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.

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.

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.

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.

Meal size can be decreased in obese subjects through pharmacological acceleration of gastric emptying (The OBERYTH trial).

BACKGROUND: Entry of nutrients into the small intestine activates neuro-hormonal signals that regulate food intake through induction of satiation. OBJECTIVE: To evaluate whether caloric intake can be decreased by pharmacologically accelerating gastric emptying (GE) of nutrients into the small intestine. METHODS: Subjects were tested in 2 days, at baseline (day1) and after randomly receiving, in a double-blind manner, a 1 h infusion of erythromycin (3 mg Kg(-1), to accelerate GE) or placebo (day 2). Ad libitum caloric intake and postprandial gastrointestinal symptoms were evaluated using a validated nutrient drink test, simultaneously measuring gastric emptying [corrected] by scintigraphy. Plasma levels of satiation factors were also measured to evaluate their role in the modification of caloric intake and postprandial symptoms. Acceleration of GE was assessed as the difference in percentage emptied between day 2 and day 1 (DGE). The effects of DGE on caloric intake and symptoms were evaluated using multiple (lineal) regression. RESULTS: Among 30 overweight/obese subjects (24F and 6 M), 15 received erythromycin and 15 placebo. The overall median age was 36 years (IQR: 30-42) and body mass index was 30 Kg m(-2) (IQR: 27-36). Subjects receiving erythromycin on day 2 presented accelerated GE as compared with placebo (P = 0.0002). DGE at 15 min after initiating eating had a significant effect on prospective caloric intake (P = 0.004). From the best-fitted regression model (R (2) = 81%, P < 0.0001), a 10% increase in GE at 15 min induced on an average a 135 ± 43.5 Kcal decrease in caloric intake. Postprandial increase in cholecystokinin (CCK) (P = 0.03) and insulin (P = 0.02) was associated with decreased caloric intake. Acceleration of GE at 60 min after initiating eating increased postprandial symptom scores measured 30 min after the completion of food consumption (P = 0.01). Postprandial increase in CCK (P = 0.002) and PP (P = 0.02) was associated with postprandial symptoms. CONCLUSION: Meal size can be reduced in overweight/obese subjects by pharmacologically accelerating GE. This may be a reasonable target in obesity management.

The efficacy of octreotide LAR as firstline therapy for patients with newly diagnosed acromegaly is independent of tumor extension: predictive factors of tumor and biochemical response.

Surgical outcome of acromegaly depends on the preoperatory tumor size and extension. Somatostatin analogues are also a highly effective treatment for acromegalic patients. Nevertheless, the response of GH-secreting adenomas to primary medical therapy is variable. The aim of the present study was to evaluate the efficacy of octreotide LAR as primary therapy for acromegalic patients as a function of initial tumor extension. We performed a multicentre, prospective, observational and analytical study recruiting 19 "naive" acromegalic patients (5 microadenomas, 10 intrasellar, and 4 extrasellar macroadenomas). All of them were treated with octreotide LAR for 12 months. Basal GH and fasting IGF-I concentrations, and tumor volume were measured at baseline and after 6 and 12 months of treatment. Six patients withdrew the study. The patients who completed the protocol showed a significant reduction of tumor volume (25+/-23%, Wilk's lambda=0.506, F=4.400, p=0.046) independently of tumor extension at study entry (Wilk's lambda=0.826, F=0.452, p=0.769). A shrinkage >25% of baseline tumor volume was achieved in 8 (42%) patients with no differences between tumor extension subgroups. Basal GH levels (76+/-18%) and fasting IGF-I (52+/-31%) decreased throughout the study. Six (46%) patients normalized their IGF-I levels. Octreotide LAR is an effective first-line treatment for a large group of acromegalic patients independent of initial tumor extension.

Role of two nutritional hepatic markers (insulin-like growth factor 1 and transthyretin) in the clinical assessment and follow-up of acute intermittent porphyria patients.

