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Background Metformin, which is known to produce profound changes in gut microbiota, is being increasingly used in gestational diabetes mellitus (GDM). The aim of this study was to elucidate the differences in gut microbiota composition and function in women with GDM treated with metformin compared to those treated with insulin. Methods From May to December 2018, 58 women with GDM were randomized to receive insulin (INS; n = 28) or metformin (MET; n = 30) at the University Hospital Virgen de la Victoria, Malaga, Spain. Basal visits, with at least 1 follow-up visit and prepartum visit, were performed. At the basal and prepartum visits, blood and stool samples were collected. The gut microbiota profile was determined through 16S rRNA analysis. Results Compared to INS, women on MET presented a lower mean postprandial glycemia and a lower increase in weight and body mass index (BMI). Firmicutes and Peptostreptococcaceae abundance declined, while Proteobacteria and Enterobacteriaceae abundance increased in the MET group. We found inverse correlations between changes in the abundance of Proteobacteria and mean postprandial glycemia (p = 0.023), as well as between Enterobacteriaceae and a rise in BMI and weight gain (p = 0.031 and p = 0.036, respectively). Regarding the metabolic profile of gut microbiota, predicted metabolic pathways related to propionate degradation and ubiquinol biosynthesis predominated in the MET group. Conclusion Metformin in GDM affects the composition and metabolic profile of gut microbiota. These changes could mediate, at least in part, its clinical effects. Studies designed to assess how these changes influence metabolic control during and after pregnancy are necessary.

Men with obesity tend to be insulin resistant and often have low-normal testosterone concentrations. We conducted a clinical trial aimed to evaluate potential therapeutic strategies for low testosterone in men with obesity.We did a 1-year, parallel, randomized, double-blind, placebo-controlled trial, where we evaluated the independent and combined effects of metformin and testosterone in 106 men with obesity, aged 18-50 years, who had low levels of testosterone and no diabetes mellitus. The primary outcome was change in insulin resistance, measured as Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) index. Secondary outcomes included changes in total and free serum testosterone, body composition, metabolic variables, erectile function, and health-related quality of life (HRQoL).In the intention-to-treat analysis, the HOMA-IR index decreased significantly in all active groups compared to placebo (metformin -2.4, 95 % CI -4.1 to -0.8, p = 0.004; testosterone -2.7, 95 % CI -4.3 to -1.1, p = 0.001; combination -3.4, 95 % CI -5.0 to -1.8, p 0.001). Combination therapy was not superior to testosterone alone in decreasing insulin resistance (-0.7, 95 % CI -2.3 to 0.9, p = 0.383). Only the combination of metformin plus testosterone significantly increased total and free testosterone concentrations, compared to placebo. No significant changes in body composition (except for a higher decrease in fat mass in the metformin and combination group), metabolic variables, erectile function, or HRQoL were found with any treatment.Among men with obesity and low testosterone concentrations, the combination of metformin plus testosterone, metformin only, and testosterone only, compared to placebo, reduced insulin resistance with no evidence of additive benefit.

Objective To study the prevalence of postprandial hyperglycaemia (PPH) in type 2 diabetes mellitus (T2DM) patients treated with basal insulin, having fasting glucose 7.0% (53 mmol/mol). Methods This was an observational prospective multicentric study conducted in Spain. During 2 weeks, patients recorded a 6-point self-measured blood glucose profile (before and 2 h after eating) every 2 days. PPH was defined according to IDF and ADA guidelines (> 160 and > 180 mg/dL, respectively). Results We included 98 patients (males: 56.1%; mean age: 64.3 ± 10.4 years) who were treated with basal insulin for at least 1 year at stable doses in the last 2 months, 88.8% of them received concomitant oral antidiabetic drugs. Overall, 95.7% (95% CI 91.6–99.8) and 93.5% (95% CI 88.6–98.5) of patients showed ≥ 1 episode of PPH according to IDF and ADA criteria respectively. PPH was more frequently observed after lunch and dinner. The proportion of patients with ≥ 40% readings in range of PPH was 59.1% (95% CI 49.1–69.1) and 40.9% (95% CI 30.9–50.9), according to IDF and ADA criteria, respectively. Conclusions PPH is very common and should be considered a priority target in basal insulin-treated T2DM patients with elevated HbA1c despite controlled fasting glucose.

