Prediabetes remission after bariatric surgery: a 4-years follow-up study.

BACKGROUND: Bariatric surgery leads to weight loss and to cardiometabolic risk improvement. Although prediabetes remission after bariatric surgery is biologically plausible, data on this topic is scarce. We aimed to assess prediabetes remission rate and clinical predictors of remission in a 4 year follow up period. METHODS: Observational longitudinal study including patients with obesity and prediabetes who had undergone bariatric surgery in our centre. Prediabetes was defined as having a baseline glycated haemoglobin (A1c) between 5.7% and 6.4% and absence of anti-diabetic drug treatment. We used logistic regression models to evaluate the association between the predictors and prediabetes remission rate. RESULTS: A total of 669 patients were included, 84% being female. The population had a mean age of 45.4 ± 10.1 years-old, body mass index of 43.8 ± 5.7 kg/m2, and median A1c of 5.9 [5.8, 6.1]%. After bariatric surgery, prediabetes remission rate was 82%, 73%, 66%, and 58%, respectively in the 1st, 2nd, 3rd, and 4th years of follow-up. Gastric sleeve (GS) surgery was associated with higher prediabetes remission rate than Roux-en-Y gastric bypass surgery in the 3rd year of follow-up. Men had a higher remission rate than women, in the 1st and 3nd years of follow-up in the unadjusted analysis. Younger patients presented a higher remission rate comparing to older patients in the 3rd year of follow-up. CONCLUSION: We showed a high prediabetes remission rate after bariatric surgery. The remission rate decreases over the follow-up period, although most of the patients maintain the normoglycemia. Prediabetes remission seems to be more significant in patients who had undergone GS, in male and in younger patients.

Changes in attitudes to awareness of hypoglycaemia during a hypoglycaemia awareness restoration programme are associated with avoidance of further severe hypoglycaemia episodes within 24 months: the A2A in HypoCOMPaSS study.

AIMS/HYPOTHESIS: The aims of this study were to assess cognitions relating to hypoglycaemia in adults with type 1 diabetes and impaired awareness of hypoglycaemia before and after the multimodal HypoCOMPaSS intervention, and to determine cognitive predictors of incomplete response (one or more severe hypoglycaemic episodes over 24 months). METHODS: This analysis included 91 adults with type 1 diabetes and impaired awareness of hypoglycaemia who completed the Attitudes to Awareness of Hypoglycaemia (A2A) questionnaire before, 24 weeks and 24 months after the intervention, which comprised a short psycho-educational programme with optimisation of insulin therapy and glucose monitoring. RESULTS: The age and diabetes duration of the participants were 48±12 and 29±12 years, respectively (mean±SD). At baseline, 91% reported one or more severe hypoglycaemic episodes over the preceding 12 months; this decreased to <20% at 24 weeks and after 24 months (p=0.001). The attitudinal barrier 'hyperglycaemia avoidance prioritised' (η2p=0.250, p=0.001) decreased from baseline to 24 weeks, and this decrease was maintained at 24 months (mean±SD=5.3±0.3 vs 4.3±0.3 vs 4.0±0.3). The decrease in 'asymptomatic hypoglycaemia normalised' from baseline (η2p=0.113, p=0.045) was significant at 24 weeks (1.5±0.3 vs 0.8±0.2). Predictors of incomplete hypoglycaemia response (one or more further episodes of severe hypoglycaemia) were higher baseline rates of severe hypoglycaemia, higher baseline scores for 'asymptomatic hypoglycaemia normalised', reduced change in 'asymptomatic hypoglycaemia normalised' scores at 24 weeks, and lower baseline 'hypoglycaemia concern minimised' scores (all p<0.05). CONCLUSIONS/INTERPRETATION: Participation in the HypoCOMPaSS RCT was associated with improvements in hypoglycaemia-associated cognitions, with 'hyperglycaemia avoidance prioritised' most prevalent. Incomplete prevention of subsequent severe hypoglycaemia episodes was associated with persistence of the cognition 'asymptomatic hypoglycaemia normalised'. Understanding and addressing cognitive barriers to hypoglycaemia avoidance is important in individuals prone to severe hypoglycaemia episodes. CLINICAL TRIALS REGISTRATION: www.isrctn.org : ISRCTN52164803 and https://eudract.ema.europa.eu : EudraCT2009-015396-27.