OBJECTIVE: Acute intermittent porphyria (AIP) is caused by a deficiency of hydroxymethylbilane synthase. Clinical manifestations are abdominal pain and neurovisceral symptoms, accompanied by overproduction of heme-precursors in the liver, which frequently remains long-lasting in AIP patients. We tested the hypothesis that this condition may be associated with alterations of hepatic proteins known to be either increased or decreased in serum according to diverse pathological conditions including malnutrition, inflammation or liver disease. DESIGN: Serum proteins were analyzed in 26 biochemically active AIP patients that were classified according to the EPI (European Porphyria Initiative) guidelines as follows: (i) patients who presented a single acute attack having remained so far free of clinical symptoms; (ii) patients who present recurrent attacks or chronic symptoms associated with exacerbations of AIP. RESULTS: Most of the serum proteins were within normal limits, however insulin-like growth factor 1 (IGF-1) was decreased in 53.8% of AIP patients (z-score = -2.86 +/- 0.37) and transthyretin (prealbumin) was found significantly decreased in 38.5% of them. The IGF-1 z-score was lower in group B versus group A patients (-2.66 vs. -1.43; P = 0.024). The coincident decrease of both IGF-1 and transthyretin was associated with worsening of the clinical condition. CONCLUSIONS: This first study in humans suggests that the clinical expression AIP is associated with a state of under-nutrition and/or with hepatic inflammation due to the sustained accumulation of heme-precursors. We propose the use of both IGF-1 and transthyretin as biomarkers of disease morbidity/severity for the clinical follow-up of AIP patients.

Iodine status and thyroid volume changes during pregnancy: results of a survey in Aran Valley (Catalan Pyrenees).

The Aran Valley (Catalan Pyrenees, Spain) has a long-standing history of iodine deficiency. A survey was performed to determine the prevalence of iodine deficiency (urinary iodine<150 microg/l) in pregnant women from this region during the 1st and 3rd trimesters of gestation and to evaluate the changes in thyroid volume (TV). Of all the registered pregnancies in the area, in the first semester of the year 2000, 35 women (90%) were studied. Urinary iodine (UI) was measured and a thyroid ultrasonography performed during the 1st and 3rd trimester and their iodized salt consumption was recorded. Of the whole group, 77.1% of pregnant women reported regular intake of iodized salt.Median UI in the first trimester was 134.5 microg/l. Iodine deficiency was observed in 57.1%of women in the 1st trimester and in 46.7% in the 3rd trimester (p=0.1). In 10 women supplemented with iodine (150 microg/day) from the 1st trimester, median UI increased from 138.5 microg/l in the 1st trimester to 168 mug/l in the 3rd trimester (p=0.037), and no changes were observed in the rest. TV increased in the whole group during pregnancy (median 7.5 ml in the 1st trimester vs 9.5 ml in the 3rd trimester; p<0.001). The change in TV was significant in those cases with iodine deficiency in the 1st trimester, 3rd trimester or both (median 7.5ml in the 1st trimester vs 10.01 ml in the 3rd trimester; p=0.001) and between multiparous women (8.2 vs 10.9 ml; p=0.005). In 2000, iodine deficiency among pregnant women in the Aran Valley was still very high. Iodine deficiency as well as multiparity contributes to goitrogenesis during pregnancy. Taking this data in account, pre-conceptional supplements with iodine are required for its prevention.

A short acute octreotide test for response prediction of long-term treatment with somatostatin analogues in acromegalic patients.

The usefulness of the acute octreotide test in the selection of acromegalic patients for chronic somatostatin depot analogues treatment is controversial. The aim of the present study was to determine its accuracy for chronic response prediction, and the reliability of a short version of the classic 6-hour test. The data from 26 acromegalics (19 women, 7 men, mean age 52.6+/-13.1 years) studied with an acute octreotide test (6 hours sampling for GH measurement after octreotide 100 microg s. c.) were retrospectively analyzed. Eighteen of them followed chronic somatostatin depot analogues treatment for 12 months. GH nadir was always detected at 2 hours (mean decrease 75.9+/-24%). GH levels at 2 hours positively correlated with the other time-points (r(s) 0.97, 0.98, 0.97, 0.96 at 3, 4, 5 and 6 h, respectively; p<0.0001). During chronic treatment with maximal effective dose for 12 months, 61% of the patients achieved IGF1 <3 SD and 22% reached IGF1 <2 SD. GH nadir correlated with IGF1 decrease at 12 months (r(s) 0.76, p<0001). GH nadir of 9.2 ng/ml predicts IGF1 <3 SD with 82% sensitivity and 58% specificity (75% PPV, 67% NPV); for IGF1<2 SD, 75% sensitivity and 58% specificity are obtained for GH nadir 3.6 ng/ml, with 33% PPV and 89% NPV. Acute octreotide test reliably predicts response to long-term treatment; the short, 2-hour version is fully informative for therapeutic decisions in acromegalic patients.