Despite bariatric surgery being the most effective treatment for obesity, some individuals do not respond adequately, especially in the long term. Identifying the predictors of correct weight maintenance in the medium (from 1 to 3 years after surgery) and long term (from 3 years and above) is of vital importance to reduce failure after bariatric surgery; therefore, we summarize the evidence about certain factors, among which we highlight surgical technique, psychological factors, physical activity, adherence to diet, gastrointestinal hormones or neurological factors related to appetite control. We conducted a search in PubMed focused on the last five years (2015–2021). Main findings are as follows: despite Roux-en-Y gastric bypass being more effective in the long term, sleeve gastrectomy shows a more beneficial effectiveness–complications balance; pre-surgical psychological and behavioral evaluation along with post-surgical treatment improve long-term surgical outcomes; physical activity programs after bariatric surgery, in addition to continuous and comprehensive care interventions regarding diet habits, improve weight loss maintenance, but it is necessary to improve adherence; the impact of bariatric surgery on the gut–brain axis seems to influence weight maintenance. In conclusion, although interesting findings exist, the evidence is contradictory in some places, and long-term clinical trials are necessary to draw more robust conclusions.

Options for treatment of obesity include dietary approaches and bariatric surgery. Previous studies have shown that weight loss interventions have an impact on gut microbiota. However, a pattern of gut microbiota changes associated with weight loss independently of the type of intervention has not been described yet. This study includes 61 individuals who followed different weight loss strategies in three different trials: 21 followed a hypocaloric Mediterranean diet (MedDiet), 18 followed a very-low-calorie ketogenic diet (VLCKD) and 22 patients underwent sleeve gastrectomy bariatric surgery (BS). Gut microbiota profile was assessed by next-generation sequencing. A common taxon that had significantly changed within the three weight loss interventions could not be find. At the family level, Clostiridiaceae significantly increased its abundance with MedDiet and VLCKD, whilst Porphyromonadacean and Rikenellaceae significantly increased with VLCKD and BS. At genus level, in VLCKD and BS, Parabacteroides and Alistipes significantly increased their abundance whilst Lactobacillus decreased. At the species level, BS and VLCKD produced an increase in Parabacteroidesdistasonis and a decrease in Eubactieriumventriosum and Lactobacillusrogosae, whilst Orodibactersplanchnicus increased its abundance after the BS and MedDiet. Predicted metagenome analysis suggested that most of the changes after VLCKD were focused on pathways related to biosynthesis and degradation/utilization/assimilation, while BS seems to decrease most of the biosynthesis pathways. MedDiet was enriched in several pathways related to fermentation to short-chain fatty acids. Our results show that weight loss is not associated with a specific pattern of gut microbiota changes independently of the strategy used. Indeed, gut microbiota changes according to type of weight loss intervention.

Background Gestational diabetes that is not properly controlled with diet has been commonly treated with insulin. In recent years, several studies have published that metformin can lead to, at least, similar obstetrical and perinatal outcomes as insulin. Nevertheless, not all clinical guidelines endorse its use, and clinical practice is heterogeneous. Objective This study aimed to test whether metformin could achieve the same glycemic control as insulin and similar obstetrical and perinatal results, with a good safety profile, in women with gestational diabetes that is not properly controlled with lifestyle changes. Study Design The metformin for gestational diabetes study was a multicenter, open-label, parallel arms, randomized clinical trial performed at 2 hospitals in Malaga (Spain), enrolling women with gestational diabetes who needed pharmacologic treatment. Women at the age of 18 to 45 years, in the second or third trimesters of pregnancy, were randomized to receive metformin or insulin (detemir or aspart). The main outcomes were (1) glycemic control (mean glycemia, preprandial and postprandial) and hypoglycemic episodes and (2) obstetrical and perinatal outcomes and complications (hypertensive disorders, type of labor, prematurity, macrosomia, large for gestational age, neonatal care unit admissions, respiratory distress syndrome, hypoglycemia, jaundice). Outcomes were analyzed on an intention-to-treat basis. Results Between October 2016 and June 2019, 200 women were randomized, 100 to the insulin-treated group and 100 to the metformin-treated group. Mean fasting and postprandial glycemia did not differ between groups, but postprandial glycemia was significantly better after lunch or dinner in the metformin-treated-group. Hypoglycemic episodes were significantly more common in the insulin-treated group (55.9% vs 17.7% on metformin; odds ratio, 6.118; 95% confidence interval, 3.134–11.944; P=.000). Women treated with metformin gained less weight from the enrollment to the prepartum visit (36–37 gestational weeks) (1.35±3.21 vs 3.87±3.50 kg; P=.000). Labor inductions (45.7% [metformin] vs 62.5% [insulin]; odds ratio, 0.506; 95% confidence interval, 0.283–0.903; P=.029) and cesarean deliveries (27.6% [metformin] vs 52.6% [insulin]; odds ratio, 0.345; 95% confidence interval, 0.187–0.625; P=.001) were significantly lower in the metformin-treated group. Mean birthweight, macrosomia, and large for gestational age and babies’ complications were not different between treatment groups. The lower cesarean delivery rate for women treated with metformin was not associated with macrosomia, large or small for gestational age, or other complications of pregnancy. Conclusion Metformin treatment was associated with a better postprandial glycemic control than insulin for some meals, a lower risk of hypoglycemic episodes, less maternal weight gain, and a low rate of failure as an isolated treatment. Most obstetrical and perinatal outcomes were similar between groups.