Magnetic resonance imaging as a predictor of therapeutic response to pasireotide in acromegaly.

OBJECTIVE: Hyperintensity signal in T2-weighted magnetic resonance imaging (MRI) has been related to better therapeutic response during pasireotide treatment in acromegaly. The aim of the study was to evaluate T2 MRI signal intensity and its relation with pasireotide therapeutic effectiveness in real-life clinical practice. DESIGN, PATIENTS AND MEASUREMENTS: Retrospective multicentre study including acromegaly patients treated with pasireotide. Adenoma T2-weighted MRI signal at diagnosis was qualitatively classified as iso-hyperintense or hypointense. Insulin-like growth factor (IGF-I), growth hormone (GH) and tumour volume reduction were assessed after 6 and 12 months of treatment and its effectiveness evaluated according to baseline MRI signal. Hormonal response was considered 'complete' when normalization of IGF-I levels was achieved. Significant tumour shrinkage was defined as a volume reduction of ≥25% from baseline. RESULTS: Eighty-one patients were included (48% women, 50 ± 1.5 years); 93% had previously received somatostatin receptor ligands (SRLs) treatment. MRI signal was hypointense in 25 (31%) and hyperintense in 56 (69%) cases. At 12 months of follow-up, 42/73 cases (58%) showed normalization of IGF-I and 37% both GH and IGF-I. MRI signal intensity was not associated with hormonal control. 19/51 cases (37%) presented a significant tumour volume shrinkage, 16 (41%) from the hyperintense group and 3 (25%) from the hypointense. CONCLUSIONS: T2-signal hyperintensity was more frequently observed in pasireotide treated patients. Almost 60% of SRLs resistant patients showed a complete normalization of IGF-I after 1 year of pasireotide treatment, regardless of the MRI signal. There was also no difference in the percentage tumour shrinkage over basal residual volume between the two groups.

Glucagon-like peptide 1 receptor agonists in patients with type 2 diabetes with and without chronic heart failure: A meta-analysis of randomized placebo-controlled outcome trials.

AIM: Glucagon-like peptide 1 receptor agonists (GLP1-RA) reduce atherosclerotic events in patients with type 2 diabetes (T2D) and a high cardiovascular risk. The effect of GLP1-RA to reduce heart failure (HF) has been inconsistent across T2D trials, and individual trials were underpowered to assess the effect of GLP1-RA according to HF history. In this meta-analysis we aim to assess the effect of GLP1-RA in patients with and without HF history in stable ambulatory patients with T2D. METHODS: Random-effects meta-analysis of placebo-controlled trials. The hazard ratio (HR) and 95% confidence intervals (95% CI) were extracted from the treatment effect estimates of HF subgroup analyses reported in each individual study. The primary outcome was a composite of HF hospitalization or cardiovascular death. RESULTS: In total, 54 092 patients with T2D from seven randomized controlled trials were included, of whom 8460 (16%) had HF history. Compared with placebo, GLP1-RA did not reduce the composite of HF hospitalization or cardiovascular death in patients with HF history: HR 0.96, 95% CI: 0.84-1.08, but reduced this outcome in patients without HF history: HR 0.84, 95% CI: 0.76-0.92. GLP1-RA did not reduce all-cause death in patients with HF history: HR 0.98, 95% CI: 0.86-1.11, but reduced mortality in patients without HF history: HR 0.85, 95% CI: 0.79-0.92. GLP1-RA reduced atherosclerotic events regardless of HF history: HR 0.85, 95% CI: 0.75-0.97 with HF, and HR 0.88, 95% CI: 0.83-0.93 without HF. CONCLUSIONS: Treatment with GLP1-RA did not reduce HF hospitalizations and mortality in patients with concomitant T2D and HF, but may prevent new-onset HF and mortality in patients with T2D without HF. The reduction of atherosclerotic events with GLP1-RA was not influenced by HF history status.

Risk of adverse events with liraglutide in heart failure with reduced ejection fraction: A post hoc analysis of the FIGHT trial.

