Gonzalo Díaz-Soto

Beneficial effects of liraglutide on adipocytokines, insulin sensitivity parameters and cardiovascular risk biomarkers in patients with Type 2 diabetes: A prospective study

AIMS To evaluate the effects of liraglutide after 14 weeks of treatment on serum adipokines, insulin resistance index and cardiovascular risk biomarkers in overweight or obese T2DM patients unable to achieve glycemic control with metformin alone or in association with a sulfonylurea in daily clinical practice. METHODS Prospective study in 59 consecutive overweight or obese (BMI≥25kg/m(2)) T2DM patients unable to achieve glycemic control (HbA1c>7%, 53mmol/mol) with metformin alone or in association with sulfonylurea that require initiation of liraglutide in progressive dose increase up to 1.8mg/day subcutaneously. Weight, body composition, blood pressure, glucose, HbA1c, C-peptide, insulin, plasma lipids, adipokines (leptin, adiponectin, resistin and visfatin) as well as cardiovascular biomarkers (IL-6 and TNF-a) levels were measured fasting at baseline and 14 weeks after liraglutide initiation. RESULTS 14 weeks of liraglutide treatment significantly reduced HbA1c, BMI and total body fat mass by 0.9%, 1.4kg/m(2) and 0.5% respectively. Statistically significant lower insulin resistance and higher insulin secretion was found by HOMA-IR 8.4 (1.6) vs 4.6 (0.9)molmIU/L(2) and HOMA-B 48.2 (9.0) vs 87.6 (16.3)μIU/mmol. Statistically significantly higher levels of visfatin 6.3 (2.1) vs 6.8 (2.1)ng/ml and resistin 3.6 (2.0) vs 4.3 (2.3)ng/ml were also observed after treatment. Baseline visfatin was negatively correlated with basal fasting plasma glucose r=-0.360 (p<0.05). CONCLUSIONS Liraglutide treatment for 14 weeks in daily clinical practice led to reduction of BMI and improvement of glucose control and insulin sensitivity and resistance parameters. Additionally, circulating levels of adipokines and pro-inflammatory factors could play an important role in GLP-1 treatment response.

Estructura diagnóstica y funcional de una consulta de alta resolución de nódulo tiroideo: un modelo de eficiencia económica

Appearance of a thyroid nodule has become a daily occurrence in clinical practice. Adequate thyroid nodule assessment requires several diagnostic tests and multiple medical appointments, which results in a substantial delay in diagnosis. Implementation of a highresolution thyroid nodule clinic largely avoids these drawbacks by condensing in a single appointment all tests required for adequate evaluation of thyroid nodule. This paper reviews the diagnostic and functional structure of a high-resolution thyroid nodule clinic.

Impacto económico y satisfacción de la implantación de una consulta de alta resolución de patología nodular tiroidea en Endocrinología

BACKGROUND AND OBJECTIVE No conclusive data exist on the value of a high resolution thyroid nodule clinic for management of nodular thyroid disease. The aim of this study was to evaluate the economic impact of and user satisfaction with a high resolution thyroid nodule clinic (HRTNC) in coordination with primary care. PATIENTS AND METHOD A prospective, observational, descriptive study was conducted to analyze data from 3,726 patients (mean age 61±12 years; 85% women) evaluated at an HRTNC during 2014 and 2015. Demographic data (sex and age), number of ultrasound examinations and fine needle aspiration cytologies (FNAC), referral center and consultation type were assessed. RESULTS In 2014 and 2015, 3,726 neck ultrasound examinations and 926 FNACs (3.8% rated as non-diagnostic) were performed. Among the 1,227 patients evaluated for the first time, 21.5% did not require a second endocrine appointment, which resulted in mean estimated savings of 14,354.55 euros. Of all patients, 41.1% were referred from primary care, 33.4% from endocrinology, and 26.5% from other specialties. As compared to 2013, the number of thyroid ultrasound examinations requested decreased by 65.3% and 59.7% in 2014 and 2015 respectively, with mean estimated savings of 137,563.92 euros. Mean user satisfaction assessed was 4.0 points (95% confidence interval, 3.7-4.3) on a 5-point scale. CONCLUSIONS HRTNCs at endocrinology departments, coordinated with primary care, are a viable, cost-effective alternative with a positive user perception.

Clinical Expression of Calcium Sensing Receptor Polymorphism (A986S) in Normocalcemic and Asymptomatic Hyperparathyroidism.