The interaction between genetic susceptibility, epigenetic, endogenous, and environmental factors play a key role in the initiation and progression of autoimmune thyroid diseases (AITDs). Studies have shown that gut microbiota alterations take part in the development of autoimmune diseases. We have investigated the possible relationship between gut microbiota composition and the most frequent AITDs. A total of nine Hashimoto&rsquo, s thyroiditis (HT), nine Graves&ndash, Basedow&rsquo, s disease (GD), and 11 otherwise healthy donors (HDs) were evaluated. 16S rRNA pyrosequencing and bioinformatics analysis by Quantitative Insights into Microbial Ecology and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) were used to analyze the gut microbiota. Beta diversity analysis showed that gut microbiota from our groups was different. We observed an increase in bacterial richness in HT and a lower evenness in GD in comparison to the HDs. GD showed a significant increase of Fusobacteriaceae, Fusobacterium and Sutterella compared to HDs and the core microbiome features showed that Prevotellaceae and Prevotella characterized this group. Victivallaceae was increased in HT and was part of their core microbiome. Streptococcaceae, Streptococcus and Rikenellaceae were greater in HT compared to GD. Core microbiome features of HT were represented by Streptococcus, Alistipes, Anaerostipes, Dorea and Haemophilus. Faecalibacterium decreased in both AITDs compared to HDs. PICRUSt analysis demonstrated enrichment in the xenobiotics degradation, metabolism, and the metabolism of cofactors and vitamins in GD patients compared to HDs. Moreover, correlation studies showed that some bacteria were widely correlated with autoimmunity parameters. A prediction model evaluated a possible relationship between predominant concrete bacteria such as an unclassified genus of Ruminococcaceae, Sutterella and Faecalibacterium in AITDs. AITD patients present altered gut microbiota compared to HDs. These alterations could be related to the immune system development in AITD patients and the loss of tolerance to self-antigens.

Despite the fact that circulating levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) remain unchanged after fat load in healthy lean individuals, PCSK9 has been suggested to have a role in postprandial lipemia regulation in obese individuals. On the other hand, intestinal permeability and endotoxemia have been observed to increase more in obese individuals than in non-obese individuals after a lipid load. This study aimed to analyze the relationship between PCSK9, intestinal permeability, and endotoxemia after a high fat load in obese individuals. We included 39 individuals with morbid obesity. Serum PCSK9 levels, intestinal permeability marker (zonulin), endotoxemia markers (LPS and LBP), and lipid parameters were measured before and after 3 h of fat load. A significant rise in triglycerides, apolipoprotein A1, zonulin, LPS, and LBP, and a significant decline in PCSK9, were observed after a lipid load. Linear regression analysis showed that low-density lipoprotein cholesterol (LDL-C) was independently related to PCSK9 at baseline, whereas both zonulin and LDL-C were independently related to PCSK9 levels after fat load. A relationship between zonulin and PCSK9 levels after fat load in individuals with morbid obesity may exist.