AIM: To perform a post hoc analysis of the FIGHT trial, evaluating the effect of liraglutide (vs. placebo) on the totality of events in patients with heart failure with reduced ejection fraction (HFrEF). MATERIALS AND METHODS: FIGHT was a double-blind randomized controlled trial (RCT) that studied liraglutide versus placebo in 300 recently hospitalized patients with HFrEF followed for 180 days. The main outcome of the present analysis was total events of hospitalizations for heart failure (HF) or all-cause death. Secondary outcomes included total arrhythmic events and prespecified total events of interest (arrhythmias, sudden cardiac death, acute coronary syndrome, worsening HF, cerebrovascular event, venous thromboembolism, lightheadedness, presyncope/syncope or worsening renal function). Treatment effect was evaluated with negative binomial regression. RESULTS: Compared to placebo, there was a trend towards increased risk with liraglutide of total HF hospitalizations or all-cause deaths (96 vs. 143 events, incidence rate ratio [IRR] 1.41, 95% confidence interval [CI] 0.98-2.04; P = 0.064) and total arrhythmias (21 vs. 39, IRR 1.76, 95% CI 0.92-3.37; P = 0.088). Total prespecified events of interest were increased with liraglutide compared to placebo (196 vs. 295, IRR 1.43, 95% CI 1.06-1.92; P = 0.018). The risk of HF hospitalizations or all-cause deaths with liraglutide was higher among patients in New York Heart Association (NYHA) Class III to IV (IRR 1.86, 95% CI 1.21-2.85) than in those in NYHA Class I to II (IRR 0.62, 95% CI 0.31-1.23; interaction P = 0.008), and among patients with diabetes (interaction P = 0.051). The risk of arrhythmic events was higher among those without an implanted cardiac device (interaction P = 0.047). CONCLUSIONS: In patients with HFrEF, liraglutide might increase the risk of cardiovascular adverse effects, an effect possibly driven by excess risk of arrhythmias and worsening HF events. As this was a post hoc analysis, these results should be interpreted as exploratory and hypothesis-generating. Further RCTs must be conducted before drawing definitive conclusions.

The effect of high-voltage monophasic pulsed current on diabetic ulcers and their potential pathophysiologic factors: A systematic review and meta-analysis.

The present review was conducted to determine the efficacy of high-voltage monophasic pulsed current (HVMPC) in treating diabetic ulcers, assess its effect on skin lesions with each of the pathophysiologic factors potentially contributing to diabetic ulcers, evaluate its safety, and identify treatment parameters. Electronic search of PubMed, Scopus, PEDro and Google Scholar databases was conducted. The revised tool for assessing risk of bias in randomised trials (RoB 2), the risk of bias in non-randomised studies-of interventions (ROBINS-I) and the Joanna Briggs Institute (JBI) critical appraisal tool were used to assess risk of bias and methodological quality. Overall quality of evidence was determined using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principles. Thirty-two studies matched the eligibility criteria, and included 1061 patients with 1103 skin lesions of selected aetiologies; 12 randomised controlled trials were included in quantitative synthesis. HVMPC plus standard wound care (SWC) likely increased the probability of complete wound healing of pressure ulcers (PrUs) compared with sham/no stimulation plus SWC; relative risk (RR) 2.08; 95% CI: [1.42, 3.04], p = 0.0002; I2  = 0%, p = 0.61; eight studies, 358 ulcers. Although conclusive evidence regarding the effect of HVMPC on diabetic ulcers was not found, collateral evidence might suggest a potential benefit. Direct evidence, with moderate certainty, may support its efficacy in treating PrUs, albeit few adverse reactions were reported. Other observations, moreover, might indicate that this efficacy may not be limited to PrUs. Nonetheless, several aspects remain to be clarified for safe and effective application of electrical stimulation for wound healing.

The Impact of Bariatric Surgery on Bone Health: State of the Art and New Recognized Links.

Bariatric surgery (BS) is the most effective therapy for severe obesity, which improves several comorbidities (such as diabetes, hypertension, dyslipidemia, among others) and results in marked weight loss. Despite these consensual beneficial effects, sleeve gastrectomy and Roux-en-Y gastric bypass (the two main bariatric techniques) have also been associated with changes in bone metabolism and progressive bone loss. The objective of this literature review is to examine the impact of bariatric surgery on bone and its main metabolic links, and to analyze the latest findings regarding the risk of fracture among patients submitted to bariatric surgery.

Influence of diabetes on response to ultrasound guided hydrodistension treatment of adhesive capsulitis: a retrospective study.