Normocalcemic and asymptomatic hyperparathyroidism diagnosis are becoming more common. However, their pathophysiology is incompletely known. The aim of the present study was to evaluate the clinical effect of calcium-sensing receptor polymorphism (A986S) in normocalcemic and asymtomatic HPT. Prospective study conducted with 61 consecutive normocalcemic and asymptomatic HPT patients was followed up during a minimum period of 1 year. Secondary causes of hyperparathyroidism were ruled out. Calcium and phosphorus metabolism parameters were evaluated in at least 2 determinations during follow-up to classify as normocalcemic or asymptomatic hyperparathyroidism. Bone mineral density and A986S polymorphism genotype were also analyzed. Thiry-eight patients (62.3%) had the genotype A986A, and 23 (36.7%) patients had A986S (20 patients, 32.8%) or S986S (3 patients, 4.9%). Age, sex, and genotype distributions were comparable in both normocalcemic and asymptomatic hyperparathyroidism. In normocalcemic patients, S allele genotype was associated to statistically significant higher level of intact PTH: 92.0 (SD 18.5) vs. 110.6 (SD 24.4) pg/ml, p<0.05; and remained significant after adjustment by multiple linear regression. In asymptomatic hyperparathyroidism, A986A genotype resulted in a statistically significant higher level of intact PTH, alkaline phosphatase and procollagen amino-terminal propeptide; but only serum calcium remained as an independent predictor of serum intact PTH levels after a multiple linear regression. Bone mineral densitometry between genotypes did not show statistically significant differences. A986S polymorphism of CaSR is an independent predictor of PTH level in normocalcemic hyperparathyroidism patients, but not in asymptomatic hyperparathyroidism. More studies are needed to evaluate the effect of other polymorphisms in normocalcemic and asymptomatic hyperparathyroidism.

Polymorphisms of the vitamin D receptor and their effect on bone mass density in patients with normocalcemic hyperparathyroidism

Normocalcemic hyperparathyroidism (NPHPT) is a form of hyperparathyroidism (HPT) characterized by total and ionized calcium within normal limits, associated with consistently elevated parathyroid hormone (PTH) levels, and with secondary causes of elevated PTH ruled out [1, 2]. NPHPT has been associated with a high prevalence of osteoporosis [3, 4]. Vitamin D plays a key role in regulating the calcium metabolism and maintaining bone mass [5]. Various vitamin D polymorphisms have been identified using different restriction enzymes, including bsml, apaI, fokl, and taq1 [6, 7]. There are no data of the role of the VDR in HPHPT and its possible influence on changes in bone mineral density (BMD). Therefore, we designed a descriptive study to determine the prevalence of four VDR SNPs (rs1073580, rs1544410, rs731236, rs7975232) in patients with NPHPT and their influence on BMD. Patients and methods

Early-onset type 2 diabetes mellitus is associated to HNF4A T130I polymorphism in families of central Spain

Purpose Type 2 diabetes mellitus (type 2 DM) and maturity-onset diabetes of the young present some similar clinical and biochemical characteristics that make them difficult to differentiate. Currently, the polymorphism T130I (rs1800961) in the HNF4A (hepatocyte nuclear factor 4A) gene has been described as a risk factor to type 2 DM and shows an autosomal dominant inheritance pattern associated to β-cell function decrease. The aim of the present work was to characterize the phenotypic profile of the T130I carrier and noncarrier relatives included in 3 unrelated families. Methods We studied GCK, HNF1A, and HNF4A genes by polymerase chain reaction and sequencing in 3 unrelated subjects from Valladolid, Spain, in which maturity-onset diabetes of the young was suspected. We collected genetic, clinical, and biochemical data from these subjects and their relatives in order to check the presence of the T130I polymorphism. Results The heterozygous T130I mutation was the unique functional gene variation that could explain diabetes phenotype. We observed significant differences in glucose metabolism, lipid profile, and Homeostasis Model Assessment index when we compared T130I mutation carriers and noncarriers. Diabetes diagnosed in T130I mutation carriers was related to stressful situations in an earlier age and tightly associated with gestational diabetes. Fasting plasma glucose and HbA1c levels increased with age in all carriers (r = 0.69 and r = 0.66, P < 0.01), respectively. Conclusions Our study supports the T130I variant in HNF4A as a major susceptibility genotype associated with early-onset type 2 DM. Healthy carriers of this mutation require a stricter control in the population of central Spain.