Phenotype changes at the onset of type 1 diabetes in young adults from a mediterranean area throughout the last decade.

The Accelerator hypothesis postulates that Type 1 Diabetes (T1D) and Type 2 Diabetes are mostly the same disorder. Till now, the data testing the hypothesis and the importance of BMI and insulin resistance in the development of T1D comes almost exclusively from childhood. Our study aimed to investigate changes in clinical and metabolic characteristics of young adults at diagnosis of T1D during the last decade in a Mediterranean area. Ninety-three adults (> or =18 years) with newly diagnosed T1D were evaluated from our database. Thirty-one of them were diagnosed in the period 07/1994-1995 (G95), 39 between 07/1998 and 1999 (G99) and 23 in 2003 (G03). Plasma C-peptide measurements were performed before and 6 min after intravenous injection of 1 mg of glucagon. In those subjects with a basal C-peptide > 0.2 nmol/l, insulin resistance was evaluated using the HOMA-2 model. HbAc, GAD, IA2 and insulin autoantibodies were measured. There was not a significant rise in BMI at diagnosis of T1D in young adults admitted to our Hospital. This was also the case when BMI after 4 weeks of diagnosis was considered (23.7 +/- 3.6, 23,6 +/- 2.4 and 23.4 +/- 3.3 kg/m2, G95 G99 and G03, respectively). In the entire group of subjects, we could not observed any relationship between the patients BMI and age at diagnosis. Likewise, we could not observed differences in any of the clinical, immunological or metabolic characteristics. IR was not different between groups (G95 n=18, 0.73 +/- 0.21; G99 n=29, 0.86 +/- 0.33; G3 n=13, 0.66 +/- 0.34) and was not related to the age at diagnosis. In summary, our data collected from young adults with newly diagnosed T1D from a Mediterranean area indicates that the phenotype, including BMI, at the onset of the disease has not substantially varied during the last decade. In spite of our data do not fit with the accelerator hypothesis the postulate could be of interest in a different age group.

The role of ghrelin in the energy homeostasis of elderly people: a population-based study.

OBJECTIVE: Ghrelin is a hormone secreted mainly in the stomach which stimulates appetite and food intake. Endocrine factors are among the causes of anorexia in elderly people. The main objective of the present study was to examine the effect of age on ghrelin levels in non-institutionalized elderly people. DESIGN AND SETTING: Observational, cross-sectional, population-based study. PARTICIPANTS: A random sample of men aged 70 yr or older was taken from the municipal census. MEASUREMENTS: All participants underwent a physical examination which measured weight and height, grip strength, functional capacity (according to the Barthel Index) and nutritional status (according to the short form of the Mini Nutritional Assessment). Blood was taken for basic biochemical analysis, determination of somatotropic, corticotropic, and gonadotropic hormones, and for measurement of ghrelin and cholecystokinin. RESULTS: 152 men with a mean (SD) age of 76.7 (5.4) yr were recruited. Mean ghrelin levels were 1143 (401) pg/ml. A weak negative correlation was found between ghrelin levels and age (r=-0.16, p=0.057). Multiple linear regression analysis showed a significant and independent effect of age (beta=-12.1, p=0.049), body mass index (BMI) (beta=-22.0, p=0.021), and creatinine levels (beta=407.7, p=0.002) on ghrelin. No correlations with age and BMI were found for cholecystokinin. CONCLUSIONS: There is a slight decrease in ghrelin levels with age in older men aged 70 yr or more, although the clinical relevance of this finding remains unclear.

Lack of effect of intermittently administered sodium fusidate in patients with newly diagnosed type 1 diabetes mellitus: the FUSIDM trial.