BACKGROUND: Diabetes is associated with microvascular and macrovascular complications. Although it is less recognized, diabetes also has an important role in the development of musculoskeletal disorders. Our objective was to evaluate the effect of type 2 diabetes (T2D) on the severity of adhesive capsulitis of the shoulder (AC) and on the efficacy of ultrasound guided hydrodistension treatment. METHODS: We conducted a retrospective longitudinal observational study, of patients with AC who underwent ultrasound guided hydrodistension at our Centre. Severity was measured with DASH (Disabilities of Arm, Shoulder and Hand) score and pain was evaluated with a score between 0 and 10. The association of T2D with baseline characteristics of AC, and with outcomes at 6-12 months was analyzed using linear and logistic regression models. RESULTS: We evaluated 120 ultrasound guided hydrodistension treatments of AC, 85 in patients without diabetes and 35 in patients with T2D. Patients with diabetes had a higher prevalence of dyslipidemia, hypertension and higher HbA1c values. The average duration of diabetes was 4.8 years (2.0, 7.9). The baseline characteristics of AC were not significantly different between patients with and without diabetes. Patients with T2D relapsed more frequently and required more reinterventions than patients without diabetes (20.0% vs 4.7%, p = 0.008), had higher post-intervention pain scale values [4.0 (0.0-5.0) vs 0.0 (0.0-5.0), p = 0.022] and higher post-intervention DASH score [0.8 (0.0-1.8) vs 0.0 (0.0-0.8), p = 0.038]. CONCLUSION: Although baseline characteristics of AC in patients with diabetes were similar to those without diabetes, patients with diabetes had a worse response to treatment, more frequent relapses and a greater need for new interventions.

A Common Variant in the CDK8 Gene Is Associated with Sporadic Pituitary Adenomas in the Portuguese Population: A Case-Control Study.

The majority of pituitary adenomas occur in a sporadic context, and in the absence of known genetic predisposition. Three common variants at the NEBL (rs2359536), PCDH15 (rs10763170) and CDK8 (rs17083838) loci were previously associated with sporadic pituitary adenomas in the Han Chinese population, but these findings have not yet been replicated in any other population. The aim of this case-control study was to assess if these variants are associated with susceptibility to sporadic pituitary adenomas in the Portuguese population. Genotype and allele frequencies were determined in 570 cases and in 546 controls. The CDK8 rs17083838 minor allele (A allele) was significantly associated with sporadic pituitary adenomas, under an additive (odds ratio (OR) 1.73, 95% confidence interval (CI) 1.19-2.50, p = 0.004) and dominant (OR 1.82, 95% CI 1.24-2.68, p = 0.002) inheritance model. The NEBL rs2359536 and PCDH15 rs10763170 variants were not associated with the overall risk for the disease, although a borderline significant association was observed between the PCDH15 rs10763170 minor allele (T allele) and somatotrophinomas (dominant model, OR 1.55, 95% CI 1.02-2.35, p = 0.035). These findings suggest that the CDK8 rs17083838 variant, and possibly the PCDH15 rs10763170 variant, may increase susceptibility to sporadic pituitary adenomas in the Portuguese population.

Effects of sodium-glucose co-transporter 2 inhibitors on liver parameters and steatosis: A meta-analysis of randomized clinical trials.

AIMS: Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in Western countries and a common comorbidity with type 2 diabetes (T2D). It lacks effective pharmacotherapy. We aimed to summarize the evidence on the effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on liver structure and function. MATERIALS AND METHODS: Meta-analysis of randomized clinical trials in PubMed, Web of Science and ClinicalTrials.gov from their inception to April 2019. Trials evaluating liver function and/or structure and comparing SGLT2 inhibitors with placebo or other oral antidiabetic drugs in patients with T2D were included. Twenty studies (from 3033) were included. A total of 1950 patients with T2D, with or without NAFLD, were treated with SGLT2 inhibitors for at least 8 weeks, and 1900 patients were used as controls. Independent extraction was carried out by two observers. This study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis. RESULTS: SGLT2 inhibitors induced a significant decrease in serum alanine (-7.43U/L, [95%CI -12.14, -2.71], p < 0.01), in aspartate aminotransferases (-2.83U/L, [-4.71, -0.95], p < 0.01), as well as in gamma glutamyl transferase (-8.21U/L, [-9.52, -6.91], p < 0.01), and an increase in total plasma bilirubin (8.19% [0.79, 15.59], p < 0.01), comparing with placebo or other oral antidiabetic drugs. SGLT2 inhibitors treatment was associated with a decrease in liver steatosis (-3.39% [-6.01, -0.77], p < 0.0.1). CONCLUSIONS: Treatment with SGLT2 inhibitors improves liver structure and function in patients with T2D. This meta-analysis suggests that SGLT2 inhibitors are a promising pharmacological approach for treatment of NAFLD.