A national survey on the efficacy and safety of continuous subcutaneous insulin infusion in patients with type 1 diabetes in Spain

AIMS To assess safety and benefits of continuous subcutaneous insulin infusion (CSII) therapy in a cohort of type 1 diabetes patients in Spain. METHODS A web-based national registry was created by the Working Group of the Spanish Diabetes Association. All patients on CSII being followed at selected referral centers were included. A cross-sectional analysis was performed. RESULTS A total of 1275 patients were included. Data completion for patients on CSII was 67 ± 32%. Indications for treatment were suboptimal glycemic control (32%), high glucose variability (24%), preconception care (14%) and hypoglycemia (11%). In the patients on CSII for ≥1 year (n = 843, mean CSII duration of 5 years), HbA1c decreased by 5 mmol/mol (0.5%) in the whole population and by 8 mmol/mol (0.7%) in subjects with suboptimal glycemic control as CSII indication. Percentage of patients achieving HbA1c ≤ 53 mmol/mol (7%) increased from 20% before CSII to 34% at the end of follow-up. Severe hypoglycemia decreased from 29% to 5%. The rate of discontinuation was 9.5%. HbA1c was lower in patients using bolus advisor and temporary basal rates. CONCLUSIONS CSII was associated with a sustained improvement in glycemic control and a reduction in severe hypoglycemia. The use of advanced CSII settings was related to better glycemic control.

TRABECULAR BONE SCORE IN PATIENTS WITH NORMOCALCEMIC HYPERPARATHYROIDISM

OBJECTIVE The effects of normocalcemic hyperparathyroidism (NHPT) on bone remain unclear. The objective of this study was to evaluate differences in the trabecular bone score (TBS) of NHPT patients and asymptomatic hypercalcemic hyperparathyroidism (HHPT) patients. METHODS We performed a prospective study that enrolled consecutive patients with asymptomatic hyperparathyroidism (NHPT and HHPT) with a follow-up ≥1 year at the University Hospital of Valladolid, Spain. Metabolic phosphocalcium plasma and urine parameters were evaluated in ≥2 determinations during follow-up to classify patients as NHPT patients or asymptomatic HHPT patients. A control group was enrolled during the same period. TBS and bone mineral density (BMD) were evaluated. RESULTS Thirty-nine patients with asymptomatic HPT (24 with NHPT and 15 with HHPT) and 24 controls were recruited. NHPT patients and HHPT patients had a similar mean age, vitamin D level, TBS, and areal BMD (all sites). Compared to controls, symptomatic HPT patients had significantly higher parathyroid hormone (PTH) and calcium levels and significantly lower TBS and areal BMD at all sites (all P<.05). A significant negative relationship between TBS and PTH was found in asymptomatic HPT patients (r = -0.320, P = .043), which remained significant after adjustment for age, sex, and body mass index. CONCLUSION There was no difference in the TBS between NHPT and HHPT patients. However, there was a reduction in the TBS of patients with asymptomatic HPT that was related to PTH levels but had no repercussion on bone mass. Higher levels of PTH seem to be responsible for this alteration in microarchitecture texture. ABBREVIATIONS aBMD = areal bone mineral density BMD = bone mineral density BMI = body mass index DXA = dual-energy X-ray absorptiometry HHPT = hypercalcemic hyperparathyroidism HPT = hyperparathyroidism HR-MRI = high-resolution magnetic resonance HR-pQcT = high-resolution peripheral quantitative computed tomography NHPT = normocalcemic hyper-parathyroidism PTH = parathyroid hormone TBS = trabecular bone score 25vitD = 25-hydroxyvitamin D.

Normocalcemic Primary Hyperparathyroidism

Normocalcemic primary hyperparathyroidism is a new entity which possibly represents a fruste form of the classic clinically symptomatic disease and which has generated a considerable scientific interest in the last decade. Its official recognition is just as recent as in 2008, when an international conference took place for clarifying its nature and relevance (Bilezikian et al., 2009). Its true prevalence is mostly unknown although it is clear that it is recognized more and more in different clinical settings, from internal medicine outpatient clinics to endocrine or rheumatologists consultations. It is a challenging situation for either the clinician and the patient, as therapeutic recommendations are nowadays nor established and different patients may be advised to receive certain active treatment or just follow-up, or even no follow-up. In this chapter the current data in relation to this emergent condition are presented.