(1) Background&mdash, low-dose radioiodine ablation is an accepted strategy for the treatment of low- and intermediate-risk thyroid carcinomas, although there is no international consensus. The aim of this study is to describe the clinical experience with low-dose radioiodine ablation in patients with low- and intermediate-risk thyroid cancer compared to high-dose ablation. (2) Methods&mdash, 174 patients with low- and intermediate-risk thyroid cancer, 90 treated with low-dose ablation and 84 treated with high-dose ablation, were included. The primary endpoint was response to treatment one year after ablation, defined by stimulated thyroglobulin, whole body scan and ultrasound imaging. (3) Results&mdash, an excellent response rate of 79.8% in the low-dose group and 85.7% in the high-dose group was observed (p = 0.049). Stimulated thyroglobulin at the moment of ablation (p = 0.032) and positive antithyroglobulin antibodies (p &lt, 0.001) were independent predictive factors for nonexcellent response. Young age (p = 0.023), intermediate initial recurrence risk (p &lt, 0.001) and low-dose ablation (p = 0.004) were independent predictive factors for recurrence. (4) Conclusion&mdash, low-dose ablation seemed to be less effective than high-dose ablation, especially in those patients with positive antithyroglobulin antibodies or higher stimulated thyroglobulin levels at the moment of ablation. Low dose was associated with higher recurrence rates, and lower age and intermediate initial recurrence risk were independent risk factors for recurrence in our sample.

Fish consumption is very high in the European Mediterranean nations since fish is an important component of the Mediterranean diet. Many health benefits have been shown for fish. Amino acids present in fish proteins have been observed to have positive effects, especially on blood pressure and lipid profile. In addition, fish contains minerals such as iodine, calcium, iron, zinc, selenium, or phosphorus and vitamins B, D, A, and K, which are very important for human health. However, the most studied components of fish are polyunsaturated fatty acids, mainly n-3 fatty acids including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), present in oily fish. EPA and DHA have been found to be beneficial in cardiovascular health, lipid profile, inflammation, insulin resistance, neurocognitive disorders, or cancer. Despite some risks that have been observed with fish consumption, they are widely outweighed by benefits.

Objective: To analyze the effect of applying alternative diagnostic criteria for gestational diabetes mellitus (GDM) during the COVID-19 pandemic on GDM prevalence and obstetrical and perinatal outcomes, in comparison to usual diagnostic approaches. Methods: Data from women referred to GDM diagnosis from 1 September to 30 November 2019 were retrospectively collected (2019-group). The same data from the same period in 2020 were prospectively collected (2020-group). In both cases, a two-step diagnostic approach was used, the first step being a screening test (1 h 50 goral glucose tolerance test, OGTT). In 2019 it was followed by a 100 gr OGTT for diagnosis. In 2020, this was replaced by a blood test for the measurement of plasma glucose and HbA1c, according to alternative GDM diagnostic criteria during the COVID-19 pandemic. Results: From 237 women in the 2019 group, 40 (16.9%) were diagnosed with GDM, while from 255 women in the 2020 group, 37 (14.5%) had GDM (p = 0.470). More women in the 2020 group, in comparison to the 2019 group, were nulligravid (41.9% vs. 47.2%, p = 0.013), had a personal history of GDM (11.4% vs. 4.6%, p = 0.013) and had macrosomia in previous pregnancies (10.2% vs. 2.1%, p = 0.001). Obstetrical and perinatal outcomes were similar when comparing women with GDM to non-GDM women in the 2019 and 2020 groups and between GDM women and non-GDM women. Conclusion: In a Spanish population, GDM prevalence during the COVID-19 pandemic using the alternative diagnostic criteria was similar to that found in 2019 using the usual diagnostic criteria. Despite women referred for GDM diagnosis during the pandemic having more GDM risk factors, obstetrical and perinatal outcomes were comparable to those observed before the pandemic.