Sodium-Glucose Co-transporter 2 Inhibitors in the Failing Heart: a Growing Potential.

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a new drug class designed to treat patients with type 2 diabetes (T2D). However, cardiovascular outcome trials showed that SGLT2i also offer protection against heart failure (HF)-related events and cardiovascular mortality. These benefits appear to be independent of glycaemic control and have recently been demonstrated in the HF population with reduced ejection fraction (HFrEF), with or without T2D. This comprehensive, evidence-based review focuses on the published studies concerning HF outcomes with SGLT2i, discussing issues that may underlie the different results, along with the impact of these new drugs in clinical practice. The potential translational mechanisms behind SGLT2i cardio-renal benefits and the information that ongoing studies may add to the already existing body of evidence are also reviewed. Finally, we focus on practical management issues regarding SGLT2i use in association with other T2D and HFrEF common pharmacological therapies. Safety considerations are also highlighted. Considering the paradigm shift in T2D management, from a focus on glycaemic control to a broader approach on cardiovascular protection and event reduction, including the potential for wide SGLT2i implementation in HF patients, with or without T2D, we are facing a promising time for major changes in the global management of cardiovascular disease.

Dopamine agonists in prolactinomas: when to withdraw?

Dopamine agonists (DAs) are well recognized as the first-line therapy for prolactinomas due to their efficacy in achieving tumoral shrinkage and normoprolactinemia. However, it remains to be established the best timing to withdraw DAs and in which patients this should be attempted. Studies in the 1980s, mainly using bromocriptine, started to defy the concept that DAs should be regarded as a lifelong therapy considering that sustained normoprolactinemia was attained in a small subset of patients after drug withdrawal. The introduction of the more effective agent cabergoline led to an increase in the percentages of remission. The most recent meta-analysis on the topic stated than remission rates after withdrawal can range from 15% in macroprolactinoma patients treated with bromocriptine to 41% in those with microprolactinomas previously treated with cabergoline. When more stringent criteria were applied before attempting withdrawal, sustained remission ensued in more than 50% of the individuals. Treatment duration for more than 24 months, the achievement of normoprolactinemia, marked reduction (≥ 50%) in tumoral size and DAs tapering till a low maintenance dose (e.g. cabergoline 0.5 mg/week) have been the most consistently identified predictors of success. In addition, a growing amount of evidence suggests that the post-pregnancy/breastfeeding period and menopause are reasonable timings to re-access the need for continuing DAs therapy. Considering that the achievement of sustained normoprolactinemia is still far from being universal after the withdrawal, even in highly selected cohorts, future larger prospective studies should continue to address this issue.

Long-term diabetes outcomes after bariatric surgery-managing medication withdrawl.

BACKGROUND/OBJECTIVES: Bariatric surgery leads to type 2 diabetes mellitus (T2DM) remission, but recurrence can ensue afterwards. However, literature provides heterogenous remission/recurrence criteria and there is no consensus on long-term T2DM management after surgery. We aim to assess T2DM remission/recurrence rates using standardized criteria and to identify relapse predictors. We also intend to analyze the management of residual T2DM and the impact of maintaining/withdrawing metformin in avoiding future relapse. SUBJECTS/METHODS: We investigated a cohort of 110 obese patients with T2DM who underwent bariatric surgery and were followed for 5 years (Y0-Y5). Patients who ever attained remission were accounted for cumulate remission, while prevalent remission was considered for individuals who were on remission in a specific visit. RESULTS: A complete prevalent remission of 47.3% was reached at Y1 and it remained stable till Y5 (46.4-48.2%). Complete cumulative rate was of 57.3% at Y5. Five-year T2DM recurrence rate was 15.9% and it was associated with higher pre-operative HbA1c levels (ß = 1.06; p < 0.05) and a milder excess body weight loss (EBWL) (ß = 0.49; p < 0.05). Glucose-lowering agents were fully stopped in 51.4% of the patients till Y1 and in 16.2% of them afterwards. Medication withdrawal was mainly attempted in patients with a lower baseline HbA1c (ß = 0.54; p < 0.01) and higher first-year EBWL (ß = 1.04; p < 0.01). Patients that kept metformin after reaching a HbA1c in the complete remission range (<6.0%) did not have greater odds of avoiding relapse in the next visit (OR = 0.33; p = 0.08). CONCLUSIONS: Baseline HbA1c and EBWL were the main variables driving both T2DM relapse after bariatric surgery and the attempt to withdrawal anti-diabetic medication. In our population keeping metformin once an HbA1c < 6.0% is achieved did not seem to diminish relapse but further studies on this matter are needed.