AIMS/HYPOTHESIS: We evaluated in a double-blind study the effect of early treatment with the immunomodulatory drug fusidin in patients with newly diagnosed type 1 diabetes mellitus. METHODS: Twenty-eight adults with newly diagnosed type 1 diabetes were included in the study. The patients were randomly assigned (computer-generated random number sequence) to two experimental groups. Patients allocated to the fusidin (FUS) group (n=15) received sodium fusidate (fusidin; 500 mg orally three times daily for 4 weeks). Subsequently the drug was given at the same dose and scheduled for two consecutive weeks a month followed by 2 weeks a month without the drug for 20 weeks. Subjects allocated to the placebo (PCB) group (n=13) received placebo according to the same schedule and conditions described for sodium fusidate in the FUS group. All patients received a diet adjusted to their age and BMI, and intensive insulin therapy. RESULTS: There were no statistically significant differences between the FUS and PCB groups in beta cell function, evaluated by basal and glucagon-stimulated C-peptide values during the follow-up (24 and 48 weeks). There was also no difference between the two groups in insulin requirement after 48 weeks (0.4+/-0.2 and 0.4+/-0.2 U/kg body weight for the FUS and PCB groups, respectively). Antibody titres, including insulin autoantibodies, were similar in the two groups during the follow-up. CONCLUSIONS/INTERPRETATION: Early treatment of newly diagnosed type 1 diabetes patients with intermittently administered fusidin failed to influence the natural course of the disease.

The importance of diagnostic criteria in the association between the metabolic syndrome and cardiovascular disease in obese subjects.

OBJECTIVE: To investigate whether the association between the metabolic syndrome (MS) and cardiovascular disease (CVD) in obese adults is influenced by the criteria used to diagnose the MS. DESIGN AND SUBJECTS: Cross-sectional study in 389 obese adults (male/female: 26%/74%; body mass index (BMI): 30.1-63.2 kg/m2; age: 18-79 y). MEASUREMENTS: To diagnose the MS by the WHO or the ATPIII criteria, body mass index, waist circumference, fasting and 2-h oral Glucose tolerance test plasma glucose, fasting plasma triglycerides and HDL cholesterol, systolic and diastolic blood pressure, 24-h albumin excretion, and fasting insulin were measured. The association between the MS diagnosed with either definition and self-referred CVD was investigated. RESULTS: The prevalence of the MS by the WHO was higher than by the ATPIII criteria (WHO 69.1%, ATPIII 49.4%; P<0.001). The MS diagnosed by the WHO criteria was significantly associated with self-referred CVD (odds ratio (OR) 5.80, 95% CI 1.35-24.95, P<0.05), whereas the ATPIIII MS was not (OR 1.34, 95% CI 0.59-3.03). An elevated blood pressure (OR 5.04, 95% CI 1.41-18.01, P<0.05) and microalbuminuria (OR 2.61, 95% CI 1.06-6.40, P<0.05) were independently associated with CVD. Consideration of the OGTT data as part of the ATPIII MS definition improved its associations with CVD (OR 4.39, 95% CI 1.29-14.94, P<0.05). CONCLUSION: The WHO criteria appear to identify a greater number of obese adults at risk for CVD. Nevertheless, the addition of an OGTT at least in nondiabetic patients with two ATPIII-defined metabolic risk factors may help to improve the association between the MS and CVD in obese adults.

Clinical characteristics, beta-cell function, HLA class II and mutations in MODY genes in non-paediatric subjects with Type 1 diabetes without pancreatic autoantibodies.