The aim of this study is to describe our clinical experience with tyrosine kinase inhibitors (TKIs) and to evaluate their efficacy and tolerability in patients with iodine-refractory differentiated thyroid cancer (DTC). There were 17 patients (47.1% women, mean age: 65.7) with DTC iodine-refractory (9 papillary, 2 follicular and 3 Hurthle cell), treated with TKIs: 16 with sorafenib and 1 with lenvatinib as first-line treatment; 7 required second-line treatment (4 lenvatinib and 3 axitinib). Primary endpoints were progression-free survival (PFS) and radiographic response (determinate at 3, 6, 12, 18, and 24 months after the initiation of treatment) and second endpoints were determining differences in baseline characteristics depending on clinical course and describing toxicities and tolerability. Median PFS was 18 months. During the first 24 months of treatment with TKIs PR rate was 35.3% (only 5.8% ≥ 6 months) and SD ≥ 6 months was observed in 58.8%. There were no significant differences in baseline characteristics between patients with good and poor evolution. Adverse events (AEs) were present in 100% of patients, but most of them were grade 1 and 2. In our population of patients with iodine-refractory DTC, treatment with sorafenib, lenvatinib, and axitinib allows the stabilization of the disease in a high percentage of cases, with acceptable tolerability.

Introduction: Thyroid nodules are a common finding. A high-resolution thyroid nodule clinic (HR-TNC) condenses all tests required for the evaluation of thyroid nodules into a single appointment. We aimed to evaluate the clinical outcomes at HR-TNCs. Design and Methods: A retrospective cross-sectional multicenter study including data from four HR-TNCs in Spain. We evaluated fine-needle aspiration (FNA) indications and the association between clinical and ultrasound characteristics with cytological and histopathological outcomes. Results: A total of 2809 thyroid nodules were included, FNA was performed in 82.1%. Thyroid nodules that underwent FNA were more likely larger, isoechoic, with microcalcifications, and in younger subjects. The rate of nondiagnostic FNA was 4.3%. A solid component, irregular margins or microcalcifications, significantly increased the odds of Bethesda IV-V-VI (vs. Bethesda II). Irregular margins and a solid component were independently associated with increased odds of malignancy. Thyroid nodules &lt, 20 mm and &ge, 20&ndash, &lt, 40 mm had a 6.5-fold and 3.3-fold increased risk for malignancy respectively in comparison with those &ge, 40 mm. Conclusion: In this large multicenter study, we found that the presence of a solid component and irregular margins are factors independently related to malignancy in thyroid nodules. Since nodule size &ge, 40 mm was associated with the lowest odds of malignancy, this cut-off should not be a factor leading to indicate thyroid surgery. HR-TNCs were associated with a low rate of nondiagnostic FNA.

Introduction: Obesity has been associated with increased risk of presenting hypogonadism. Free testosterone (FT) is the fraction of testosterone that carries out the biological function of testosterone, and is determined from total testosterone (TT) and sex-hormone binding globulin (SHBG) levels. We aimed to study the SHBG polymorphism rs1799941 in a cohort of young non-diabetic obese males to unravel the possible implication of this polymorphism in obesity-related hypogonadism. Methodology: 212 young (&lt, 45 years) non-diabetic obese (BMI &ge, 30 kg/m2) males participated in this study. Subjects were classified according to TT and FT levels in: Eugonadal (n = 55, TT &gt, 3.5 ng/mL and FT &ge, 70 pg/mL, EuG), normal FT hypogonadism (n = 40, TT &lt, 3.5 and FT &ge, normal FT HG) and hypogonadism (n = 117, TT &lt, 3.5 ng/mL and TL &lt, HG). The SHBG rs1799941 polymorphism (GG/GA/AA) was analyzed using the Taqman Open Array (Applied biosystem). Results: The rs1799941 frequencies were different among the groups. Higher proportion of the allele (A) was found in HG, compared to EuG and normal FT HG. Among the genotypes, the rare homozygous (AA) were found in the normal FT HG group and higher levels of serum SHBG and lower of FT were observed. The presence of the allele A was related (according to lineal regression models) to an increased of SHBG levels ((GA) &beta, = 3.28, (AA) &beta, = 12.45) and a decreased of FT levels ((GA) &beta, = &minus, 9.19, 18.52). The presence of the allele (A) increased the risk of presenting HG compared to normal FT HG (OR = 2.54). Conclusions: The rs1799941 of the SHBG gene can partially determine the presence of obesity-related hypogonadism in young non-diabetic males and whether these subjects have normal FT HG.