Preoperative thyroid function and weight loss after bariatric surgery.

Thyroid function has an important role on body weight regulation. However, the impact of thyroid function on weight loss after bariatric surgery is still largely unknown. We evaluated the association between preoperative thyroid function and the excess weight loss 1 year after surgery, in 641 patients with morbid obesity who underwent bariatric surgery. Patients with a history of thyroid disease, treatment with thyroid hormone or antithyroid drugs and those with preoperative evaluation consistent with overt hypothyroidism or hyperthyroidism were excluded. The preoperative levels of TSH and FT4 were not associated with weight loss after bariatric surgery. The variation of FT3 within the reference range was also not associated with weight loss. In contrast, the subgroup with FT3 above the reference range (12.3% of patients) had a significantly higher excess weight loss than patients with normal FT3. This difference remained significant after adjustment for age, sex, BMI, type of surgery, TSH and FT4. In conclusion, we observed an association between high FT3 and a greater weight loss after bariatric surgery, highlighting a group of patients with an increased benefit from this intervention. Our results also suggest a novel hypothesis: the pharmacological modulation of thyroid function may be a potential therapeutic target in patients undergoing bariatric surgery.

Pituitary incidentalomas in paediatric age are different from those described in adulthood.

PURPOSE: Guidelines on pituitary incidentalomas evaluation and management are limited to adults since there are no data on this matter in the paediatric population. We aim to analyse the morphologic characteristics, hormonal profile and follow-up of these lesions in children. METHODS: We have searched for pituitary incidentalomas in the neuroimaging reports and electronic medical records of the Paediatric Endocrinology Clinic of our centre. Patients with 18 years-old or less were included. RESULTS: Forty-one incidentalomas were identified, 25 of them (62.4%) in females. The mean age at diagnosis was 12.0 ± 4.96 years-old. Headaches were the main reason that led to image acquisition (51.2%) and MRI was the imaging method that detected the majority of the incidentalomas (70.7%). The most prevalent lesion was pituitary hypertrophy (29.3%), which was mainly diagnosed in female adolescents (91.7%), followed by arachnoid cysts (17.1%), pituitary adenomas (14.6%) and Rathke's cleft cysts (12.2%). Most patients (90.2%) did not present clinical or laboratorial findings of hypopituitarism or hormonal hypersecretion. Four patients presented endocrine dysfunction: three had growth hormone deficiency and one had a central precocious puberty. Twenty-three patients (56.1%) underwent imagiological revaluation during a median follow-up time of 24.6 months (interquartile range 5.07). None of them presented dimensional progression. CONCLUSIONS: To the best of our knowledge, this is the first series of pituitary incidentalomas in pediatric age. Comparing our series with those conducted in adults, we have observed a higher preponderance of pituitary hypertrophy over adenomas, a lower prevalence of hormonal hyper/hyposecretion and lower risk of dimensional progression during follow-up.

Intergenerational transmission of war-related trauma assessed 40 years after exposure.

