsening to diabetes mellitus type 2. Body mass index seems to play a precipitating role in the progression to diabetes mellitus type 2.

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.

Evaluation of Health-Related Quality of Life according to Carbohydrate Metabolism Status: A Spanish Population-Based Study (Di@bet.es Study).

Objective. To evaluate the association between diabetes mellitus and health-related quality of life (HRQOL) controlled for several sociodemographic and anthropometric variables, in a representative sample of the Spanish population. Methods. A population-based, cross-sectional, and cluster sampling study, with the entire Spanish population as the target population. Five thousand and forty-seven participants (2162/2885 men/women) answered the HRQOL short form 12-questionnaire (SF-12). The physical (PCS-12) and the mental component summary (MCS-12) scores were assessed. Subjects were divided into four groups according to carbohydrate metabolism status: normal, prediabetes, unknown diabetes (UNKDM), and known diabetes (KDM). Logistic regression analyses were conducted. Results. Mean PCS-12/MCS-12 values were 50.9 ± 8.5/ 47.6 ± 10.2, respectively. Men had higher scores than women in both PCS-12 (51.8 ± 7.2 versus 50.3 ± 9.2; P < 0.001) and MCS-12 (50.2 ± 8.5 versus 45.5 ± 10.8; P < 0.001). Increasing age and obesity were associated with a poorer PCS-12 score. In women lower PCS-12 and MCS-12 scores were associated with a higher level of glucose metabolism abnormality (prediabetes and diabetes), (P < 0.0001 for trend), but only the PCS-12 score was associated with altered glucose levels in men (P < 0.001 for trend). The Odds Ratio adjusted for age, body mass index (BMI) and educational level, for a PCS-12 score below the median was 1.62 (CI 95%: 1.2-2.19; P < 0.002) for men with KDM and 1.75 for women with KDM (CI 95%: 1.26-2.43; P < 0.001), respectively. Conclusion. Current study indicates that increasing levels of altered carbohydrate metabolism are accompanied by a trend towards decreasing quality of life, mainly in women, in a representative sample of Spanish population.

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.

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.

Short- and long-term effect of a long-acting somatostatin analogue, lanreotide (SR-L) on metastatic gastrinoma.

Medical treatment is the elective therapy for patients with gastrinoma when the tumor is not found at surgery or is unresectable or when there is a metastatic disease. H2-blockers and omeprazol are able to control gastric acid secretion and, in addition, somatostatin analogues decrease gastrin levels. A new long-acting and slow release formulation of a somatostatin analogue (lanreotide, SR-L) has been developed. We treated two patients suffering from gastrinoma, total gastrectomy and hepatic metastases with 30 mg intramuscular injections of SR-L every 15 and 10 days, respectively, for a seven-month period. After the treatment, gastrin levels decreased from 35,494 and 15,086 ng/l to 3,211 and 167 ng/l (92 and 98% below pre-treatment levels) in case 1 and 2 respectively, with a relief of symptoms and no side effects.

Acromegaly: an epidemiological study.

Although morbility and mortality in acromegaly are higher than in the general population, there have been very few previous epidemiological studies. This study tries to answer "why". Seventy-four patients affected by acromegaly in Vizcaya (Spain) between 1970 and 1989 were considered for an epidemiological study. The prevalence of known cases at the end of 1989 was 60 per million inhabitants. The average incidence of newly diagnosed cases was 3.1 per million people per year. Unexpectedly, acromegaly was more frequent in women (n = 48) than in men (n = 26), with a ratio of 1.8:1. Mean age at diagnosis was significantly higher in women (46.1 +/- 2.2 yr) than in men (39.5 +/- 2.2 yr) (p < 0.05) There was a positive correlation between age at diagnosis and the estimated duration of the disease (r = 0.56, p < 0.05) and a negative one between age and basal GH serum levels (r = -0.52 p < 0.002). The age at diagnosis was significantly higher in patients with invasive tumors (grade III and IV) than in those with enclosed tumors (grade I and II) (47.7 +/- 1.8 vs 40.1 +/- 3.3 p < 0.05). In general, mortality was higher than the expected for the control population (standardized mortality ratio, SMR = 3.2, 95% confidence interval. Cl = 1.55-5.93). However, mortality was higher in men (SMR = 7, 95% Cl = 2.81-14.4) but not in women (SMR = 1.4 95% Cl = 0.29-4.17).(ABSTRACT TRUNCATED AT 250 WORDS)

Giant pituitary adenomas: clinical characteristics and surgical results.

Although most pituitary neoplasms are benign, some grow rapidly, spreading to extrasellar tissues. Definition of these 'giant' pituitary adenomas (PAs) is not clear. In order to clarify this question, we studied all pituitary macroadenomas operated in our hospital during the last 20 years, differentiating those with diameter > or = 3 cm (n = 43) and attempting to identify their typical features and prognosis. The reason for consultation was local in 58.3% of giant PAs, hormonal in 22.9% and tumour recurrence in 16.7%. Surgery was performed via a trans-sphenoidal approach in 92.5% of cases and succeeded in completely removing the tumour in only 27% of cases. In conclusion, we found that giant PAs are not a special type but the extreme case in the gradient of invasiveness of tumours of adenohypophyseal origin. They are characterized by a higher frequency of neuro-ophthalmological symptoms and hormonal deficits, and poorer response to surgical treatment.

Course and prognosis of 132 patients with diabetic non ketotic hyperosmolar state.

One hundred and thirty two episodes of diabetic non ketotic hyperosmolar states were studied after a prospective schedule of treatment was designed. The admission data, the prognostic factors and their outcome were analyzed. Initial high osmolarity, urea and sodium plasma levels and low plasma pH were related to the admission level of consciousness (p < 0.01). High glucose, osmolarity, urea and sodium plasma levels at entry were related to the admission level of dehydration (p < 0.01). In multivariate regression analysis, osmolarity was the most influential variable in both the level of consciousness and the admission level of dehydration (p < 0.0001). Twenty two patients died (16.9%). Septic shock was the most frequent cause of death (31%) and mortality was higher in patients with cardiovascular disease (acute myocardial infarction or stroke) as the precipitating factor for diabetic hyperosmolar state (p < 0.002). Older age, low blood pressure, low sodium, pH and bicarbonate plasma levels, and high urea plasma levels were related to mortality (p < 0.01). In multiple regression analysis, urea was the most influential mortality risk factor (p < 0.0118). Non survivors received higher doses of insulin than survivors (p < 0.01). All these data suggest that it is not the hyperosmolarity itself, but the hemodynamical state of the patients, which is the most influential factor on the prognosis of a diabetic hyperosmolar state.