Obesity-associated hypoandrogenemia is increasing in parallel to the obesity epidemic. The prevalence of hypoandrogenemia in nondiabetic young men with obesity is not known. This study aimed to evaluate the prevalence of hypoandrogenemia and associated risk factors in this population.This cross-sectional study included 266 nondiabetic men 50 years of age with obesity who were referred from primary care. Total testosterone (high-performance liquid chromatography mass spectrometry), sex hormone-binding globulin, free testosterone (FT), luteinizing hormone (LH), high-sensitivity C-reactive protein, and homeostatic model assessment of insulin resistance were determined. Body composition and erectile function were also assessed. Hypoandrogenemia was defined as FT level 70 pg/mL.Subnormal FT concentrations were found in 25.6% of participants. Hypoandrogenemia prevalence was different along the BMI continuum, being 75% in individuals with BMI ≥ 50 kg/mIn a primary care-based cohort of nondiabetic young men with obesity, hypoandrogenemia was a very prevalent finding and was directly associated with adiposity. Obesity, age, and reduced LH levels were independent risk factors associated with hypoandrogenemia. Further prospective studies are needed to evaluate the long-term consequences of hypoandrogenemia in this population.

Background Monoamine oxidase (MAO) activity has been traditionally implicated in blood pressure through its effects on biogenic amine levels such as catecholamines, serotonin, and dopamine. Nowadays, this role is considered relegated to side‐effects such as orthostatic hypotension and/or hypertensive crisis derived from MAO‐inhibitory treatments in patients with psychiatric disease. Methods In the present work we have found an association between a polymorphic variant of MAOB gene and arterial hypertension in obese hypogonadic patients. The study cases comprised a series of 219 nondiabetic males with a body mass index ≥30 kg/m2 and aged, Male hypogonadism is a disorder in which the testes are not functional or there is a genetic inability of the hypothalamus to secrete normal amounts of GnRH. The masculine sexual characteristics are not developed and can bring a wide range of clinical manifestations. We have found an association between a polymorphic variant of MAOB gene and arterial hypertension in obese hypogonadic patients.

Introduction Lack of control in diabetic patients has stimulated the development of new insulin analogues. One of these was basal insulin peglispro (BIL) or LY2605541; it had a large hydrodynamic size, flat pharmacokinetic profile, half life of 2–3 days and acted preferably in the liver. Methods We reviewed the recent literature examining the pharmacokinetics, pharmacodynamics, efficacy and safety of BIL treatment in type 2 diabetes patients. Results The pharmacodynamic and pharmacokinetic outline of BIL seemed to have an advantage over neutral protamine Hagedorn and glargine insulins. Recently, phase 3 studies suggested BIL was superior to glargine in reducing glucose levels in type 1 and type 2 diabetes patients in addition to causing less weight gain. It showed a different hypoglycaemia rate profile depending on the study population, with less nocturnal hypoglycaemia compared to glargine. Unfortunately, it caused higher transaminase and triglyceride levels, which led the company to discontinue development. The decision came after it had been analysed by the regulatory authorities and other external experts concerning the worse liver profile data from the IMAGINE trials. Conclusions BIL was an adequate basal insulin analogue with interesting specific properties. Unfortunately the disadvantages as shown in the lipid values and liver function tests led to its failure.

Obesity is associated with decreased circulating testosterone levels, the main male sex hormone. However, there are a number of different male sex hormones whose dynamics remain poorly understood regarding this pathology. In this regard, 17 hydroxyprogesterone (17-OH progesterone), as an important precursor of testosterone synthetized in testes and adrenal glands, could play an essential role in testosterone deficiency in male obesity. Moreover, similarly to testosterone, 17-OH progesterone could be closely associated with visceral fat distribution and metabolic dysfunction. Thus, the aim of this study was to assess serum 17-OH progesterone levels in non-diabetic obese young men and to evaluate their relationship with clinical, analytical, and anthropometric parameters. We conducted a cross-sectional study including 266 non-diabetic men with obesity (BMI &ge, 30 kg/m2) aged 18&ndash, 49 years, 17-OH progesterone and total testosterone (TT) were determined by high-performance liquid chromatography mass spectrometry. 17-OH progesterone levels were significantly lower in tertile 3 of body fat percentage in comparison with tertile 1 (0.74 ng/mL vs. 0.94 ng/mL, p &lt, 0.01, Bonferroni correction) and in comparison with tertile 2 (0.74 ng/mL vs. 0.89 ng/mL, p = 0.02, Bonferroni correction). 17-OH progesterone levels correlated negatively with weight, BMI, waist circumference, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), and visceral fat, and positively with TT, free testosterone (FT), luteinizing hormone, and fat-free mass percentage. Multivariate linear-regression analysis showed that body fat percentage and HOMA-IR were inversely associated with 17-OH progesterone levels, while FT and ACTH were positively linked to circulating 17-OH progesterone levels. In conclusion, in a population of non-diabetic obese young men, 17-OH progesterone levels were inversely associated with adiposity. Body fat percentage and insulin resistance were negatively related to 17-OH progesterone levels, whereas FT and ACTH levels were positively associated with 17-OH progesterone levels.