BACKGROUND: The intergenerational transmission of posttraumatic stress disorder (PTSD) from parent to offspring has been suggested in the literature, but this is highly controversial. We aimed to study the association between veterans' war exposure and lifetime PTSD and the psychological characteristics of their respective offspring, 40 years after war-related trauma. METHODS: Forty-four adult offspring of veterans with PTSD and 29 offspring of veterans without PTSD were included in the study, from a total of 46 veterans. War exposure intensity, lifetime PTSD, and the general psychopathology (with Brief Symptom Inventory-BSI) of the veterans were studied, as were childhood trauma, attachment, and the general psychopathology (with BSI) of their offspring. RESULTS: Veterans' war exposure was associated with BSI in the offspring with regard to somatisation (ß = 0.025; CI 0.001, 0.050), phobic anxiety (ß = 0.014; CI: 0.000, 0.027), Global Severity Index (GSI) (ß = 0.022; CI 0.005, 0.038), and Positive Symptom Distress Index (ß = 0.020; CI 0.006, 0.033). The fathers' GSI mediated only 18% of the effect of the veterans' total war exposure on offspring's GSI. Fathers' war exposure was associated with offspring's physical neglect as a childhood adversity, although non-significantly (p = 0.063). None of the other variables was associated with veterans' war exposure, and veterans' lifetime PTSD was not associated with any of the variables studied. CONCLUSIONS: The offspring of war veterans showed increased psychological suffering as a function of their fathers' war exposure intensity, but not of their fathers' lifetime PTSD. These results could be used to suggest that mental health support for veterans' offspring should consider the war exposure intensity of their fathers, and not just psychopathology. This could spare offspring's suffering if this mental health support could be delivered early on, after veterans return from war.

Visceral adipose tissue and carotid intima-media thickness in HIV-infected patients undergoing cART: a prospective cohort study.

BACKGROUND: Combined antiretroviral therapy (cART) in HIV-infected patients has been associated with lipodystrophy, metabolic abnormalities, and an increased risk of cardiovascular disease. Ultrasound measures of carotid artery intima-media thickness (cIMT) have been used as a valid measure of subclinical atherosclerosis and as a tool to predict the risk of cardiovascular events. Our aim was to evaluate the progression of cIMT in HIV-infected patients subjected to cART, with and without lipodystrophy, over a one-year period. METHODS: We performed a one-year prospective cohort study to compare changes in cIMT, metabolic and inflammation markers in HIV-infected patients undergoing cART. Body composition was assessed by dual-energy X-ray absorptiometry (DXA) and abdominal computed tomography (CT). Levels of blood pressure, lipids and inflammatory markers were evaluated, as well as ultrasound measures of cIMT. Lipodystrophy defined by Fat Mass Ratio (L-FMR) is measured as the ratio of the percentage of trunk fat mass to the percentage of lower limb fat mass by DXA. Categorical variables were compared, using the chi-square or Fisher's exact test. Wilcoxon ranks tests and the McNemar chi-square tests were used to compare results of selected variables, from the first to the second year of evaluation. Means of cIMT, adjusted for age, glucose, triglycerides levels, systolic blood pressure (SBP), and waist to hip ratio were calculated, using generalised linear models for repeated measures. RESULTS: L-FMR was present in 44.3% of patients, and the mean of cIMT increased significantly in this group [0.82 (0.26) vs 0.92 (0.33); p = 0.037], as well as in patients without lipodystrophy [0.73 (0.20) vs 0.84 (0.30); p = 0.012]. In the overall sample, the progression of cIMT was statistically significant after the adjustment for age, glucose, triglycerides, and SBP, but the significance of the progression ceased after the adjustment for waist/hip ratio [0.770 (0.737-0.803) vs 0.874 (0.815-0.933); p = 0.514]. CONCLUSIONS: Carotid IMT progressed significantly in both groups of this HIV-infected cohort, however no association between the progression of cIMT and the presence of lipodystrophy defined by FMR was found. Visceral adipose tissue had an impact on the increment of cIMT, both in patients with, and without lipodystrophy defined by FMR.

Diabetes mellitus in HIV-infected patients: fasting glucose, A1c, or oral glucose tolerance test - which method to choose for the diagnosis?