OBJECTIVE: To study clinical characteristics, beta-cell function, HLA typing and mutations in the hepatocyte nuclear factor (HNF)-1alpha and HNF-4alpha genes in Type 1 diabetes mellitus (T1D) patients without pancreatic autoantibodies. DESIGN AND METHODS: Twenty patients without pancreatic autoantibodies (Ab neg) and 20 with autoantibodies (Ab pos), age/gender matched, were included (age 17-34 years). Islet cell, glutamic acid decarboxylase, tyrosine phosphatase and insulin autoantibodies, basal and stimulated C-peptide were measured. HLA-DRB1-DQA1-DQB1 typing and screening for mutations in the HNF-1alpha and HNF-4alpha genes were performed. RESULTS: No differences were found in clinical presentation, metabolic control and beta-cell function in the two groups (onset or after 12 months). DRB1*0301-DQA1*0501-DQB1*0201 was the most frequent haplotype in both groups but we found a higher proportion of protective T1D haplotypes and Asp(beta57) in the Ab neg group, but in all the cases in combination with susceptible T1D haplotypes. We found two previously reported polymorphisms (HNF-1alpha, Ala98Val; HNF-4alpha, Thr130Ile) in Ab neg and a new variant (Ser165Gly) in the HNF-4alpha gene in an Ab pos subject. Conclusions In a non-paediatric population with newly diagnosed T1D, the absence of islet antibodies does not imply clinical or metabolic differences when compared with those cases with islet antibodies. Despite a similar HLA-DR/DQ typing, the presence of protective alleles and molecular properties in a higher proportion in the Ab neg group suggests that these factors could modulate the presence or absence of islet antibodies. Variants in HNF-1alpha and HNF-4alpha are unlikely to be major contributors to the pathogenesis of diabetes in antibody-negative T1D.

Relationship between 25-(OH) D3, the IGF-I system, leptin, anthropometric and body composition variables in a healthy, randomly selected population.

OBJECTIVE: This study prompted us to investigate the relationship between 25-(OH) D (3) and the IGF-I system, leptin, sex, age, anthropometric and body composition variables in healthy adults. We hypothesised that these variables would regulate 25-(OH) D (3) concentrations. DESIGN: We included 253 subjects--126 men and 127 women. Body mass index (BMI) and body composition was determined, along with serum leptin, total IGF-I, free IGF-I, IGFBP3 and plasma 25-(OH) D (3) concentrations. RESULTS: 25-(OH) D (3) deficiency was observed in 69 subjects. There was a difference between 25-(OH) D (3) values and season (summer vs. winter). We observed similar 25-(OH) D (3) concentrations in men to those in women. The differential characteristics in subjects without 25-(OH) D (3) deficiency were lower BMI, fat mass and body fat and higher free IGF-I. We observed that leptin increased in the last decades and IGF-I system decreased by decade in both men and women. In subjects without 25-(OH) D (3) deficiency, there was a correlation between free IGF-I and 25-(OH) D (3) in men, and a negative correlation between 25-(OH) D (3) and age, BMI, fat mass and leptin and a positive correlation with total IGF-I in women. The multivariate linear regression analysis explained 37.8 % of 25-(OH) D (3) variability in men and 39 % in women, and only season and free IGF-I made an independent contribution to 25-(OH) D (3) in men, and season and fat mass in women. CONCLUSION: These data suggest that free IGF-I in men and fat mass in women could regulate 25-(OH) D (3) concentrations.

Effects of atorvastatin on glucose homeostasis, postprandial triglyceride response and C-reactive protein in subjects with impaired fasting glucose.

AIMS: To investigate the effects of atorvastatin on glucose homeostasis, the basal and postprandial lipid profiles and the CRP levels (C reactive protein) in subjects with impaired fasting glucose (IFG). METHODS: Thirty-three subjects (22 men and 11 women) were included in our study. All displayed an IFG (fasting plasma glucose between 6.1 and 7.0 mmol/l) on at least two occasions during the last 6 months prior the study. They were randomly assigned to receive either 40 mg atorvastatin/day (n=16) or placebo (n=17) over 16 weeks, in a double-blind design. Before and after the end of the study all participants underwent on three consecutive days: a 75-g oral glucose tolerance test, a frequent sampling intravenous glucose tolerance test with Minimal Model analysis and a meal tolerance test (glucose, insulin and triglycerides). CRP was measured before and after the treatment period. RESULTS: CRP decreased significantly in the atorvastatin-treated group compared with the placebo group (percent change respect initial values; -42.3 %[-21.5 to - 63.1] and -9.6%[15.0 to -34.0], respectively, p<0.01). Atorvastatin treatment did not produce any change in oral glucose tolerance categories or induce any change in glucose and insulin response in OGTT. The statin produced a trend towards a significant improvement in insulin sensitivity as expressed by a change in Si from baseline to the end of treatment. Atorvastatin reduced the postprandial response of triglycerides to the meal test compared with placebo (19-26 % across the meal test, p<0.05) correlating with the amelioration observed in Si (-0.34, p<0.05; percentage changes). CONCLUSION: Our results suggest that the use of statins in subjects with IFG seems to include other potentially beneficial actions in addition to their cholesterol-lowering effects.