Environmental temperature has been described to affect plasma glucose levels after oral glucose tolerance testing (OGTT).We evaluated the relationship between seasons and environmental temperature and gestational diabetes mellitus (GDM) diagnosis and treatment.We analyzed data from 2374 women retrospectively. GDM was diagnosed in 473 patients by a 100-g OGTT. OGTT results and needing of insulin therapy were evaluated in relation to seasons and environmental temperature (mean temperature and temperature change) the day of the OGTT and the preceding 14 and 28 days.We found significant seasonal differences in the percentage of GDM: 24.4% in summer vs. 15.6% in autumn (p 0.01). The odds ratio (OR) for being diagnosed with GDM was 1.78 in summer relative to autumn, after controlling for age. A higher mean temperature the day of the OGTT and the preceding 14 and 28 days increased the risk of being diagnosed with GDM the months in which temperature was rising (March-August) but not the months in which temperature was decreasing (September-February). We observed a negative correlation between temperature and fasting glucose and a positive correlation with post-load glucose. Neither the season nor the environmental temperature affected the risk of requiring insulin therapy.There is a higher prevalence of GDM diagnosis at warmer seasons and at rising temperatures the 2-4 weeks prior to the OGTT. The impact of temperature is different between fasting and post-load glucose.

Type 2 diabetes (T2D), a multifactorial and chronic disease, requires in an elevated percentage of patients the association of several antidiabetic drugs to achieve optimal glycemic control. Dipeptidyl peptidase-4 inhibitors (DPP-4i) and sodium-glucose cotransporter inhibitors (SGLT2i) are new classes of oral antidiabetic drugs developed over the last years.This paper summarizes the safety of DPP-4i and SGLT2i combination therapies. Relevant studies were identified through searches in PubMed.DPP4i and SGLT2i are antidiabetic drugs that lower blood glucose without causing hypoglycaemia or weight increase. More importantly, cardiovascular trials have clearly demonstrated the cardiovascular safety of DPP4i and a reduction in cardiovascular events with SGLT2i (empagliflozin and canagliflozin). Therefore, the association of both therapeutic groups could be an attractive option to achieve optimal blood glucose control in T2D because of their complementary mechanism of action. Clinical trials evaluating the combination of SGLT2i and DPP4i show that the co-administration of these drugs in fixed-dose combinations in comparison to separate tablets does not carry additional safety concerns that each individual drug, but increases therapeutic effects. Therefore, this antidiabetic combination is a safe and effective therapy for patients with T2D.

Prader⁻Willi syndrome (PWS) is a complex genetic disorder that, besides cognitive impairments, is characterized by hyperphagia, obesity, hypogonadism, and growth impairment. Proprotein convertase subtilisin/kexin type 1 (PCSK1) deficiency, a rare recessive congenital disorder, partially overlaps phenotypically with PWS, but both genetic disorders show clear dissimilarities as well. The recent observation that PCSK1 is downregulated in a model of human PWS suggests that overlapping pathways are affected. In this review we will not only discuss the mechanisms by which PWS and PCSK1 deficiency could lead to hyperphagia but also the therapeutic interventions to treat obesity in both genetic disorders. ispartof: GENES vol:9 issue:6 ispartof: location:Switzerland status: published