BACKGROUND: Antiretroviral therapy dramatically reduced HIV-related morbidity and mortality, prolonging the lifespan of HIV-infected patients. Greater duration of infection and exposure to antiretroviral therapy makes these patients susceptible to traditional cardio-metabolic risk factors and pathologies. The optimal diagnostic protocol for Diabetes Mellitus in these patients is still controversial. Haemoglobin A1c (HbA1c) has been shown to underestimate glycaemia levels and the oral glucose tolerance test (OGTT) has been shown to reveal cases of glucose metabolism disturbances in patients with normal fasting glucose. Thus, this study aimed to determine the prevalence of prediabetes and diabetes in a population of HIV-infected patients undergoing combined antiretroviral therapy, using three different diagnostic methods (fasting glucose, OGTT and HbA1c), to determine the agreement between the different methods and the characteristics associated with each one. METHODS: This study analyzed 220 HIV-infected patients on antiretroviral therapy. Patient characteristics were collected using a standardized protocol. Disturbances of glucose homeostasis were defined by the ADA 2017 criteria. Patients were characterized according to the presence or absence of clinical lipodystrophy, and distributed into four different categories, according to the presence, or absence of either clinical lipoatrophy, or abdominal prominence. Insulin resistance was assessed by HOMA-IR and QUICKI indexes. Agreement between the diagnostic methods was assessed by Cohen's kappa coefficient. RESULTS: There were no patients diagnosed with diabetes with HbA1c. 5.9% prevalence was obtained when OGTT was used, and 3.2% prevalence when fasting glucose was used. Prediabetes had a prevalence of 14.1% when using HbA1c, 24.1% when using OGTT, and 20% when using fasting glucose. In all three methods, glucose homeostasis disturbances were associated with older age and higher resistance to insulin. Regarding other characteristics, associations varied between the three methods. The agreement between them was fair, or slight. CONCLUSIONS: We observed that HbA1c was the method that diagnosed the least amount of cases and that OGTT was the one that diagnosed the most cases. Accordingly, our results indicate that HbA1c underestimated glycaemia levels in this population and that the use of OGTT might allow an earlier diagnosis of glucose homeostasis disturbances, potentially making it possible to avoid severe complications of DM.

HIV-Infected Patients With and Without Lipodystrophy Under Combined Antiretroviral Therapy: Evaluation of Body Composition.

In HIV-infected patients, combined antiretroviral therapy (cART) is associated to adipose tissue redistribution known as lipodystrophy and associated cardiometabolic risk. This study aimed to evaluate the evolution of body composition in HIV-infected patients, with and without lipodystrophy, over 2 yr. We evaluated anthropometric parameters and body composition by whole-body dual-energy X-ray absorptiometry in 144 HIV-infected patients on cART. We defined lipodystrophy by fat mass ratio. Lipodystrophy was present in 45.77% of the patients. These patients presented higher HIV infection duration, cART duration, and CD4+ cell count, with no differences regarding gender, age, body mass index, and viral load. Patients with lipodystrophy showed an increase in total fat mass (9.9%) and upper-limbs fat mass (17.6%), with a decrease in total, trunk, and lower-limbs fat-free mass (2.2%; 2.2%, and 3.9%, respectively), over 2 yr. In patients without lipodystrophy, the trunk fat-free mass decreased 1.9% over time, and no changes were observed in the other studied parameters. In patients with lipodystrophy, there was predominantly a central fat mass gain, with no changes in lower limbs, suggesting that peripheral adipocytes lose their regenerative capacity.

Pregnancy after bariatric surgery: Maternal and fetal outcomes of 39 pregnancies and a literature review.

AIM: We aimed to evaluate the impact of bariatric surgery (BS) on maternal and fetal outcomes. METHODS: A retrospective, descriptive, observational study of 39 pregnant women who underwent BS in our institution between 2010 and 2014 was carried out. A sample of women who became pregnant after BS was evaluated, based on data concerning pregnancy, childbirth, and newborns. RESULTS: Of the 1182 patients who underwent BS at our institution during the study period, 1016 (85.9%) were women. Thirty-nine of these women (with an average age of 31 ± 4.8 years) became pregnant (one twin pregnancy) and 29 of the 39 had undergone a gastric bypass. The mean time interval between BS and pregnancy was 16.6 ± 4.8 months; however, 16 (41%) women became pregnant less than a year after BS. The pre-BS body mass index (BMI) of the 39 women was 44.5 ± 6.2 kg/m2 . The women had a mean BMI of 30.2 ± 3.8 kg/m2 when they got pregnant and they gained 13.2 ± 7.3 kg during pregnancy. Iron deficiency was observed in 18 (46.1%) women, 16 (45.7%) had vitamin B12 deficiency, 12 (66.8%) had zinc deficiency, and 20 (60.6%) had vitamin D deficiency. Three women developed gestational diabetes mellitus. Premature rupture of membranes occurred in two pregnancies, preterm delivery in five, and there was one spontaneous abortion. Cesarean section was performed in seven cases. The average newborn weight was 3002 ± 587 g, five were small for gestational age, and one had macrosomia. Three infants had to be admitted to an intensive care unit. CONCLUSION: Although pregnancy after BS is safe and well tolerated, close monitoring by a multidisciplinary team is required to evaluate complications resulting from BS, especially a deficit of micronutrients.