Lower rate of tumor necrosis factor-alpha -863A allele and higher concentration of tumor necrosis factor-alpha receptor 2 in first-degree relatives of subjects with type 2 diabetes.

Allelic variants of the tumor necrosis factor-alpha (TNF-alpha) gene seem to contribute to insulin resistance increasing the transcription rate of TNF-alpha. The TNF-alpha -863A allele is associated with a lower expression of TNF-alpha gene and less secretion of the cytokine. To investigate whether an abnormal TNF-alpha system regulation may contribute to early impairment of insulin action in first-degree relatives of patients with type 2 diabetes mellitus (DM), we studied the TNF-alpha -863C/A polymorphism and the soluble fraction of TNF-alpha receptor-2 (sTNFR2) concentration in these subjects in comparison to a control group. A total of 52% of subjects in the relatives' group showed an abnormal oral glucose tolerance (either as impaired glucose tolerance [IGT] or diabetes) and had more features of the insulin resistance syndrome, despite showing similar body composition as controls. The plasma concentration of the sTNFR2 was higher and insulin sensitivity (%S) was lower in the relatives' group than in the controls. Likewise, the TNF-alpha -863A allele was more commonly detected in the control group (10 of 41) than in the relative's group (2 of 36, P =.029). In a multivariate linear regression analysis, neither TNF-alpha -863A allele nor sTNFR2 independently determined %S. Only body mass index (BMI) and the presence of a positive family history of DM were independent determinants of insulin resistance. In summary, our study showed a lower rate of TNF-alpha -863A allele and higher concentrations of sTNFR2 in first-degree relatives of DM subjects. These findings could be included among the genetic, metabolic, and clinical heterogeneity that characterizes the pathophysiology of DM. The presence of abnormalities in the TNF-alpha pathway could predispose to the development of DM in subjects at risk for the disease.

A pharmacokinetic and endocrine comparison of recombinant follicle-stimulating hormone and human menopausal gonadotrophin in polycystic ovary syndrome.

Elevated LH concentrations are frequently encountered in patients with polycystic ovary syndrome (PCOS) and increased LH (either endogenous or superimposed through the use of HMG) may have detrimental effects on reproductive function. In spite of this, FSH-only products and HMG have been used indiscriminately for ovulation induction - on the basis that the administration of HMG to patients with PCOS, who are not receiving GnRH agonists, does not result in significant increases in serum LH concentrations as judged by daily single blood samples. However, both endogenous and exogenous LH have a relatively short terminal half-life and studies have reported normal serum LH, but abnormal urinary LH and emphasized that early morning urinary measurements are more informative than those in serum because they reflect nocturnal LH secretion. Therefore, the present study was undertaken to perform a pharmacokinetic and endocrine comparison of recombinant human FSH and HMG in PCOS patients including LH measurements in the urine. Five PCOS patients receiving s.c. recombinant human FSH (rhFSH) and five PCOS patients receiving i.m. HMG for ovulation induction according to a chronic low-dose step-up regimen underwent blood and urine sampling at the following study points: Point 0 was the day of HCG injection; Points 1 to 5 corresponded to days HCG -1 to -2; -3 to -4; -5 to -6; -7 to -8; and -9 to -10; respectively. Serum hormone measurements included oestradiol, FSH, LH, progesterone, inhibin A, androstenedione, testosterone, and free testosterone index. FSH and LH were also measured daily in 8-h urine samples reflecting overnight renal urine secretion. Hormone concentrations calculated as the area under the curve showed that both FSH and LH concentrations in urine were significantly higher in HMG group than in group rhFSH. It is concluded that both LH and FSH concentrations significantly accumulate in the urine of PCOS patients receiving HMG for ovulation induction in a chronic low-dose protocol as compared with rhFSH treatment.