Background: In patients with nutritional risk, the European Society for Clinical Nutrition and Metabolism (ESPEN) recommends nutritional supplements during cancer treatment to prevent weight loss. Objectives: Our goal is to determine the acceptability, compliance and tolerance of a hyperproteic, high-calorie, omega-3 enriched supplement in cancer patients. Methods: Unicentric, prospective observational study in cancer patients with hyperproteic, high-calorie, rich in omega 3 and low volume nutritional supplement. Thirty patients with malnutrition or risk of malnutrition were included. Supplementation lasted six days. Compliance (packaging used), acceptability (Madrid scale), anthropometric variables and gastrointestinal adverse events (AEs) were evaluated. Results: Seventy per cent were men, with an average age of 60 years (range 32-79), with lung (43.3%), ENT (26.7%) and breast neoplasms (13.3%), stage III-IV (56.7%), and treated with radiotherapy (93.3%), chemotherapy (60%) and surgery (16.7%). The product was accepted by all patients. A compliance rate of 100% was observed. Gastrointestinal AE (grade II) related to the supplement was observed in two patients (6.7%). Both subjects had previous gastrointestinal diseases. The median weight, body mass index (BMI) and protein intake increased during supplementation (0.2 kg, 0.1 kg/m2 and 6.2 g). No differences were observed regarding calorie, fat and carbohydrates intake. Conclusion: The high acceptance and compliance with the specific nutritional supplement was associated with an improved nutritional status for cancer patients, and reversed the weight loss without severe gastrointestinal problems, or producing intake displacement.Introducción: en pacientes con riesgo nutricional, la Sociedad Europea de Clínica y Metabolismo (ESPEN) y Parenteral recomienda suplementos nutricionales durante el tratamiento oncológico para prevenir la pérdida de peso involuntaria. Objetivos: nuestro objetivo es conocer el cumplimiento, la aceptabilidad y la tolerancia de un suplemento hiperproteico, hipercalórico, rico en omega 3 en pacientes oncológicos. Métodos: estudio unicéntrico, observacional y prospectivo en pacientes oncológicos con un suplemento nutricional hiperproteico, hipercalórico, rico en omega 3 y de bajo volumen. Fueron incluidos 30 pacientes con desnutrición o en riesgo de desnutrición. La suplementación duró seis días. Se evaluaron el cumplimiento (envases utilizado), la aceptabilidad (escala Madrid), las variables antropométricas y los acontecimientos adversos (AA) gastrointestinales. Resultados: el 70% fueron hombres, con una edad media de 60 años (rango: 32 a 79) y con neoplasias de pulmón (43,3%), ORL (26,7%) y mama (13,3%), en estadio III-IV (56,7%), tratados con radioterapia (93,3%), quimioterapia (60%) y cirugía (16,7%). El producto fue aceptado por todos los pacientes. Se observó un cumplimiento del 100%. En dos pacientes (6,7%) se observaron AA gastrointestinales (grado II) relacionados con el suplemento; ambos sujetos presentaban patologías gastrointestinales previas. La mediana del peso, índice de masa corporal (IMC) y proteínas ingeridas aumentó durante la suplementación (0,2 kg, 0,1 kg/m2 y 6,2 g). No se observaron diferencias respecto a la ingesta de calorías, lípidos y carbohidratos. Conclusión: la elevada aceptación y cumplimiento del suplemento nutricional específico se asoció con la mejora nutricional de los pacientes oncológicos, pues revirtió la pérdida de peso, sin presentar problemas gastrointestinales severos ni producir desplazamiento de la ingesta.

Male hypogonadism associated with obesity is a very prevalent condition and is increasing in parallel with the epidemic prevalence of obesity. Low testosterone levels promote higher fat mass with reduced lean mass. Male hypogonadism is related to an increase in associated cardiometabolic complications, such as hypertension, type 2 diabetes mellitus, the metabolic syndrome, and cardiovascular disease. Its influence as a comorbidity of obesity is becoming more evident and should be evaluated and treated in at-risk patients. Mechanisms involved in this relationship include body composition changes, the presence of adipokines, insulin resistance, and other factors, some of which are still unknown. Weight loss and treatment to replace testosterone levels improve the metabolic profile and quality of life in patients with obesity and hypogonadism; these beneficial effects depend on treatment modality and duration of therapy. The use of testosterone replacement therapy may be indicated, as it has not been shown to increase cardiovascular risk, and retrospective studies suggest a reduction in events in men with metabolic syndrome and type 2 diabetes.